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Lau J, Khoo AMG, Choe L, Hoon A, Tan KK. Quantifying chemotherapy-induced cognitive impairment in gastrointestinal cancer patients: A scoping review of methodological concerns in the literature. Asia Pac J Clin Oncol 2025; 21:141-149. [PMID: 38808735 DOI: 10.1111/ajco.14082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 12/19/2023] [Accepted: 05/13/2024] [Indexed: 05/30/2024]
Abstract
PURPOSE Chemotherapy is one of the common treatments in cancer management. However, chemotherapy-induced cognitive impairment (CICI) is one notable side effect that can greatly impact a patient's quality of life. Literature on CICI in gastrointestinal (GI) cancers are few and inconsistent. This review aims to identify the methodological differences in such studies. METHODS A systematic search was performed in four electronic databases. All peer-reviewed primary literature published in English that evaluated cognitive-related functioning scores related to chemotherapy in GI cancer patients were included. Information about each study such as CICI findings, study limitations, methodology, and sample characteristics was extracted and synthesized. RESULTS A total of 19 studies were included. Evidence of CICI was found in 50.0% (8 of 16) and 62.5% (5 of 8) studies that used objective and subjective measures, respectively. Methodological differences such as groups used for comparison, instruments used, and assessment from the length of time since chemotherapy were highlighted between studies that did and did not find evidence of CICI. CONCLUSIONS This review suggests that the mixed findings can be attributed to the heterogeneous methodologies adopted in the evaluation of CICI in this field. IMPLICATIONS FOR CANCER SURVIVORS Further studies are necessary to establish the presence and chronicity of CICI, and in which groups of patients to facilitate targeted interventions and treatments.
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Affiliation(s)
- Jerrald Lau
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Athena Ming-Gui Khoo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Lina Choe
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Alyssa Hoon
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Ker-Kan Tan
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
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2
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Mitea G, Iancu IM, Schröder V, Roșca AC, Iancu V, Crețu RM, Mireșan H. Therapeutic Potential of Prunus Species in Gastrointestinal Oncology. Cancers (Basel) 2025; 17:938. [PMID: 40149274 PMCID: PMC11940452 DOI: 10.3390/cancers17060938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/01/2025] [Accepted: 03/06/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Gastrointestinal tract cancers represent a significant worldwide health concern, accounting for almost one-third of cancer-related deaths. The existing chemotherapy drugs used in gastrointestinal cancers are ineffective, so prognosis is poor, recurrence and metastasis rates are high, and survival time remains short, necessitating the development of novel antitumor drugs that exhibit low toxicity and less potential for the development of drug resistance. This challenge is considerable, but evidence from the past decades supports the medicinal properties and functionalities of bioactive compounds such as flavonoids and acid phenolics with anticancer activities. Our purpose was to find data on the relationship between gastrointestinal cancer and bioactive compounds from Prunus species, focusing on their molecular mechanisms of action. RESULTS Studies highlight the potential of bioactive compounds from Prunus species to modulate the cancer cell signaling pathways involved in gastrointestinal tumorigenesis. CONCLUSIONS The studies reviewed suggest that polyphenols from Prunus species exhibit promising gastrointestinal anticancer activities and could represent an adjunctive therapeutic strategy in cancer treatment. Further studies are necessary to validate these compounds' therapeutic potential and their feasibility as cost-effective treatments for cancer.
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Affiliation(s)
- Gabriela Mitea
- Department of Pharmacology, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania;
| | - Irina Mihaela Iancu
- Department of Toxicology, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania;
| | - Verginica Schröder
- Department of Cellular and Molecular Biology, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania
| | - Adrian Cosmin Roșca
- Department of Analysis and Quality Control of Drugs, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania;
| | - Valeriu Iancu
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania;
| | - Ruxandra-Mihaela Crețu
- National Institute of Research and Development for Biological Sciences, “Stejarul” Biological Research Centre, 060031 Bucharest, Romania;
| | - Horațiu Mireșan
- Department of Toxicology, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania;
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Zheng X, Wu L, Li L, Wang Y, Yin Q, Han L, Wu X, Bian Y. Development and validation of a prediction model for VTE risk in gastric and esophageal cancer patients. Front Pharmacol 2025; 16:1448879. [PMID: 40093315 PMCID: PMC11906997 DOI: 10.3389/fphar.2025.1448879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 02/10/2025] [Indexed: 03/19/2025] Open
Abstract
Objective This study focuses on the risk of venous thromboembolism (VTE) in patients with gastric or esophageal cancer (GC/EC), investigating the risk factors for VTE in this population. Utilizing machine learning techniques, the research aims to develop an interpretable VTE risk prediction model. The goal is to identify patients with gastric or esophageal cancer who are at high risk of VTE at an early stage in clinical practice, thereby enabling precise anticoagulant prophylaxis and thrombus management. Methods This study is a real-world investigation aimed at predicting VTE in patients with GC/EC. Data were collected from inpatients diagnosed with GC/EC at Sichuan Provincial People's Hospital between 1 January 2018, and 31 June 2023. Using nine supervised learning algorithms, 576 prediction models were developed based on 56 available variables. Subsequently, a simplified modeling approach was employed using the top 12 feature variables from the best-performing model. The primary metric for assessing the predictive performance of the models was the area under the ROC curve (AUC). Additionally, the training data used to construct the best model in this study were employed to externally validate several existing assessment models, including the Padua, Caprini, Khorana, and COMPASS-CAT scores. Results A total of 3,742 cases of GC/EC patients were collected after excluding duplicate visit information. The study included 861 (23.0%) patients, of which 124 (14.4%) developed VTE. The top five models based on AUC for full-variable modeling are as follows: GBoost (0.9646), Logic Regression (0.9443), AdaBoost (0.9382), CatBoost (0.9354), XGBoost (0.8097). For simplified modeling, the models are: Simp-CatBoost (0.8811), Simp-GBoost (0.8771), Simp-Random Forest (0.8736), Simp-AdaBoost (0.8263), Simp-Logistic Regression (0.8090). After evaluating predictive performance and practicality, the Simp-GBoost model was determined as the best model for this study. External validation of the Padua score, Caprini score, Khorana score, and COMPASS-CAT score based on the training set of the Simp-GBoost model yielded AUCs of 0.4367, 0.2900, 0.5000, and 0.3633, respectively. Conclusion In this study, we analyzed the risk factors of VTE in GC/EC patients, and constructed a well-performing VTE risk prediction model capable of accurately identifying the extent of VTE risk in patients. Four VTE prediction scoring systems were introduced to externally validate the dataset of this study. The results demonstrated that the VTE risk prediction model established in this study held greater clinical utility for patients with GC/EC. The Simp-GB model can provide intelligent assistance in the early clinical assessment of VTE risk in these patients.
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Affiliation(s)
| | | | | | | | | | - Lizhu Han
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xingwei Wu
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yuan Bian
- Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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4
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Wang J, Yang X, Shen W, Huang Y, Mao W, Zhao A. Insights into the characteristics of cancer incidence in China. SCIENCE CHINA. LIFE SCIENCES 2025:10.1007/s11427-024-2839-4. [PMID: 40029450 DOI: 10.1007/s11427-024-2839-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/10/2025] [Indexed: 03/05/2025]
Affiliation(s)
- Jiahui Wang
- Zhejiang Cancer Institute, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310011, China
| | - Xuping Yang
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310011, China
| | - Wenhui Shen
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310011, China
| | - Yueyu Huang
- Zhejiang Cancer Institute, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310011, China
| | - Weimin Mao
- Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310011, China.
- Thoracic Oncology Laboratory, Jiangxi Cancer Hospital, Nanchang Medical College, Nanchang, 330029, China.
| | - An Zhao
- Zhejiang Cancer Institute, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, 310011, China.
- Thoracic Oncology Laboratory, Jiangxi Cancer Hospital, Nanchang Medical College, Nanchang, 330029, China.
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Chen Y, Liu D, Wei K, Lin Y, Wang Z, Sun Q, Wang H, Peng J, Lian L. Carcinoembryonic antigen trajectory predicts pathological complete response in advanced gastric cancer after neoadjuvant chemotherapy. Front Oncol 2025; 15:1525324. [PMID: 39995833 PMCID: PMC11847669 DOI: 10.3389/fonc.2025.1525324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Accepted: 01/22/2025] [Indexed: 02/26/2025] Open
Abstract
Aims This study aims to develop a simple, clinically applicable classification system to predict pCR based on carcinoembryonic antigen (CEA) trajectory during NAC. Methods This study included 366 AGC patients who received NAC followed by radical gastrectomy. CEA levels were measured before, during, and after NAC, with changes classified into three trajectory types: Type I (>=80% decline), Type II (>=40% but <80% decline), and Type III (<40% decline or increase). We analyzed associations between these CEA trajectories, pCR, lymph node remission, and survival. Results pCR was achieved in 10.4% (38/366) of patients. pCR rates were significantly higher in Type I (41%) and Type II (15.8%) trajectories compared to Type III (6.7%). Lymph node remission also correlated with CEA trajectories, with Type I having the highest proportion of ypN0 (79.2%). Multivariate analysis identified CEA trajectory subtypes and tumor differentiation as independent predictors of pCR. This classification system proved robust across subgroups. Although no significant differences in overall survival were observed between subtypes, higher initial CEA levels were associated with worse survival. Conclusion The trajectory of CEA change during NAC is a promising predictor of pCR in AGC. This simple and accessible classification system may facilitate personalized surgical strategies for patients with AGC.
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Affiliation(s)
- Yonghe Chen
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dan Liu
- Department of Laboratory Science, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Kaikai Wei
- Department of Radiology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yi Lin
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhong Wang
- School of Nursing, Sun Yat-sen University, Guangzhou, China
| | - Qian Sun
- School of Nursing, Sun Yat-sen University, Guangzhou, China
| | - Huashe Wang
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junsheng Peng
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lei Lian
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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6
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Liu B, Xie Y, Zhang Y, Tang G, Lin J, Yuan Z, Liu X, Wang X, Huang M, Luo Y, Yu H. Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity. Cell Biosci 2025; 15:7. [PMID: 39844296 PMCID: PMC11756021 DOI: 10.1186/s13578-024-01337-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 12/09/2024] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure and drug resistance. However, the lack of a quick and convenient approach to determine the intratumoral epigenetic heterogeneity (eITH) limit the application of eITH in clinical settings. Here, we aimed to develop a tool that can evaluate the eITH using the DNA methylation profiles from bulk tumors. METHODS Genomic DNA of three laser micro-dissected tumor regions, including digestive tract surface, central bulk, and invasive front, was extracted from formalin-fixed paraffin-embedded sections of colorectal cancer patients. The genome-wide methylation profiles were generated with methylation array. The most variable methylated probes were selected to construct a DNA methylation-based heterogeneity (MeHEG) estimation tool that can deconvolve the proportion of each reference tumor region with the support vector machine model-based method. A PCR-based assay for quantitative analysis of DNA methylation (QASM) was developed to specifically determine the methylation status of each CpG in MeHEG assay at single-base resolution to realize fast evaluation of epigenetic heterogeneity. RESULTS In the discovery set with 79 patients, the differentially methylated CpGs among the three tumor regions were found. The 7 most representative CpGs were identified and subsequently selected to develop the MeHEG algorithm. We validated its performance of deconvolution of tumor regions in an independent cohort. In addition, we showed the significant association of MeHEG-based epigenetic heterogeneity with the genomic heterogeneity in mutation and copy number variation in our in-house and TCGA cohorts. Besides, we found that the patients with higher MeHEG score had worse disease-free and overall survival outcomes. Finally, we found dynamic change of epigenetic heterogeneity based on MeHEG score in cancer cells under the treatment of therapeutic drugs. CONCLUSION By developing a 7-loci panel using a machine learning approach combined with the QASM assay for PCR-based application, we present a valuable method for evaluating intratumoral heterogeneity. The MeHEG algorithm offers novel insights into tumor heterogeneity from an epigenetic perspective, potentially enriching current knowledge of tumor complexity and providing a new tool for clinical and research applications in cancer biology.
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Affiliation(s)
- Binbin Liu
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
| | - Yumo Xie
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
| | - Yu Zhang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
| | - Guannan Tang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
| | - Jinxin Lin
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
| | - Ze Yuan
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
| | - Xiaoxia Liu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Ministry of Education, Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Guangzhou, Guangdong, China
- Innovation Center of the Sixth Affiliated Hospital, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaolin Wang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Ministry of Education, Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Guangzhou, Guangdong, China
- Innovation Center of the Sixth Affiliated Hospital, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Meijin Huang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Ministry of Education, Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Guangzhou, Guangdong, China
- Innovation Center of the Sixth Affiliated Hospital, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yanxin Luo
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Ministry of Education, Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Guangzhou, Guangdong, China
- Innovation Center of the Sixth Affiliated Hospital, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Huichuan Yu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China.
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
- Ministry of Education, Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Guangzhou, Guangdong, China.
- Innovation Center of the Sixth Affiliated Hospital, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
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7
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Li L, Geng Y, Chen T, Lin K, Xie C, Qi J, Wei H, Wang J, Wang D, Yuan Z, Wan Z, Li T, Luo Y, Niu D, Li J, Yu H. Deep learning model targeting cancer surrounding tissues for accurate cancer diagnosis based on histopathological images. J Transl Med 2025; 23:110. [PMID: 39849586 PMCID: PMC11755804 DOI: 10.1186/s12967-024-06017-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 12/18/2024] [Indexed: 01/25/2025] Open
Abstract
Accurate and fast histological diagnosis of cancers is crucial for successful treatment. The deep learning-based approaches have assisted pathologists in efficient cancer diagnosis. The remodeled microenvironment and field cancerization may enable the cancer-specific features in the image of non-cancer regions surrounding cancer, which may provide additional information not available in the cancer region to improve cancer diagnosis. Here, we proposed a deep learning framework with fine-tuning target proportion towards cancer surrounding tissues in histological images for gastric cancer diagnosis. Through employing six deep learning-based models targeting region-of-interest (ROI) with different proportions of no-cancer and cancer regions, we uncovered the diagnostic value of non-cancer ROI, and the model performance for cancer diagnosis depended on the proportion. Then, we constructed a model based on MobileNetV2 with the optimized weights targeting non-cancer and cancer ROI to diagnose gastric cancer (DeepNCCNet). In the external validation, the optimized DeepNCCNet demonstrated excellent generalization abilities with an accuracy of 93.96%. In conclusion, we discovered a non-cancer ROI weight-dependent model performance, indicating the diagnostic value of non-cancer regions with potential remodeled microenvironment and field cancerization, which provides a promising image resource for cancer diagnosis. The DeepNCCNet could be readily applied to clinical diagnosis for gastric cancer, which is useful for some clinical settings such as the absence or minimum amount of tumor tissues in the insufficient biopsy.
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Affiliation(s)
- Lanlan Li
- Fujian Key Lab for Intelligent Processing and Wireless Transmission of Media Information, College of Physics and Information Engineering, Fuzhou University, Fuzhou, 350108, China
| | - Yi Geng
- Fujian Key Lab for Intelligent Processing and Wireless Transmission of Media Information, College of Physics and Information Engineering, Fuzhou University, Fuzhou, 350108, China
| | - Tao Chen
- Fujian Key Lab for Intelligent Processing and Wireless Transmission of Media Information, College of Physics and Information Engineering, Fuzhou University, Fuzhou, 350108, China
| | - Kaixin Lin
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China
| | - Chengjie Xie
- Fujian Key Lab for Intelligent Processing and Wireless Transmission of Media Information, College of Physics and Information Engineering, Fuzhou University, Fuzhou, 350108, China
| | - Jing Qi
- Fujian Key Lab for Intelligent Processing and Wireless Transmission of Media Information, College of Physics and Information Engineering, Fuzhou University, Fuzhou, 350108, China
| | - Hongan Wei
- Fujian Key Lab for Intelligent Processing and Wireless Transmission of Media Information, College of Physics and Information Engineering, Fuzhou University, Fuzhou, 350108, China
| | - Jianping Wang
- Department of Gastroenterology, Third People's Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, Fujian, China
| | - Dabiao Wang
- College of Chemical and Engineering, Fuzhou University, Fuzhou, 350108, China
| | - Ze Yuan
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
| | - Zixiao Wan
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
| | - Tuoyang Li
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
| | - Yanxin Luo
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China
| | - Decao Niu
- Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, 510000, China.
| | - Juan Li
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
- Department of Endoscopic Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
| | - Huichuan Yu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Guangdong Institute of Gastroenterology, Guangzhou, 510655, Guangdong, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, Guangdong, China.
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, China.
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8
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Chen Y, He J, Zheng J, Lin Y, Wang H, Lian L, Peng J. Impact of pathological complete response on survival in gastric cancer after neoadjuvant chemotherapy: a propensity score matching analysis. BMC Gastroenterol 2025; 25:11. [PMID: 39789426 PMCID: PMC11720295 DOI: 10.1186/s12876-025-03594-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 01/06/2025] [Indexed: 01/12/2025] Open
Abstract
PURPOSE The survival benefits of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) patients are inconsistent. This study aims to investigate how different tumor regression grades (TRG) influence the survival gains associated with NAC treatment. METHODS This study compared the treatment outcomes of patients who underwent CSC (neoadjuvant chemotherapy - surgery - adjuvant chemotherapy) with those receiving traditional SC (surgery - adjuvant chemotherapy) treatment. Propensity score matching (PSM) was employed to minimize potential biases arising from differences in baseline characteristics and intervention factors between the treatment groups. After PSM, the CSC cohort was stratified according to TRGs, and their survival outcomes were compared to assess the impact of TRGs on survival gains associated with NAC. RESULTS Before PSM, a total of 506 patients were enrolled: 291 in the CSC cohort and 215 in the SC cohort. The CSC cohort had a lower 3-year survival rate (3Y-SR) than the SC cohort (64.6% vs. 76%). In the CSC cohort, patients who achieved pathological complete response (pCR, 12.1%, 26/215) demonstrated significantly improved 3Y-SR (95.5%). After PSM, 110 patients were matched in each cohort. The 3Y-SR was similar between the CSC cohort (68.3%) and the SC cohort (63.6%). In the CSC cohort, 12.7% (14/110) of patients achieved pCR. Subgroup analysis revealed that the pCR subgroup (3Y-SR 100%) was the only subgroup within the CSC cohort that maintained significantly improved survival compared to the SC cohort. Better tumor differentiation was the only pre-treatment factor significantly associated with achieving pCR (p < 0.001). CONCLUSION In this retrospective study, LAGC patients who achieved pCR after NAC demonstrated significantly better survival outcomes compared to other response groups. The study found tumor differentiation was a potential predictor of pCR.
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Affiliation(s)
- Yonghe Chen
- Department of General Surgery (Gastrointestinal Surgery, Unit 1), The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Jiasheng He
- Department of Thoracic Surgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China
| | - Jiabo Zheng
- Department of General Surgery (Gastrointestinal Surgery, Unit 1), The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Yi Lin
- Department of General Surgery (Gastrointestinal Surgery, Unit 1), The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Huashe Wang
- Department of General Surgery (Gastrointestinal Surgery, Unit 1), The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China
| | - Lei Lian
- Department of General Surgery (Gastrointestinal Surgery, Unit 1), The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
| | - Junsheng Peng
- Department of General Surgery (Gastrointestinal Surgery, Unit 1), The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China.
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9
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Anderesen CK, Al-Najami I, Liu W, Orwoll E, Folkestad L. Risk of Gastrointestinal Diseases in Osteogenesis Imperfecta: A Nationwide, Register-Based Cohort Study. Calcif Tissue Int 2025; 116:15. [PMID: 39751887 DOI: 10.1007/s00223-024-01311-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 11/19/2024] [Indexed: 01/04/2025]
Abstract
Osteogenesis imperfecta (OI) is a group of rare genetic disorders most commonly caused by reduced amount of biologically normal collagen type I, a structural component of the gastrointestinal tract and abdominal wall. The risk of gastrointestinal (GI) disease in individuals with OI is not well understood, despite GI complaints being frequently reported by the OI population. To investigate the risk of GI diseases in individuals with OI. A Danish nationwide register-based cohort study utilizing data from the Danish National Patient Register and the Danish National Prescription Register. All individuals registered with an OI diagnosis in Denmark from 1995 through 2018, along with a reference population matched 1:5 based on sex, birth year, and month. Sub-hazard ratios (SHR) for peptic ulcer disease, diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, constipation, abdominal wall hernia, and other reasons for abdominal discomfort. The study included 864 individuals with OI (472 women) and 4,276 in the reference population (2,332 women). The SHR was significantly increased for ulcer (3.28 [95% CI 2.21-4.28]), constipation (2.67 [1.91-3.74]), and hernia (among women: 1.85 [1.22-2.80]). Higher SHRs were also observed for inflammatory bowel disease, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain. SHRs were not statistically significantly increased for diverticular disease, gastrointestinal cancers, intestinal obstruction with ileus, kidney stones or hemorrhoid disease. Individuals with OI have a higher risk of peptic ulcer disease, constipation, hernia among women, inflammatory bowel diseases, biliary and pancreatic diseases, appendicitis, and unspecified abdominal pain, compared with the general population.
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Affiliation(s)
| | - Issam Al-Najami
- Department of Surgery, Odense University Hospital, Odense, Denmark
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Winnie Liu
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Eric Orwoll
- Department of Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Lars Folkestad
- Department of Endocrinology, Odense University Hospital, Odense, Denmark.
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
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Chen J, Zhang Y, Chen X, Luo D, Liu D, Yu Z, Lin Y, He X, Huang J, Lian L. Raddeanin A Inhibits Colorectal Cancer Growth and Ameliorates Oxaliplatin Resistance Through the WNT/β-Catenin Signaling Pathway. Cancer Biother Radiopharm 2025; 40:41-53. [PMID: 39585204 DOI: 10.1089/cbr.2024.0061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2024] Open
Abstract
Background: Chemotherapy based on oxaliplatin (OXA) is the first-line treatment for advanced colorectal cancer (CRC), and acquired resistance to OXA is the main reason for clinical treatment failure in CRC. Methods: To search for compounds that can reverse OXA resistance, we screened a small molecule inhibitor drug library and identified a drug, Raddeanin A (RA), that enhanced the anticancer effect of OXA. Using human CRC cell lines, CRC organoid models, and in vivo subcutaneous tumorigenic studies, we determined that RA inhibits the proliferation of CRC cells by promoting apoptosis and inducing cell cycle arrest. Results: We constructed OXA-resistant CRC cell lines and demonstrated that RA enhances the sensitivity of these cells to OXA. Further experiments showed that the mechanism by which RA enhanced the anticancer effects of OXA in CRC was by inhibiting the activation of the WNT/β-catenin signaling pathway. Conclusions: Because RA has been shown to be biocompatible in animal models, there is a possibility that RA could be developed as a sensitizer for resistant cancer cells or as a novel lead compound to enhance the therapeutic efficacy of OXA in resistant CRCs.
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Affiliation(s)
- Junguo Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Thoracic Surgery, Thoracic Cancer Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanhong Zhang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xijie Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of General Surgery (Gastrointestinal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dandong Luo
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of General Surgery (Gastrointestinal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Danlin Liu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhaoliang Yu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yanyun Lin
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xiaosheng He
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Juanni Huang
- Department of Geriatrics, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China
| | - Lei Lian
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of General Surgery (Gastrointestinal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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11
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Zhang Y, Zhao F, Guo J, Liu Y, Cai M, Ding X, Li B, Zhang L, Zhang R, Deng J. The clinical significance assessment of the transverse lymph node metastasis in gastric cancer: The establishment and validation of nomogram from a single clinical medical center. Dig Liver Dis 2025; 57:125-133. [PMID: 39034188 DOI: 10.1016/j.dld.2024.07.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 06/22/2024] [Accepted: 07/07/2024] [Indexed: 07/23/2024]
Abstract
BACKGROUND Lymph node metastasis is an important route for gastric cancer metastasis. The clinical significance of transverse lymph node metastasis (TLNM) is still unclear. AIMS This study investigates effects of TLNM on the prognosis of GC patients and establishes two nomograms for evaluating the prognosis of GC patients and for predicting the risk clinicopathological factors to TLNM based on a Chinese medical database. METHODS A total of 902 GC patients with lymph node metastasis (LNM) who underwent R0 gastrectomy was included in this study. According to results of Cox proportional hazards analyses and logistic regression analyses, the prognostic and the predictive nomograms were established and validated. RESULTS The overall survival of patients with TLNM was significantly worse than those without TLNM (P < 0.001) and similar to patients with extra-gastric LNM (P > 0.05). TLNM independently influenced prognosis of GC patients. Prognostic and predictive nomograms were established and validated. Both nomograms were proven that have high accuracy by calculating each AUC (Area Under Cure) value. Calibration curves aligned well with actual outcomes. DCA (Decision Curve Analyses) analyses indicated the high clinical utility. CONCLUSION These nomograms offer precise survival and TLNM occurrence predictions, which may aid clinical decisions.
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Affiliation(s)
- Yizhao Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Fucheng Zhao
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Jiamei Guo
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Yong Liu
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Mingzhi Cai
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Xuewei Ding
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Bin Li
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Li Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Rupeng Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Jingyu Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
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12
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Vieira Maroun E, Argente Pla M, Pedraza Serrano MJ, Muresan BT, Ramos Prol A, Gascó Santana E, Martín Sanchis S, Durá De Miguel Á, Micó García A, Cebrián Vázquez A, Durbá Lacruz A, Merino-Torres JF. Phase Angle and Ultrasound Assessment of the Rectus Femoris for Predicting Malnutrition and Sarcopenia in Patients with Esophagogastric Cancer: A Cross-Sectional Pilot Study. Nutrients 2024; 17:91. [PMID: 39796524 PMCID: PMC11723315 DOI: 10.3390/nu17010091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 12/15/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Disease-related malnutrition (DRM) and sarcopenia are prevalent conditions in gastrointestinal cancer patients, whose early diagnosis is essential to establish a nutritional treatment that contributes to optimizing adverse outcomes and improving prognosis. Phase angle (PhA) and rectus femoris ultrasound measurements are considered effort-independent markers of muscle wasting, which remains unrecognized in oncology patients. OBJECTIVE This study aimed to evaluate the potential utility of PhA, rectus femoris cross-sectional area (RFCSA), and rectus femoris thickness (RF-Y-axis) in predicting malnutrition and sarcopenia in patients with esophagogastric cancer (EGC). METHODS This was a cross-sectional study of patients diagnosed with EGC. PhA was obtained using bioelectrical impedance vector analysis (BIVA) along with ASMMI. The RFCSA and RF-Y-axis were measured using nutritional ultrasound (NU®). Muscle capacity was assessed using handgrip strength (HGS), and functionality by applying the Short Physical Performance Battery (SPPB). Malnutrition and sarcopenia were determined according to the GLIM and EWGSOP2 criteria, respectively. RESULTS Out of the 35 patients evaluated, 82.8% had malnutrition and 51.4% had sarcopenia. The RFCSA (r = 0.582) and RF-Y-axis (r = 0.602) showed significant, moderate correlations with ASMMI, unlike PhA (r = 0.439), which displayed a weak correlation with this parameter. However, PhA (OR = 0.167, CI 95%: 0.047-0.591, p = 0.006), RFCSA (OR = 0.212, CI 95%: 0.074-0.605, p = 0.004), and RF-Y-axis (OR = 0.002, CI 95%: 0.000-0.143, p = 0.004) all showed good predicting ability for sarcopenia in the crude models, but only the RF-Y-axis was able to explain malnutrition in the regression model (OR = 0.002, CI 95%: 0.000-0.418, p = 0.023). CONCLUSIONS The RF-Y-axis emerged as the only independent predictor of both malnutrition and sarcopenia in this study, likely due to its stronger correlation with ASMMI compared to PhA and RFCSA.
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Affiliation(s)
- Erika Vieira Maroun
- Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Health Research Institute La Fe, 46026 Valencia, Spain; (E.V.M.); (J.F.M.-T.)
- Department of Medicine, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
- Facultad Ciencias de la Salud, Universidad Europea de Valencia, 46010 Valencia, Spain;
| | - María Argente Pla
- Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Health Research Institute La Fe, 46026 Valencia, Spain; (E.V.M.); (J.F.M.-T.)
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
| | | | - Bianca Tabita Muresan
- Facultad Ciencias de la Salud, Universidad Europea de Valencia, 46010 Valencia, Spain;
| | - Agustín Ramos Prol
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
| | - Eva Gascó Santana
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
| | - Silvia Martín Sanchis
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
| | - Ángela Durá De Miguel
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
| | - Andrea Micó García
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
| | - Anna Cebrián Vázquez
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
| | - Alba Durbá Lacruz
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
| | - Juan Francisco Merino-Torres
- Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Health Research Institute La Fe, 46026 Valencia, Spain; (E.V.M.); (J.F.M.-T.)
- Department of Medicine, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
- Endocrinology and Nutrition Department, La Fe University and Polytechnic Hospital in Valencia, 46026 Valencia, Spain; (A.R.P.); (E.G.S.); (S.M.S.); (Á.D.D.M.); (A.M.G.); (A.C.V.); (A.D.L.)
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Yang Y, Li S, Shi W, Jin G, Guo D, Li A, Wang B, Lu B, Feng S. Pterostilbene suppresses the growth of esophageal squamous cell carcinoma by inhibiting glycolysis and PKM2/STAT3/c-MYC signaling pathway. Int Immunopharmacol 2024; 142:113247. [PMID: 39321706 DOI: 10.1016/j.intimp.2024.113247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/19/2024] [Accepted: 09/20/2024] [Indexed: 09/27/2024]
Abstract
Pterostilbene (PTS) is a dietary phytochemical that has shown antitumor activity in many types of cancer, but the molecular mechanism remains unclear. It has also not been adequately studied on PTS against esophageal squamous cell carcinoma (ESCC). Thus, this study investigated the effect of PTS on ESCC in vitro and in vivo and explored the underlying molecular mechanism. We found that PTS can inhibit the proliferation, colony formation, and migration of ESCC cells. According to the bioinformatics analysis of proteomics, PTS had a great influence on the metabolic process of ESCC cells. KEGG analysis showed that PTS down-regulated the pyruvate metabolism pathway. Moreover, PTS can inhibit the PK activity, glucose consumption, and lactate production in ESCC cells. By administration of PTS into xenograft mice, experiment results demonstrated that PTS can suppress tumor progress and the PKM2/STAT3/c-MYC signaling pathway. We found that PTS inhibited the PKM2/STAT3/c-MYC signaling pathway by targeting PKM2 in ESCC cells. Collectively, this study revealed that PTS inhibited ESCC growth by suppressing PKM2 mediated aerobic glycolysis and PKM2/STAT3/c-MYC signaling pathway, which enriching the anti-tumor molecular mechanism of PTS and providing a theoretical basis for its clinical application.
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Affiliation(s)
- Yi Yang
- Medical College, Henan University of Chinese Medicine, Zhengzhou 450046 China; Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou 450046 China
| | - Shan Li
- Medical College, Henan University of Chinese Medicine, Zhengzhou 450046 China; Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou 450046 China
| | - Wenjie Shi
- The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450046 China
| | - Guoguo Jin
- Henan Key Laboratory of Chronic Disease Management, Fuwai Central China Cardiovascular Hospital, Zhengzhou 450018 China
| | - Dandan Guo
- Medical College, Henan University of Chinese Medicine, Zhengzhou 450046 China; Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou 450046 China
| | - Aifang Li
- Medical College, Henan University of Chinese Medicine, Zhengzhou 450046 China; Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou 450046 China
| | - Baiyan Wang
- Medical College, Henan University of Chinese Medicine, Zhengzhou 450046 China; Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou 450046 China
| | - Baoping Lu
- Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou 450046 China; The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou 450046 China.
| | - Shuying Feng
- Medical College, Henan University of Chinese Medicine, Zhengzhou 450046 China; Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou 450046 China.
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14
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Zhang R, Chen F, Weng J, Ye Z, Li X. Elevated CA19-9 within the normal range suggests poorer prognosis in stage II CRC: A retrospective analysis of a large sample in a single center. J Cancer Res Ther 2024; 20:2013-2020. [PMID: 39792411 DOI: 10.4103/jcrt.jcrt_338_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 08/21/2024] [Indexed: 01/12/2025]
Abstract
OBJECTIVE Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) serve as pivotal tumor markers in colorectal cancer (CRC). However, uncertainty persists regarding the prognostic significance of the two tumor markers when falling within the normal range. We attempt to compare the prognostic differences of tumor markers at different levels within the reference range. METHODS This retrospective study scrutinized 2,167 cases of stage II CRC verified by pathology after surgery at the Fudan University Shanghai Cancer Center. Using R software to calculate the optimal critical value to compare the clinical and pathological characteristics and prognosis of different levels of tumor markers. The survival and regression modeling strategies packages of R software drew the nomograms. RESULTS Utilizing R software, the optimal critical value of CA19-9 was determined as 12.12 U/mL and that of CEA as 1.89 U/mL. Kaplan-Meier survival analysis unveiled that, within the normal range, higher levels of CEA were linked to poorer overall survival (OS) [HR = 1.829 (1.280, 2.989), P = 0.0033] and disease-free survival (DFS) [HR = 1.472 (1.114, 1.944), P = 0.0444]. Similarly, heightened levels of CA19-9 also indicated inferior OS [HR = 1.750 (1.203, 2.455), P = 0.0076] and DFS [HR = 1.361 (1.098, 1.686), P = 0.0049]. Furthermore, multivariate analysis identified CA19-9 as an independent risk factor for OS (HR = 1.49,95% CI: 1.086-2.045, P = 0.014) and DFS (HR = 1.327,95% CI: 1.070-1.647, P = 0.01), while the impact of CEA on OS and DFS was not statistically significant. A nomogram constructed based on the Cox regression model can effectively evaluate the prognosis of CRC patients. CONCLUSION Although within the normal range, elevated CA19-9 was associated with an inferior prognosis, chemotherapy decisions of different intensities can be adjusted based on nomograms. This work will contribute to standardizing the diagnosis and treatment of stage II CRC and provide clinicians with essential insights for chemotherapy decisions.
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Affiliation(s)
- Ruoxin Zhang
- Department of Colorectal Surgery, Shanghai Cancer Center, Fudan University, Xuhui District, Shanghai, China
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Ye HY, Shang ZZ, Gao X, Zha XQ, Zhang FY, Li QM, Liu J, Luo JP. Dendrobium huoshanense stem polysaccharide exhibits gastroprotective effect via regulating PI3K/AKT, NF-κB and Nrf-2 signaling in high-salt diet-induced gastritis mice. FOOD BIOSCI 2024; 62:105309. [DOI: 10.1016/j.fbio.2024.105309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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16
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Zhang H, Yang W, Tan X, He W, Zhao L, Liu H, Li G. Long-term relative survival of patients with gastric cancer from a large-scale cohort: a period-analysis. BMC Cancer 2024; 24:1420. [PMID: 39558281 PMCID: PMC11571998 DOI: 10.1186/s12885-024-13141-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 11/04/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND Gastric cancer poses a significant global health challenge. We aim to use period analysis to assess the changes in gastric cancer treatment at our center over the past 15 years. This study reflects the current state of gastric cancer treatment at our center and provides valuable data to support clinical advancements. METHOD We used period analysis to evaluate the survival status of 3915 patients with gastric cancer at Nanfang Hospital, Southern Medical University, over a 15-year period spaning from 2008 to 2022. The 5-year relative survival rates were analyzed. RESULT Our findings indicate that the 5-year relative survival rate at our center from 2018 to 2022 is 71.4%. From 2018 to 2022, the 5-year relative survival rates for patients aged < 40, 40-54, 55-69, and ≥ 70 reached 67.5%, 73.5%, 72.0%, and 67.1%, respectively. For stage IV patients, the 5-year relative survival rate reached 29% in 2018-2022. For stage I-III patients, the 5-year relative survival rate reached 89.7% in 2018-2022. The five-year relative survival rate for patients who underwent laparoscopic surgery at our center rose from 50.3% in 2008-2012 to 71.4% in 2018-2022. Overall, there has been a notable increase in the 5-year relative survival rates, regardless of age, gender, region, or tumor stage. CONCLUSION Period analysis over the past 15 years shows significant improvement in the 5-year survival rate for gastric cancer at our center. This progress is due to standardized surgical techniques, perioperative management, and immunotherapy, providing robust data for evaluating the efficacy of recent treatments.
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Affiliation(s)
- Hengyi Zhang
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Weihao Yang
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xin Tan
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Wenjun He
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Liying Zhao
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Hao Liu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Guoxin Li
- Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
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Li P, Zhou D, Xie Y, Yuan Z, Huang M, Xu G, Huang J, Zhuang Z, Luo Y, Yu H, Wang X. Targeting G-quadruplex by TMPyP4 for inhibition of colorectal cancer through cell cycle arrest and boosting anti-tumor immunity. Cell Death Dis 2024; 15:816. [PMID: 39528472 PMCID: PMC11554887 DOI: 10.1038/s41419-024-07215-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/30/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024]
Abstract
G-quadruplex (G4) is a noncanonical DNA secondary structure known to induce DNA damage and regulate the expression of immune-related genes. We aim to exploit the G4 folding as a treatment strategy to trigger anti-tumor immune response. In this study, we observe that the abundant genomic G4 in epithelial cells coexists with increased infiltration of CD8+ T cells in colorectal cancer tissue. Furthermore, our data substantiate the inhibitory effect of the G4 ligand TMPyP4 on cancer progression while concurrently stimulating anti-tumor immunity. Mechanistically, TMPyP4 impedes cancer cell proliferation and induces G2/M cell cycle arrest. Additionally, in vivo experiments demonstrate that TMPyP4 enhances the anti-tumor immune response by triggering DNA damage and activating the cGAS-STING pathway, which fosters CD8+ T cell activation and dendritic cell maturation. Importantly, the combined treatment of TMPyP4 and anti-PD1 exhibits a synergistic therapeutic effect on colorectal cancer. In summary, our findings underscore the potential of the G4 ligand TMPyP4 as a dual strategy to target colorectal cancer: inhibiting cancer progression and augmenting anti-tumor immunity through the activation of cGAS-STING pathway.
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Grants
- the Postdoctoral Fellowship Program of CPSF (No. GZC20242094, PL)
- the Project 5010 of Clinical Medical Research of Sun Yat-sen University-5010 Cultivation Foundation (No. 2018026, YL), the Sixth Affiliated Hospital of Sun Yat-sen University Clinical Research-'1010' Program (YL), the National Natural Science Foundation of China (No. 81972245, YL; No. 82173067, YL), the Scientific Research Project of the Sixth Affiliated Hospital Of Sun Yat-Sen University (2022JBGS07), the Talent Project of the Sixth Affiliated Hospital of Sun Yat-sen University (No. P20150227202010251, YL), the Excellent Talent Training Project of the Sixth Affiliated Hospital of Sun Yat-sen University (No. R2021217202512965, YL), the Program of Introducing Talents of Discipline to Universities (YL)
- the National Natural Science Foundation of China (No. 82272965, HY), the Natural Science Foundation of Guangdong Province (No. 2022A1515012656), the Science and Technology Program of Guangzhou (202201011004, HY), the Fundamental Research Funds for the Central Universities, Sun Yat-sen University (No. 23ykbj007, HY)
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Affiliation(s)
- Peisi Li
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Dawang Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China
| | - Yumo Xie
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ze Yuan
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Mingzhe Huang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Gaopo Xu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Junfeng Huang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhuokai Zhuang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yanxin Luo
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
| | - Huichuan Yu
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
| | - Xiaolin Wang
- Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
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18
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Memon F, Nadeem M, Sulaiman M, Arain MI, Hani UE, Yuan S. Unraveling molecular and clinical aspects of ALKBH5 as dual role in colorectal cancer. J Pharm Pharmacol 2024; 76:1393-1403. [PMID: 39321327 DOI: 10.1093/jpp/rgae108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 08/14/2024] [Indexed: 09/27/2024]
Abstract
OBJECTIVES This study investigates the dual role of ALKBH5, an eraser enzyme, in colorectal cancer (CRC), focusing on how N6-methyladenosine (m6A) mutations influence CRC development and progression. METHODS We reviewed various studies that highlighted the role of ALKBH5 in colorectal cancer (CRC). This includes the impact of ALKBH5 on tumor cell behavior including immune system interactions, invasion, and proliferation in CRC. We also looked into how ALKBH5 acts as a tumor suppressor under different conditions analyzed clinical data to assess the impact of ALKBH5 expression on outcomes in colorectal cancer patients. KEY FINDINGS In CRC, ALKBH5 plays a dual role. In certain situations, it inhibits the progression of the tumor, but in other circumstances, it promotes tumor growth and immunosuppression. The interaction with RABA5 plays a role in the development of CRC. Having elevated levels of ALKBH5 has been associated with unfavorable patient outcomes, such as reduced survival rates and more advanced cancer stages. Various factors, including tumor differentiation, TNM stages, and carcinoembryonic antigen (CEA) levels, be linked to ALKBH5 expression. CONCLUSIONS ALKBH5 plays a complicated and situation-specific role in colorectal cancer (CRC). Targeting ALKBH5 could result in novel therapy options that balance its tumor-promoting and tumor-fighting properties in CRC. Further research into m6A alterations and ALKBH5 could enhance CRC treatment approaches and patient outcomes.
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Affiliation(s)
- Furqan Memon
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China
| | - Momina Nadeem
- Faculty of Pharmacy, University of Sindh, Jamshoro-76080, Sindh, Pakistan
| | - Muhammad Sulaiman
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China
| | - Mudassar Iqbal Arain
- San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, CA 92035, United States
- School of Pharmacy, University of Kansas, 2010 Becker Dr., Lawrenece, KS 66047, United States
- Pharmacy Practice, University of Sindh, Jamshoro, 76080 Sindh, Pakistan
| | - Umm-E- Hani
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing, 211198, China
| | - Shengtao Yuan
- Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China
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Dieudonne M, Lv R, Xie W, Liu Q, Jiang J, Fu Y. Esophagojejunostomy using a circular stapler vs. a linear stapler for gastric cardia cancer patients: impact of upper margin length and tumor size on the survival rate. Front Surg 2024; 11:1385754. [PMID: 39444376 PMCID: PMC11496302 DOI: 10.3389/fsurg.2024.1385754] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 08/26/2024] [Indexed: 10/25/2024] Open
Abstract
Background The incidence of gastric cancer is concomitantly rising with gastric cardia cancer worldwide. While the improvement of gastric cancer surgical techniques is glowing, this study assesses the impact of the upper margin length and tumor size on the survival rate for gastric cardia cancer patients who underwent total laparoscopic total gastrectomy(TLTG) or laparoscopic assisted total gastrectomy(LATG). Materials and methods A total of 63 patients with gastric cardia cancer who underwent laparoscopic total gastrectomy were retro-prospectively collected from January 2021 to May 2023. While assessing the impact of upper margin length and tumor size on the survival rate, esophagojejunostomy using a linear stapler has been compared to a circular stapler. Results The sixty-three patients met inclusion criteria; 32 (51%) underwent LATG and 31 (49%) underwent TLTG. Their mean age was 65 years (range, 45-77). The blood loss means in LATG and TLTG was 74.69 and 50.16 ml, respectively (p = 0.005), and surgery duration was higher in LATG than LATG with respective means of 247 min and 222.42 min. (p = 0.006). However, the tumor size means (p = 0.5), and upper margin length means (p = 0.052) were not significantly different in the LATG and TLTG groups, respectively. The number of resected and assessed lymph node was adequate in the LATG and TLTG groups. The current study still does not find an independent related risk from the upper margin length and tumor size to the survival rate according to the multiple regression analysis (p = 0.080). Conclusion The upper margin length and tumor size do not have a relationship with the survival rate of the compared esophagojejunostomy (EJS) methods. The EJS using a linear stapler requires a shorter surgery duration and less blood loss than EJS using a circular stapler.
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Affiliation(s)
- Maniragaba Dieudonne
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Gastrointestinal Surgery Department, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Renguang Lv
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Gastrointestinal Surgery Department, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Wenjie Xie
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Gastrointestinal Surgery Department, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Qi Liu
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Gastrointestinal Surgery Department, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jianwu Jiang
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Gastrointestinal Surgery Department, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Yang Fu
- First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Gastrointestinal Surgery Department, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
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20
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Montaseri Z, Kargar H, Sharafi M, Afrashteh S. Spatial analysis of risk factors related to colorectal cancer in Iran: An ecological study. Health Sci Rep 2024; 7:e70120. [PMID: 39377026 PMCID: PMC11456510 DOI: 10.1002/hsr2.70120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 08/20/2024] [Accepted: 09/18/2024] [Indexed: 10/09/2024] Open
Abstract
Background and aims Colorectal cancer is the third most common cancer worldwide, accounting for 10% of cancer deaths. Therefore, this study was performed with the aim of spatial analysis of risk factors for colorectal cancer in Iran. Method This study was conducted ecologically using STEPS information (The WHO Stepwise Approach to NCD Risk Factor Surveillance) in Iran. To analyze the data, the researcher used cluster analysis and Geographically Weighted Regression methods with the help of ArcGIS version 10. Results The results of OLS analysis showed that there was a significant relationship between tobacco consumption (B = 0.571, p-value = 0.044) and smoking (B = 0.772, p-value = 0.010) and the incidence of colon cancer (CC). There was also a significant relationship between abdominal obesity and the incidence of rectal cancer (RC) (B = 0.061, p-value = 0.027). Conclusion This study showed that (CC) high-risk areas are located in central and northern parts of Iran, and the significant risk factors related to CC and RC were found to be tobacco use, cigarette smoking, and abdominal obesity. These findings are helpful to inform policymakers to plan screening services to reduce CC and RC, especially in high-risk populations.
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Affiliation(s)
- Zahra Montaseri
- Department of Infectious Diseases, School of MedicineFasa University of Medical SciencesFasaIran
| | - Hossein Kargar
- School of MedicineFasa University of Medical SciencesFasaIran
| | - Mehdi Sharafi
- Tobacco and Health Research CenterHormozgan University of Medical SciencesBandar AbbasIran
| | - Sima Afrashteh
- Department of Biostatistics and Epidemiology, Faculty of Health and NutritionBushehr University of Medical SciencesBushehrIran
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Xu L, Chen XJ, Yan Q, Lei XT, Liu HL, Xu JP, Shang WT, Huang JL, Chen ZT, Tan XL, Lin HJ, Fu XH, Zheng LS, Lan P, Huang Y. Zinc finger protein 180 induces an apoptotic phenotype by activating METTL14 transcriptional activity in colorectal cancer. Oncol Rep 2024; 52:125. [PMID: 39054954 PMCID: PMC11294910 DOI: 10.3892/or.2024.8784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Accepted: 07/04/2024] [Indexed: 07/27/2024] Open
Abstract
Zinc finger protein 180 (ZNF180) is a multifunctional protein that interacts with nucleic acids and regulates various cellular processes; however, the function of ZNF180 in colorectal cancer (CRC) remains unclear. The present study investigated the role and function of ZNF180 in CRC, and aimed to reveal the underlying molecular mechanism. The results revealed that ZNF180 was downregulated in CRC tissues and was associated with a good prognosis in patients with CRC. Additionally, the expression of ZNF180 was downregulated by methylation in CRC. In vivo and in vitro experiments revealed that ZNF180 overexpression was functionally associated with the inhibition of cell proliferation and the induction of apoptosis. Mechanistically, chromatin immunoprecipitation‑PCR and luciferase assays demonstrated that ZNF180 markedly regulated the transcriptional activity of methyltransferase 14, N6‑adenosine‑methyltransferase non‑catalytic subunit (METTL14) by directly binding to and activating its promoter region. Simultaneous overexpression of ZNF180 and knockdown of METTL14 indicated that the reduction of METTL14 could suppress the effects of ZNF180 on the induction of apoptosis. Clinically, the present study observed a significant positive correlation between ZNF180 and METTL14 expression levels, and low expression of ZNF180 and METTL14 predicted a poor prognosis in CRC. Overall, these findings revealed a novel mechanism by which the ZNF180/METTL14 axis may modulate apoptosis and cell proliferation in CRC. This evidence suggests that this axis may serve as a prognostic biomarker and therapeutic target in patients with CRC.
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Affiliation(s)
- Liang Xu
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Xi-Jie Chen
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
- Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Qian Yan
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Xin-Tao Lei
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Hai-Ling Liu
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Jing-Ping Xu
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Wei-Te Shang
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Jing-Lin Huang
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Zhi-Ting Chen
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Xiao-Li Tan
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Han-Jie Lin
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Xin-Hui Fu
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
| | - Li-Sheng Zheng
- Department of Pathology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong 510080, P.R. China
| | - Ping Lan
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
- State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510655, P.R. China
| | - Yan Huang
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510655, P.R. China
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Liu Y, Ju H, Yao Y, Yuan Y, Li T, Liang Y, Liao H, Li T, Lei X. Analysis of the impact on sexual function in early-onset overweight male patients with rectal cancer following robotic surgery. J Robot Surg 2024; 18:357. [PMID: 39348029 DOI: 10.1007/s11701-024-02085-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Accepted: 08/15/2024] [Indexed: 10/01/2024]
Abstract
The effect of radical resection of male rectal cancer on sexual function has been the focus of attention. Despite this, there remains a dearth of robust evidence regarding the influence of robotic radical resection of rectal cancer on postoperative sexual function, particularly in men diagnosed at an early age. This study aims to explore the implications of robotic radical resection of rectal cancer on sexual function in early-onset overweight male patients diagnosed with this disease. A retrospective analysis was performed on male patients under 50 years old and over 20 years old who were diagnosed with rectal cancer (cT1-3N0M0) and underwent surgical treatment in the First Affiliated Hospital of Nanchang University from May 2015 to August 2020. Sexual function was evaluated by the International Index of Erectile Function (IIEF) test and scored at 1, 3, 6, and 12 months postoperatively. The sexual function of traditional laparoscopic radical resection of rectal cancer (L-RE) and robotic radical resection of rectal cancer (R-RE) were compared. According to body mass index, L-RE and R-RE groups were further divided into normal body weight groups (LN-RE and RN-RE) and overweight groups (LO-RE and RO-RE), and the sexual function of each group was compared successively. Neither L-RE nor R-RE patients had significant differences in number of lymph nodes removed, tumour size, pathological TNM stage, or first exhaust time or time to eat liquids. The OS and DFS of the L-RE and R-RE groups, as well as the LO-RE and RO-RE groups, did not differ statistically after the logarithmic rank test (P > 0.05). IIEF scores in both the L-RE and R-RE groups declined sharply 1 month after surgery and then steadily increased. The R-RE group's IIEF scores significantly recovered in 6 months, compared to 12 months in the L-RE group. In comparison of subgroups, the results of sexual function in the LN-RE and RN-RE groups were similar to those in the L-RE and R-RE groups. Conversely, the RO-RE group showed slightly improved sexual function recovery than the LO-RE group 3 and 6 months post-surgery. 12 months after surgery, no significant difference was observed between the two groups. With similar long-term oncology outcomes, the robot-assisted surgical approach provided better protection of sexual function for men with early-onset rectal cancer, especially for those with a higher body mass index (BMI).
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Affiliation(s)
- Yang Liu
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Houqiong Ju
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Yao Yao
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Yuli Yuan
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Tao Li
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Yahang Liang
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Hualin Liao
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Taiyuan Li
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China.
| | - Xiong Lei
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
- Gastrointestinal Surgical Institute, Nanchang University, Nanchang, 330006, Jiangxi, China.
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Ai D, Du Y, Duan H, Qi J, Wang Y. Tumor Heterogeneity in Gastrointestinal Cancer Based on Multimodal Data Analysis. Genes (Basel) 2024; 15:1207. [PMID: 39336798 PMCID: PMC11430818 DOI: 10.3390/genes15091207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/11/2024] [Accepted: 09/12/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Gastrointestinal cancer cells display both morphology and physiology diversity, thus posing a significant challenge for precise representation by a single data model. We conducted an in-depth study of gastrointestinal cancer heterogeneity by integrating and analyzing data from multiple modalities. METHODS We used a modified Canny algorithm to identify edges from tumor images, capturing intricate nonlinear interactions between pixels. These edge features were then combined with differentially expressed mRNA, miRNA, and immune cell data. Before data integration, we used the K-medoids algorithm to pre-cluster individual data types. The results of pre-clustering were used to construct the kernel matrix. Finally, we applied spectral clustering to the fusion matrix to identify different tumor subtypes. Furthermore, we identified hub genes linked to these subtypes and their biological roles through the application of Weighted Gene Co-expression Network Analysis (WGCNA) and Gene Ontology (GO) enrichment analysis. RESULTS Our investigation categorized patients into three distinct tumor subtypes and pinpointed hub genes associated with each. Genes MAGI2-AS3, MALAT1, and SPARC were identified as having a differential impact on the metastatic and invasive capabilities of cancer cells. CONCLUSION By harnessing multimodal features, our study enhances the understanding of gastrointestinal tumor heterogeneity and identifies biomarkers for personalized medicine and targeted treatments.
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Affiliation(s)
- Dongmei Ai
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China; (Y.D.); (J.Q.); (Y.W.)
| | - Yang Du
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China; (Y.D.); (J.Q.); (Y.W.)
| | - Hongyu Duan
- Department of Statistics and Financial Mathematics, School of Mathematics, South China University of Technology, Guangzhou 510641, China;
| | - Juan Qi
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China; (Y.D.); (J.Q.); (Y.W.)
| | - Yuduo Wang
- School of Mathematics and Physics, University of Science and Technology Beijing, Beijing 100083, China; (Y.D.); (J.Q.); (Y.W.)
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24
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Mousavi SE, Ilaghi M, Mirzazadeh Y, Mosavi Jarrahi A, Nejadghaderi SA. Global epidemiology and socioeconomic correlates of hypopharyngeal cancer in 2020 and its projection to 2040: findings from GLOBOCAN 2020. Front Oncol 2024; 14:1398063. [PMID: 39286014 PMCID: PMC11402725 DOI: 10.3389/fonc.2024.1398063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 07/26/2024] [Indexed: 09/19/2024] Open
Abstract
Background Hypopharyngeal cancer (HC) comprises less than 5% of all malignant tumors in the head and neck. They often present at an advanced stage, thereby resulting in high mortalities. We aimed to report the epidemiology of HC globally, regionally, and nationally by age, sex, and socioeconomic status in 2020 and its projection to 2040. Methods Data on HC incidence and mortality were extracted from the GLOBOCAN 2020. Age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and mortality-to-incidence ratios (MIRs) were calculated. We used bivariate correlation test, presenting results through Pearson's correlation coefficient (r) to investigate the correlation between the metrics, human development index (HDI), and current healthcare expenditure (CHE) as a percentage of gross domestic product (GDP) (CHE/GDP). Results In 2020, there were 84254 new HC cases globally (ASIR: 0.91 per 100000). Moreover, HC resulted in 38599 mortalities in 2020 (ASMR: 0.41). Furthermore, the global MIR of HC was 0.45. The ASIR and ASMR of HC were higher in men than women. Also, HDI demonstrated significant correlations with HC ASIR (r= 0.249, p<0.01), ASMR (r= 0.185, p<0.05), and MIR (r= -0.449, p<0.001). Moreover, a weak significant correlation was also observed between CHE/GDP and MIR (r= -0.295, p<0.001). Moreover, a weak significant correlation was also observed between CHE/GDP and MIR (r= 0.279, p<0.001). The number of new HC cases and mortalities were estimated to increase by 50% and 55% in 2040, respectively. Conclusion HC is a relatively rare cancer but with a substantial sex and geographic divide in distribution. Key priorities should thus include establishing high-quality cancer registries worldwide.
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Affiliation(s)
- Seyed Ehsan Mousavi
- Neurosciences Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Community Medicine, Social Determinants of Health Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehran Ilaghi
- Institute of Neuropharmacology, Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Yasaman Mirzazadeh
- Faculty of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Alireza Mosavi Jarrahi
- Cancer Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- West Asia Organization for Cancer Prevention, Sabzevar, Iran
| | - Seyed Aria Nejadghaderi
- HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
- Systematic Review and Meta−analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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25
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Chen M, Deng S, Cao Y, Wang J, Zou F, Gu J, Mao F, Xue Y, Jiang Z, Cheng D, Huang N, Huang L, Cai K. Mitochondrial DNA Copy Number as a Biomarker for Guiding Adjuvant Chemotherapy in Stages II and III Colorectal Cancer Patients with Mismatch Repair Deficiency: Seeking Benefits and Avoiding Harms. Ann Surg Oncol 2024; 31:6320-6330. [PMID: 38985229 PMCID: PMC11300489 DOI: 10.1245/s10434-024-15759-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 06/24/2024] [Indexed: 07/11/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) status are conventionally perceived as unresponsive to adjuvant chemotherapy (ACT). The mitochondrial transcription factor A (TFAM) is required for mitochondrial DNA copy number (mtDNA-CN) expression. In light of previous findings indicating that the frequent truncating-mutation of TFAM affects the chemotherapy resistance of MSI CRC cells, this study aimed to explore the potential of mtDNA-CN as a predictive biomarker for ACT efficacy in dMMR CRC patients. METHODS Levels of MtDNA-CN were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) in a cohort of 308 CRC patients with dMMR comprising 180 stage II and 128 stage III patients. Clinicopathologic and therapeutic data were collected. The study examined the association between mtDNA-CN levels and prognosis, as well as the impact of ACT benefit on dMMR CRC patients. Subgroup analyses were performed based mainly on tumor stage and mtDNA-CN level. Kaplan-Meier and Cox regression models were used to evaluate the effect of mtDNA-CN on disease-free survival (DFS) and overall survival (OS). RESULTS A substantial reduction in mtDNA-CN expression was observed in tumor tissue, and higher mtDNA-CN levels were correlated with improved DFS (73.4% vs 85.7%; P = 0.0055) and OS (82.5% vs 90.3%; P = 0.0366) in dMMR CRC patients. Cox regression analysis identified high mtDNA-CN as an independent protective factor for DFS (hazard ratio [HR] 0.547; 95% confidence interval [CI] 0.321-0.934; P = 0.0270) and OS (HR 0.520; 95% CI 0.272-0.998; P = 0.0492). Notably, for dMMR CRC patients with elevated mtDNA-CN, ACT significantly improved DFS (74.6% vs 93.4%; P = 0.0015) and OS (81.0% vs 96.7%; P = 0.0017), including those with stage II or III disease. CONCLUSIONS The mtDNA-CN levels exhibited a correlation with the prognosis of stage II or III CRC patients with dMMR. Elevated mtDNA-CN emerges as a robust prognostic factor, indicating improved ACT outcomes for stages II and III CRC patients with dMMR. These findings suggest the potential utility of mtDNA-CN as a biomarker for guiding personalized ACT treatment in this population.
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Affiliation(s)
- Mian Chen
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong, Guangzhou, China
| | - Shenghe Deng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yinghao Cao
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
- Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jun Wang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Falong Zou
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Junnang Gu
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Fuwei Mao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yifan Xue
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhenxing Jiang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Denglong Cheng
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ning Huang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Liang Huang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong, Guangzhou, China.
| | - Kailin Cai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Mihailov R, Beznea A, Popazu C, Voicu D, Toma A, Tudorașcu I, Rebegea L, Mihailov OM, Lutenco V, Constantin GB, Țocu G, Niculeț E, Bîrlă R, Georgescu DE, Șerban C. The pathological and immunohistochemical profile of tumor angiogenesis in perforated sigmoid carcinoma–Case report and short literature review. ELECTRONIC JOURNAL OF GENERAL MEDICINE 2024; 21:em600. [DOI: 10.29333/ejgm/14847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
<b>Background:</b> Little is known about the physiopathological factors or mechanisms that underlie tumor invasion of the serosa and lead to perforation in the peritoneal cavity. The aim of the work was to analyze the pathological and immunohistochemical factors of tumor neoangiogenesis which could influence tumor perforation in colorectal cancer.<br />
<b>Results and discussions:</b> 451 cases of complicated colorectal carcinomas were statistically analyzed, of which 19 cases were perforated sigmoid tumors. The immunohistochemical detection of mutant p53 proteins was the first molecular parameter examined in the context of the search for markers predicting the natural evolution mode in colorectal carcinomas.<br />
<b>Conclusions</b>: Both loss of p53 and overexpression of bcl-2 proteins confer immortalization on cancer cells by inhibiting the processes leading to apoptosis. The paper proposes a review of the specialized literature, but also the presentation of a clinical case.
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Affiliation(s)
- Raul Mihailov
- Surgery Clinic, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galati, ROMANIA
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | - Adrian Beznea
- Surgery Clinic, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galati, ROMANIA
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | - Constantin Popazu
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | - Dragoș Voicu
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | - Alexandra Toma
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | - Iulia Tudorașcu
- University of Medicine and Pharmacy of Craiova, Craiova, ROMANIA
| | - Laura Rebegea
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | | | - Valerii Lutenco
- Surgery Clinic, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galati, ROMANIA
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | | | - George Țocu
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | - Elena Niculeț
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
| | - Rodica Bîrlă
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, ROMANIA
| | - Dragoș Eugen Georgescu
- “Carol Davila” University of Medicine and Pharmacy, Bucharest, ROMANIA
- Department of General Surgery, Dr. Ion Cantacuzino Hospital, Bucharest, ROMANIA
| | - Cristina Șerban
- Surgery Clinic, “Sf. Ap. Andrei” Emergency Clinical Hospital, Galati, ROMANIA
- Faculty of Medicine and Pharmacy, “Dunarea de Jos” University, Galati, ROMANIA
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Liu C, Chen Z. ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on gastric cancer cell malignancy by regulating the N6-methyladenosine modification of the lncRNA DLX6-AS1. Heliyon 2024; 10:e35722. [PMID: 39220970 PMCID: PMC11365301 DOI: 10.1016/j.heliyon.2024.e35722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2024] [Revised: 07/30/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open
Abstract
Sevoflurane, an inhalation anesthetic, has been shown to suppress cancer development. In this study, we investigated the specific mechanisms involving sevoflurane, zinc-finger CCCH-type containing 13 (ZC3H13), and lncRNA DLX6-AS1 in gastric cancer (GC) progression, focusing on the N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs). We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses to measure the levels of ZC3H13 and lncRNA DLX6-AS1 in GC tissues and cells. Furthermore, we conducted Cell Counting Kit-8, colony formation, Transwell, and tumor xenograft assays to evaluate changes in GC cell malignancy following cell transfection and sevoflurane treatment. Additionally, actinomycin D, methylated RNA immunoprecipitation, and qRT-PCR assays were performed to examine the regulatory effects of ZC3H13 on the DLX6-AS1 m6A modification. We detected elevated levels of ZC3H13 in GC samples, while ZC3H13 silencing inhibited GC cell proliferation, migration, and invasion. Silencing ZC3H13 also enhanced the inhibitory effects of sevoflurane on GC cell malignancy. Moreover, we found that the increased expression of DLX6-AS1 in GC cells could be suppressed by ZC3H13 through the mediation of the m6A modification of DLX6-AS1, thereby reducing DLX6-AS1 stability. In conclusion, ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on GC cell malignancy by inducing DLX6-AS1 m6A modification. Our findings may help identify potential therapeutic targets for the treatment of GC.
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Affiliation(s)
- Chundong Liu
- Department of Anesthesiology, Wuhan Fourth Hospital, Wuhan 430033, Hubei, China
| | - Zeguang Chen
- Operating Room, Wuhan Fourth Hospital, Wuhan 430033, Hubei, China
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28
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Furtado M, Davis D, Groarke JM, Graham-Wisener L. Experiences of informal caregivers supporting individuals with upper gastrointestinal cancers: a systematic review. BMC Health Serv Res 2024; 24:932. [PMID: 39143501 PMCID: PMC11325824 DOI: 10.1186/s12913-024-11306-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 07/10/2024] [Indexed: 08/16/2024] Open
Abstract
BACKGROUND Upper gastrointestinal cancers (UGICs) are increasingly prevalent. With a poor prognosis and significant longer-term effects, UGICs present significant adjustment challenges for individuals with cancer and their informal caregivers. However, the supportive care needs of these informal caregivers are largely unknown. This systematic review of qualitative studies synthesises and critically evaluates the current evidence base on the experience of informal caregivers of individuals with UGIC. METHODS A Joanna Briggs Institute systematic review was conducted. Searches were performed in four databases (MEDLINE, PsycINFO, Embase, CINAHL) from database inception to February 2021. Included studies explored experiences of informal caregivers of individuals diagnosed with primary cancer of the oesophagus, stomach, pancreas, bile duct, gallbladder, or liver. Studies were independently screened for eligibility and included studies were appraised for quality by two reviewers. Data were extracted and synthesised using meta-aggregation. RESULTS 19 papers were included in this review, and 328 findings were extracted. These were aggregated into 16 categories across three findings: (1) UGIC caregiver burden; UGIC caregivers undertake extensive responsibilities, especially around patient diet as digestion is severely impacted by UGICs. (2) Mediators of caregiver burden; The nature of UGICs, characterised by disruptive life changes for caregivers, was identified as a mediator for caregiver burden. (3) Consequences of caregiver burden: UGIC caregivers' experiences were shaped by unmet needs, a lack of information and a general decline in social interaction. CONCLUSIONS The findings of this review suggest the need for a cultural shift within health services. Caregiving for UGIC patients is suggested to adversely affect caregivers' quality of life, similarly to other cancer caregiving populations and therefore they should be better incorporated as co-clients in care-planning and execution by including them in discussions about the patient's diagnosis, treatment options, and potential side effects.
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Affiliation(s)
- Melinda Furtado
- School of Psychology, Queen's University Belfast, University Road, Belfast, BT7 1NN, UK.
| | - Dawn Davis
- School of Psychology, Queen's University Belfast, University Road, Belfast, BT7 1NN, UK
| | - Jenny M Groarke
- School of Psychology, Queen's University Belfast, University Road, Belfast, BT7 1NN, UK
- School of Psychology, University of Galway, University Road, Galway, Ireland
| | - Lisa Graham-Wisener
- School of Psychology, Queen's University Belfast, University Road, Belfast, BT7 1NN, UK
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Schuld GJ, Schlager L, Monschein M, Riss S, Bergmann M, Razek P, Stift A, Unger LW. Does surgeon or hospital volume influence outcome in dedicated colorectal units?-A Viennese perspective. Wien Klin Wochenschr 2024:10.1007/s00508-024-02405-6. [PMID: 39093419 DOI: 10.1007/s00508-024-02405-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 06/30/2024] [Indexed: 08/04/2024]
Abstract
OBJECTIVE A clear relationship between higher surgeon volume and improved outcomes has not been convincingly established in rectal cancer surgery. The aim of this study was to evaluate the impact of individual surgeon's caseload and hospital volume on perioperative outcome. METHODS We retrospectively analyzed 336 consecutive patients undergoing oncological resection for rectal cancer at two Viennese hospitals between 1 January 2015 and 31 December 2020. The effect of baseline characteristics as well as surgeons' caseloads (low volume: 0-5 cases per year, high volume > 5 cases per year) on postoperative complication rates (Clavien-Dindo Classification groups of < 3 and ≥ 3) were evaluated. RESULTS No differences in baseline characteristics were found between centers in terms of sex, smoking status, or comorbidities of patients. Interestingly, only 14.7% of surgeons met the criteria to be classified as high-volume surgeons, while accounting for 66.3% of all operations. There was a significant difference in outcomes depending on the treating center in univariate and multivariate binary logistic regression analysis (odds ratio (OR) = 2.403, p = 0.008). Open surgery was associated with lower complication rates than minimally invasive approaches in univariate analysis (OR = 0.417, p = 0.003, 95%CI = 0.232-0.739) but not multivariate analysis. This indicated that the center's policy rather than surgeon volume or mode of surgery impact on postoperative outcomes. CONCLUSION Treating center standards impacted on outcome, while individual caseload of surgeons or mode of surgery did not independently affect complication rates in this analysis. The majority of rectal cancer resections are performed by a small number of surgeons in Viennese hospitals.
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Affiliation(s)
- Gabor J Schuld
- Division of Visceral Surgery, Dept. of General Surgery, Medical University of Vienna, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Lukas Schlager
- Division of Visceral Surgery, Dept. of General Surgery, Medical University of Vienna, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Matthias Monschein
- Hospital Floridsdorf, Department of General Surgery, Brünner Straße 68, 1221, Vienna, Austria
| | - Stefan Riss
- Division of Visceral Surgery, Dept. of General Surgery, Medical University of Vienna, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Michael Bergmann
- Division of Visceral Surgery, Dept. of General Surgery, Medical University of Vienna, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Peter Razek
- Hospital Floridsdorf, Department of General Surgery, Brünner Straße 68, 1221, Vienna, Austria
| | - Anton Stift
- Division of Visceral Surgery, Dept. of General Surgery, Medical University of Vienna, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
| | - Lukas W Unger
- Division of Visceral Surgery, Dept. of General Surgery, Medical University of Vienna, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
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30
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Ye F, Ruan L, Liu Z, Xie H, Wan T, Zhu W, Li Z, Xiao W, Zheng H, Lei D, Zhou Y, Zheng X, Liang Z, Liu H, Huang P, Kang L, Huang L. Postoperative urinary retention following transanal versus laparoscopic total mesorectal excision for rectal cancer: A randomized trial report from an experienced center. Heliyon 2024; 10:e34753. [PMID: 39149012 PMCID: PMC11325049 DOI: 10.1016/j.heliyon.2024.e34753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2024] [Revised: 07/15/2024] [Accepted: 07/16/2024] [Indexed: 08/17/2024] Open
Abstract
Background Transanal total mesorectal excision has emerged as a potential solution to certain limitations associated with laparoscopic total mesorectal excision in rectal cancer patients. Differences in surgical approaches have raised questions regarding their impact on the risk of postoperative urinary retention, with limited data available from large scale randomized clinical study. Objective To report incidence of postoperative urinary retention and evaluate the associated risk factors for transanal total mesorectal excision. Design In this randomized controlled trial (ClinicalTrials. gov NCT06147492), we retrieved 524 patients who received total mesorectal excision (TME) for stage I-III rectal cancer between June 2019 and April 2022, and the patients were randomly assigned in a 1:1 ratio to undergo either taTME or laTME. Patients We enrolled 524 patients who underwent total mesorectal excision for stage I-III rectal cancer between June 2019 and April 2022. Main outcome measures The incidence of postoperative urinary retention. Results Among the 524 enrolled patients, 261 were randomized to the laTME group, while 263 were were randomized the taTME group. The median age was 58 years, and 340 participants (64.8 %) were male. Notably, 37 individuals (7.0 %) experienced postoperative urinary retention during the follow-up period, with no significant disparity was observed between the taTME and laTME groups (6.8 % and 7.2 %, respectively, P = 0.98). Risk factors associated with PUR in patients following taTME encompassed early removal of the urinary catheter (P = 0.006), net infusion rate >4.09 ml kg-1.h-1 (P = 0.006), and an age surpassing 65 years (P = 0.0321). Limitations The generalizability of the findings outside specialist rectal cancer centers may be limited. Conclusions Transanal total mesorectal excision was not found to heighten the risk of postoperative urinary retention. Nonetheless, it is advisable removing postoperative catheter beyond the initial day and exercising caution in the administration of intravenous fluids in clinical practice for taTME procedures.
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Affiliation(s)
- Fujin Ye
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Lei Ruan
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Zhanzhen Liu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Department of Medical Oncology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
- Department of Emergency, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Hao Xie
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Taixuan Wan
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Wenliang Zhu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Department of Urology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Ze Li
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Wei Xiao
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Haoqi Zheng
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Dongxu Lei
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Yebohao Zhou
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Xiaobin Zheng
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Department of Emergency, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Zhenxing Liang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Huashan Liu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Pinzhu Huang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Liang Kang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
| | - Liang Huang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, China
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Yousefnia S. A comprehensive review on lncRNA LOXL1-AS1: molecular mechanistic pathways of lncRNA LOXL1-AS1 in tumorigenicity of cancer cells. Front Oncol 2024; 14:1384342. [PMID: 39136001 PMCID: PMC11317273 DOI: 10.3389/fonc.2024.1384342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 07/15/2024] [Indexed: 08/15/2024] Open
Abstract
Long non-coding RNAs (lncRNAs) are versatile RNAs that regulate various cellular processes, such as gene regulation, by acting as signals, decoys, guides, and scaffolds. A novel recognized lncRNA, LOXL1-antisense RNA 1 (LOXL1-AS1), is dysregulated in some diseases, including cancer, and acts as an oncogenic lncRNA in many types of cancer cells. Upregulation of LOXL1-AS1 has been involved in proliferation, migration, metastasis, and EMT, as well as inhibiting apoptosis in cancer cells. Most importantly, the malignant promoting activity of LOXL1-AS1 can be mostly mediated by sequestering specific miRNAs and inhibiting their binding to the 3´UTR of their target mRNAs, thereby indirectly regulating gene expression. Additionally, LOXL1-AS1 can decoy transcription factors and proteins and prevent their binding to their regulatory regions, inhibiting their mechanistic activity on the regulation of gene expression and signaling pathways. This review presents the mechanistic pathways of the oncogenic role of LOXL1-AS1 by modulating its target miRNAs and proteins in various cancer cells. Having information about the molecular mechanisms regulated by LOXL1-AS1 in cancer cells can open ways to find out particular prognostic biomarkers, as well as discover novel therapeutic approaches for different types of cancer.
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Affiliation(s)
- Saghar Yousefnia
- Department of Cell and Molecular Biology, Semnan University, Semnan, Iran
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Zheng D, Elnegiry AA, Luo C, Bendahou MA, Xie L, Bell D, Takahashi Y, Hanna E, Mias GI, Tsoi MF, Gu B. Brd4::Nutm1 fusion gene initiates NUT carcinoma in vivo. Life Sci Alliance 2024; 7:e202402602. [PMID: 38724194 PMCID: PMC11082452 DOI: 10.26508/lsa.202402602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 04/26/2024] [Accepted: 04/29/2024] [Indexed: 05/12/2024] Open
Abstract
NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a BRD4::NUTM1 fusion gene. Because the BRD4::NUTM1 gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the Brd4::Nutm1 fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, Brd4::Nutm1 can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.
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Affiliation(s)
- Dejin Zheng
- Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
| | - Ahmed A Elnegiry
- Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
- Home Institution: Department of Cytology and Histology, Faculty of Veterinary Medicine, Aswan University, Aswan, Egypt
| | - Chenxiang Luo
- Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
- Home Institution: Center for Reproductive Medicine and Department of Gynecology & Obstetrics, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, PR China
| | - Mohammed Amine Bendahou
- Infection Biology and Cancer Biology Program, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Liangqi Xie
- Infection Biology and Cancer Biology Program, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Diana Bell
- City of Hope Comprehensive Cancer Center, Pathology, Duarte, CA, USA
| | - Yoko Takahashi
- Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ehab Hanna
- Department of Head and Neck Surgery, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - George I Mias
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
- Department of Biochemistry and Molecular Biology, College of Nature Science, Michigan State University, East Lansing, MI, USA
| | - Mayra F Tsoi
- Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI, USA
| | - Bin Gu
- Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, East Lansing, MI, USA
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA
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Zhang H, Tang X, Zhang J, Man C, Jiang D, Xu Y, Zhang W, Gong D, Fan Y. Cachexia Index as a Predictor of Reduced Survival in Patients with Gastrointestinal Cancer: A Systematic Review and Meta-Analysis. Nutr Cancer 2024; 76:815-823. [PMID: 38943494 DOI: 10.1080/01635581.2024.2372115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/16/2024] [Accepted: 06/19/2024] [Indexed: 07/01/2024]
Abstract
The cachexia index is a novel indicator of cachexia, but its prognostic implications for survival outcomes have not been systematically assessed in patients with gastrointestinal cancer. This systematic review and meta-analysis aimed to examine the association between the cachexia index and survival outcomes in gastrointestinal cancer patients. Two independent reviewers searched PubMed, Embase, and Web of Science to identify studies that evaluated the prognostic significance of the cachexia index in patients with gastrointestinal cancer. The prognostic value of the cachexia index was determined by combining the adjusted hazard ratios (HR) and 95% confidence intervals (CI). Thirteen studies were identified, including a total of 4207 patients. Meta-analysis indicated that a lower cachexia index was associated with shorter overall survival (HR 2.18; 95% CI 1.78-2.66) and disease-free survival (HR 1.72; 95% CI 1.50-1.97) in gastrointestinal cancer patients. Further stratified analysis confirmed the significant association between a lower cachexia index and shorter overall survival in different study designs, regions, patients' age, sample sizes, gastrointestinal cancer subtypes, tumor stages, and follow-up duration subgroups. The cachexia index could be utilized as a predictor of overall survival and disease-free survival in patients with gastrointestinal cancer. However, future prospective studies are required to confirm these findings.
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Affiliation(s)
- Heng Zhang
- Department of General Surgery, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
| | - Xuan Tang
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Junfang Zhang
- Department of Medical Nutrition, Nanjing Lishui District People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China
| | - Changfeng Man
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Dapeng Jiang
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Ying Xu
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Wenbo Zhang
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Dandan Gong
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
| | - Yu Fan
- Cancer Institute, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, China
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Chen M, Ye F, Zheng W, Xiong L, Liang Z, Liu H, Zheng X, Li W, Kang L, Huang L. Changes to circulating tumor cells in the central vein during laparoscopic versus transanal endoscopic surgeries for rectal cancer: can surgical approach make a difference? Gastroenterol Rep (Oxf) 2024; 12:goae062. [PMID: 38939193 PMCID: PMC11208727 DOI: 10.1093/gastro/goae062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 03/22/2024] [Accepted: 05/24/2024] [Indexed: 06/29/2024] Open
Abstract
Background The oncological safety of transanal total mesorectal excision (taTME) remains uncertain, and its special surgical approach may contribute to tumor cell dissemination. Thus, we conducted a study to investigate the impact of surgical approach on circulating tumor cell (CTC) counts and phenotypes in rectal cancer. Methods This is a prospective randomized controlled study (ClinicalTrials: NCT05109130). The patients were randomized to either the taTME (n = 49) or laparoscopic TME (laTME) (n = 48) groups. Blood samples were collected from the central vein to measure CTC counts and phenotypes at three time points: preoperative (t1), immediately post-tumor removal (t2), and one week post-surgery (t3). The effect of surgical procedure on CTCs at each time point was analyzed, with the primary endpoint being the change in CTC counts from t1 to t3 for each surgical approach. This study adheres to Consolidated Standards of Reporting Trials Guidelines. Results The baseline clinicopathologic characteristics of the laTME and taTME groups were balanced. The change in CTC count from t1 to t3 was 1.81 ± 5.66 in the laTME group and 2.18 ± 5.53 in the taTME group. The taTME surgery was non-inferior to laTME in terms of changing CTC counts (mean difference [MD]: -0.371; 95% confidence interval [CI]: -2.626 to 1.883, upper-sided 95% CI of 1.883 < 2, non-inferiority boundary value). Compared with that at t1, the CTC count at t2 did not change significantly. However, higher CTC counts were detected at t3 than at t2 in the taTME (P = 0.032) and laTME (P = 0.003) groups. From t1 to t3, CTC counts significantly increased in both the taTME (P = 0.008) and laTME (P = 0.031) groups. There were no significant differences in CTC phenotype changes between the two groups from t1 to t3. Conclusions Compared with laTME, taTME did not affect CTC counts and phenotypes. Our findings indicate that taTME is not inferior to laTME in terms of CTC changes from an oncological perspective.
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Affiliation(s)
- Mian Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Fujin Ye
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Wenwen Zheng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Li Xiong
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Zhenxing Liang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Huashan Liu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Xiaobin Zheng
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Wenxin Li
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Liang Kang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
| | - Liang Huang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
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Abedizadeh R, Majidi F, Khorasani HR, Abedi H, Sabour D. Colorectal cancer: a comprehensive review of carcinogenesis, diagnosis, and novel strategies for classified treatments. Cancer Metastasis Rev 2024; 43:729-753. [PMID: 38112903 DOI: 10.1007/s10555-023-10158-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 11/27/2023] [Indexed: 12/21/2023]
Abstract
Colorectal cancer is the third most common and the second deadliest cancer worldwide. To date, colorectal cancer becomes one of the most important challenges of the health system in many countries. Since the clinical symptoms of this cancer appear in the final stages of the disease and there is a significant golden time between the formation of polyps and the onset of cancer, early diagnosis can play a significant role in reducing mortality. Today, in addition to colonoscopy, minimally invasive methods such as liquid biopsy have received much attention. The treatment of this complex disease has been mostly based on traditional treatments including surgery, radiotherapy, and chemotherapy; the high mortality rate indicates a lack of success for current treatment methods. Moreover, disease recurrence is another problem of traditional treatments. Recently, new approaches such as targeted therapy, immunotherapy, and nanomedicine have opened new doors for cancer treatment, some of which have already entered the market, and many methods have shown promising results in clinical trials. The success of immunotherapy in the treatment of refractory disease, the introduction of these methods into neoadjuvant therapy, and the successful results in tumor shrinkage without surgery have made immunotherapy a tough competitor for conventional treatments. It seems that the combination of those methods with such targeted therapies will go through promising changes in the future of colorectal cancer treatment.
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Affiliation(s)
- Roya Abedizadeh
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Fateme Majidi
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Hamid Reza Khorasani
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran
| | - Hassan Abedi
- Department of Internal Medicine, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.
| | - Davood Sabour
- Department of Cancer Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Isar 11, Babol, 47138-18983, Iran.
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Bani-Hashem Square, Tehran, 16635-148, Iran.
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Hajjafari A, Sadr S, Rahdar A, Bayat M, Lotfalizadeh N, Dianaty S, Rezaei A, Moghaddam SP, Hajjafari K, Simab PA, Kharaba Z, Borji H, Pandey S. Exploring the integration of nanotechnology in the development and application of biosensors for enhanced detection and monitoring of colorectal cancer. INORG CHEM COMMUN 2024; 164:112409. [DOI: 10.1016/j.inoche.2024.112409] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2024]
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Nonikashvili M, Kereselidze M, Toidze O, Beruchashvili T. Colorectal cancer prevention in Central, Eastern European and South Caucasus countries: a review of policy approaches. J Health Organ Manag 2024; ahead-of-print. [PMID: 38796752 DOI: 10.1108/jhom-02-2023-0030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2024]
Abstract
PURPOSE This study aims to examine the availability and comprehensiveness of policies pertaining to colorectal cancer (CRC) in Central, Eastern European and South Caucasus countries, as it is a major public health concern in these regions and the second most common cause of cancer deaths among women. DESIGN/METHODOLOGY/APPROACH We performed a scoping review using the Arksey and O'Malley methodology, searching for publicly available policy documents from 18 countries. We described the prevention methods and activities in each country based on the World Health Organization guidelines for CRC screening. FINDINGS Our research found that most countries had at least five policies related to CRC prevention, which most commonly included primary, secondary and tertiary prevention measures. Elements such as promoting healthy lifestyle choices and implementing screening methods such as fecal occult blood tests, fecal immunochemical tests or colonoscopy were frequently mentioned in these policies. However, target age ranges varied among countries. Our analysis revealed a pressing need to increase the availability and utilization of CRC screening in these countries. RESEARCH LIMITATIONS/IMPLICATIONS One of the main limitations of this study is that it is a desk review conducted using internet-based resources, which may have missed important sources or recent policy documents that are not yet available online. Despite our efforts to include all relevant policies, it is possible that we overlooked other policies that contain relevant information, such as those that cover cancer treatment methods. Additionally, our search excluded primary healthcare and universal healthcare coverage policies, which could include important information on CRC prevention and control activities. Additionally, as a scoping review approach was used, no critical assessment of the included studies or literature was conducted. Furthermore, due to the limited number of countries included, the comparability of the findings is limited. In future research, it would be beneficial to expand the study and collect new data from decision-makers and stakeholders to further investigate these hypotheses. It is also important to note that the presence of a policy document is not the end goal, as it is simply a step toward better outcomes. PRACTICAL IMPLICATIONS In summary, our research highlights the need for improved and unified efforts toward preventing and detecting CRC in Central, Eastern European and South Caucasus countries. This knowledge can be used to focus efforts on developing a standardized policy document and national screening program that can be adapted to meet the unique needs of each country. The importance of CRC screening, regardless of need, must be emphasized in order to aid in the transition from curative to preventive cancer care. Our study highlights the need for more detailed and science-based policies for CRC prevention and screening in Central, Eastern European and South Caucasus countries. While many countries have policies in place, they often lack key components and do not fully reflect current evidence-based guidelines. To improve population health outcomes, further research is needed to understand the implementation and enforcement of these policies as well as their impact on cancer incidence and survival. As the screening landscape evolves, countries may learn from each other and a better understanding of the complex policy frameworks that impact CRC screening is needed so that countries can update and tailor policy documents to their specific situations. SOCIAL IMPLICATIONS In conclusion, policymakers in Central, Eastern European and South Caucasus countries have implemented various policy approaches to prevent and control the CRC. The effectiveness of these approaches varies across countries and depends on several factors, including the availability of resources, the level of public awareness and the political will to implement effective policies. Further research is needed to determine the most effective policy approaches for CRC prevention in these regions and to ensure that the right policies are in place to reduce the incidence and impact of this disease. ORIGINALITY/VALUE The study aimed to identify gaps in existing research and areas for future work by mapping, categorizing and organizing existing evidence on CRC policies in Central, Eastern European and South Caucasus countries. Additional research is necessary to understand the implementation and enforcement of these policies and how they impact health outcomes such as cancer incidence and survival. HIGHLIGHTS CRC policy is heterogeneous in Central and Eastern Europe and the South Caucasus region.There are particularly important differences regarding the implementation of CRC screening.Cancer screening and palliative care approaches were less frequently included.Variations exist in the comprehensiveness of policy by prevention level and country.
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Affiliation(s)
| | - Maia Kereselidze
- National Center for Disease Control and Public Health, Tbilisi, Georgia
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Chen X, Ze Y, Yi W, Yang Y, Sun R, Tu H. Barriers to upper gastrointestinal screening among the general population in high-prevalence areas: a cross-sectional study. JBI Evid Implement 2024; 22:218-227. [PMID: 37975301 PMCID: PMC11107892 DOI: 10.1097/xeb.0000000000000396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2023]
Abstract
BACKGROUND In China, there are large differences between regions in the use of gastroscopies and public awareness of upper gastrointestinal (UGI) screening. OBJECTIVE This study investigated the current context and analyzed the barriers that influence UGI screening behavior among the general population in UGI cancer high-prevalence areas. METHODS A total of 320 participants anonymously answered an online questionnaire. The rank sum test was used to analyze the difference in the scores of the UGI screening awareness questionnaire among participants with different socio-demographic characteristics. Using the awareness level of UGI screening and gastroscopy as the dependent variable, and the socio-demographic characteristics as the independent variable, simple linear regression and binary logistic regression analysis were used to determine the factors influencing attitudes toward gastroscopy screening. We used Spearman's correlation analysis to examine the correlation between UGI screening awareness level and willingness to undergo a gastroscopy. RESULTS There was a correlation between the willingness to undergo gastroscopy and the awareness level of UGI screening (r = 0.243, p < 0.001). Linear regression analysis found that age, type of residence, education level, employment status, monthly income, history of gastroscopy, dietary habits, physical exercise, and convenience in obtaining information were significantly correlated with the awareness level of UGI screening ( p < 0.05). Binary logistic regression analysis found that factors significantly associated with gastric cancer screening behavior include residence, monthly income, and self-perceived health status ( p < 0.05). CONCLUSION It is necessary to improve education about UGI cancer and screening knowledge, with a focus on populations with lower education and income.
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Affiliation(s)
- Xin Chen
- Department of Nursing, School of Medicine, Jiangnan University, Wuxi, China
| | - Yuan Ze
- Department of Nursing, School of Medicine, Jiangnan University, Wuxi, China
| | - Wanya Yi
- Department of Nursing, School of Medicine, Jiangnan University, Wuxi, China
| | - Yuling Yang
- Department of Endoscopy Center, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Renjuan Sun
- Department of Outpatient, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Huiming Tu
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Wuxi, China
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Cai J, Lin K, Luo T, Weng J, Liu H, Yuan Z, Wan Z, Han J, Lin J, Liu X, Wang X, Huang M, Luo Y, Yu H. Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial. Br J Cancer 2024; 130:1434-1440. [PMID: 38472421 PMCID: PMC11058860 DOI: 10.1038/s41416-024-02652-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 02/29/2024] [Accepted: 03/04/2024] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment. METHODS In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs. RESULTS We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR = 3.75, 95% CI = 1.37-10.27; complications: HR = 11.35, 95% CI = 1.46-88.31) compared with late-onset group (pCR: OR = 5.33, 95% CI = 1.83-15.58; complications: HR = 5.80, 95% CI = 2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR = 1.37, 95% CI = 0.49-3.87) and DFS (HR = 1.05, 95% CI = 0.58-1.90) for early-onset patients. CONCLUSION Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.
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Affiliation(s)
- Jinlin Cai
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Kaixin Lin
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Tongfeng Luo
- Department of Anaesthesia, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jingrong Weng
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Haotian Liu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Ze Yuan
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Zixiao Wan
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Junyi Han
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jinxin Lin
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiaoxia Liu
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Xiaolin Wang
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Meijin Huang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Yanxin Luo
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China
| | - Huichuan Yu
- Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
- Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-sen University), Ministry of Education, Guangzhou, Guangdong, China.
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Stefanowicz-Hajduk J, Graczyk P, Hering A, Gucwa M, Nowak A, Hałasa R. An In Vitro Study on the Cytotoxic, Antioxidant, and Antimicrobial Properties of Yamogenin-A Plant Steroidal Saponin and Evaluation of Its Mechanism of Action in Gastric Cancer Cells. Int J Mol Sci 2024; 25:4627. [PMID: 38731847 PMCID: PMC11083171 DOI: 10.3390/ijms25094627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Revised: 04/21/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024] Open
Abstract
Yamogenin is a steroidal saponin occurring in plant species such as Asparagus officinalis, Dioscorea collettii, Trigonella foenum-graecum, and Agave sp. In this study, we evaluated in vitro cytotoxic, antioxidant, and antimicrobial properties of yamogenin. The cytotoxic activity was estimated on human colon cancer HCT116, gastric cancer AGS, squamous carcinoma UM-SCC-6 cells, and human normal fibroblasts with MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The amount of apoptotic and dead AGS cells after treatment with yamogenin was estimated with flow cytometry. Also, in yamogenin-treated AGS cells we investigated the reactive oxygen species (ROS) production, mitochondrial membrane depolarization, activity level of caspase-8 and -9, and gene expression at mRNA level with flow cytometry, luminometry, and RT-PCR, respectively. The antioxidant properties of yamogenin were assessed with DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assays. The antimicrobial potential of the compound was estimated on Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae, Escherichia coli, Salmonella enterica, Helicobacter pylori, Campylobacter coli, Campylobacter jejuni, Listeria monocytogenes, Lactobacillus paracasei, and Lactobacillus acidophilus bacteria strains. Yamogenin showed the strongest cytotoxic effect on AGS cells (IC50 18.50 ± 1.24 µg/mL) among the tested cell lines. This effect was significantly stronger in combinations of yamogenin with oxaliplatin or capecitabine than for the single compounds. Furthermore, yamogenin induced ROS production, depolarized mitochondrial membrane, and increased the activity level of caspase-8 and -9 in AGS cells. RT-PCR analysis revealed that this sapogenin strongly up-regulated TNFRSF25 expression at the mRNA level. These results indicate that yamogenin induced cell death via the extrinsic and intrinsic way of apoptosis. Antioxidant study showed that yamogenin had moderate in vitro potential (IC50 704.7 ± 5.9 µg/mL in DPPH and 631.09 ± 3.51 µg/mL in ABTS assay) as well as the inhibition of protein denaturation properties (with IC50 1421.92 ± 6.06 µg/mL). Antimicrobial test revealed a weak effect of yamogenin on bacteria strains, the strongest one being against S. aureus (with MIC value of 350 µg/mL). In conclusion, yamogenin may be a potential candidate for the treatment and prevention of gastric cancers.
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Affiliation(s)
- Justyna Stefanowicz-Hajduk
- Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, Poland; (P.G.); (A.H.); (M.G.)
| | - Piotr Graczyk
- Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, Poland; (P.G.); (A.H.); (M.G.)
| | - Anna Hering
- Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, Poland; (P.G.); (A.H.); (M.G.)
| | - Magdalena Gucwa
- Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, 80-416 Gdańsk, Poland; (P.G.); (A.H.); (M.G.)
| | - Anna Nowak
- Department of Cosmetic and Pharmaceutical Chemistry, Pomeranian Medical University in Szczecin, 70-204 Szczecin, Poland;
| | - Rafał Hałasa
- Department of Pharmaceutical Microbiology, Medical University of Gdańsk, 80-416 Gdańsk, Poland;
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Chen H, Wang C, Chen Z, Huang T, Lin Y, Chen J, Zhang B, He X. The depth of perineural invasion is an independent prognostic factor for stage II colorectal cancer. BMC Cancer 2024; 24:433. [PMID: 38589842 PMCID: PMC11003015 DOI: 10.1186/s12885-024-12206-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Accepted: 03/29/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Perineural invasion (PNI) is the invasion of nerves by cancer cells and is associated with poor survival in stage II colorectal cancer. However, PNI can be further subdivided according to the depth of invasion, and the depth of PNI has not been clearly linked to prognosis. METHOD This study aimed to assess the prognostic value of different depths of PNI in stage II colorectal cancer. We defined PNI in the submucosal plexus and myenteric plexus as superficial perineural invasion (sup-PNI) and PNI in the subserous plexus as deep perineural invasion (deep-PNI). Patients were divided into three groups based on the depth of PNI: sup-PNI, deep-PNI and non-PNI. Then, univariate and multivariate Cox regression analyses were conducted to evaluate the role of PNI in the prognosis of stage II colorectal cancer. RESULTS This study enrolled 3508 patients with stage II colorectal cancer who underwent resection for primary colorectal lesions between January 2013 and September 2019. Clinicopathological features, including elevated carcinoembryonic antigen (CEA) levels, T4 stage, poor differentiation, deficient DNA mismatch repair (dMMR), and vascular invasion, were correlated with deep-PNI. Multivariate analyses revealed that deep-PNI was associated with worse overall survival (OS; hazard ratio [HR], 3.546; 95% confidence interval [CI], 2.307-5.449; P < 0.001) and disease-free survival (DFS; HR, 2.921; 95% CI, 2.032-4.198; P < 0.001), compared with non-PNI. Conversely, no significant difference in OS or DFS was observed between the sup-PNI and non-PNI groups in multivariate analyses. CONCLUSIONS The study demonstrated that the depth of PNI was an independent prognostic factor for patients with stage II colorectal cancer, and patients with deep PNI had a worse prognosis. Thus, patients with PNI require further subdivision according to the depth of invasion.
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Affiliation(s)
- Hao Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong, 510655, China
| | - Chao Wang
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
| | - Zexian Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong, 510655, China
| | - Tianze Huang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong, 510655, China
| | - Yanyun Lin
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong, 510655, China
| | - Junguo Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong, 510655, China
| | - Bin Zhang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong, 510655, China.
| | - Xiaosheng He
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510655, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, Guangdong, 510655, China.
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Yang L, Feng L, Zhu Y, Wang N, Lu X, Gu F, Zhang X, Ji J. Reducing the global cancer burden with gastrointestinal screening: China's 30 years practice. Cancer Biol Med 2024; 21:j.issn.2095-3941.2023.0516. [PMID: 38544481 PMCID: PMC10976323 DOI: 10.20892/j.issn.2095-3941.2023.0516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 02/22/2024] [Indexed: 08/21/2024] Open
Affiliation(s)
- Lei Yang
- Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Cancer Center, Hohhot 010020, China
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Li Feng
- Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Cancer Center, Hohhot 010020, China
| | - Yong Zhu
- Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Cancer Center, Hohhot 010020, China
| | - Ning Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xinpu Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Fanghui Gu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Xiaotian Zhang
- Peking University Cancer Hospital (Inner Mongolia Campus)/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Cancer Center, Hohhot 010020, China
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jiafu Ji
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
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Ebrahimi P, Karami M, Delavari S, Shojaie L, Hosseini-Berneti SH, Bayani F, Moghaddasi M, Babazade O, Nikbakht HA. Investigating the mortality trend of gastrointestinal cancers in Babol, North Iran (2013-2021). BMC Gastroenterol 2024; 24:100. [PMID: 38448828 PMCID: PMC10916231 DOI: 10.1186/s12876-024-03189-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 02/28/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND AND AIM This study aims to examine the mortality rate and trend of gastrointestinal cancers, particularly gastric cancer, as the leading cause of death among cancers in northern Iran over a 9-year period. In light of the changing incidence and mortality rates of cancer in Iran and around the world, the importance of these diseases in people's lives, and the necessity of updating and monitoring the trend of cancer mortality, we have decided to report on the mortality trend of gastrointestinal cancers, based on crude and age-standardized rates. METHOD This study is a cross-sectional examination of deaths caused by gastrointestinal cancers in Babol city, Iran, between 2013 and 2021. Data was collected from the cause of death registration and classification system of Babol University of Medical Sciences. Population estimation was obtained from the latest census reports. The crude and age-standardized mortality rates and trends of the cancers were calculated. RESULTS Overall, there were 1345 deaths from gastrointestinal cancers with an average age of 69.11 ± 14.25 years. The crude and age-standardized rates of these cancers rose from 24.1 to 20.1 per hundred thousand people in 2012 to 29.5 and 25.5 per hundred thousand people, respectively. This trend became more prevalent significantly with the increase of each decade of age for both men (P-value Trend = 0.002) and women (P-value Trend = 0.012). An analysis of gastrointestinal cancers revealed a decreasing trend for cancers of the small intestine, an increasing trend for cancers of the colon, pancreas, and gallbladder, and a stable trend for the remaining cancers over the study period. CONCLUSION The age-standardized rate and the number of gastrointestinal cancers is rising, highlighting the importance of preventative measures such as screening, increasing public awareness, and appropriate diagnostic methods.
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Affiliation(s)
- Pouyan Ebrahimi
- Student Research Committee, Babol University of Medical Science, Babol, Iran
| | - Mohsen Karami
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Department of Parasitology and Mycology, Babol University of Medical Sciences, Babol, Iran
| | - Sahar Delavari
- Institute for the Developing Mind, Children's Hospital Los Angeles, , Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Layla Shojaie
- Division of GI/Liver, Department of Medicine, Keck school of Medicine, University of Southern California, Los Angeles, CA, USA
| | | | - Fatemeh Bayani
- Department of Health, Health Systems Research, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Mehdi Moghaddasi
- Department of Health, Health Systems Research, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Ozra Babazade
- Department of Health, Health Systems Research, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Hossein-Ali Nikbakht
- Social Determinants of Health Research Center, Health Research Institute, Department of Biostatistics & Epidemiology, School of Public Health, Babol University of Medical Sciences, Babol, Iran.
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Chen M, Liu H, Liang W, Huang P, Ye F, Cai Y, Liang Z, Xiong L, Kang L, Huang L. Mitochondrial DNA copy number plays opposing roles in T-lymphocyte infiltration of colorectal cancer based on mismatch repair status: new directions for immunotherapy? Br J Cancer 2024; 130:798-807. [PMID: 38218920 PMCID: PMC10912653 DOI: 10.1038/s41416-023-02568-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 12/13/2023] [Accepted: 12/21/2023] [Indexed: 01/15/2024] Open
Abstract
BACKGROUND Researchers have previously reported that mitochondrial DNA copy number (mtDNA-CN) can play different roles in microsatellite instable/mismatch repair-deficient (MSI/dMMR) and microsatellite stable/mismatch repair-proficient (MSS/pMMR) colorectal cancer (CRC). To support malignancy, dMMR CRC relies on glycolysis, while pMMR CRC favors oxidative phosphorylation. However, it is unclear whether mtDNA-CN changes are related to T cell infiltration in CRC. METHODS The mtDNA-CN was detected by qRT-PCR in 532 patients, and the expression of CD3 and CD8 in 485 patients was detected by immunohistochemistry. The correlation between mtDNA-CN and the prognosis of CRC patients was further analyzed, and the correlation between mtDNA-CN and T lymphocyte infiltration was also analyzed. Biopsy specimens from the immune checkpoint inhibitors (ICIs) treatment cohort were obtained to verify the correlation between mtDNA-CN and the efficacy of ICIs. The effects of mtDNA-CN and MMR status on gene expression were analyzed by RNA-seq. RESULTS Our results show that mtDNA-CN has inverse relationships to CRC prognosis in cases with different MMR statuses, potentially inducing the U-shaped association in CRC. The opposing correlations between mtDNA-CN and T lymphocyte infiltration in cases of dMMR CRC and pMMR CRC further suggest that mtDNA-CN might play an important role in CRC development. More importantly, cases of pMMR CRC with lower mtDNA-CN and of dMMR CRC with higher mtDNA-CN can benefit more dramatically from ICIs. Furthermore, RNA-seq revealed a link between the level of mtDNA-CN and T lymphocyte infiltration in CRC cases with different MMR statuses. CONCLUSION Our study found a potential relationship between mtDNA-CN and CRC development that differs by MMR status, potentially providing a rationale for the use of mtDNA-CN as both a predictive biomarker and a therapeutic target for ICIs.
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Affiliation(s)
- Mian Chen
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huashan Liu
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenfeng Liang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Pinzhu Huang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Fujin Ye
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yebing Cai
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhenxing Liang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Li Xiong
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Liang Kang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
| | - Liang Huang
- Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
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Yang Q, Xu D, Yang Y, Lu S, Wang D, Wang L. Global, Regional, and National Burden of Gastric Cancer in Adolescents and Young Adults, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Am J Gastroenterol 2024; 119:454-467. [PMID: 37800697 PMCID: PMC10904006 DOI: 10.14309/ajg.0000000000002551] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 09/22/2023] [Indexed: 10/07/2023]
Abstract
INTRODUCTION Gastric cancer is a significant global health concern, ranking as the fifth most common cancer worldwide and the third leading cause of cancer-related mortality. While improvements in health awareness and medical technology have contributed to a decline in the incidence of gastric cancer in many countries, the rate of gastric cancer in adolescents and young adults (GCAYA) has shown an upward trend. Timely and effective strategies for screening, detection, and treatment are crucial for managing the burden of GCAYA and optimizing the allocation of medical resources. To this end, our study aimed to examine the distribution of the burden of GCAYA across different factors at the global, regional, and national levels between 1990 and 2019. By identifying and analyzing these factors, we can better inform efforts to combat this growing health challenge. METHODS This study used data from the Global Burden of Disease database to analyze the global, regional, and national incidence, mortality, and disability-adjusted life years (DALY) GCAYA from 1990 to 2019. The age-standardized incidence rate (ASIR), age-standardized mortality rate, and age-standardized DALY rate (ASDR) of GCAYA were summarized and presented in a visually intuitive manner at the global, regional, and national levels. In addition, we calculated the estimated annual percentage change for each indicator of GCAYA globally, regionally, and nationally and visually displayed the results. Furthermore, we conducted an age-based analysis of adolescents and young adults with gastric cancer, comparing the age composition of deaths and the age burden of patients between 1990 and 2019. For the sake of brevity, we will use the abbreviation GCAYA to refer to gastric cancer among adolescents and young adults throughout the remainder of this article. RESULTS From 1990 to 2019, the incidence of GCAYA has slightly increased globally. The number of newly diagnosed cases rose from 47,932 (95% uncertainty interval 44,592.9-51,005.7) in 1990 to 49,007 (45,007.7-53,078.1) in 2019, while the number of deaths decreased from 35,270 (32,579-37,678.5) to 27,895 (25,710.9-30,240.4). The global ASIR showed a declining trend, decreasing from 22.4 (95% uncertainty interval 21.2-23.6) per 100,000 in 1990 to 15.6 (14.1-17.2) per 100,000 in 2019. The age-standardized mortality rate also showed a declining trend, decreasing from 20.5 (19.2-21.6) per 100,000 in 1990 to 11.9 (10.8-12.8) per 100,000 in 2019. The ASDR also showed a declining trend, decreasing from 493.4 (463.7-523.7) per 100,000 in 1990 to 268.4 (245.5-290.6) per 100,000 in 2019. From 1990 to 2019, the incidence, mortality, and DALY of gastric cancer among male adolescents and young adults were higher than those of female adolescents and young adults. In 2019, the number of male adolescents and young adults with gastric cancer was 2.1 times higher than that of female individuals (368.9 [328.2-410.3] vs 178.2 [160.5-196.9]), the number of deaths was 1.1 times higher (14,971.6 [13,643.3-16,520.5] vs 12,923.6 [11,550.3-14,339]), and the DALY were 1.1 times higher (841,920.5 [766,655.5-927,598.8] vs 731,976.3 [653,421-814,242.8]). The incidence and DALY of GCAYA were higher in regions with high-middle and middle sociodemographic index countries. The age-standardized mortality rate of GCAYA in 198 countries and territories showed a decreasing trend, with the Republic of Korea showing the greatest decrease from 1,360.5 (1,300.3-51,416.5) per 100,000 in 1990 to 298.7 (270.1-328.4) per 100,000 in 2019, with an estimated annual percentage change of -5.14 (95% confidence interval -7.23 to -2.99). The incidence and DALY of GCAYA increased with age, with the highest proportion of patients being in the 35-39 years age group. In both 1990 and 2019, the age of death from GCAYA was mainly concentrated in the 35-39 years age group, accounting for approximately half of the total population. DISCUSSION In the past 30 years, although the total number of new cases of GCAYA has increased with population growth, the ASIR and overall disease burden have shown a decreasing trend. This indicates progress in screening, diagnosis, treatment, education, and awareness efforts. However, the distribution of this disease remains uneven in terms of sex, age, development level, region, and country. To address these challenges, global health authorities should take appropriate measures such as optimizing screening programs, strengthening awareness and screening efforts for male individuals, enhancing prevention and control among the 35-39 years age group, improving infrastructure and health care resources in developing countries, promoting international cooperation, and implementing tailored measures.
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Affiliation(s)
- Qizhi Yang
- Medical College of Yangzhou University, Yangzhou, Jiangsu, China;
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China;
- General Surgery Institute of Yangzhou, Yangzhou, Jiangsu, China;
- Department of Thoracic Surgery, No.6 People's Hospital of Xuzhou, Xuzhou, Jiangsu, China;
| | - Dandan Xu
- Department of Intensive Care Unit, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yapeng Yang
- Medical College of Yangzhou University, Yangzhou, Jiangsu, China;
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China;
- General Surgery Institute of Yangzhou, Yangzhou, Jiangsu, China;
| | - Sen Lu
- Department of Thoracic Surgery, No.6 People's Hospital of Xuzhou, Xuzhou, Jiangsu, China;
| | - Daorong Wang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China;
- General Surgery Institute of Yangzhou, Yangzhou, Jiangsu, China;
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, Jiangsu, China.
| | - Liuhua Wang
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China;
- General Surgery Institute of Yangzhou, Yangzhou, Jiangsu, China;
- Yangzhou Key Laboratory of Basic and Clinical Transformation of Digestive and Metabolic Diseases, Yangzhou, Jiangsu, China.
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Jiang X, Yang L, Chen G, Feng X, Liu Y, Gao Q, Mai M, Chen CYC, Ye S, Yang Z. Discovery of Kinetin in inhibiting colorectal cancer progression via enhancing PSMB1-mediated RAB34 degradation. Cancer Lett 2024; 584:216600. [PMID: 38159835 DOI: 10.1016/j.canlet.2023.216600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Revised: 11/29/2023] [Accepted: 12/12/2023] [Indexed: 01/03/2024]
Abstract
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Understanding the underlying mechanism driving CRC progression and identifying potential therapeutic drug targets are of utmost urgency. We previously utilized LC-MS-based proteomic profiling to identify proteins associated with postoperative progression in stage II/III CRC. Here, we revealed that proteasome subunit beta type-1 (PSMB1) is an independent predictor for postoperative progression in stage II/III CRC. Mechanistically, PSMB1 binds directly to onco-protein RAB34 and promotes its proteasome-dependent degradation, potentially leading to the inactivation of the MEK/ERK signaling pathway and inhibition of CRC progression. To further identify potential anticancer drugs, we screened a library of 2509 FDA-approved drugs using computer-aided drug design (CADD) and identified Kinetin as a potentiating agent for PSMB1. Functional assays confirmed that Kinetin enhanced the interaction between PSMB1 and RAB34, hence facilitated the degradation of RAB34 protein and decreased the MEK/ERK phosphorylation. Kinetin suppresses CRC progression in patient-derived xenograft (PDX) and liver metastasis models. Conclusively, our study identifies PSMB1 as a potential biomarker and therapeutic target for CRC, and Kinetin as an anticancer drug by enhancing proteasome-dependent onco-protein degradation.
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Affiliation(s)
- Xuefei Jiang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Lanlan Yang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Guanxing Chen
- Artificial Intelligence Medical Research Center, School of Intelligent Systems Engineering, Shenzhen Campus of Sun Yat-sen University, Shenzhen, Guangdong, 510275, China
| | - Xingzhi Feng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Yiting Liu
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Qianling Gao
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Mingru Mai
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Calvin Yu-Chian Chen
- Department of AI for Science, School of Electronic and Computer Engineering, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, 518055, China
| | - Shubiao Ye
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510655, China
| | - Zihuan Yang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China; Department of Clinical Laboratory, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510655, China.
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Chen Y, Chen X, Lin Y, Zhang S, Zhou Z, Peng J. Oncological risk of proximal gastrectomy for proximal advanced gastric cancer after neoadjuvant chemotherapy. BMC Cancer 2024; 24:255. [PMID: 38395845 PMCID: PMC10885455 DOI: 10.1186/s12885-024-11993-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Accepted: 02/11/2024] [Indexed: 02/25/2024] Open
Abstract
PURPOSE This study assesses the metastasis rate of the key distal lymph nodes (KDLN) that are not routinely dissected in proximal gastrectomy, aiming to explore the oncological safety of proximal gastrectomy for upper gastric cancer who underwent neoadjuvant chemotherapy. METHODS We analyzed a cohort of 150 patients with proximal locally advanced gastric cancer (cT3/4 before chemotherapy) from two high-volume cancer centers in China who received preoperative neoadjuvant chemotherapy (NAC) and total gastrectomy with lymph node dissection. Metastasis rate of the KDLN (No.5/6/12a) and the risk factors were analyzed. RESULTS Key distal lymph node metastasis was detected in 10% (15/150) of patients, with a metastasis rate of 6% (9/150) in No. 5 lymph nodes, 6.7% (10/150) in No. 6 lymph nodes, and 2.7% (2/75) in No. 12a lymph nodes. The therapeutic value index of KDLN as one entity is 5.8. Tumor length showed no correlation with KDLN metastasis, while tumor regression grade (TRG) emerged as an independent risk factor (OR: 1.47; p-value: 0.04). Of those with TRG3 (no response to NAC), 80% (12/15) was found with KDLN metastasis. CONCLUSION For cT3/4 proximal locally advanced gastric cancer patients, the risk of KDLN metastasis remains notably high even after NAC. Therefore, proximal gastrectomy is not recommended; instead, total gastrectomy with thorough distal lymphadenectomy is the preferred surgical approach.
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Affiliation(s)
- Yonghe Chen
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, 510655, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, Guangzhou, Chinaf, China
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, Guangzhou, China
| | - Xiaojiang Chen
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China
| | - Yi Lin
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, 510655, Guangzhou, China
| | - Shenyan Zhang
- Department of Pathology, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, Guangzhou, China
| | - Zhiwei Zhou
- Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, 510060, Guangzhou, China.
| | - Junsheng Peng
- Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Road, 510655, Guangzhou, China.
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, Guangzhou, Chinaf, China.
- Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, Guangzhou, China.
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Wang W, Lin CC, Liang WY, Chang SC, Jiang JK. Adenocarcinoma of sigmoid colon with metastasis to an ovarian mature teratoma: A case report. World J Clin Cases 2024; 12:853-858. [PMID: 38322677 PMCID: PMC10841131 DOI: 10.12998/wjcc.v12.i4.853] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 11/22/2023] [Accepted: 01/08/2024] [Indexed: 01/25/2024] Open
Abstract
BACKGROUND Colorectal cancer ranks third in global cancer-related mortality, often due to metastases to liver and lungs. Ovarian metastases are less common, accounting for 3.6% to 7.4% of cases. In contrast, mature ovarian teratomas are frequently benign. Tumor-to-tumor metastasis is a rare phenomenon, with a limited number of documented cases. Three cases of mature ovarian teratomas metastasizing from different cancers have been reported. This report focuses on a case of tumor-to-tumor metastasis from sigmoid colon adenocarcinoma to a mature ovarian teratoma. CASE SUMMARY A 41-year-old Taiwanese woman with no known systemic diseases presented with lower back pain, which led to imaging revealing malignant lesions in the spine, pelvis, liver, and multiple lung metastases. She was diagnosed with sigmoid colon adenocarcinoma with metastases to the liver, lung, bone, and a left ovarian teratoma. Treatment involved radiotherapy and chemotherapy, resulting in regression of the primary tumor and stable lung and liver lesions. Due to abdominal symptoms, she underwent exploratory surgery, unveiling a mature teratoma in the left ovary with signs of metastatic adenocarcinoma. CONCLUSION Consider resecting mature ovarian teratomas with concurrent colorectal adenocarcinoma to prevent tumor-to-tumor metastasis.
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Affiliation(s)
- Wei Wang
- Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan
| | - Chun-Chi Lin
- Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Wen-Yi Liang
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
- Department of Pathology, Taipei Veteran General Hospital, Taipei 11217, Taiwan
| | - Shih-Ching Chang
- Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
| | - Jeng-Kai Jiang
- Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
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Sunagua Aruquipa M, D'Alpino Peixoto R, Jacome A, Cesar F, Lorandi V, Dienstmann R. Association of KRAS G12C Status with Age at Onset of Metastatic Colorectal Cancer. Curr Issues Mol Biol 2024; 46:1374-1382. [PMID: 38392206 PMCID: PMC10887791 DOI: 10.3390/cimb46020088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/31/2024] [Accepted: 01/31/2024] [Indexed: 02/24/2024] Open
Abstract
The association of age at the onset of CRC and the prevalence of a KRAS G12C mutation is unclear. A retrospective, multicenter study evaluating metastatic CRC patients from January 2019 to July 2023, treated at the Oncoclinicas units and tested for tissue based KRAS/NRAS and BRAF mutations in a centralized genomics lab. A mismatch repair (MMR) status was retrieved from different labs and electronic medical records, as were patient demographics (age, gender) and tumor sidedness. The chi-square test was used to examine the association between clinical and molecular variables, with p value < 0.05 being statistically significant. A total of 858 cases were included. The median age was 63.7 years (range 22-95) and 17.4% were less than 50 years old at the diagnosis of metastatic CRC. Male patients represented 50.3% of the population. The sidedness distribution was as follows: left side 59.2%, right side 36.8% and not specified 4%. The prevalence of the KRAS mutation was 49.4% and the NRAS mutation was 3.9%. Among KRAS mutated tumors, the most common variants were G12V (27.6%) and G12D (23.5%), while KRAS G12C was less frequent (6.4%), which represented 3.1% of the overall population. The BRAF mutant cases were 7.3% and most commonly V600E. Only five (<1%) non-V600E mutations were detected. MSI-high or dMMR was present in 14 cases (1.6%). In the age-stratified analysis, left-sidedness (p < 0.001) and a KRAS G12C mutation (p = 0.046) were associated with a younger age (<50 years). In the sidedness-stratified analysis, a BRAF mutation (p = 0.001) and MSI-high/dMMR status (p = 0.009) were more common in right-sided tumors. Our data suggest that KRAS G12C mutations are more frequent in early-onset metastatic CRC. To the best of our knowledge, this is the largest cohort in the Latin American population with metastatic CRC reporting RAS, BRAF and MSI/MMR status.
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Affiliation(s)
| | | | - Alexandre Jacome
- Oncoclinicas Gastrointestinal Oncology Department, Belo Horizonte 34006-059, MG, Brazil
| | - Fernanda Cesar
- Oncoclinicas Gastrointestinal Oncology Department, Vitoria 29050-400, ES, Brazil
| | - Vinicius Lorandi
- Oncoclinicas Gastrointestinal Oncology Deparment, Porto Alegre 90610-001, RS, Brazil
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Qumseya B, Yang S, Guo Y. Trends in prevalence of esophageal adenocarcinoma: Findings from a statewide database of over 6 million patients. Endosc Int Open 2024; 12:E218-E226. [PMID: 38362358 PMCID: PMC10869210 DOI: 10.1055/a-2221-7974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Accepted: 12/01/2023] [Indexed: 02/17/2024] Open
Abstract
Esophageal cancer (EC) is a leading cause of cancer-related death in the west 1 . Esophageal squamous cell carcinoma (SCC) is the most common type of EC worldwide. However, in Western countries, including the United States, esophageal adenocarcinoma (EAC) is the most common 2 . EAC is most common in the lower esophagus whereas SCC is most common in the middle and upper esophagus 3 . The incidence of EAC has increased dramatically in western countries over the past few decades. 2 3 The exact reason for this rise in EAC has not been clearly understood. However, an increase in the prevalence of EAC risk factors is postulated as a potential explanation 4 . Although there are many identifiable EAC risk factors, including gastroesophageal reflux disease (GERD), obesity, male sex, White race, and smoking 5 6 7 , Barrett's esophagus (BE) remains the major precursor lesion of esophageal adenocarcinoma. BE develops when there is a change in the normal squamous lining of the esophageal mucosa into intestinal metaplasia 8 9 . The incidence has also increased in the population over the past few decades 10 11 . There is a well-described progression within BE from non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), intramucosal carcinoma (IMC), to invasive EAC 12 13 . Recent data suggest that the increased incidence of EAC may have plateaued 1 . However, we questioned whether the prevalence of EAC is still increasing, especially at younger ages in lieu of recent trends showing an increase in the prevalence of colorectal cancer in younger patients. These findings resulted in a lowering of the colorectal cancer screening age cutoff to 45 years from 50 years 14 15 16 . Therefore, we aimed to assess the time trends in the prevalence and incidence of EAC and some of its risk factors in a large population of patients in Florida and to assess these trends based on age categories. We hypothesized that the prevalence of EAC and BE has increased over time at younger age groups.
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Affiliation(s)
- Bashar Qumseya
- Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, United States
| | - Shuang Yang
- Division of Gastroenterology, University of Florida, GAINESVILLE, United States
| | - Yi Guo
- Department of Health Outcomes and Biomedical Informatics, University of Florida, GAINESVILLE, United States
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