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Cho H, Jun HS. Relationship between perceived depression, suicidal ideation, and return to work among cancer survivors in South Korea: A national survey analysis. Asia Pac J Oncol Nurs 2025; 12:100611. [PMID: 39737447 PMCID: PMC11683217 DOI: 10.1016/j.apjon.2024.100611] [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: 03/24/2024] [Accepted: 10/23/2024] [Indexed: 01/01/2025] Open
Abstract
Objective This study aimed to investigate the relationship between perceived depression, suicidal ideation, and return to work among cancer survivors in South Korea, with a focus on sociodemographic and employment-related factors. Methods A secondary analysis of data from 874 cancer survivors, retrieved from the 2015, 2017, and 2019 Korean National Health and Nutrition Examination Surveys, was conducted. Key variables included employment status, household income, marital status, perceived depression, and suicidal ideation. Data were analyzed using descriptive statistics and chi-square tests. Results Female cancer survivors reported higher rates of perceived depression compared to male survivors. Survivors with lower household incomes or without spouses experienced elevated levels of both perceived depression and suicidal ideation. Those in the nonworking group exhibited significantly higher rates of these psychological challenges compared to those who had returned to work. However, the type of job performed was not associated with perceived depression or suicidal ideation. Conclusions Returning to work, regardless of job type, is associated with improved psychological health among cancer survivors, emphasizing the importance of employment in fostering social interaction and emotional stability. Interventions supporting the return-to-work process and addressing the specific needs of vulnerable groups are critical for improving the overall well-being of cancer survivors.
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Affiliation(s)
- Haeryun Cho
- Department of Nursing, Wonkwang University, Iksan, Republic of Korea
| | - Hye Suk Jun
- Department of Nursing, Kangdong Sacred Heart Hospital, Hallym University, Seoul, Republic of Korea
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Gao Z, Yang S, Jiang S, Wu Q, Jia Y, Zhang M, Hao M, Jiang J, Yang J, Duan X, Li Y. Transcription factor KLF5 regulates MsrB1 to promote colorectal cancer progression by inhibiting ferroptosis through β-catenin. Free Radic Biol Med 2025; 234:34-48. [PMID: 40210135 DOI: 10.1016/j.freeradbiomed.2025.04.014] [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: 12/30/2024] [Revised: 04/06/2025] [Accepted: 04/07/2025] [Indexed: 04/12/2025]
Abstract
Methionine sulfoxide reductase B1 (MsrB1), a member of the selenoprotein family with a catalytic site containing a selenocysteine (Sec) residue, has been identified as an oncogene in colorectal cancer (CRC). However, the regulatory mechanisms of MsrB1 and the relationship between its oncogenic role and antioxidant capacity are not well understood. In this study, we show that either overexpression or suppression of MsrB1 in CRC cells leads to significant phenotypic changes, confirming its role in oncogenesis. To explore the molecular regulatory mechanisms of MsrB1, we used bioinformatic analyses to predict transcription factors within its promoter region, and validated these predictions using dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays. These assays revealed that Krüppel-like factor 5 (KLF5), acting as a transcription factor, binds to the MsrB1 promoter and activates it. Additionally, through Weighted Gene Co-expression Network Analysis (WGCNA) and Co-IP experimental validation, we identified β-catenin, a key component of the Wnt signaling pathway, as being co-expressed with MsrB1. The interaction between MsrB1 and β-catenin leads to the activation of GPX4 transcription, a known ferroptosis marker, which results in the inhibition of ferroptosis and promotion of oncogenesis in CRC. In conclusion, this study elucidates the transcriptional regulatory mechanism of MsrB1 and its role in inhibiting ferroptosis in conjunction with β-catenin. These findings suggest that MsrB1 may be a promising predictive biomarker and therapeutic target for CRC, extending its role beyond that of a conventional antioxidant selenoprotein.
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Affiliation(s)
- Zhengdan Gao
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Shengyong Yang
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Shanshan Jiang
- School of Life Sciences, Chongqing University, Chongqing, 401331, China
| | - Qian Wu
- Quality and Safety Management Office, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400011, China
| | - Yi Jia
- Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering (School of Modern Industry for Health and Medicine), Guizhou Medical University, Guiyang, 550025, China; Immune Cells and Antibody Engineering Research Center of Guizhou Province, Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, 550025, China
| | - Mengmeng Zhang
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Meng Hao
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Jianan Jiang
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Jun Yang
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Xudong Duan
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China
| | - Yi Li
- Department of Biochemistry and Molecular Biology, Molecular Medicine and Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, China.
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Gharepapagh E, Akhoundi N, Fakhari A, Seifi B, Sedghian S, Ranjkesh M, Sarfaraz T, Siami A, Nia IY. Can Scintimammography Help Differentiate the Nature of Suspected Masses Identified in Breast Ultrasound among Young Patients? World J Nucl Med 2025; 24:155-160. [PMID: 40336858 PMCID: PMC12055256 DOI: 10.1055/s-0045-1805044] [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] [Indexed: 05/09/2025] Open
Abstract
Background Breast cancer is the second leading cause of cancer deaths among women. Given the limitations of mammography in detecting breast cancer among young patients with suspected masses identified through ultrasound, our study aims to assess the effectiveness of scintimammography in distinguishing the nature of these masses. Methods The study included 123 patients between the ages of 18 and 35, who were presented with breast masses categorized as Breast Imaging-Reporting and Data System III and IV based on ultrasound findings. A total of 134 breast masses were identified in the patients through ultrasound examination. Patients underwent radiopharmaceutical injection of 99mTc-MIBI (technetium-99m methoxyisobutylisonitrile) with a 15 to 20 mCi dose. The radiopharmaceutical uptake in the scans was assessed using a scoring system ranging from 0 to 3. Then, the scores were compared with biopsy results. Results There was a statistically significant relationship between the absorption score reported by scintimammography and the pathological findings ( p = 0.001). The sensitivity and specificity of scintimammography in malignant masses considering cutoff point of 2 for absorption score were 96 and 92%, respectively. Conclusion Based on the obtained results, scintimammography could be considered a diagnostic and complementary method to ultrasound in evaluating benign and malignant breast masses in young patients with dense breasts.
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Affiliation(s)
- Esmaeil Gharepapagh
- Department of Medical Radiation Sciences Research, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Akhoundi
- Department of Radiology, Hillcrest Hospital, University of California San Diego, San Diego, California, United States
| | - Ashraf Fakhari
- Department of Medical Radiation Sciences Research, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Batool Seifi
- Department of Radiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sonia Sedghian
- Department of Medical Radiation Sciences Research, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahnaz Ranjkesh
- Department of Medical Radiation Sciences Research, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Tohid Sarfaraz
- Department of Anesthesiology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Siami
- Department of Biostatistical Analyzer, Amirkabir University of Technology, Tehran, Iran
| | - Iman Yazdani Nia
- Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins Medicine, Baltimore, Maryland, United States
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Del Castillo Falconi VM, Godinez Rodriguez JA, Fragoso-Ontiveros V, Contreras-Espinosa L, Pedroza-Torres A, Díaz-Chávez J, Herrera LA. Role of DNA methylation and non‑coding RNAs expression in pathogenesis, detection, prognosis, and therapy‑resistant ovarian carcinoma (Review). Mol Med Rep 2025; 31:144. [PMID: 40183399 PMCID: PMC11979574 DOI: 10.3892/mmr.2025.13509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 12/17/2024] [Indexed: 04/05/2025] Open
Abstract
Ovarian cancer is the deadliest gynecological cancer globally, with epithelial ovarian cancer (EOC) comprising up to 90% of cases. A molecular characterization linking the histological subtypes with tumor grade in EOC has been suggested. Variations in genetic biomarkers such as BRCA1/2, MSH2, MLH1/6, BRIP1, and RAD51C/D have been studied in EOC. In addition, molecular characteristics, including DNA methylation and RNA transcription, are being explored as potential new biomarkers for the diagnosis and prognosis of this type of neoplasia. The present review focused on the role of DNA methylation and non‑coding RNA expression in the development of ovarian carcinomas and their association with diagnosis, prognosis, and the resistance of cancer cells to radiotherapy and chemotherapy. The present review considered the transition from the DNA structure to the RNA expression in ovarian carcinoma.
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Affiliation(s)
- Victor M. Del Castillo Falconi
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
| | | | - Verónica Fragoso-Ontiveros
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
| | - Laura Contreras-Espinosa
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
- Biological Sciences Postgrade, UNAM, Mexico City 04510, Mexico
| | - Abraham Pedroza-Torres
- Investigadores por México Program - SECIHTI, Hereditary Cancer Clinic, INCan, Mexico City 14080, Mexico
| | - José Díaz-Chávez
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
- School of Medicine and Health Sciences, Mexico-Monterrey Institute of Technology, Mexico City 14380, Mexico
| | - Luis A. Herrera
- Carcinogenesis Laboratory, Biomedical Cancer Research Unit of Biomedicine - National Autonomous University of Mexico (UNAM), National Cancer Institute (INCan), Mexico City 14080, Mexico
- School of Medicine and Health Sciences, Mexico-Monterrey Institute of Technology, Mexico City 14380, Mexico
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Barry C, Shahi A, Kidane D. DNA glycosylase (NEIL3) overexpression associated with low tumor immune infiltration and poor overall patient survival in endometrial cancer. Sci Rep 2025; 15:16308. [PMID: 40348794 PMCID: PMC12065799 DOI: 10.1038/s41598-025-00393-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 04/28/2025] [Indexed: 05/14/2025] Open
Abstract
Endometrial cancer (EC) is the most common gynecological malignancy. Although prognosis is favorable for patients with an early-stage disease, those with recurrent or more advanced disease have low response rates to chemotherapy and poor clinical outcomes. Previously, we have shown that DNA repair gene (NEIL3) is required for retaining replication fork integrity during replication stress. Here, we examined whether the overexpression of NEIL3 in endometrial cancer associated with altered genomic instability, tumor immunogenicity and anti-tumor immunity in endometrial tumor. In this study, we show that endometrial cancer patients with tumors that a have high NEIL3 expression associated with worse overall survival (OS) outcomes in patients. In addition, tumor with high NEIL3 expression is associated with high number of mutation and chromosomal instability. Furthermore, NEIL3 expression in EC tumors positively correlated with mutation of DNA polymerase eta (POLE) and TP53 as well as high expression of replicative polymerases genes (POLE, POLD1 and POLA1). In contrast, tumor with high NEIL3 expression exhibit low tumor immunogenicity and poor anti-tumor immune cell infiltration. Our findings may have important clinical implications for utilizing NEIL3 as a potential prognostic biomarker to stratify EC patients and as a target to enhance immunotherapy response in endometrial cancer. However, our NEIL3 overexpression associated observation still requires further experimental-based scientific validation studies.
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Affiliation(s)
- Cristofer Barry
- Department of Physiology & Biophysics, College of Medicine, Howard University, 520 W Street N.W, Washington, DC, 20059, USA
| | - Aashirwad Shahi
- Department of Physiology & Biophysics, College of Medicine, Howard University, 520 W Street N.W, Washington, DC, 20059, USA
| | - Dawit Kidane
- Department of Physiology & Biophysics, College of Medicine, Howard University, 520 W Street N.W, Washington, DC, 20059, USA.
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Abdel-Rashid RS, El-Leithy ES, Ibrahim IT, Attallah KM. Radiolabelling and bioequivalence of modified Tamoxifen solid lipid nanoparticles as a targeted chemotherapeutic drug. Drug Deliv Transl Res 2025:10.1007/s13346-025-01865-1. [PMID: 40335856 DOI: 10.1007/s13346-025-01865-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/15/2025] [Indexed: 05/09/2025]
Abstract
There are several types of breast cancer where the breast's cells proliferate uncontrollably. A selective oestrogen receptor modulator called Tamoxifen citrate (TAM) is used to treat and prevent breast cancer in both men and women. TAM is classified as class II under the biopharmaceutical categorization system (BCS) of medications. It exhibits low plasma levels, which can result in therapeutic failure due to its poor water solubility. To improve its chemotherapeutic efficiency and drug targeting, nanotechnology was exploited. In this article, TAM-loaded SLNs were prepared, characterized, and radiolabelled with Technetium-99m ([99mTc]Tc) using stannous salts followed by the assessment of their radiochemical efficiency and in vivo biodistribution compared to the radiolabelled free TAM ([99mTc]Tc-TAM). The results showed that the concentration of lipid had a highly prominent effect on the particle size and encapsulation efficiency of the drug, where the best selected formula showed spherical, non-aggregated morphology with a 134.6 ± 0.3 nm size and 83.9 ± 2.5% drug encapsulation. The radiolabelling purity was more than 97.4%, and it was stable for at least 6 h. In solid tumor-bearing mice, [99mTc]Tc-TAM-SLNs exhibited around 3 times more uptake than [99mTc]Tc-TAM solution. Accordingly, [99mTc]Tc-TAM-SLNs can be suggested as a useful targeted delivery strategy for chemotherapy drugs.
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Affiliation(s)
- Rania S Abdel-Rashid
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Ain Helwan, P.O. Box 11795, Cairo, Egypt
- Nanotechnology Research Center, Helwan University, Cairo, Egypt
| | - Eman S El-Leithy
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Helwan University, Ain Helwan, P.O. Box 11795, Cairo, Egypt
| | - Ismail T Ibrahim
- Labeled Compound Department, Hot Lab Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt
| | - Khaled M Attallah
- Labeled Compound Department, Hot Lab Center, Egyptian Atomic Energy Authority, P.O. Box 13759, Cairo, Egypt.
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Aragie H, Adugna DG, Negash HK, Maru L, Baye ND. Survival status and predictors of mortality among patients with breast cancer in Ethiopia: a systematic review and meta-analysis. BMJ Open 2025; 15:e092725. [PMID: 40341151 PMCID: PMC12060883 DOI: 10.1136/bmjopen-2024-092725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 03/28/2025] [Indexed: 05/10/2025] Open
Abstract
OBJECTIVES This study aimed to evaluate survival outcomes and identify key mortality predictors among patients with breast cancer in Ethiopia. STUDY DESIGN A systematic review and meta-analysis. STUDY PARTICIPANTS The study used 11 primary studies, involving a total of 4131 participants. DATA SOURCES We searched PubMed, Embase, Web of Science, Scopus and Google Scholar until 7 March 2025, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. ELIGIBILITY CRITERIA FOR SELECTING STUDIES All observational studies that had reported the survival status and/or at least one predictor of mortality of women patients with breast cancer were considered. DATA EXTRACTION AND SYNTHESIS Three independent reviewers (HA, HKN and DGA) used a structured data extraction form to extract the data. To compute the pooled survival and mortality rates, the survival rates at different observation periods and the mortality rates reported in the included studies were extracted. RESULTS Eleven studies were analysed. All studies were of good quality based on Newcastle-Ottawa Scale. However, heterogeneity was high (I² = 98.2%, p=0.00). Funnel plots showed significant publication bias. The Grading of Recommendations, Assessment, Development, and Evaluations assessment indicated moderate certainty for mortality rates and predictors, limited by heterogeneity and regional data gaps. The pooled mortality rate was 36% (95% CI: 25% to 46%). The survival rates at 1, 3 and 5 years were 85% (95% CI: 75% to 96%), 66% (95% CI: 48% to 84%) and 22% (95% CI: 1% to 43%), respectively. Key mortality predictors included advanced clinical stage (Adjusted Hazard Ratio (AHR): 4.14; CI: 2.53 to 6.78), rural residence (AHR: 1.65; 95% CI: 1.27 to 2.14), positive lymph node status (AHR: 2.85; 95% CI: 1.50 to 5.44), no hormonal therapy (AHR: 2.02; 95% CI: 1.59 to 2.56), histologic grade III (AHR: 1.76; 95% CI: 1.29 to 2.41), hormone receptor negativity (AHR: 1.54; 95% CI: 1.05 to 2.25) and comorbidities (AHR: 2.24; 95% CI: 1.41 to 3.56). CONCLUSION Breast cancer in Ethiopia poses a high mortality rate primarily due to late-stage diagnosis, rural residency, histologic grade III, positive lymph node status and comorbidities. To improve survival outcomes, it is crucial to expand access to early screening, particularly in rural areas, implement comprehensive treatment protocols and strengthen healthcare infrastructure to address these critical factors. PROSPERO REGISTRATION NUMBER CRD42024575074.
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Affiliation(s)
- Hailu Aragie
- Department of Human Anatomy, University of Gondar, Gondar, Ethiopia
| | | | | | - Lemlemu Maru
- Department of Human Physiology, University of Gondar, Gondar, Ethiopia
| | - Nega Dagnew Baye
- Department of Human Anatomy, University of Gondar, Gondar, Ethiopia
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Arana-Chicas E, Zhang Y, Chávez-Iñiguez A, Lin PJ, Mattick LJ, Kamen C, Clark V, Cartujano-Barrera F, Mustian KM. Use of cultural appropriateness strategies and behavioral frameworks in behavioral interventions for black and hispanic cancer survivors: a systematic review. BMC Cancer 2025; 25:835. [PMID: 40329190 PMCID: PMC12057219 DOI: 10.1186/s12885-025-14182-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Accepted: 04/17/2025] [Indexed: 05/08/2025] Open
Abstract
BACKGROUND Black and Hispanic cancer survivors experience significant inequities in supportive cancer care. Incorporating cultural appropriateness strategies and behavioral frameworks into supportive care interventions can improve cancer outcomes of Black and Hispanic survivors. This review evaluated behavioral oncology trials for Black and Hispanic cancer survivors to assess their use of cultural appropriateness strategies and behavioral frameworks. METHODS A systematic search was conducted across seven databases with a cutoff date of November 15, 2023: 1) PubMed, 2) Cochrane Central Register of Controlled Trials, 3) Embase, 4) Cumulative Index of Nursing and Allied Health Literature, 5) APA PsycInfo, 6) Scopus, and 7) Web of Science. Studies with Black or Hispanic cancer survivors, with or without a comparator, were included. RESULTS Thirty-seven trials met the inclusion criteria. Most focused on Black survivors (n = 19, 51.4%) and breast cancer survivors (n = 32, 86.5%). Most were psychosocial interventions addressing quality of life or distress (n = 20, 54.1%). Culturally appropriate strategies were reported in 86.5% (n = 32) of trials, with the most common being sociocultural (n = 30, 81.1%;), constituent-involving (n = 27, 73.0%;), and linguistic (n = 20, 54.1%;). Behavioral frameworks were reported in 56.8% (n = 21) of trials, with Social Cognitive Theory (n = 10, 52.6%) and Stress and Coping Theory (n = 3, 15.8%) being the most frequent. Less than half combined cultural adaptation strategies and a behavioral framework (n = 18, 48.6%). CONCLUSION While most trials incorporated cultural appropriateness strategies, fewer utilized behavioral frameworks, and even fewer used both. Future research should integrate these approaches to improve cancer outcomes and address disparities.
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Affiliation(s)
- Evelyn Arana-Chicas
- Department of Medicine, Rutgers Cancer Institute, 120 Albany Street, 8th Floor, Tower 2, New Brunswick, NJ, 08901, USA.
| | - Yingting Zhang
- Robert Wood Johnson Library of the Health Sciences, Department of Medicine, Robert Wood Johnson Medical School, Rutgers University, 1 RWJ Place, New Brunswick, NJ, 08901, USA
| | - Arlette Chávez-Iñiguez
- Department of Medicine, Rutgers Cancer Institute, 120 Albany Street, 8th Floor, Tower 2, New Brunswick, NJ, 08901, USA
| | - Po-Ju Lin
- James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
- Department of Surgery, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
| | - Lindsey J Mattick
- James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
- Department of Surgery, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
| | - Charles Kamen
- James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
- Department of Surgery, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
| | - Viktor Clark
- James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
- Department of Surgery, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
| | - Francisco Cartujano-Barrera
- Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
| | - Karen M Mustian
- James P. Wilmot Cancer Institute, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
- Department of Surgery, University of Rochester School of Medicine and Dentistry, 265 Crittenden Blvd, Rochester, NY, 14642, USA
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Guo W, Yin J, Gu Y, Shan Y, Wang W, Li Y, Qin M, Chen J, Jin Y, Pan L. Patients with macroscopic lymph node metastasis expect poor prognosis after neoadjuvant chemotherapy in advanced ovarian cancer: a retrospective cohort study based on a single gynecological team. BMC Cancer 2025; 25:832. [PMID: 40329194 PMCID: PMC12057188 DOI: 10.1186/s12885-025-14237-2] [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: 03/03/2024] [Accepted: 04/28/2025] [Indexed: 05/08/2025] Open
Abstract
OBJECTIVE To investigate the prognostic impact of metastatic lymph nodes (MLNs) on advanced epithelial ovarian cancer (EOC) patients receiving neoadjuvant chemotherapy (NACT). METHODS This was a retrospective cohort study using data from patients managed by a single gynecological team between June 2012 and June 2023. Among EOC patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV disease, patients who received NACT and who underwent complete cytoreduction during interval debulking surgery were included (the NACT cohort), together with patients who received primary debulking surgery (PDS, including those with both complete and incomplete cytoreduction). Clinically suspicious lymph nodes at diagnosis and/or debulking surgeries were resected. Differences in terms of clinicopathological features, survival profiles, and recurrence patterns were analyzed between groups with different lymph node statuses. RESULTS The NACT cohort comprised 166 patients (53.6% underwent lymphadenectomy), of whom 58 presented with MLNs (the MLN group) and 108 did not (the NLN group). Among those who underwent lymphadenectomy, a median of 24 pelvic lymph nodes and 13 para-aortic lymph nodes were resected. The MLN group was significantly associated with inferior progression-free survival (PFS) and time to platinum-resistant recurrence (TTPR), even when adjusted by multivariate models. The hazard ratio (95% confidence interval) was 1.90 (1.06-3.41) for the multivariate PFS analysis and 2.50 (1.22-5.13) for the multivariate TTPR analysis. For the PDS cohort (143 patients, 68.5% underwent lymphadenectomy), a median of 25 pelvic lymph nodes and 14 para-aortic lymph nodes were resected. The MLN group (66 patients) manifested non-inferior PFS and TTPR outcomes compared to the NLN group (77 patients). CONCLUSIONS MLNs may have a negative impact on the prognosis of patients receiving NACT. For such patients, PDS is a preferred choice to delay recurrence and platinum resistance.
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Affiliation(s)
- Wen Guo
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
| | - Jie Yin
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
| | - Yu Gu
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
| | - Yin Shan
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
| | - Wei Wang
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
| | - Yan Li
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
| | - Meng Qin
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
| | - Jiayu Chen
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
| | - Ying Jin
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China.
| | - Lingya Pan
- Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan 1#, Dongcheng District, Beijing, 100730, China
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10
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Chen J, Zhao J, Zuo J, Fu Y, Dong H, Shi H, Zhang Y, Wang H, Fu S. HDL cholesterol esters mediate the genetic link between sedentary behavior and urological cancers: Insights from mediation and validation analyses. Medicine (Baltimore) 2025; 104:e42369. [PMID: 40324228 PMCID: PMC12055118 DOI: 10.1097/md.0000000000042369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/12/2025] [Accepted: 04/20/2025] [Indexed: 05/07/2025] Open
Abstract
This study explores the causal relationship between sedentary behavior and urological cancers, focusing on bladder cancer (BC), prostate cancer, and kidney cancer, using Bayesian Mendelian randomization and mediation analysis. A two-sample Mendelian randomization (MR) framework was employed, using genetic variants as instrumental variables. Bayesian and multivariate MR assessed causal effects of sedentary behaviors (TV watching, computer use, driving) on urological cancers. Sensitivity analyses (MR-Egger, MR-PRESSO, and Cochran Q) ensured robustness. Mediation analysis identified high-density lipoprotein (HDL) cholesterol ester levels as a primary mediator, validated through meta-analysis. Prolonged TV watching was significantly associated with increased BC risk (OR = 2.908; 95% CI = 1.221-6.930; P = .015). Mediation analysis showed small HDL cholesterol ester levels mediated 17.5% of this effect. No causal relationships were observed between computer use or driving and the cancers. Sensitivity analyses confirmed robust findings without heterogeneity or pleiotropy. Prolonged TV watching increases BC risk, mediated by small HDL cholesterol ester levels. Sedentary behavior is a modifiable risk factor, highlighting the importance of lifestyle interventions in prevention.
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Affiliation(s)
- Junhao Chen
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Junxian Zhao
- Department of Urology, 920th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Kunming, Yunnan Province, China
| | - Jieming Zuo
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - YuanZhi Fu
- Kunming University of Science and Technology, Kunming, China
| | - Haonan Dong
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Hongjin Shi
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yawei Zhang
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Haifeng Wang
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Shi Fu
- Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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11
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Zhou JM, Dai WX, Wang RJ, Xu WQ, Xiang Z, Wang YX, Zhang T, Zhao YM, Wang L, Mao AR. Organoid modeling identifies USP3-AS1 as a novel promoter in colorectal cancer liver metastasis through increasing glucose-driven histone lactylation. Acta Pharmacol Sin 2025; 46:1404-1418. [PMID: 39837984 PMCID: PMC12032002 DOI: 10.1038/s41401-024-01465-8] [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: 10/01/2024] [Accepted: 12/18/2024] [Indexed: 01/23/2025]
Abstract
Dysregulation of long non-coding RNAs (lncRNAs) is common in colorectal cancer liver metastasis (CRLM). Emerging evidence links lncRNAs to multiple stages of metastasis from initial migration to colonization of distant organs. In this study we investigated the role of lncRNAs in metabolic reprogramming during CRLM using patient-derived organoid (PDO) models. We established five pairs of PDOs from primary tumors and matched liver metastatic lesions, followed by microarray analysis. We found that USP3-AS1 was significantly upregulated in CRLM-derived PDOs compared to primary tumors. High level of USP3-AS1 was positively associated with postoperative liver metastasis and negatively correlated with the prognosis of colorectal cancer (CRC) patients. Overexpression of USP3-AS1 significantly enhanced both sphere formation efficiency and liver metastasis in PDOs. Gene set enrichment analysis revealed that USP3-AS1 upregulation significantly enriched glycolysis and MYC signaling pathways. Metabolomics analysis confirmed that USP3-AS1 promoted glycolysis in PDOs, whereas glycolysis inhibition partially attenuated the effects of USP3-AS1 overexpression on PDO growth and liver metastasis. We revealed that USP3-AS1 stabilized MYC via post-translational deubiquitination, thereby promoting glycolysis. We demonstrated that USP3-AS1 increased the stability of USP3 mRNA, resulting in higher USP3 protein expression. The elevated USP3 protein then interacted with MYC and promoted its stability by deubiquitination. The USP3-AS1-MYC-glycolysis regulatory axis modulated liver metastasis by promoting H3K18 lactylation and CDC27 expression in CRC. In conclusion, USP3-AS1 is a novel promoter of CRLM by inducing histone lactylation.
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Affiliation(s)
- Jia-Min Zhou
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Wei-Xing Dai
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Department of Colorectal Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
| | - Ren-Jie Wang
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
- Department of Colorectal Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
| | - Wei-Qi Xu
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Zhen Xiang
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yi-Xiu Wang
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Ti Zhang
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yi-Ming Zhao
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Lu Wang
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
| | - An-Rong Mao
- Department of Hepatic Surgery, Shanghai Cancer Center, Fudan University, Shanghai, 200032, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
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12
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Jaiswal A, Negi M, Choi EH, Kaushik NK, Kaushik N. Upstream-binding protein-1 promotes breast tumorigenesis by inducing NRG2-mediated metastasis, plasticity, and macrophage polarization. Int J Biol Macromol 2025; 307:141915. [PMID: 40064277 DOI: 10.1016/j.ijbiomac.2025.141915] [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: 10/21/2024] [Revised: 03/07/2025] [Accepted: 03/07/2025] [Indexed: 03/18/2025]
Abstract
Upstream binding protein 1 (UBP1) is a transcription factor (TF) of the CP2/grainyhead family involved in various biological processes, including cancer cell proliferation, differentiation, and embryonic development. While other mammalian grainyhead-like TFs have been linked to different cancers, including breast cancer (BC), the role of UBP1 in BC remains unexplored. In this study, we provide a preliminary investigation into the novel functions of UBP1 in BC. Using online database screening, we first demonstrated that elevated UBP1 levels in breast carcinoma are associated with poor prognosis and adverse clinical outcomes. We further showed that UBP1 promotes epithelial-mesenchymal transition (EMT) and stemness in BC cells while regulating key signaling pathways, including the PI3K-Akt. Additionally, UBP1 modulates tumor metastasis by influencing tumor-associated macrophage (TAM) polarization, promoting an immunosuppressive macrophage phenotype, and driving tumor progression. Our findings highlight UBP1's pivotal role in BC progression through multiple mechanisms, including EMT induction, stemness maintenance, and macrophage polarization via activation of the NRG2/Akt axis. Moreover, higher UBP1 expression correlates with lower overall and recurrence-free survival, underscoring its potential as a prognostic marker and therapeutic target for aggressive BC.
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Affiliation(s)
- Apurva Jaiswal
- Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea
| | - Manorma Negi
- Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea
| | - Eun Ha Choi
- Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea.
| | - Nagendra Kumar Kaushik
- Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul 01897, Republic of Korea.
| | - Neha Kaushik
- Department of Biotechnology, College of Engineering, The University of Suwon, Hwaseong 18323, Republic of Korea.
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13
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Aktepe OH, Erdemir AG, Caliskan Yildirim E, Demirciler E, Ulasli T, Guven DC, Onur MR, Unek IT, Semiz HS, Erman M, Yalcin S. Early Changes in Volumetric Body Composition Parameters Predict Survival Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with Targeted Therapy. J Clin Med 2025; 14:3140. [PMID: 40364170 DOI: 10.3390/jcm14093140] [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: 03/19/2025] [Revised: 04/13/2025] [Accepted: 04/19/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: The precise role of volumetric body composition (VBC) parameters, visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and skeletal muscle index (SMI) on the survival of metastatic renal cell carcinoma (mRCC) is not fully elucidated. Herein, the present study investigated the clinical significance of baseline VBC parameters and their changes after 3-4 months from treatment initiation in patients with mRCC treated with first-line targeted therapy. Methods: A total of 108 patients were enrolled. VBC parameters were depicted from computerized tomography (CT) images at the third lumbar vertebra level. Kaplan-Meier curves were used to estimate survival probability, and the differences between prognostic subgroups were compared with the log-rank test. The association of baseline VBC variables and their change values (First CT value minus baseline CT value) with progression-free survival (PFS) and overall survival (OS) was evaluated in univariate and multivariate analyses. Results: The median PFS and OS of the whole patients were 11 and 46 months, respectively. Patients with increased VATI and SATI change values had poorer OS than those with decreased values. However, patients with higher SMI change values had superior OS than those with lower values. Among VBC variables, the independent predictors of worse OS were high VATI change (HR 5.10, p = 0.001) and low SMI change values (HR 2.66, p = 0.007), in addition to International Metastatic Renal Cell Carcinoma Database Consortium prognostic stratification (p = 0.001). Conclusions: Our findings showed that high VATI and low SMI changes were associated with worse OS in mRCC patients treated with first-line targeted therapy.
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Affiliation(s)
- Oktay Halit Aktepe
- Department of Medical Oncology, Dokuz Eylul University, 35330 Izmir, Turkey
| | - Ahmet Gurkan Erdemir
- Department of Radiology, Faculty of Medicine, Hacettepe University, 06230 Ankara, Turkey
| | - Eda Caliskan Yildirim
- Department of Medical Oncology, Sincan Research and Training Hospital, 06949 Ankara, Turkey
| | - Erkut Demirciler
- Department of Medical Oncology, Izmir City Hospital, 35540 Izmir, Turkey
| | - Tugce Ulasli
- Department of Medical Oncology, Dokuz Eylul University, 35330 Izmir, Turkey
| | - Deniz Can Guven
- Department of Medical Oncology, Hacettepe University Cancer Institute, 06230 Ankara, Turkey
| | - Mehmet Ruhi Onur
- Department of Radiology, Faculty of Medicine, Hacettepe University, 06230 Ankara, Turkey
| | - Ilkay Tugba Unek
- Department of Medical Oncology, Dokuz Eylul University, 35330 Izmir, Turkey
| | | | - Mustafa Erman
- Department of Medical Oncology, Hacettepe University Cancer Institute, 06230 Ankara, Turkey
| | - Suayib Yalcin
- Department of Medical Oncology, Hacettepe University Cancer Institute, 06230 Ankara, Turkey
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14
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Tseng TY, Lin AYH, Chou PY, Toh CH, Wu YM, Yeh CH. Nomogram for predicting postoperative temporomandibular joint degeneration after mandibulectomy for oral cavity cancer: a study on patients using CT and MRI data. Int J Oral Maxillofac Surg 2025; 54:395-403. [PMID: 39488457 DOI: 10.1016/j.ijom.2024.10.010] [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: 04/11/2024] [Revised: 08/11/2024] [Accepted: 10/15/2024] [Indexed: 11/04/2024]
Abstract
The aim of this study was to develop a model for predicting the risk of postoperative temporomandibular joint osteoarthritis (TMJOA) in patients receiving a segmental or marginal mandibulectomy for oral cavity cancer . A total of 371 patients with buccal or gingival cancer who underwent mandibulectomy were included in this retrospective cohort study. Demographic data, computed tomography, and magnetic resonance images were reviewed. Univariate and multivariate Cox regression analyses were performed to develop a nomogram to predict post-mandibulectomy TMJOA. TMJOA was identified in 81 of the 371 patients at 2 years and 107 at 4 years. The predictors of post-mandibulectomy TMJOA were segmental mandibulectomy (hazard ratio (HR) 2.51, 95% confidence interval (CI) 1.64-3.83, P < 0.001), age ≥ 62.5 years (HR 2.28, 95% CI 1.53-3.40, P < 0.001), BMI < 24.1 kg/m2 (HR 2.13, 95% CI 1.45-3.13, P < 0.001), and American Joint Committee on Cancer stage IVa/IVb (HR 2.21, 95% CI 1.38-3.56, P = 0.001). The nomogram developed in this study exhibited good predictive capacity (area under the curve 0.742, 95% CI 0.679-0.804). The proposed model for predicting post-mandibulectomy TMJOA in patients with buccal or gingival cancer can identify high-risk individuals for early preventive oral rehabilitation.
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Affiliation(s)
- T-Y Tseng
- Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Keelung, Taiwan; Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - A Y-H Lin
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Oral and Maxillofacial Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - P-Y Chou
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Plastic and Reconstructive Surgery and Craniofacial Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - C-H Toh
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Y-M Wu
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - C-H Yeh
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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15
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Ulrich CM, Himbert C, Barnes CA, Boucher KM, Daniels B, Bandera VM, Ligibel JA, Wetter DW, Hess R, Kim J, Lundberg K, Mitzman B, Marcus R, Finlayson SRG, LaStayo PC, Varghese TK. Precision Exercise Effect on Fatigue and Function in Lung Cancer Surgery: A Randomized Clinical Trial. JAMA Surg 2025; 160:495-519. [PMID: 40072448 PMCID: PMC11904799 DOI: 10.1001/jamasurg.2025.0130] [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: 10/18/2024] [Accepted: 12/30/2024] [Indexed: 03/15/2025]
Abstract
Importance Exercise intervention studies have shown benefits for patients with lung cancer undergoing surgery, yet most interventions to date have been resource intensive and have followed a one-size-fits-all approach. Objective To determine whether a personalized, clinic-aligned perioperative exercise program with remote monitoring and instructions can improve physical function and fatigue among patients undergoing surgery for lung cancer. Design, Setting, and Participants The Precision-Exercise-Prescription (PEP) randomized clinical trial is a single-center phase 3 trial. Adult patients with primary lung cancer (stages I-IIIa) or oligometastatic disease to the lung (where all disease could be removed) were assessed for eligibility and randomized to either an exercise intervention or standard care. Patients were enrolled between November 2017 and 2021, and the trial continued during the COVID-19 pandemic. Data were analyzed from November 2022 to December 2023. Interventions The structured exercise program, personalized based on mobility scores, was a home-based exercise intervention prescribed and monitored remotely by a licensed physical therapist. The program started approximately 2 weeks before surgery and continued after surgery. Standard care included use of incentive spirometer and encouragement to exercise without a formal program. Main Outcomes and Measures Physical function (6-minute walk test [6MWT]), the Short Physical Performance Battery, and cancer-related fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue) were assessed at baseline and 2 months after surgery. Results A total of 182 patients (92 receiving exercise intervention, 90 receiving standard care) were assessed in the intention-to-treat population. Patients had a mean (SD) age of 62.7 (13.8) years, 108 (59%) were female, and 89 (49%) had low mobility scores (Activity Measure for Post-Acute Care scores, 1-3). Physical function in the exercise group increased at 2 months after surgery (mean [SE] 6MWT at baseline, 467.9 [13.0] m; at 2 months, 482.2 [14.1] m), compared with a decrease in the standard-care group (mean [SE] 6MWT at baseline, 481.4 [11.1] m; at 2 months, 471.5 [14.0] m). Mean (SE) between-group changes in 6MWT distance for intent to treat from baseline to 2 months were 22.7 (12.7) m (P = .08), with greater effect sizes among women (mean [SE], 37.8 [17.3] m; P = .03). Similarly, women showed greater improvements in the Short Physical Performance Battery (mean [SE], 0.9 [0.4]; P = .04). Patients in the exercise group maintained stable fatigue scores at 2 months, whereas participants in the standard-care group deteriorated (mean [SD], 3.7 [1.4]; P = .009), with greater effect sizes among individuals who were younger, from rural areas, had overweight or obesity, and had primary lung cancer. Conclusions and Relevance The PEP intervention, a personalized, clinic-aligned, and remotely monitored perioperative exercise program for patients with lung cancer undergoing surgery demonstrated improvements in physical function for women and significant improvements in fatigue scores across all groups. Trial Registration ClinicalTrials.gov Identifier: NCT03306992.
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Affiliation(s)
- Cornelia M. Ulrich
- Huntsman Cancer Institute, Salt Lake City, Utah
- Department of Population Health Sciences, University of Utah, Salt Lake City
| | - Caroline Himbert
- Huntsman Cancer Institute, Salt Lake City, Utah
- Department of Population Health Sciences, University of Utah, Salt Lake City
| | - Christopher A. Barnes
- Huntsman Cancer Institute, Salt Lake City, Utah
- Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City
| | - Kenneth M. Boucher
- Huntsman Cancer Institute, Salt Lake City, Utah
- Division of Epidemiology, University of Utah, Salt Lake City
| | | | - Victoria M. Bandera
- Huntsman Cancer Institute, Salt Lake City, Utah
- Department of Population Health Sciences, University of Utah, Salt Lake City
| | - Jennifer A. Ligibel
- Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
| | - David W. Wetter
- Huntsman Cancer Institute, Salt Lake City, Utah
- Department of Population Health Sciences, University of Utah, Salt Lake City
| | - Rachel Hess
- Department of Population Health Sciences, University of Utah, Salt Lake City
- Division of General Internal Medicine, University of Utah, Salt Lake City
| | - Jaewhan Kim
- Huntsman Cancer Institute, Salt Lake City, Utah
- Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City
| | - Kelly Lundberg
- Department of Psychiatry, University of Utah, Salt Lake City
| | - Brian Mitzman
- Huntsman Cancer Institute, Salt Lake City, Utah
- Department of Surgery, University of Utah, Salt Lake City
- Division of Cardiothoracic Surgery, University of Utah, Salt Lake City
| | - Robin Marcus
- Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City
| | | | - Paul C. LaStayo
- Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City
| | - Thomas K. Varghese
- Huntsman Cancer Institute, Salt Lake City, Utah
- Department of Surgery, University of Utah, Salt Lake City
- Division of Cardiothoracic Surgery, University of Utah, Salt Lake City
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16
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Liu C, Liu C, Liu GJ, Wang MM, Jiao Y, Sun YJ, Guo H, Wang L, Lu YX, Chen Y, Ding YH. BE-43547A 2 exerts hypoxia-selective inhibition on human pancreatic cancer cells through targeting eEF1A1 and disrupting its association with FoxO1. Acta Pharmacol Sin 2025; 46:1433-1444. [PMID: 39837983 PMCID: PMC12032368 DOI: 10.1038/s41401-024-01461-y] [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: 07/15/2024] [Accepted: 12/16/2024] [Indexed: 01/23/2025]
Abstract
Hypoxia is a key feature of the tumor microenvironment that leads to the failure of many chemotherapies and induces more aggressive and resistant cancer phenotypes. Up to date, there are very few compounds and treatments that can target hypoxia. BE-43547A2 from Streptomyces sp. was one of the most hypoxia-selective compounds against PANC-1, MCF-7, and K562 cell lines. In this study, we investigated the molecular mechanism underlying the hypoxia selectivity of BE-43547A2 in human pancreatic cancer cells. We showed that BE-43547A2 displayed hypoxia-selective cytotoxicity in five pancreatic cancer cells (PANC-1, Capan-2, MIA PaCa-2, AsPC-1, and PaTu8988T) with IC50 values under hypoxia considerably lower than those under normoxia. We demonstrated that BE-43547A2 is directly bound to eEF1A1 protein in PaTu8988T cells under hypoxia. Furthermore, we revealed that hypoxia significantly elevated the expression levels of HIF1α, FoxO1, and eEF1A1 in the five pancreatic cancer cells; eEF1A1 interacted with FoxO1 in the cytoplasm, which was disrupted by BE-43547A2 followed by the nuclear translocation of FoxO1 and ultimate inhibition of JAK/STAT3 signaling pathway under hypoxia. This study reveals that BE-43547A2, targeting eEF1A1, disrupts its interaction with FoxO1 in human pancreatic cancer cells under hypoxia. This compound could serve as a potential hypoxia-selective therapy.
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Affiliation(s)
- Can Liu
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350, China
- College of Biotechnology, Tianjin University of Science & Technology, Tianjin, 300457, China
| | - Can Liu
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China
| | - Guang-Ju Liu
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China
| | | | - Yan Jiao
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China
| | - Yuan-Jun Sun
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China
| | - Hui Guo
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China
| | - Liang Wang
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China
| | - Ya-Xin Lu
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China
| | - Yue Chen
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China.
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350, China.
| | - Ya-Hui Ding
- State Key Laboratory of Medicinal Chemical Biology, Haihe Laboratory of Sustainable Chemical Transformations, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300350, China.
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350, China.
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17
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Xie L, Liu J, Yang Z, Chen H, Wang Y, Du X, Fu Y, Song P, Yu J. Microrobotic Swarms for Cancer Therapy. RESEARCH (WASHINGTON, D.C.) 2025; 8:0686. [PMID: 40302783 PMCID: PMC12038165 DOI: 10.34133/research.0686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 03/27/2025] [Accepted: 04/04/2025] [Indexed: 05/02/2025]
Abstract
Microrobotic swarms hold great promise for the revolution of cancer treatment. The coordination of miniaturized microrobots offers a unique approach to treating cancers at the cellular level with enhanced delivery efficiency and environmental adaptability. Prior studies have summarized the design, functionalization, and biomedical applications of microrobotic swarms. The strategies for actuation and motion control of swarms have also been introduced. In this review, we first give a detailed introduction to microrobot swarming. We then explore the design of microrobots and microrobotic swarms specifically engineered for cancer therapy, with a focus on tumor targeting, infiltration, and therapeutic efficacy. Moreover, the latest developments in active delivery methods and imaging techniques that enhance the precision of these systems are discussed. Finally, we categorize and analyze the various cancer therapies facilitated by functional microrobotic swarms, highlighting their potential to revolutionize treatment strategies for different cancer types.
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Affiliation(s)
- Leiming Xie
- Shenzhen Institute of Artificial Intelligence and Robotics for Society (AIRS), Shenzhen 518129, China
- School of Science and Engineering,
The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China
| | - Jinbo Liu
- Shenzhen Institute of Artificial Intelligence and Robotics for Society (AIRS), Shenzhen 518129, China
- School of Science and Engineering,
The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China
| | - Zhen Yang
- Shenzhen Institute of Artificial Intelligence and Robotics for Society (AIRS), Shenzhen 518129, China
- School of Science and Engineering,
The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China
| | - Hui Chen
- Shenzhen Institute of Artificial Intelligence and Robotics for Society (AIRS), Shenzhen 518129, China
- School of Science and Engineering,
The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China
| | - Yibin Wang
- Shenzhen Institute of Artificial Intelligence and Robotics for Society (AIRS), Shenzhen 518129, China
- School of Science and Engineering,
The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China
| | - Xingzhou Du
- Shenzhen Institute of Artificial Intelligence and Robotics for Society (AIRS), Shenzhen 518129, China
- School of Science and Engineering,
The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China
| | - Yongping Fu
- Department of Cardiovascular Medicine,
Affiliated Hospital of Shaoxing University, Shaoxing 312000, China
| | - Peng Song
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital,
Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China
| | - Jiangfan Yu
- Shenzhen Institute of Artificial Intelligence and Robotics for Society (AIRS), Shenzhen 518129, China
- School of Science and Engineering,
The Chinese University of Hong Kong, Shenzhen, Shenzhen 518172, China
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18
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Huang Y, Wei C, Chen F, Zhang Y, Pu F. Comparing the biopsy strategies of prostate cancer: a systematic review and network meta-analysis. BMC Cancer 2025; 25:786. [PMID: 40289077 PMCID: PMC12036175 DOI: 10.1186/s12885-025-14203-y] [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: 03/11/2025] [Accepted: 04/23/2025] [Indexed: 04/29/2025] Open
Abstract
The introduction of three kinds of magnetic resonance imaging-guided prostate biopsies (MRI-PB) has changed the paradigm regarding prostate biopsies (PB). We aimed to compare and rank PB strategies to provide the latest evidence of PB option for prostate cancer (PCa) diagnosis. We searched PubMed, the Cochrane Library Central, Scopus, Embase and the reference lists of relevant articles for randomized controlled trials published up to Dec, 2024, of different PB strategies. Finally, 24 randomized trials were included. Eleven PB strategies published were considered. For overall PCa detection rates exclusively previously negative biopsy patients, we found robust improvements of 3.92 (95% CI: 2.17-6.41) for MRI-cognitive- and 1.78 (95% CI: 1.02-3.07) for MRI/TRUS- compared to TRUS(10-12)-PB. For PCa detection when prostate volume ≤ 50 mm3, only MRI/TRUS- was significantly effective than TRUS(10-12)-PB (OR 1.78, 95% CI: 1.0-2.89). Our study indicated that MRI-cognitive-PB was associated with better overall PCa detection rates compared with TRUS(10-12)-PB, but it had no remarkable advantages in csPCa and ciPCa detection. More head-to-head comparisons of MRI-PB techniques are needed in the future.
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Affiliation(s)
- Yiqi Huang
- Department of Nephrology, Shaoxing Second Hospital, Shaoxing, Zhejiang, China
| | - Cailiu Wei
- Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China
| | - Fenjuan Chen
- Department of Internal Medicine, Shaoxing Second Hospital, Shaoxing, Zhejiang, China
| | - Yanling Zhang
- Department of Nephrology, Shaoxing Second Hospital, Shaoxing, Zhejiang, China
| | - Feifei Pu
- Department of Ultrasonic, Shaoxing Second Hospital, Shaoxing, Zhejiang, China.
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19
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Lv T, Yang J, Cheng B. Oncological and functional outcomes of Retzius-sparing vs. standard robot-assisted radical prostatectomy: evidence on randomized-controlled trials studies. J Robot Surg 2025; 19:165. [PMID: 40257521 DOI: 10.1007/s11701-025-02335-z] [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: 02/05/2025] [Accepted: 04/06/2025] [Indexed: 04/22/2025]
Abstract
RS-RARP appears to offer better functional outcomes compared to traditional RARP, particularly in terms of urinary continence. However, its oncological outcomes remain a topic of debate. Additionally, there is a lack of comparative analyses focusing on results from randomized-controlled trials (RCTs) in the current review. A comprehensive examination and synthesis of existing RCTs research were conducted to compare follow-up outcomes of RS-RARP versus RARP in PCa patients. A comprehensive search was conducted in PubMed, Web of Science, and the Cochrane Library, and SpringerLink databases for that compare RS-RARP to RARP before December 1st, 2024. Oncological and functional outcomes were used as outcomes to compare. This meta-analysis included 549 people from five research papers. RS-RARP outperformed RARP in immediate continence recovery, with an odds ratio of 0.39, a 95% confidence range of 0.18-0.81, and a p value of less than 0.05. Later follow-ups showed that RARP hampered the patient's functional recovery. At every time point, the RS-RARP group had less incontinence than the RARP group. For these reasons: 1 month (OR: 0.38, 95% CI 0.21-0.69), 3 months (OR: 0.34, 95% CI 0.13-0.90), 6 months (OR: 0.25, 95% CI 0.15-0.40), and 12 months (OR: 0.36, 95% CI 0.16-0.80). p < 0.05. There were no significant differences in BCR rates between RS-RARP and RARP (OR: 1.16, 95% confidence interval: 0.42 to 3.19, p = 0.78). This was the researchers' conclusion. The odds ratio of 0.45, with a 95% confidence range of 0.29 to 0.70 and a p value of less than 0.05, showed that RS-RARP was linked with more PSMs. In terms of functional recovery after surgery, our results show that RS-RARP is much better than RARP. Having said that, it does come with a greater incidence of PSMs. When comparing the two methods for BCR, we found no statistically significant differences. Based on these findings, RS-RARP may be considered as a surgical option for patients with prostate cancer; nevertheless, the choice should be made taking into account the surgeon's skill level and the patient's unique situation. To thoroughly assess the effects of these two techniques, further randomized-controlled studies are required, ideally with large sample numbers, multicenter participation, and long-term follow-up.
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Affiliation(s)
- Tingxuan Lv
- Department of Urology, Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, Weifang, China
| | - Jinhui Yang
- Department of Urology, Shengli Oilfield Central Hospital, Dongying, China
| | - Bo Cheng
- Department of Urology, Shengli Oilfield Central Hospital, Dongying, China.
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20
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Theodoulidis V, Kissoudi K, Chatzistamatiou K, Tzitzis P, Zouzoulas D, Theodoulidis I, Anthoulakis C, Moysiadis T, Topalidou M, Timotheadou E, Grimpizis G, Tsolakidis D. Neutrophil-Lymphocyte Ratio and KELIM Score as Prognostic Markers in High-Grade Serous Advanced Ovarian Cancer Patients Treated with Neoadjuvant Chemotherapy. Biomedicines 2025; 13:975. [PMID: 40299674 PMCID: PMC12024925 DOI: 10.3390/biomedicines13040975] [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: 03/22/2025] [Revised: 04/10/2025] [Accepted: 04/13/2025] [Indexed: 05/01/2025] Open
Abstract
Background/Objectives: Advanced ovarian cancer (AOC) is frequently diagnosed at late stages, with a 5-year overall survival (OS) rate of approximately 25%. While primary debulking surgery followed by chemotherapy remains the standard treatment, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative for patients with extensive disease. Achieving complete cytoreduction is a critical prognostic factor for OS and progression-free survival (PFS). This study evaluated the prognostic value of two biomarkers-the neutrophil-lymphocyte ratio (NLR) and the cancer antigen-125 (CA-125) ELIMination rate constant K (KELIM)-in predicting survival outcomes and recurrence rates in patients with AOC undergoing NACT. Methods: A retrospective, single-center analysis was conducted on 78 patients with high-grade serous AOC (stages III-IV) treated with platinum-based NACT followed by IDS between January 2013 and December 2023. NLR was calculated from prechemotherapy complete blood counts, with a threshold of ≥3 indicating elevated levels. KELIM, a marker of tumor chemosensitivity, was derived from CA-125 kinetics during the first 100 days of chemotherapy, with a cutoff of ≥1 denoting a favorable outcome. Clinical outcomes, including PFS and OS were analyzed using Kaplan-Meier survival curves, log-rank tests, and Cox regression models. Results: Results demonstrated that elevated NLR (≥3) and low KELIM (<1) were associated with poorer PFS and OS. KELIM score was identified as a strong prognostic marker for both PFS and OS, while NLR demonstrated weak association. Complete cytoreduction was achieved in 69.2% of patients, significantly correlating with improved survival outcomes. Postoperative complications, assessed using the Clavien-Dindo classification, were observed in a small subset of patients, with a total median hospital stay of 8 days. Conclusions: This study highlights the potential of NLR and KELIM as prognostic tools in AOC, aiding in patient selection for radical surgical interventions and predicting chemosensitivity. Future multicenter studies with larger cohorts are needed to validate these results and further explore the clinical utility of these biomarkers in optimizing treatment strategies for AOC.
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Affiliation(s)
- Vasilis Theodoulidis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Kalliopi Kissoudi
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Kimon Chatzistamatiou
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Panagiotis Tzitzis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Dimitris Zouzoulas
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Iakovos Theodoulidis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Christos Anthoulakis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Theodoros Moysiadis
- Department of Computer Science, School of Sciences and Engineering, University of Nicosia, 2417 Nicosia, Cyprus;
| | - Maria Topalidou
- Radiotherapy Department, “Papageorgiou” Hospital, 56429 Thessaloniki, Greece;
| | - Eleni Timotheadou
- Department of Oncology, Aristotle University of Thessaloniki, Genaral Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece;
| | - Grigoris Grimpizis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
| | - Dimitris Tsolakidis
- 1st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, General Hospital of Thessaloniki “Papageorgiou” Greece, 56429 Thessaloniki, Greece; (K.K.); (K.C.); (P.T.); (D.Z.); (I.T.); (C.A.); (G.G.); (D.T.)
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21
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Assaf W, Qarawani A, Abboud Y, Shalabna E, Nahshon C, Zilberlicht A, Reiss A, Schmidt M, Segev Y. Pathology results of risk-reducing salpingo-oophorectomy in BRCA1/2 carriers and long-term clinical outcomes. Int J Gynaecol Obstet 2025. [PMID: 40231745 DOI: 10.1002/ijgo.70110] [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: 12/16/2024] [Revised: 03/08/2025] [Accepted: 03/18/2025] [Indexed: 04/16/2025]
Abstract
INTRODUCTION BRCA1/2 mutation carriers have a lifetime ovarian cancer risk of 40%-45% for BRCA1 and 15%-20% for BRCA2. The most effective risk-reduction strategy for women with known BRCA mutations remains bilateral risk-reducing salpingo-oophorectomy (RRSO), which reduces the risk by 80%. The primary objective of this study is to assess the long-term incidence of primary peritoneal carcinoma (PPC) following RRSO and to evaluate the occurrence of premalignant and malignant lesions. METHODS This retrospective cohort study followed BRCA1/2-positive patients who underwent RRSO, using data from two medical centers in Haifa Israel between 2002 and 2023. Data collected included demographic characteristics and pathology results post-surgery. Outcomes included rates of occult cancer (OC), serous tubal intraepithelial carcinoma (STIC), and PPC. RESULTS A total of 214 women underwent RRSO. Of these, 126 (58.8%) had a BRCA1 mutation, 76 (35.5%) had a BRCA2 mutation, and 12 (5.6%) carried both BRCA1 and BRCA2 mutations. During a mean follow-up of 122.4 months (SD ± 84.0), three patients (1.5%) developed PPC. OC was identified in 13 patients (6.1%) during RRSO. Out of the 13 OC patients, eight (61.5%) were classified as stage 1. The overall survival for the OC population was 117.2 ± 55.9 months. STIC was detected in two patients. CONCLUSION In this large retrospective analysis of BRCA carriers who underwent RRSO, we confirmed that long-term follow-up is crucial for BRCA mutation carriers undergoing RRSO, as malignancies can still arise over time. In our study, the incidence of PPC was 1.5%, highlighting the need for extended surveillance. These findings underscore the importance of meticulous surgical protocols, expert pathology review, and ongoing monitoring to optimize patient outcomes.
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Affiliation(s)
- Wisam Assaf
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Amalfi Qarawani
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Yousef Abboud
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
- Department of Obstetrics and Gynecology, Rambam Health Care Campus, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
| | - Eiman Shalabna
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Chen Nahshon
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Ariel Zilberlicht
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Ari Reiss
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
- Department of Obstetrics and Gynecology, Emek Medical Center, Rappaport Faculty of Medicine, Technion University, Haifa, Israel
| | - Meirav Schmidt
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
| | - Yakir Segev
- Department of Obstetrics and Gynecology, Lady Davis Carmel Medical Center, Technion University, Rappaport Faculty of Medicine, Haifa, Israel
- Rappaport Faculty of Medicine, Technion-Israel Institution of Technology, Haifa, Israel
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22
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Liu H, Yang Z, Li J, Zhang J, Sun C. Expanding the horizons of bicyclol in multiple diseases: Mechanisms, therapeutic implications and challenges. Eur J Pharmacol 2025; 993:177381. [PMID: 39954842 DOI: 10.1016/j.ejphar.2025.177381] [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: 11/01/2024] [Revised: 01/25/2025] [Accepted: 02/11/2025] [Indexed: 02/17/2025]
Abstract
Bicyclol, a drug stemmed from the traditional Chinese medicine Schisandra chinensis, has been widely utilized in clinical practice due to its efficacy and safety to manage hepatopathy. Its diverse biological properties-including antiviral, anti-inflammatory, antifibrotic, immunomodulatory, antioxidative, antisteatotic, and antitumor effects-underscore its significant medicinal effects in versatile hepatic disorders, incorporating viral hepatitis, non-alcoholic fatty liver disease, hepatocellular carcinoma, acute hepatic failure, hepatic fibrosis as well as drug-induced liver injury. Furthermore, ongoing researches into the molecular mechanisms, biological activities and mode of actions concerning bicyclol have uncovered its potential therapeutic implications in other multiple diseases/conditions. Studies have indicated promising efficacy pertaining to bicyclol to treat idiopathic pulmonary fibrosis, acute lung injury, cerebral ischemia/reperfusion injury, renal dysfunction, renal cell carcinoma, and cardiovascular diseases. Accordingly, this narrative review article summarizes the current understanding of diverse biological activities and underpinning mechanisms of bicyclol across a range of diseases, as well as its pharmacokinetics, toxicity profile and shed light on future perspectives.
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Affiliation(s)
- Heng Liu
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China
| | - Ziyi Yang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
| | - Jia Li
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China
| | - Jie Zhang
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China.
| | - Chao Sun
- Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Anshan Road 154, Heping District, Tianjin, 300052, China; Department of Gastroenterology, Tianjin Medical University General Hospital Airport Hospital, East Street 6, Tianjin Airport Economic Area, Tianjin, 300308, China.
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23
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Zhang S, Pan J, Guo H, Guan X, Yan C, Ji L, Wu X, Huangfu H. Prognostic value and immunotherapy analysis of immune cell-related genes in laryngeal cancer. PeerJ 2025; 13:e19239. [PMID: 40247837 PMCID: PMC12005187 DOI: 10.7717/peerj.19239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Accepted: 03/11/2025] [Indexed: 04/19/2025] Open
Abstract
Background Laryngeal cancer (LC) is a prevalent head and neck carcinoma. Extensive research has established a link between immune cells in the tumor microenvironment (TME) and cancer progression, as well as responses to immunotherapy. This study aims to develop a prognostic model based on immune cell-related genes and examine the TME in LC. Methods RNA-seq data for LC were sourced from The Cancer Genome Atlas (TCGA), and GSE27020 and GSE51985 datasets were retrieved from the Gene Expression Omnibus (GEO) database. Key genes were identified through the intersection of differentially expressed genes (DEGs) between normal and LC samples and module genes derived from weighted gene co-expression network analysis (WGCNA), followed by functional enrichment analysis. The prognostic risk model was constructed using univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Gene Set Variation Analysis (GSVA) was subsequently performed for hallmark and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses in high- and low-risk groups. Immune infiltration analysis between risk groups was conducted via Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and single sample gene set enrichment analysis (ssGSEA). Finally, the relationship between the risk model and immunotherapy response was explored. Results A total of 124 key genes were identified through the overlap analysis, predominantly enriched in GO terms such as defense response to viruses and regulation of response to biotic stimuli, as well as KEGG pathways related to phagosome and Epstein-Barr virus infection. Machine learning indicated that the optimal prognostic model was constructed from two biomarkers, RENBP and OLR1. GSVA revealed that in the high-risk group, epithelial-mesenchymal transition and ECM-receptor interaction were the most significantly enriched pathways, while autoimmune thyroid disease, ribosome, and oxidative phosphorylation predominated in the low-risk group. Additionally, the stromal score was significantly higher in the high-risk group, while CD8+ T cells, cytolytic activity, inflammation promotion, and T cell co-stimulation were elevated in the low-risk group. Tumor Immune Dysfunction and Exclusion (TIDE) analysis showed higher TIDE and exclusion scores in the high-risk group, whereas the CD8 score was higher in the low-risk group. Finally, CD274 (PD-L1) expression was significantly elevated in the low-risk group. Conclusions This study identified two key prognostic biomarkers, RENBP and OLR1, and characterized TME differences across risk groups, offering novel insights into the diagnosis and treatment of LC.
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Affiliation(s)
- Sen Zhang
- The First Hospital of Shanxi Medical University, Department of Otolaryngology Head and Neck Surgery, Taiyuan, Shanxi, China
- Shanxi Medical University, First Clinical Medical College, Taiyuan, Shanxi, China
- Shanxi Medical University, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, China
| | - Jianrui Pan
- The First Hospital of Shanxi Medical University, Department of Otolaryngology Head and Neck Surgery, Taiyuan, Shanxi, China
- Shanxi Medical University, First Clinical Medical College, Taiyuan, Shanxi, China
- Shanxi Medical University, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, China
| | - Huina Guo
- The First Hospital of Shanxi Medical University, Department of Otolaryngology Head and Neck Surgery, Taiyuan, Shanxi, China
- Shanxi Medical University, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, China
| | - Xiaoya Guan
- The First Hospital of Shanxi Medical University, Department of Otolaryngology Head and Neck Surgery, Taiyuan, Shanxi, China
- Shanxi Medical University, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, China
| | - Chenxu Yan
- The First Hospital of Shanxi Medical University, Department of Otolaryngology Head and Neck Surgery, Taiyuan, Shanxi, China
- Shanxi Medical University, First Clinical Medical College, Taiyuan, Shanxi, China
- Shanxi Medical University, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, China
| | - Lingling Ji
- The First Hospital of Shanxi Medical University, Department of Otolaryngology Head and Neck Surgery, Taiyuan, Shanxi, China
- Shanxi Medical University, First Clinical Medical College, Taiyuan, Shanxi, China
- Shanxi Medical University, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, China
| | - Xiansha Wu
- The First Hospital of Shanxi Medical University, Department of Otolaryngology Head and Neck Surgery, Taiyuan, Shanxi, China
- Shanxi Medical University, First Clinical Medical College, Taiyuan, Shanxi, China
- Shanxi Medical University, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, China
| | - Hui Huangfu
- The First Hospital of Shanxi Medical University, Department of Otolaryngology Head and Neck Surgery, Taiyuan, Shanxi, China
- Shanxi Medical University, First Clinical Medical College, Taiyuan, Shanxi, China
- Shanxi Medical University, Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan, Shanxi, China
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24
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Lin Z, Lv J, Dai C, Zhai Y, Jiang J, Gao Y, Li R, Fan J, Yu Y, Wu L, Yang Y. Identification of the disulfidptosis-related key gene CD2AP as a potential biomarker and new therapeutic target for LUAD patients by comprehensive multi-omics analysis. Discov Oncol 2025; 16:515. [PMID: 40214854 PMCID: PMC11992263 DOI: 10.1007/s12672-025-02308-6] [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: 12/30/2024] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
BACKGROUND Lung Adenocarcinoma (LUAD) is a major subtype of Non-Small Cell Lung Cancer (NSCLC) with poor prognosis. Despite advances in molecular targeted therapy and immunotherapy, the five-year survival rate remains low. Disulfidptosis, a novel cell death mechanism, may play a role in tumor progression. CD2AP (CD2-associated protein), a key gene related to Disulfidptosis, is involved in cytoskeleton reorganization and signaling. This study aimed to explore CD2AP's function in LUAD and its potential as a biomarker and therapeutic target through multi-omics analysis. METHODS We analyzed CD2AP expression and clinical significance in LUAD using data from TCGA, GEO, and other public databases. We employed transcriptomics, methylation analysis, immune infiltration assays, and spatial transcriptomics. Kaplan-Meier survival analysis was used to assess the relationship between CD2AP expression and prognosis. Enrichment analysis identified biological processes and pathways related to CD2AP, while its association with the immune microenvironment and drug sensitivity was also evaluated. RESULTS CD2AP was significantly overexpressed in LUAD, and high expression correlated with poorer prognosis, including overall survival and progression-free survival. Enrichment analysis showed CD2AP is involved in cell adhesion, PI3K-Akt signaling, and immune escape, suggesting it promotes LUAD progression through these pathways. High CD2AP expression was associated with alterations in the tumor immune microenvironment and drug sensitivity, particularly to chemotherapeutics like Cisplatin, Etoposide, and Paclitaxel, and resistance to targeted therapies like Gefitinib. Spatial transcriptomics revealed higher CD2AP expression in tumor regions, especially in malignant cell-enriched areas. CONCLUSION This study highlights CD2AP's critical role in LUAD, particularly in immune microenvironment modulation, metabolic reprogramming, and drug response. CD2AP's high expression is linked to poor prognosis and may serve as a potential target for immunotherapy and drug response prediction.
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Affiliation(s)
- Zhiwu Lin
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Jing Lv
- Department of Orthopedics, Ziyang Central Hospital, Ziyang, 641300, China
| | - Chuanqiang Dai
- Department of Orthopedics, Ziyang Central Hospital, Ziyang, 641300, China
| | - Yuanwei Zhai
- Department of Medical Imaging, Ziyang Central Hospital, Ziyang, 641300, China
| | - Jiudong Jiang
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Yang Gao
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Rulin Li
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Jiangang Fan
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Yang Yu
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Liang Wu
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China
| | - Yanchun Yang
- Department of Thoracic Surgery, Ziyang Central Hospital, Ziyang, 641300, China.
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25
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Katz L, Ben-Arush M, Blanche E, Meir I, Mordechai O. The Clinical Utility of Next-Generation Sequencing in Childhood and Adolescent/Young Adult Solid Tumors: A Systematic Review and Meta-Analysis. Cancers (Basel) 2025; 17:1292. [PMID: 40282467 PMCID: PMC12026244 DOI: 10.3390/cancers17081292] [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: 03/22/2025] [Revised: 04/01/2025] [Accepted: 04/08/2025] [Indexed: 04/29/2025] Open
Abstract
BACKGROUND Next-generation sequencing (NGS) has emerged as a transformative tool in precision medicine, offering insights into actionable genomic alterations and informing clinical decision-making in childhood and adolescent/young adult (AYA) solid tumors. METHODS We conducted a systematic review and meta-analysis to assess the utility of NGS in identifying actionable genomic alterations and its impact on clinical decision-making. Studies involving patients aged 0-40 years with solid tumors were included. Data were extracted using Covidence, and pooled estimates were calculated using a random-effects model. Bias was assessed using Begg-Mazumdar, Egger, and Harbord tests. RESULTS Out of 13,624 references screened, 24 studies met eligibility criteria, comprising 5278 patients and 5359 samples, of which 5207 provided usable data. The pooled proportion of actionable alterations was 57.9% (95% CI: 49.0-66.5%), with minimal evidence of publication bias. Clinical decision-making outcomes were reported in 21 studies, with a pooled proportion of 22.8% (95% CI: 16.4-29.9%). Germline mutation rates, reported in 11 studies, yielded a pooled proportion of 11.2% (95% CI: 8.4-14.3%), consistent with rates typically observed in childhood cancers. Significant heterogeneity was observed across studies due to differences in sequencing methodologies, tumor types, and sampling strategies. CONCLUSIONS NGS demonstrates considerable potential in identifying actionable genomic targets and guiding clinical decision-making in childhood and AYA solid tumors. However, the variability in methodologies underscores the need for standardized protocols and reporting practices to enhance comparability and generalizability. This meta-analysis highlights the promise of genomic medicine while acknowledging challenges posed by heterogeneity in study designs.
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Affiliation(s)
- Lior Katz
- Pediatrics, Ruth Rappaport Children’s Hospital, Rambam Medical Center, Haifa 3109601, Israel
| | - Myriam Ben-Arush
- Joan and Sanford Weill Pediatric Hematology Oncology and Bone Marrow Transplantation Division, Ruth Rappaport Children’s Hospital, Rambam Medical Center, Haifa 3109601, Israel
| | - Einav Blanche
- Joan and Sanford Weill Pediatric Hematology Oncology and Bone Marrow Transplantation Division, Ruth Rappaport Children’s Hospital, Rambam Medical Center, Haifa 3109601, Israel
| | - Inbar Meir
- Joan and Sanford Weill Pediatric Hematology Oncology and Bone Marrow Transplantation Division, Ruth Rappaport Children’s Hospital, Rambam Medical Center, Haifa 3109601, Israel
| | - Oz Mordechai
- Joan and Sanford Weill Pediatric Hematology Oncology and Bone Marrow Transplantation Division, Ruth Rappaport Children’s Hospital, Rambam Medical Center, Haifa 3109601, Israel
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26
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Lv X, Liu J, Islam K, Ruan J, He C, Chen P, Huang C, Wang H, Dhar A, Moness M, Shi D, Murphy S, Zhao X, Yang S, Montoute I, Polakkattil A, Chung A, Ruiz E, Carbajal B, Padavala A, Chen L, Hua G, Chen X, Davis JS, Wang C. Hyperactivated YAP1 is essential for sustainable progression of renal clear cell carcinoma. Oncogene 2025:10.1038/s41388-025-03354-8. [PMID: 40210757 DOI: 10.1038/s41388-025-03354-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 02/12/2025] [Accepted: 03/17/2025] [Indexed: 04/12/2025]
Abstract
The most notable progress in renal clear cell carcinoma (ccRCC) in the past decades is the introduction of drugs targeting the VHL-HIF signaling pathway-associated angiogenesis. However, mechanisms underlying the development of VHL mutation-independent ccRCC are unclear. Here we provide evidence that the disrupted Hippo-YAP signaling contributes to the development of ccRCC independent of VHL alteration. We found that YAP1 and its primary target genes are frequently upregulated in ccRCC and the upregulation of these genes is associated with unfavorable patient outcomes. Research results derived from our in vitro and in vivo experimental models demonstrated that, under normoxic conditions, hyperactivated YAP1 drives the expression of FGFs to stimulate the proliferation of tumor and tumor-associated endothelial cells in an autocrine/paracrine manner. When rapidly growing cancer cells create a hypoxic environment, hyperactivated YAP1 in cancer cells induces the production of VEGF, which promotes the angiogenesis of tumor-associated endothelial cells, leading to improved tumor microenvironment and continuous tumor growth. Our study indicates that hyperactivated YAP1 is essential for maintaining ccRCC progression, and targeting the dual role of hyperactivated YAP1 represents a novel strategy to improve renal carcinoma therapy.
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Affiliation(s)
- Xiangmin Lv
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jiyuan Liu
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Kazi Islam
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Jinpeng Ruan
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Chunbo He
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Obstetrics and Gynecology, Olson Center for Women's Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - Peichao Chen
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Cong Huang
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Hongbo Wang
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Anjali Dhar
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Chemistry, Dartmouth College, Hanover, NH, USA
| | - Madelyn Moness
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Davie Shi
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Neurobiology, Northwestern University, Evanston, IL, USA
| | - Savannah Murphy
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Xingeng Zhao
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Siyi Yang
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Isabelle Montoute
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Human Evolutionary Biology, Harvard University, Cambridge, MA, USA
| | - Aneeta Polakkattil
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Andie Chung
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Emily Ruiz
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA
| | - Brianna Carbajal
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Department of Stem cell and Regenerative Biology, Harvard University, Cambridge, MA, USA
| | - Alekhya Padavala
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Li Chen
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Guohua Hua
- Department of Obstetrics and Gynecology, Olson Center for Women's Health, University of Nebraska Medical Center, Omaha, NE, USA
| | - Xingcheng Chen
- Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - John S Davis
- Department of Obstetrics and Gynecology, Olson Center for Women's Health, University of Nebraska Medical Center, Omaha, NE, USA
- Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
- Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA
| | - Cheng Wang
- Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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27
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Reyngold M, Schoenfeld JD, O’Reilly EM, Varghese AM, White C, Zinovoy M, Romesser PB, Wu AJ, Hajj C, Cuaron JJ, Khalil DN, Park W, Lu W, Zhang Z, Yu KH, Diaz LA, Crane CH. Nonoperative Management of Technically Resectable Pancreatic Cancer With Ablative Radiation Therapy. JAMA Oncol 2025:2832566. [PMID: 40208620 PMCID: PMC11986826 DOI: 10.1001/jamaoncol.2025.0460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 02/02/2025] [Indexed: 04/11/2025]
Abstract
Importance Surgical resection of pancreatic ductal adenocarcinoma (PDAC) modestly improves long-term survival due to the competing risk of metastatic disease. However, postoperative morbidity often interferes with administration of systemic therapy and may be unacceptable to some patients. Ablative radiation therapy (A-RT) has emerged as an effective noninvasive local treatment in many tumor types and may provide an alternative to surgery in select patients with resectable PDAC. Objective To estimate the efficacy of A-RT in technically resectable PDAC. Design, Setting, and Participants This cohort study of consecutive patients with histologically confirmed, radiographically resectable T1-2N0-1M0 PDAC treated with A-RT at Memorial Sloan Kettering Cancer Center between June 2016 and December 2022 were included from a prospectively maintained database. Patients were not eligible for surgery because of noncancer-related comorbidities. Data were frozen for analysis in December 2023, which took place between March and November 2024. Exposures All patients received A-RT exceeding 97.5-Gy biologically effective dose with daily computed tomography or magnetic resonance imaging guidance, motion management, and daily or selective adaptation of the dose distribution. Main Outcomes and Measures The primary outcome was overall survival (OS). Secondary outcomes included biochemical and radiographic objective response rate, cumulative incidence of local progression, progression-free survival, and distant metastasis-free survival. Results Of 25 patients with radiographically resectable PDAC who received A-RT, 13 (52%) were male, and the median (IQR) age at time of A-RT was 80 (74-87) years. A total of 20 patients (80%) had a Karnofsky Performance Status score of 80 or lower. A total of 15 tumors (60%) were T2, and 4 (16%) were node positive. A total of 17 patients (68%) received induction chemotherapy for a median (range) of 2.9 (1.0-6.1) months. Radiation therapy regimens delivered with conventional linear accelerators included 75 Gy in 25 fractions among 13 patients, 67.5 Gy in 15 fractions among 9 patients, 50 Gy in 5 fractions among 2 patients (magnetic resonance imaging-guided linear accelerator), and 60 Gy in 10 for 1 patient. OS, local progression, and distant metastasis-free survival at 2 years were 43.7% (95% CI, 27.4%-69.5%), 20.8% (95% CI, 7.3%-39.0%), and 20.0% (95% CI, 9.1%-43.8%), respectively. Grade 3 acute and late gastrointestinal tract toxic effects were noted in 3 and 1 patients, respectively, with no grade 4 or higher events. Conclusions and Relevance In this cohort study, A-RT in patients with technically resectable PDAC led to effective local tumor control and favorable OS despite advanced age, poor Karnofsky Performance Status score, and conservative use of chemotherapy in the cohort studied. These data support a prospective study of A-RT for the management of resectable PDAC.
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Affiliation(s)
- Marsha Reyngold
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York
| | - Joshua D. Schoenfeld
- Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Eileen M. O’Reilly
- David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York
- Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Anna M. Varghese
- David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York
- Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Charlie White
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Melissa Zinovoy
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Paul B. Romesser
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Abraham J. Wu
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Carla Hajj
- Oncology Institute at Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
| | - John J. Cuaron
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Danny N. Khalil
- Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Wungki Park
- David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York
- Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Wei Lu
- Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Zhigang Zhang
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Kenneth H. Yu
- David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York
- Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Luis A. Diaz
- Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Christopher H. Crane
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
- David M. Rubenstein Center for Pancreatic Cancer Research, New York, New York
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Connors C, Omidele O, Levy M, Wang D, Arroyave JS, Kim E, Gonzalez HA, Zaytoun O, Badani K, Palese M. Trends, outcomes, and predictors of open conversion during minimally invasive radical nephroureterectomy for upper tract urothelial carcinoma: a national analysis from 2010 to 2020. J Robot Surg 2025; 19:140. [PMID: 40202592 DOI: 10.1007/s11701-025-02311-7] [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: 02/09/2025] [Accepted: 04/01/2025] [Indexed: 04/10/2025]
Abstract
We evaluated trends, predictors, and outcomes of unplanned open conversion for patients with upper tract urothelial carcinoma (UTUC) undergoing robotic radical nephroureterectomy (R-RNU) or laparoscopic RNU (L-RNU). The National Cancer Database was queried from 2010 to 2020 for patients with non-metastatic UTUC treated with RNU. Trends in surgical approach and conversion were evaluated. Demographics and outcomes including lymph node dissection, lymph node yield, positive surgical margins (PSM), prolonged length of stay (PLOS) (≥ 90th percentile), unplanned readmission (UR), and 30- and 90-day mortality were compared between converted and unconverted cases. Multivariate logistic regression evaluated predictors of conversion and whether conversion predicted adverse clinical outcomes. 25,523 cases were included (robotic = 40.4%, laparoscopic = 36.9%, open = 22.7%), where 3.2% and 9.2% of R-RNU and L-RNU cases were converted, respectively. From 2010 to 2020, robotic cases increased while open and laparoscopic approaches decreased, p < 0.001. A higher T-stage and a ureteral tumor site predicted conversion while a higher R-RNU and L-RNU facility volume, respectively, were protective against conversion, all p < 0.05. Compared to unconverted cases, conversion generally resulted in a higher rate of all adverse outcomes, and was predictive of 30-day mortality, PLOS, UR, and PSM, all p < 0.05. Conversion to open RNU is becoming less frequent but is more common with a laparoscopic approach. Oncologic complexity and facility surgical volume influence conversion rates which in turn are associated with higher rates of morbidity, mortality, and greater resource utilization when compared to unconverted cases.
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Affiliation(s)
- Christopher Connors
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
| | - Olamide Omidele
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Micah Levy
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Daniel Wang
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Juan Sebastian Arroyave
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Esther Kim
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Herik Acosta Gonzalez
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Osama Zaytoun
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Ketan Badani
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
| | - Michael Palese
- Department of Urology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA
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29
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Pillaiyar T, Laufer S. A patent review of CXCR7 modulators (2019-present). Expert Opin Ther Pat 2025:1-27. [PMID: 40122070 DOI: 10.1080/13543776.2025.2477475] [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: 09/17/2024] [Revised: 02/13/2025] [Accepted: 03/06/2025] [Indexed: 03/25/2025]
Abstract
INTRODUCTION Atypical chemokine receptor 3 (ACKR3) (formerly CXCR7) regulates various biological processes through its ligands and is closely associated with numerous diseases, including inflammation, cancer, cardiovascular diseases (CVDs), pain, and neurological disorders. Therefore, ACKR3 has emerged as a potential target for disease treatment. AREAS COVERED This review summarizes the ACKR3 modulators published in patents from 2019 to 2024 using data from Google Patents, the European Patent Office, and the World Intellectual Property Organization's online databases. This includes information on their chemical structures, syntheses, activities, and developmental stages. EXPERT OPINION ACKR3 agonists gained traction as a treatment for cardiovascular and pain conditions. WW-12, which was derived from the chemical modifications of conolidine, became a novel small-molecule pain modulator by activating ACKR3, which in turn boosted endogenous opioid peptides for the classical opioid receptors.ACKR3 antagonist ACT-1004-1239 from Idorsia Pharmaceuticals Ltd. has demonstrated the ability to treat cancer, acute lung injury/ARDS, and autoimmune diseases, including multiple sclerosis. The outcomes of these clinical trials will direct the development and indications of future ACKR3 modulators.
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Affiliation(s)
- Thanigaimalai Pillaiyar
- Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany
- Tübingen Center for Academic Drug Discovery & Development (TüCAD2), Eberhard Karls University Tübingen, Tübingen, Germany
| | - Stefan Laufer
- Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany
- Tübingen Center for Academic Drug Discovery & Development (TüCAD2), Eberhard Karls University Tübingen, Tübingen, Germany
- iFIT Cluster of Excellence (EXC 2180) "Image-guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, Tübingen, Germany
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30
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Farooq AR, Zhang AX, Chan-Seng-Yue M, Topham JT, O'Kane GM, Jang GH, Fischer S, Dodd A, Holter S, Wilson J, Grant RC, Aung KL, Zogopoulos G, Elimova E, Prince R, Jang R, Moore M, Biagi J, Tang P, Goodwin R, Bathe OF, Marra M, Laskin J, Renouf DJ, Schaeffer DF, Karasinska JM, Notta F, Gallinger S, Knox JJ, Tsang ES. The tandem duplicator phenotype may be a novel targetable subgroup in pancreatic cancer. NPJ Precis Oncol 2025; 9:100. [PMID: 40185871 PMCID: PMC11971333 DOI: 10.1038/s41698-025-00888-8] [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: 08/04/2024] [Accepted: 03/20/2025] [Indexed: 04/07/2025] Open
Abstract
Tandem duplicator phenotype (TDP) consists of distinct genomic rearrangements where tandem duplications are randomly distributed. In this study, we characterized the prevalence and outcomes of TDP in a large series of prospectively sequenced tumors from patients with pancreatic ductal adenocarcinomas (PDAC). Whole-genome sequencing (WGS) was performed in 530 PDAC cases from the PanCuRx Initiative, COMPASS and PanGen/POG trials in Canada. Of 530 cases, 52 were identified as TDP (9.8%; 13 resected, 39 advanced). Etiological subgroups of TDP included BRCA1 (n = 9), CCNE1 (n = 4), and unknown (n = 39). Presence of TDP was not prognostic in resected specimens (p = 0.77) compared with non-HRD and non-TDP cases, described as typicals. In advanced cases, when stratified for only classical subtype cases, platinum therapy was correlated with longer response in non-BRCA1 TDP vs. typicals (p = 0.0036). There was no difference in overall survival between TDP and typicals (p = 0.5).TDP represents a potential novel targetable subgroup for chemotherapy selection in PDAC.
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Affiliation(s)
| | - Amy X Zhang
- Ontario Institute for Cancer Research, Toronto, ON, Canada
| | | | - James T Topham
- BC Cancer, University of British Columbia, Vancouver, BC, Canada
| | | | - Gun Ho Jang
- Ontario Institute for Cancer Research, Toronto, ON, Canada
| | | | - Anna Dodd
- Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Spring Holter
- Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Julie Wilson
- Ontario Institute for Cancer Research, Toronto, ON, Canada
| | | | | | | | - Elena Elimova
- Princess Margaret Cancer Centre, Toronto, ON, Canada
| | | | - Raymond Jang
- Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Malcolm Moore
- Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - James Biagi
- Cancer Centre of Southeastern Ontario/Queen's University, Kingston, ON, Canada
| | - Patricia Tang
- Department of Oncology, University of Calgary, Calgary, AB, Canada
| | - Rachel Goodwin
- Division of Medical Oncology, Department of Medicine, The Ottawa Hospital, The University of Ottawa, Ottawa, ON, K1N 6N5, Canada
| | - Oliver F Bathe
- Department of Oncology, Tom Baker Cancer Center, University of Calgary, 1331 29th St NW, Calgary, AB, T2N 4N2, Canada
| | - Marco Marra
- BC Cancer, University of British Columbia, Vancouver, BC, Canada
| | - Janessa Laskin
- BC Cancer, University of British Columbia, Vancouver, BC, Canada
| | - Daniel J Renouf
- BC Cancer, University of British Columbia, Vancouver, BC, Canada
| | - David F Schaeffer
- Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada
| | | | - Faiyaz Notta
- Ontario Institute for Cancer Research, Toronto, ON, Canada
| | | | | | - Erica S Tsang
- Princess Margaret Cancer Centre, Toronto, ON, Canada
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31
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Carcereny E, Domine M, Ortega Granados AL. Defining long-term survivors in metastatic lung cancer: insights from a Delphi study in Spain. Front Oncol 2025; 15:1546019. [PMID: 40255426 PMCID: PMC12005997 DOI: 10.3389/fonc.2025.1546019] [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: 12/16/2024] [Accepted: 03/10/2025] [Indexed: 04/22/2025] Open
Abstract
The improvement in survival rates in metastatic lung cancer (mLC) has increased the number of survivors' special care needs. This study aimed to define and characterise these long-term survivors. A Delphi method with two successive rounds was conducted to reach a consensus (defined as an agreement ≥ 70%) on 56 items among 41 medical oncologists. The items included the definition of long-term survivors, their common characteristics, and oncological and non-oncological implications. The experts had an average age of 46 years, 53.7% were men, 90.2% attended for thoracic tumours, 40% had more than 15 years' experience in mLC, and 56.1% of managing > 50 patients/month. Consensus reached 53.6% in the first round and 73.2% in the second. The definition of long-term survivors reached 58.3% consensus, defined as overall survival ≥ 3 years and/or progression-free survival ≥ 2 years. Identification of common features obtained 76.2% consensus on adenocarcinoma subtype of non-small-cell lung cancer, high PD-L1 expression, absence of brain metastasis, and fewer than two metastatic locations. Consensus was reached on specialized medical follow-up to detect immune-mediated toxicities and second neoplasms (87.8%), on pharmacological/non-pharmacological treatment for fatigue (82.9%) and sexual dysfunction (85.4%); and also on the importance of support for work and social adaptation (92.7%), integration of primary and hospital care (90.2%), implementation of quality-of-life programmes (92.7%) and electronic media (73.2%). This consensus identifies common characteristics and highlights relevant implications that should guide the follow-up and clinical management of these patients, ensuring better care and quality of life.
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Affiliation(s)
- Enric Carcereny
- Medical Oncology Department, Catalan Institute of Oncology, Badalona, Spain
- Badalona Badalona Applied Research Group in Oncology (B·ARGO), Badalona, Spain
| | - Manuel Domine
- Medical Oncology Department, Jiménez Díaz Foundation University Hospital- IIS- FJD, Madrid, Spain
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32
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Wang J, Wang Y, Zhou H, Yu G, Xu H, Gao D, Li M, Wang Y, Xu B. Identification of the specific characteristics of neuroendocrine prostate cancer: Immune status, hub genes and treatment. Transl Oncol 2025; 54:102320. [PMID: 39999729 PMCID: PMC11908612 DOI: 10.1016/j.tranon.2025.102320] [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: 11/23/2024] [Revised: 01/13/2025] [Accepted: 02/04/2025] [Indexed: 02/27/2025] Open
Abstract
Castration-resistant prostate cancer (CRPC) marks the advanced phase of prostate malignancy, manifested through two principal subtypes: castration-resistant adenocarcinoma (CRPC-adeno) and neuroendocrine prostate cancer (NEPC). This study aims to identify unique central regulatory genes, assess the immunological landscape, and explore potential therapeutic strategies specifically tailored to NEPC. We discovered 1444 differentially expressed genes (DEGs) distinguishing between the two cancer types and identified 12 critical hub genes. Notably, CHST1, MPPED2, and RIPPLY3 emerged as closely associated with the immune cell infiltration pattern, establishing them as top candidates. Prognostic analysis highlighted the potential critical roles of CHST1 and MPPED2 in prostate cancer development, findings corroborated through in vitro and in vivo assays. Moreover, we validated the functions and expression levels of CHST1, MPPED2, and RIPPLY3 in NEPC using cell lines, animal models and human tissues. In the final step, we found that imatinib might be the drug specific to NEPC, which was further confirmed by in vitro cell assay. Our results revealed the clinical characteristics, molecular features, immune cell infiltration pattern in CRPC-adeno and NEPC, and identified and confirmed CHST1, MPPED2, and RIPPLY3 as the critical genes in the development in prostate cancer and NEPC. We also predicted and validated imatinib as the potential specific drugs to NEPC.
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Affiliation(s)
- Jianqing Wang
- Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Yu Wang
- Vancouver Prostate Centre, Vancouver, BC, Canada; Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Huihui Zhou
- Department of Pathology, Affiliated Yuhuangding Hospital of Qingdao University, China
| | - Guopeng Yu
- Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Huan Xu
- Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Dajun Gao
- Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, China
| | - Minglun Li
- Urologic and Hematologic Oncology, Department of Radiation Oncology, LMU, University Hospital, Munich, Germany.
| | - Yuzhuo Wang
- Vancouver Prostate Centre, Vancouver, BC, Canada; Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
| | - Bin Xu
- Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, China.
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Weiss J, Laukhtina E, Resch I, Shariat SF. [Gender-specific differences in urological tumours]. Aktuelle Urol 2025; 56:158-163. [PMID: 40179871 DOI: 10.1055/a-2552-1170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2025]
Abstract
Gender differences in medicine are playing an increasingly important role in diagnostic testing as well as therapy choices. Risk factors and mortality vary depending on gender. Diseases often manifest differently depending on gender. In diagnostic testing, gender-specific aspects need to be taken into consideration. For instance, bladder cancer diagnosis is often delayed in women compared to men as haematuria is frequently attributed to benign conditions like urinary tract infections. In therapy, decisive gender disparities should also be considered. To state an example, immune-checkpoint inhibitors have shown better response in men than in women when treating renal cell carcinoma. Furthermore, outcomes after treatment for urological tumours differ depending on gender.
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Affiliation(s)
- Julia Weiss
- Department of Urology, Medical University of Vienna, Wien, Austria
| | | | - Irene Resch
- Department of Urology, Medical University of Vienna, Wien, Austria
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Treider MA, Romandini E, Alavi DT, Aghayan D, Rasmussen MK, Marchegiani G, Lauritzen PM, Pelanis E, Edwin B, Blomhoff R, Fretland ÅA. Postoperative changes in body composition after laparoscopic and open resection of colorectal liver metastases: data from the randomized OSLO-COMET trial. Surg Endosc 2025; 39:2450-2457. [PMID: 39994051 PMCID: PMC11933181 DOI: 10.1007/s00464-025-11613-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 02/02/2025] [Indexed: 02/26/2025]
Abstract
BACKGROUND Low muscle mass is negatively associated with survival in patients undergoing surgery for colorectal cancer. Current evidence is limited regarding whether the surgical approach for liver resection of colorectal metastasis impacts postoperative changes in body composition and whether preoperative body composition can impact complication rate and survival. METHOD This study included patients previously included in the randomized OSLO-COMET trail where patients was allocated to laparoscopic or open liver resection for colorectal liver metastasis. CT scans 0-3 months before and 2-6 months after liver resection were segmented with the artificial intelligence-based tool BodySegAI to measure skeletal muscle mass (SM), visceral adipose tissue (VAT), and inter- and intramuscular adipose tissue (IMAT). SM, VAT and IMAT was compared between the open and laparoscopic group and as predictors for 5-year survival and postoperative complications. RESULTS This study included 216 patients, median age was 67, 127 (59%) were male, 91 (42%) had primary tumor in rectum and 86 (40%) had multiple liver metastasis. There was no significant difference in postoperative change in SM, VAT or IMAT between those undergoing laparoscopy or open surgery. In multivariate analysis, high preoperative IMAT was a predictor for increased risk of postoperative complications (HR (95% CI): 1.045 (CI 95%: 1.003-1.089), p = 0.034). Moreover, postoperative increase in IMAT was a negative predictor for 5-year survival (HR (95%CI):1.009 (1.003-1.016), p = 0.003). CONCLUSION Postoperative change in body composition did not differ between patients randomly assigned to open or laparoscopic liver resection for colorectal metastasis. High preoperative IMAT was associated with an increased risk of postoperative complications.
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Affiliation(s)
- Martin Alavi Treider
- Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway.
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - Elisa Romandini
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
- Department of General and Pancreatic Surgery, Verona University Hospital, Verona, Italy
- Department of Gastrointestinal Surgery, Hamar Hospital, Hamar, Norway
| | - Dena Treider Alavi
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Davit Aghayan
- The Intervention Centre, Oslo University Hospital, Oslo, Norway
- Department of Surgery, Vestre Viken Hospital Trust, Ringerike Hospital, Hønefoss, Norway
- Department of Surgery N1, Yerevan State Medical University After M. Heratsi, Yerevan, Armenia
| | | | - Giovanni Marchegiani
- Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Padua University Hospital, Padua, Italy
| | - Peter M Lauritzen
- Department of Life Sciences and Health, Oslo Metropolitan University, Oslo, Norway
- Division of Radiology and Nuclear Medicine, Oslo University Hospital, Oslo, Norway
| | - Egidijus Pelanis
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- The Intervention Centre, Oslo University Hospital, Oslo, Norway
| | - Bjørn Edwin
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
- The Intervention Centre, Oslo University Hospital, Oslo, Norway
| | - Rune Blomhoff
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
- Department of Clinical Service, Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway
| | - Åsmund Avdem Fretland
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Hepato-Pancreato-Biliary Surgery, Oslo University Hospital, Oslo, Norway
- The Intervention Centre, Oslo University Hospital, Oslo, Norway
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Minakata N, Ikematsu H, Kiyomi F, Inoue S, Akutagawa T, Watanabe T, Yano T, Shimoda R. Usefulness of virtual scale endoscope for early gastrointestinal lesions. DEN OPEN 2025; 5:e386. [PMID: 38903962 PMCID: PMC11187934 DOI: 10.1002/deo2.386] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/22/2024] [Accepted: 04/29/2024] [Indexed: 06/22/2024]
Abstract
Objectives For early gastrointestinal lesions, size is an important factor in the selection of treatment. Virtual scale endoscope (VSE) is a newly developed endoscope that can measure size more accurately than visual measurement. This study aimed to investigate whether VSE measurement is accurate for early gastrointestinal lesions of various sizes and morphologies. Methods This study prospectively enrolled patients with early gastrointestinal lesions ≤20 mm in size visually. Lesion sizes were measured in the gastrointestinal tract visually, on endoscopic resection specimens with VSE, and finally on endoscopic resection specimens using a ruler. The primary endpoint was the normalized difference (ND) of VSE measurement. The secondary endpoints were the ND of visual measurement and the variation between NDs of VSE and visual measurements. ND was calculated as (100 × [measured size - true size] / true size) (%). True size was defined as size measured using a ruler. Results This study included 60 lesions from April 2022 to December 2022, with 20 each in the esophagus, stomach, and colon. The lesion size was 14.0 ± 6.3 mm (mean ± standard deviation). Morphologies were protruded, slightly elevated, and flat or slightly depressed type in 8, 24, and 28 lesions, respectively. The primary endpoint was 0.3 ± 8.8%. In the secondary endpoints, the ND of visual measurement was -1.7 ± 29.3%, and the variability was significantly smaller in the ND of VSE measurement than in that of visual measurement (p < 0.001, F-test). Conclusions VSE measurement is accurate for early gastrointestinal lesions of various sizes and morphologies.
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Affiliation(s)
- Nobuhisa Minakata
- Department of Gastroenterology and EndoscopyNational Cancer Center Hospital EastChibaJapan
| | - Hiroaki Ikematsu
- Department of Gastroenterology and EndoscopyNational Cancer Center Hospital EastChibaJapan
| | - Fumiaki Kiyomi
- Department of Statistics and Data CenterClinical Research Support Center KyushuFukuokaJapan
| | - Suma Inoue
- Department of Internal MedicineDivision of GastroenterologySaga UniversitySagaJapan
| | - Takashi Akutagawa
- Department of Endoscopic Diagnostics and TherapeuticsSaga University HospitalSagaJapan
| | - Takashi Watanabe
- Department of Gastroenterology and EndoscopyNational Cancer Center Hospital EastChibaJapan
| | - Tomonori Yano
- Department of Gastroenterology and EndoscopyNational Cancer Center Hospital EastChibaJapan
| | - Ryo Shimoda
- Department of Endoscopic Diagnostics and TherapeuticsSaga University HospitalSagaJapan
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Li X, Lu J, Chen F, Yuan J, Zha Y, Li Y, Yan J, Li Q, Yuan J, Tong Q. Comprehensive proteomic analysis and multidimensional model construction of peritoneal metastasis in gastric cancer. Cancer Lett 2025; 614:217509. [PMID: 39914770 DOI: 10.1016/j.canlet.2025.217509] [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: 12/02/2024] [Revised: 01/23/2025] [Accepted: 01/27/2025] [Indexed: 02/17/2025]
Abstract
Peritoneal metastasis following gastric cancer surgery is often associated with a poor prognosis. This study aimed to investigate the mechanisms underlying peritoneal metastasis and to develop a predictive model for the risk of postoperative peritoneal metastases in gastric cancer. We performed a comprehensive analysis of the protein mass spectra and tumor microenvironment in paraffin-embedded primary tumor sections from gastric cancer patients, both with and without postoperative peritoneal metastases. Using proteomic profiling, we identified 9595 proteins and stratified patients into three distinct proteomic subgroups (Pro1, Pro2, Pro3) based on differential protein expression. Simultaneously, immune cell profiling allowed us to classify patients into four immune subgroups (IG-I, IG-II, IG-III, IG-IV). The relationships between these proteomic, immune, and metastasis classifications were further explored to uncover potential associations and mechanisms driving metastasis. Building on these insights, we developed an integrative model combining proteomics, immunological, and radiomics data for predicting postoperative peritoneal metastases. This model demonstrated high predictive efficacy, offering a robust tool for identifying high-risk patients. Our findings provide a deeper understanding of the biological processes underlying peritoneal metastasis in gastric cancer, highlighting the interplay between proteomic and immune factors. By establishing novel patient subgroups and an effective prediction model, this study lays the groundwork for early diagnosis and tailored therapeutic strategies to improve outcomes for gastric cancer patients.
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Affiliation(s)
- Xiangpan Li
- Department of Clinical Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Jiatong Lu
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of WuhanUniversity, Wuhan, 430060, China
| | - Fangfang Chen
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Jingwen Yuan
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of WuhanUniversity, Wuhan, 430060, China; Colorectal Surgery Department, Changhai Hospital, Naval Medical University, Shanghai, 200433, China
| | - Yunfei Zha
- Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Ying Li
- Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Junfeng Yan
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of WuhanUniversity, Wuhan, 430060, China
| | - Qiang Li
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of WuhanUniversity, Wuhan, 430060, China
| | - Jingping Yuan
- Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
| | - Qiang Tong
- Department of Gastrointestinal Surgery I Section, Renmin Hospital of WuhanUniversity, Wuhan, 430060, China.
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Biswas L, Khatun F, Basak T, Biswas B, Biswas K, De S, Mandal S. Clinico-Demographic Profile of Carcinoma Rectum-Experience from a Tertiary Care Centre of Eastern India. Indian J Surg Oncol 2025; 16:595-600. [PMID: 40337036 PMCID: PMC12052635 DOI: 10.1007/s13193-024-02114-6] [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: 06/15/2023] [Accepted: 10/11/2024] [Indexed: 01/05/2025] Open
Abstract
Carcinoma rectum is a major health issue in India as well as the rest of the world. Cases of rectal cancers are often diagnosed late because of mimicking symptoms with haemorrhoids/fissures and lack of awareness. In this study, we analysed the clinico-demographic profile of patients with carcinoma rectum, attending a tertiary care centre of Eastern India over the last 2 years. We analysed the database of radiotherapy OPD of a tertiary care centre of Eastern India, and collected the demographic, clinical and treatment data of rectal carcinoma patients who attended our OPD between 2021 and 2023. The objective was to assess the demographic and clinical profile of these patients and compare with those reported from other parts of the India as well as rest of the world. Data of total 76 patients were analysed in this study. The mean age of the study population was 50.7 (± 13.59) years. A striking 40% of patients were below 50 years of age. Stage III was the most common (43%) TNM stage at presentation. 15.7% presented with metastatic disease with the liver being the most common site of metastasis. 15.7% of patients underwent upfront surgery either as trans-anal resection or trans-abdominal resection of tumour. Most of the patients (56.5%) had gone through surgery after neo-adjuvant therapy (either total neo-adjuvant therapy or neo-adjuvant radiotherapy). Around 64.4% (n = 49) of patients received radiation as part of total neo-adjuvant therapy (TNT). Eight (10.5%) patients received adjuvant therapy after definitive surgery. To conclude, it can be said that this study revealed involvement of younger population, emergence of poor prognostic histologies and presence of disease at an advanced stage, all of which should be counted as warning signs for the picture rectal carcinoma of India. More researches are required in this field for detection of risk factors, prevention and treatment.
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Affiliation(s)
- Linkon Biswas
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
- Department of Medical Oncology, Chittaranjan National Cancer Institute, Kolkata, India
| | - Firdoushi Khatun
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
- Department of Radiotherapy, IPGMER and SSKM Hospital, Kolkata, India
| | - Tanmoy Basak
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
| | - Bidyut Biswas
- Department of Surgery, Raiganj Government Medical College and Hospital, Uttar Dinajpur, Raiganj, West Bengal India
| | - Koustav Biswas
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
| | - Sumitava De
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
| | - Srikrishna Mandal
- Department of Radiotherapy, Nilratan Sircar Medical College and Hospital, AJC Bose Road, Kolkata, 700014 West Bengal India
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Zamani S, Bitaraf FS, Kamalabadi-Farahani M. Breast cancer brain metastasis: evaluating the effectiveness of alginate-based organoids in metastasis modeling to replace matrigel. BMC Res Notes 2025; 18:134. [PMID: 40165245 PMCID: PMC11959984 DOI: 10.1186/s13104-025-07154-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 02/17/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND One of the most important and devastating side effects of breast cancer is brain metastasis. Our understanding of cancer heterogeneity is revolutionized by tumoral organoids and seems promising for personalized medicine. This study aimed to generate a hydrogel-based brain metastasis organoid. METHODS Mouse brain metastatic tumor cells (4T1B) were isolated and cultured from the brain metastasis lesions of mice with breast cancer. Different hydrogels, including alginate, carboxymethylcellulose, gelatin, collagen, and matrigel, were prepared. Pre-coated hydrogels in 96-well plates were treated with 4T1B cells. The morphology and viability of metastatic organoids were analyzed after 7 days. RESULTS According to our results, 4T1B cells formed semi-regular cluster structures in alginate hydrogel. In this group, the cell survival rate and formation of three-dimensional structures were significantly higher than in other groups. CONCLUSION For organoid cultures, there's a lot of research on natural and synthetic scaffolds that are chemically or mechanically well-designed. In the present study, we used highly brain metastatic tumor cells and detected that alginate hydrogel is the best choice for organoid formation and breast cancer brain metastasis modeling.
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Affiliation(s)
- Sepehr Zamani
- Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
| | - Fateme Sadat Bitaraf
- Department of Medical Biotechnology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran
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Lee WR, Ha KS. Mitochondrial Ribosomal Protein S17 Silencing Inhibits Proliferation and Invasiveness of Lung Cancer Cells. J Cancer Prev 2025; 30:47-55. [PMID: 40201023 PMCID: PMC11973458 DOI: 10.15430/jcp.24.023] [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: 10/21/2024] [Revised: 01/10/2025] [Accepted: 01/15/2025] [Indexed: 04/10/2025] Open
Abstract
Chromosomal alterations are frequent events in lung cancer progression. Although gains and losses of chromosomal position have been reported, the association between copy number alteration and lung cancer patient survival has not been extensively investigated. In this study, we performed a meta-analysis of public cBioPortal datasets spanning 25 lung cancer studies to identify putative cancer driver genes with copy number alterations associated with overall patient survival. Ten copy-number altered genes enriched in deceased lung cancer patients were identified. Seven of these putative driver genes were located in the 7p11.2 chromosomal location, and two were in the 9p21.3 cytoband. Among these genes, the mitochondrial ribosomal protein S17 (MRPS17) amplification was significantly associated with a lower patient survival rate (P = 1.47e-7). To investigate the functional role of MRPS17, small interfering RNA-mediated knockdown was performed in two non-small cell lung cancer cell lines, A549 and NCI-H460. MRPS17 knockdown significantly reduced cell proliferation, migration, invasion, and anchorage-independent growth in both cell lines. Furthermore, knockdown of MRPS17 decreased the activation of the phosphatidylinositol 3-kinase/protein kinase B signaling pathway, suggesting its role in driving lung cancer progression through this critical oncogenic pathway. Our findings highlight MRPS17 as a potential cancer therapy target and a prognostic biomarker that may improve the survival rates of lung cancer patients. Future studies should explore its inhibition as a therapeutic strategy as well as elucidate its molecular mechanisms in cancer progression.
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Affiliation(s)
- Woo Rin Lee
- Department of Chemistry, The University of Suwon, Hwaseong, Korea
| | - Kook Sun Ha
- Department of Chemistry, The University of Suwon, Hwaseong, Korea
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Hill JLE, Leonard E, Parslow D, Hill DJ. Gene Dysregulation and Islet Changes in PDAC-Associated Type 3c Diabetes. Int J Mol Sci 2025; 26:3191. [PMID: 40244011 PMCID: PMC11988973 DOI: 10.3390/ijms26073191] [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: 02/21/2025] [Revised: 03/24/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, often associated with new-onset diabetes. The relationship between PDAC and diabetes, particularly type 3c diabetes, remains poorly understood. This study investigates whether PDAC-associated diabetes represents a distinct subtype by integrating transcriptomic and histological analyses. Whole-tumour RNA sequencing data from The Cancer Genome Atlas (TCGA) were analysed to compare gene expression profiles between PDAC patients with and without diabetes. Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) deconvolution was employed to assess immune cell populations. Histopathological evaluations of pancreatic tissues were conducted to assess fibrosis and islet morphology. Histological analysis revealed perivascular fibrosis and islet basement membrane thickening in both PDAC cohorts. Transcriptomic data indicated significant downregulation of islet hormone genes insulin (INS) and glucagon (GCG) but not somatostatin (SST) in PDAC-associated diabetes, consistent with a type 3c diabetes phenotype. Contrary to previous reports, no distinct immunogenic signature was identified in PDAC with diabetes, as key immune checkpoint genes (Programmed Cell Death Protein 1 (PDCD1), Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA4), Programmed Death-Ligand 1(PD-L1)) were not differentially expressed. The findings suggest that PDAC-associated diabetes arises through neoplastic alterations in islet physiology rather than immune-mediated mechanisms. The observed reductions in endocrine markers reinforce the concept of PDAC-driven β-cell dysfunction as a potential early indicator of malignancy. Given the poor response of PDAC to PD-L1 checkpoint inhibitors, further research is needed to elucidate alternative therapeutic strategies targeting tumour-islet interactions.
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Affiliation(s)
| | - Eliot Leonard
- Leeds Teaching Hospitals NHS Trust, Leeds LS1 3EX, UK;
| | | | - David J. Hill
- Lawson Research Institute, St. Joseph Health Care, London, ON N6A 4V2, Canada
- Departments of Medicine, Physiology and Pharmacology, Western University, London, ON N6A 3K7, Canada
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Wang QW, Zou WB, Masson E, Férec C, Liao Z, Chen JM. Genetics and clinical implications of SPINK1 in the pancreatitis continuum and pancreatic cancer. Hum Genomics 2025; 19:32. [PMID: 40140953 PMCID: PMC11948977 DOI: 10.1186/s40246-025-00740-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 03/06/2025] [Indexed: 03/28/2025] Open
Abstract
Serine peptidase inhibitor, Kazal type 1 (SPINK1), a 56-amino-acid protein in its mature form, was among the first pancreatic enzymes to be extensively characterized biochemically and functionally. Synthesized primarily in pancreatic acinar cells and traditionally known as pancreatic secretory trypsin inhibitor, SPINK1 protects the pancreas by inhibiting prematurely activated trypsin. Since 2000, interest in SPINK1 has resurged following the discovery of genetic variants linked to chronic pancreatitis (CP). This review provides a historical overview of SPINK1's discovery, function, and gene structure before examining key genetic findings. We highlight three variants with well-characterized pathogenic mechanisms: c.-4141G > T, a causative enhancer variant linked to the extensively studied p.Asn34Ser (c.101A > G), which disrupts a PTF1L-binding site within an evolutionarily conserved HNF1A-PTF1L cis-regulatory module; c.194 + 2T > C, a canonical 5' splice site GT > GC variant that retains 10% of wild-type transcript production; and an Alu insertion in the 3'-untranslated region, which causes complete loss of function by forming extended double-stranded RNA structures with pre-existing Alu elements in deep intronic regions. We emphasize the integration of a full-length gene splicing assay (FLGSA) with SpliceAI's predictive capabilities, establishing SPINK1 the first disease gene for which the splicing impact of all possible coding variants was prospectively determined. Findings from both mouse models and genetic association studies support the sentinel acute pancreatitis event (SAPE) model, which explains the progression from acute pancreatitis to CP. Additionally, SPINK1 variants may contribute to an increased risk of pancreatic ductal adenocarcinoma (PDAC). Finally, we discuss the therapeutic potential of SPINK1, particularly through adeno-associated virus type 8 (AAV8)-mediated overexpression of SPINK1 as a strategy for treating and preventing pancreatitis, and highlight key areas for future research.
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Affiliation(s)
- Qi-Wen Wang
- Department of Gastroenterology, Changhai Hospital; National Key Laboratory of Immunity and Inflammation, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
- Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Wen-Bin Zou
- Department of Gastroenterology, Changhai Hospital; National Key Laboratory of Immunity and Inflammation, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China
- Shanghai Institute of Pancreatic Diseases, Shanghai, China
| | - Emmanuelle Masson
- Univ Brest, Inserm, EFS, UMR 1078, GGB, 29200, Brest, France
- Service de Génétique Médicale et de Biologie de la Reproduction, CHU Brest, Brest, France
| | - Claude Férec
- Univ Brest, Inserm, EFS, UMR 1078, GGB, 29200, Brest, France
| | - Zhuan Liao
- Department of Gastroenterology, Changhai Hospital; National Key Laboratory of Immunity and Inflammation, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.
- Shanghai Institute of Pancreatic Diseases, Shanghai, China.
| | - Jian-Min Chen
- Univ Brest, Inserm, EFS, UMR 1078, GGB, 29200, Brest, France.
- Univ Brest, Inserm, EFS, UMR 1078, GGB, 22 Avenue Camille Desmoulins, 29238, Brest, France.
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Zhao H, Zhang Y, Zhu Q. Long-term trends analysis of the incidence and mortality in patients with ovarian cancer: a large sample study based on SEER database. Postgrad Med J 2025; 101:302-312. [PMID: 39475117 DOI: 10.1093/postmj/qgae143] [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: 08/07/2024] [Revised: 09/08/2024] [Accepted: 09/29/2024] [Indexed: 03/18/2025]
Abstract
BACKGROUND To analyze long-term trends of the incidence and mortality of ovarian cancer in the United States. METHODS Patients diagnosed with ovarian cancer were obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2017. Joinpoint regression analysis was used to analyze the incidence and mortality trend, and the changes were reported as average annual percentage change (AAPC) with a 95% confidence interval (CI). Kaplan-Meier survival curve and Cox regression analyses were utilized for survival analysis. RESULTS A total of 74 682 patients were included, among whom 49 491 (66.27%) died and 44 487 (59.57%) died from ovarian cancer. The mean age was 61.95 ± 15.23 years. The incidence of ovarian cancer showed a decreased trend from 2000 to 2017 with an AAPC of -1.9 (95%CI: -2.0, -1.7). Both the overall mortality and cancer-specific mortality for ovarian cancer decreased from 2000 to 2017, with AAPCs of -5.0 (95%CI: -5.7, -4.2) and -4.6 (95%CI: -5.4, -3.8), respectively. There was a significant decrease in the incidence and mortality of patients with the distant SEER stage, histological subtypes of serous and malignant Brenner carcinoma, and grades II and III from 2000 to 2017. Older age, Black race, histological subtypes of carcinosarcoma, higher tumor grade, and radiotherapy were associated with poorer overall survival and cancer-specific survival, whereas higher income, histological subtype of endometrioid, and surgery were associated with better survival. CONCLUSION This study provided evidence of a statistically significant decrease in the incidence and mortality of ovarian cancer from 2000 to 2017. Key message What is already known on this topic? Ovarian cancer is one of the most common tumors in women, with high morbidity and mortality. However, trends in long-term morbidity and mortality of patients with ovarian cancer have not been reported. What this study adds Overall incidence and mortality for ovarian cancer showed a decreased trend from 2000 to 2017, and trends in incidence and mortality varied by stage, histological subtype, and tumor grade. Factors associated with overall survival and cancer-specific survival also differ. How this study might affect research, practice, or police This study provides evidence of long-term trends in ovarian cancer incidence and mortality from 2000 to 2017.
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Affiliation(s)
- Hongwei Zhao
- Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan University People's Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, Henan 450003, P.R. China
| | - Yu Zhang
- Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan University People's Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, Henan 450003, P.R. China
| | - Qianyong Zhu
- Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Henan University People's Hospital, No. 7 Weiwu Road, Jinshui District, Zhengzhou, Henan 450003, P.R. China
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Zeng D, Chen Z, Li M, Yi Y, Hu Z, Valeria B, Shan G, Zhan C, Xi J, Wang Q, Lin Z. Survival benefit of surgery vs radiotherapy alone to patients with stage IA lung adenocarcinoma: a propensity score-matched analysis. Eur J Med Res 2025; 30:173. [PMID: 40089771 PMCID: PMC11909938 DOI: 10.1186/s40001-025-02436-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 03/05/2025] [Indexed: 03/17/2025] Open
Abstract
OBJECTIVES We compared the overall survival (OS) and cancer-specific survival (CSS) of patients who received radiotherapy and surgery, respectively, in a large population. METHODS In this study, we counted the patients diagnosed with stage IA lung adenocarcinoma in the SEER database from 2015 to 2019. We compared the overall survival (OS) and cancer-specific survival (CSS) through Kaplan Meier analysis, balanced the differences of primary data through propensity score matching (PSM), screened independent prognostic factors through Cox regression analysis, and then compared the survival differences of different treatment methods through hierarchical analysis. RESULTS Among 11,159 patients with stage IA lung adenocarcinoma, 4254 patients chose radiotherapy alone (38.1%), and 6688 patients were finally included through the propensity score matching. The median survival time for patients with radiotherapy alone was 53 months, while the patients with surgery alone did not reach the median survival time (p < 0.001). Multivariate analysis showed that age, sex, tumor size, and household income affected the prognosis of patients. The results of the stratified analysis showed that, except in the subgroup of age ≤ 50 years, almost all subgroup analyses showed that surgical treatment achieved better results. CONCLUSIONS Radiotherapy alone can be used as an option for patients with stage IA lung adenocarcinoma who cannot tolerate surgery, but the benefit to patients is limited, and surgical treatment may still be the best choice.
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Affiliation(s)
- Dejun Zeng
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Zhencong Chen
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Ming Li
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Yanjun Yi
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Zhengyang Hu
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Besskaya Valeria
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Guangyao Shan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Cheng Zhan
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Junjie Xi
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Qun Wang
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Zongwu Lin
- Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
- Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
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Zhang J, Zeng L, Song G, Peng G, Chen Z, Yuan Y, Chen T, Zhong T, Chen S, Luo Z, Xiao J, Liu L. A novel tertiary lymphoid structure-associated signature accurately predicts patient prognosis and facilitates the selection of personalized treatment strategies for HNSCC. Front Immunol 2025; 16:1551844. [PMID: 40181975 PMCID: PMC11965918 DOI: 10.3389/fimmu.2025.1551844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 02/25/2025] [Indexed: 04/05/2025] Open
Abstract
Background Head and neck squamous cell carcinoma (HNSCC) is the most common type of head and neck cancer and is characterized by its aggressive nature and variable prognosis and response to immunotherapy. Tertiary lymphoid structures (TLSs) play crucial roles in creating a favourable immune microenvironment to control tumour progression. However, the specific impact of these structures on HNSCC has not been thoroughly studied. Methods In this study, a comprehensive review of tertiary lymphoid structures was conducted by analysing 9 TLS-associated genes in a cohort of 871 HNSCC patients. Distinct TLS-related subgroups were identified through unsupervised clustering analysis, and the associated genes were explored. Prognostic genes were identified via univariate Cox and Boruta algorithms, and a novel TLS-related scoring system was developed via the GSVA algorithm. Results Our study revealed that patients with higher TLS-related scores had improved overall survival and were more likely to benefit from immunotherapy. Furthermore, we observed a significant negative correlation between sensitivity to traditional chemotherapeutic agents and the TLS-related signature score. Conclusions Our findings suggest that the TLS-related features of HNSCC patients hold promise as predictive indicators for immunotherapy efficacy and may offer novel insights for tailoring personalized treatment strategies in clinical practice.
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Affiliation(s)
- Jinhao Zhang
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
| | - Lu Zeng
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, China
| | - Guobin Song
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
| | - Gaoge Peng
- Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhezheng Chen
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, China
| | - Yamin Yuan
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
| | - Taowu Chen
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
| | - Tao Zhong
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
| | - Shixi Chen
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
| | - Zhengzhou Luo
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, China
| | - Jingang Xiao
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, China
| | - Lin Liu
- School of Stomatology, Southwest Medical University, Luzhou, Sichuan, China
- Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China
- Luzhou Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou, China
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Liu YQ, Chen F, Zhang F, Ye YM, Su YJ, Liu YT, Leng YF. New insights into tRNA-derived small RNAs in human digestive diseases. Mol Biol Rep 2025; 52:295. [PMID: 40063289 DOI: 10.1007/s11033-025-10393-7] [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: 11/20/2024] [Accepted: 02/25/2025] [Indexed: 05/13/2025]
Abstract
tRNA-derived small RNAs (tsRNAs) is a type of non-coding RNA that is present in large quantities in humans and exhibits high stability. It plays a crucial role in various physiological processes and diseases. In recent years, research on tsRNAs in tumors has expanded significantly, revealing its regulatory effects in non-neoplastic diseases as well. Additionally, tsRNAs has been extensively studied in the context of digestive system diseases, encompassing both digestive system tumors and non-tumor conditions. It is believed to influence the biological characteristics of diseases as well as clinical pathological features. Given its potential, tsRNAs is anticipated to have broad applications in disease diagnosis and prognosis prediction, and it is expected to emerge as a new class of biomarkers. Nevertheless, numerous issues remain that require in-depth discussion. This article presents an overview of the characteristics and roles of tsRNAs in digestive system diseases, aiming to provide a comprehensive perspective and to inspire new ideas for the diagnosis and treatment of these conditions.
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Affiliation(s)
- Yong-Qiang Liu
- The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, GanSu Province, China
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Feng Chen
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Fa Zhang
- Department of Urology, Gansu Provincial Hospital, Lanzhou, Gansu, China
| | - Yuan-Mei Ye
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Yu-Jie Su
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Ya-Tao Liu
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China
| | - Yu-Fang Leng
- The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, GanSu Province, China.
- Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, GanSu Province, China.
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Yang Q, Cui M, Wang J, Zhao Y, Yin W, Liao Z, Liang Y, Jiang Z, Li Y, Guo J, Qi L, Chen J, Zhao J, Bao D, Xu ZX. Circulating mitochondrial DNA promotes M2 polarization of tumor associated macrophages and HCC resistance to sorafenib. Cell Death Dis 2025; 16:153. [PMID: 40038250 PMCID: PMC11880550 DOI: 10.1038/s41419-025-07473-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Revised: 02/07/2025] [Accepted: 02/21/2025] [Indexed: 03/06/2025]
Abstract
Mitochondrial damage-associated molecular patterns (DAMPs) including mitochondrial DNA (mtDNA), TFAM (transcription factor A, mitochondrial), and ATP, which play crucial roles in the regulation of inflammatory environment in human diseases. However, the role of mitochondrial DAMPs in regulating tumor microenvironment (TME) remains unclear. Herein, we demonstrate that infiltration of M2-type tumor-associated macrophages (TAMs) was correlated with the resistance of hepatocellular carcinoma (HCC) to sorafenib. We found that cell-free mtDNA in the plasma was significantly increased in sorafenib-resistant HCC mice. Sorafenib induced mitochondrial dysfunction and promoted the release of mtDNA into extracellular matrix of HCC. Macrophages retook the mtDNA in the TME of HCC, activated TLR9 signaling, and promoted the activation of NF-κB and the polarization of TAMs into M2. Application of DNase I to digest mtDNA or depletion of macrophages with clodronate liposomes reduced M2 macrophage infiltration, decreased the growth of HCC, and sensitized the tumors to sorafenib. Furthermore, we showed that blocking the activation of TLR9 enhanced the therapeutic effect of sorafenib in HCC. Together, we demonstrate that sorafenib treatment leads to the release of mtDNA into TME in HCC, which in turn facilitates the polarization of TAMs into M2 macrophages through TLR9 activation and aggravates the resistance of HCC to sorafenib. Our study reveals a novel mechanism underlying circulating mtDAMPs in remodeling the HCC microenvironment by reprograming the TAMs and provides a new strategy for improving the therapeutic effect of sorafenib and overcoming its resistance in HCC.
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MESH Headings
- Sorafenib/pharmacology
- Sorafenib/therapeutic use
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/blood
- Animals
- DNA, Mitochondrial/blood
- DNA, Mitochondrial/genetics
- DNA, Mitochondrial/metabolism
- Liver Neoplasms/drug therapy
- Liver Neoplasms/pathology
- Liver Neoplasms/genetics
- Liver Neoplasms/blood
- Humans
- Drug Resistance, Neoplasm/drug effects
- Mice
- Tumor-Associated Macrophages/metabolism
- Tumor-Associated Macrophages/drug effects
- Tumor-Associated Macrophages/pathology
- Tumor Microenvironment/drug effects
- Toll-Like Receptor 9/metabolism
- Male
- Mitochondria/metabolism
- Mitochondria/drug effects
- Cell Line, Tumor
- Signal Transduction/drug effects
- Mice, Inbred C57BL
- Macrophages
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Affiliation(s)
- Qi Yang
- School of Life Sciences, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
- The Zhongzhou Laboratory for Integrative Biology, Henan University, Zhengzhou, Henan, 450000, China
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Mengmeng Cui
- The Zhongzhou Laboratory for Integrative Biology, Henan University, Zhengzhou, Henan, 450000, China
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475000, China
- State key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Jiaxin Wang
- The Zhongzhou Laboratory for Integrative Biology, Henan University, Zhengzhou, Henan, 450000, China
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475000, China
- State key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Yuan Zhao
- School of Life Sciences, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Weitao Yin
- School of Life Sciences, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Ziqian Liao
- The Zhongzhou Laboratory for Integrative Biology, Henan University, Zhengzhou, Henan, 450000, China
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Yixuan Liang
- The Zhongzhou Laboratory for Integrative Biology, Henan University, Zhengzhou, Henan, 450000, China
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Zhixiong Jiang
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475000, China
- State key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Yujia Li
- School of Life Sciences, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Jinrong Guo
- School of Life Sciences, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Lixia Qi
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475000, China
- State key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Jiaxing Chen
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475000, China
- State key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Jing Zhao
- School of Life Sciences, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
- The Zhongzhou Laboratory for Integrative Biology, Henan University, Zhengzhou, Henan, 450000, China
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China
| | - Dengke Bao
- School of Life Sciences, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China.
- The Zhongzhou Laboratory for Integrative Biology, Henan University, Zhengzhou, Henan, 450000, China.
- Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China.
- Department of Thoracic Surgery, The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475000, China.
- State key Laboratory of Antiviral Drugs, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China.
| | - Zhi-Xiang Xu
- School of Life Sciences, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, China.
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Abdelmageed AE, Awad AT, El-Fayoumi TA, Alhussini MA, Shalaby MO, Abdelkader AA. Skin-Reducing Mastectomy and Direct-to-Implant Breast Reconstruction Without Mesh: A Single-Institute Experience. Cureus 2025; 17:e81417. [PMID: 40296963 PMCID: PMC12036642 DOI: 10.7759/cureus.81417] [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] [Accepted: 03/28/2025] [Indexed: 04/30/2025] Open
Abstract
INTRODUCTION Performing breast reconstruction in large and ptotic breasts remains technically challenging, with a high incidence of postoperative complications and unsatisfactory cosmetic results. Skin-reducing mastectomy (SRM) was introduced for breast reconstruction for females with macromastia. In this study, we report the experience in Alexandria Main University Hospital (AMUH), Alexandria, Egypt, with SRM and direct-to-implant (DTI) breast reconstruction without the utilization of biological or synthetic meshes. PATIENTS AND METHODS A prospective study was carried out at AMUH from October 2020 to October 2022. It included 20 female patients having large and ptotic breasts who were indicated for mastectomy, with the exclusion of non-motivated patients, inflammatory breast cancer, significant clinical comorbidities, and patients indicated for postoperative radiotherapy. All the operations were done as a single stage in which the SRM was performed through a Wise-pattern skin incision, along with the creation of a dermal sling to cover the implant. RESULTS A total of 20 surgeries were performed, in which the implant was placed in a pre-pectoral position in 10 cases. In the other 10 cases, the implant was inserted partially subpectoral by creating a musculo-dermal pouch to envelop the implant. The most prevalent complication encountered was delayed wound healing at the area of the inverted T-junction. None of the studied patients experienced wound infection, capsular contracture, or implant loss. CONCLUSION SRM and DTI breast reconstruction is a feasible technique that can be safely used in patients with large and ptotic breasts. The inferior dermal sling allows for a single-stage implant-based breast reconstruction without the utilization of biological or synthetic meshes.
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Affiliation(s)
- Ahmed E Abdelmageed
- Department of General Surgery, Portsmouth Hospitals University NHS Trust, Portsmouth, GBR
- Surgical Oncology Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
| | - Ahmed T Awad
- Surgical Oncology Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
| | - Tarek A El-Fayoumi
- Surgical Oncology Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
| | - Mahmoud A Alhussini
- Surgical Oncology Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
| | - Mahmoud O Shalaby
- Department of General Surgery, Faculty of Medicine, Arab Academy for Science, Technology and Maritime Transport, Alexandria, EGY
| | - Ahmed A Abdelkader
- Surgical Oncology Unit, Faculty of Medicine, Alexandria University, Alexandria, EGY
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Piserra López-Fernández De Heredia A, Ruiz Ortiz M, Torres Llergo J, Carrillo Bailen M, Sánchez De Castro M, Fernández De La Mata M, Díaz Exposito A, Pérez Cabeza AI, Delgado Ortega M, García Fortes M, Fernández Valenzuela I, Chaparro Muñoz M, Rodríguez Fernández A, Rodríguez Almodóvar AM, Alarcón De La Lastra Cubiles I, Esteban Martínez F, Capote Huelva FJ, Sánchez Fernandez JJ, Mesa Rubio D. Clinical profile and cardiovascular events in patients with atrial fibrillation and hematologic malignancies with recent initiation of targeted therapy: Real-life data from CANAC-FA registry. Curr Probl Cardiol 2025; 50:102974. [PMID: 39706388 DOI: 10.1016/j.cpcardiol.2024.102974] [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: 12/15/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
BACKGROUND "Real-life" data on cardiovascular management and clinical outcomes in patients with atrial fibrillation (AF) and hematologic malignancies are limited. AIM To describe the clinical profile and incidence of cardiovascular events in this population. METHODS Data were obtained from the CANAC-FA Registry, an observational, multicenter and retrospective study. A review of the medical records of patients who had consulted for chronic lymphocytic leukemia (CLL) or multiple myeloma (MM) between 2017 and 2019 was conducted in five hospitals in Spain. Patients with atrial fibrillation (AF) were identified, and the initial visit during which specific treatment for the neoplasm was administered was considered the baseline visit. The follow-up period concluded in 2021. Events of interest included major bleeding, cardiovascular events (hospital admission for cardiovascular causes or cardiovascular death), and death from any cause. RESULTS A total of 7,793 patients were reviewed, of whom 1,189 (15%) had AF and 81 (1%) had AF and had initiated a specific hematological treatment within the previous year. Of these patients, 48 (59%) had MM and 33 (41%) had CLL. The mean values for the Charlson, CHA2DS2-VASc and HAS-BLED indices were 5.3 ± 1.7, 3.4 ± 1.5 and 2.4 ± 1.1, respectively. Anticoagulants were prescribed to 85% of patients, with a majority (42%) receiving direct anticoagulants. After a maximum follow-up period of 59 months, the incidences of events at 1, 2 and 3 years of follow-up were: 1.2±1.2%, 1.2±1.2 and 3.5±2.5% for major bleeding; 11.6±3.7%, 11.6±3.7 and 17.2±5.3% for cardiovascular events; and 27.6±5.0%, 41.5±6.3 and 51.3±6.9% for all-cause mortality. CONCLUSIONS The incidence of cardiovascular events was high in this population, suggesting the need to implement more effective preventive strategies.
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Affiliation(s)
| | - Martín Ruiz Ortiz
- Cardiology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Avenida Menéndez Pidal s/n, Córdoba 14004, Spain; Biomedical Research Center in Cardiovascular Diseases Network (CIBER-CV), Carlos III Health Institute, Madrid, Spain; Isabel I de Castilla International University, Burgos, Spain.
| | | | | | | | - Margarita Fernández De La Mata
- Hematology Department, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Córdoba, Spain
| | - Arancha Díaz Exposito
- Cardiology Department, Virgen de la Victoria University Hospital, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain
| | - Alejandro I Pérez Cabeza
- Cardiology Department, Virgen de la Victoria University Hospital, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain; Biomedical Research Center in Cardiovascular Diseases Network (CIBER-CV), Carlos III Health Institute, Madrid, Spain
| | - Mónica Delgado Ortega
- Cardiology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Avenida Menéndez Pidal s/n, Córdoba 14004, Spain; Biomedical Research Center in Cardiovascular Diseases Network (CIBER-CV), Carlos III Health Institute, Madrid, Spain
| | - María García Fortes
- Hematology Department, Virgen de la Victoria University Hospital, Málaga, Spain
| | | | | | | | - Ana María Rodríguez Almodóvar
- Cardiology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Avenida Menéndez Pidal s/n, Córdoba 14004, Spain; Biomedical Research Center in Cardiovascular Diseases Network (CIBER-CV), Carlos III Health Institute, Madrid, Spain
| | | | - Fátima Esteban Martínez
- Cardiology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Avenida Menéndez Pidal s/n, Córdoba 14004, Spain
| | | | | | - Dolores Mesa Rubio
- Cardiology Department, Reina Sofía University Hospital, Maimonides Institute for Biomedical Research of Córdoba (IMIBIC), Avenida Menéndez Pidal s/n, Córdoba 14004, Spain; Biomedical Research Center in Cardiovascular Diseases Network (CIBER-CV), Carlos III Health Institute, Madrid, Spain
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Rossi M, DiSilvio F, Sahagun J, Ridder D, Evans T, Anderson R. Primary Sternal Leiomyosarcoma. ANNALS OF THORACIC SURGERY SHORT REPORTS 2025; 3:219-221. [PMID: 40098841 PMCID: PMC11910758 DOI: 10.1016/j.atssr.2024.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Accepted: 07/15/2024] [Indexed: 03/19/2025]
Abstract
We report the case of a primary leiomyosarcoma of the sternum in a 70-year-old man that was discovered incidentally during prostate cancer staging with positron emission tomography combined with computed tomography. Interventional radiology biopsied the lesion; pathologic examination showed spindle cells, indicating probable leiomyosarcoma. No primary site was found on contrast computed tomography, thus suggesting that the tumor was primary rather than metastatic. Given the tumor's location and mortality risk, the patient underwent a sternotomy and reconstruction with methyl methacrylate, followed by an uneventful recovery. This case underlines a rare leiomyosarcoma presentation, constituting less than 0.7% of all primary malignant bone tumors, noted for its unusual location and rarity.
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Affiliation(s)
- Marcus Rossi
- Department of Surgery, University of Illinois College of Medicine Peoria, Peoria, Illinois
| | - Frank DiSilvio
- Department of Surgery, University of Illinois College of Medicine Peoria, Peoria, Illinois
| | - Joseph Sahagun
- Department of Surgery, University of Illinois College of Medicine Peoria, Peoria, Illinois
| | - David Ridder
- Department of Surgery, University of Illinois College of Medicine Peoria, Peoria, Illinois
| | - Tyler Evans
- Department of Surgery, University of Illinois College of Medicine Peoria, Peoria, Illinois
| | - Richard Anderson
- Department of Surgery, University of Illinois College of Medicine Peoria, Peoria, Illinois
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50
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Wang J, Sun Y, Wu R. ACSM3 Suppresses Ovarian Cancer Progression by Inactivating the IFN-γ/JAK/STAT3 Signaling Pathway. Adv Biol (Weinh) 2025; 9:e2400093. [PMID: 39913127 DOI: 10.1002/adbi.202400093] [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: 02/19/2024] [Revised: 11/12/2024] [Indexed: 02/07/2025]
Abstract
This study aimed to investigate the role of Acyl-CoA medium-chain synthetase 3 (ACSM3) in ovarian cancer (OC) progression. ACSM3 expression in OC tissues and cells is detected by real-time quantitative polymerase chain reaction, immunohistochemistry, or western blot. The influences of ACSM3 on OC progression are assessed in vitro and in vivo experiments. Gene set enrichment analysis is performed to find significantly enriched pathways related to ACSM3. In this study, ACSM3 expression in OC tissues and cells is downregulated. ACSM3 inhibited tumor growth in vivo. Knockdown of ACSM3 promoted cell proliferation, migration, and invasion, inhibited cell apoptosis, and activated JAK/STAT3 signaling pathway in SKOV3 cells, while overexpression of ACSM3 in A2780 cells led to the opposite results. Moreover, treatment with interferon-gamma (IFN-γ) in A2780 cells reversed the effects of ACSM3 on cell proliferation, migration, invasion, and apoptosis, but IFN-γ further enhanced the effects of ACSM3 knockdown on SKOV3 cell proliferation, migration, invasion, and apoptosis. In conclusion, ACSM3 inhibited OC cell proliferation, migration, and invasion, and promoted cell apoptosis by suppressing the IFN-γ/JAK/STAT3 signaling pathway, which might provide a promising therapeutic target for OC treatment.
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Affiliation(s)
- Juan Wang
- Department of Gynecology, Bin Zhou Medical University Hospital, Binzhou, Shandong, 256603, P. R. China
| | - Yanqiu Sun
- Department of obstetrics and gynecology, Bin Zhou Medical University Hospital, Binzhou, Shandong, 256603, P. R. China
| | - Ruixue Wu
- Department of Gynecology, Bin Zhou Medical University Hospital, Binzhou, Shandong, 256603, P. R. China
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