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Masuda Y, Fong KL, Yeo D, Yeo C, Chue KM, Araba SB, Lim CW, Yeung B, Lee J, Lin J, Chia C, Ng M, Ng K, Samol J, Chia D, Teh JL, Sundar R, Yong WP, Tan HL, Muro K, Lordick F, Wainburg Z, Tan BC, Kim G, Suda K, Law S, Sano T, Gurunathan R, Chiu P, Woo E, Duong C, Yang HK, Long VD, Kim HH, Mahendren HA, Lee HJ, Samarasam I, Gotoda T, Liew R, Shabbir A, Aung MO, Terashima M, Cheong E, So J, Tan J. Asia Pacific Gastroesophageal Cancer Congress (APGCC) 2024 consensus statement on stage 2 and 3 locally advanced gastric and Siewert 3 junctional adenocarcinoma. J Gastroenterol 2025:10.1007/s00535-025-02266-4. [PMID: 40514519 DOI: 10.1007/s00535-025-02266-4] [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: 02/21/2025] [Accepted: 05/27/2025] [Indexed: 06/16/2025]
Abstract
BACKGROUND While the development in multimodal therapies has helped improve treatment outcomes for patients with locally advanced gastric adenocarcinoma (LAGC), there still exist disparities in opinion with an optimal treatment plan. This consensus hopes to provide clinicians with structured guidelines to aid in the decision-making for treatment options for LAGC. METHODS The consensus statement was initiated by establishing a taskforce in collaboration with the Asia Pacific Gastroesophageal Cancer Congress (APGCC) and a multidisciplinary expert panel was selected. Clinical questions on LAGC where perceived variance in practice or opinion may exist were formulated. Studies involving patients with Stage 2 or 3 gastric or Siewert 3 junctional cancers with treatment arms of perioperative chemotherapy, neoadjuvant chemotherapy, adjuvant chemotherapy, immunotherapy and surgery were included. A total of two rounds of voting were performed. Consensus was determined to be reached when a single answer or a combination of either "strongly agree/agree" or "strongly disagree/disagree" responses exceeded 75%. RESULTS A total of thirteen clinical questions were developed. They were identified through five main categories: Distal LAGC, Proximal LAGC, Deficient mismatch repair tumors, Chemotherapy and Immunotherapy, and Elderly/Unfit patients. After two rounds of voting by our multidisciplinary expert panel, eleven out of a total thirteen clinical questions had reached consensus. No consensus was reached for two clinical questions. CONCLUSION The APGCC consensus statement aims to guide clinicians in the treatment options for LAGC and Siewert 3 junctional cancer and has clarified some of the roles of perioperative chemotherapy and immunotherapy.
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Affiliation(s)
- Yoshio Masuda
- Department of Upper Gastrointestinal & Bariatric Surgery, Division of Surgery, Singapore General Hospital, Singapore, Singapore
- Ministry of Health Holdings, Singapore, Singapore
| | - Kang Ler Fong
- Department of Upper Gastrointestinal & Bariatric Surgery, Division of Surgery, Singapore General Hospital, Singapore, Singapore
| | - Danson Yeo
- Upper Gastrointestinal & Bariatric Surgery Service, Department of General Surgery, Tan Tock Seng Hospital, Singapore, Singapore
| | - Charleen Yeo
- Upper Gastrointestinal & Bariatric Surgery Service, Department of General Surgery, Tan Tock Seng Hospital, Singapore, Singapore
| | - Koy Min Chue
- Upper Gastrointestinal & Bariatric Surgery Service, Department of General Surgery, Sengkang General Hospital, Singapore, Singapore
| | - Said Bani Araba
- Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, National University Hospital, Singapore, Singapore
| | - Chiew Woon Lim
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Baldwin Yeung
- Upper Gastrointestinal & Bariatric Surgery Service, Department of General Surgery, Sengkang General Hospital, Singapore, Singapore
| | - June Lee
- Upper Gastrointestinal & Bariatric Surgery Service, Department of General Surgery, Changi General Hospital, Singapore, Singapore
| | - Jinlin Lin
- Upper Gastrointestinal & Bariatric Surgery Service, Department of General Surgery, Changi General Hospital, Singapore, Singapore
| | - Claramae Chia
- Division of Surgery and Surgical Oncology, Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), National Cancer Centre Singapore and Singapore General Hospital, Singapore, Singapore
- SingHealth Duke-NUS Surgery & Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
| | - Matthew Ng
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Kennedy Ng
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore
| | - Jens Samol
- Department of Medical Oncology, Tan Tock Seng Hospital, Singapore, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- John Hopkins University School of Medicine, Baltimore, USA
| | - Daryl Chia
- Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, National University Hospital, Singapore, Singapore
| | - Jun Liang Teh
- Upper Gastrointestinal & Bariatric Surgery Service, Department of General Surgery, Ng Teng Fong Hospital, Singapore, Singapore
| | - Raghav Sundar
- Center for Gastrointestinal Cancers, Yale Cancer Center, New Haven, United States of America
| | - Wei-Peng Yong
- Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
| | - Hon Lyn Tan
- OncoCare Cancer Centre, Singapore, Singapore
| | - Kei Muro
- Department of Clinical Oncology and Outpatient Treatment Centre, Alchi Cancer Centre Hospital, Nagoya, Japan
| | - Florian Lordick
- Department of Medical Oncology, University Cancer Centre, Leipzig, Germany
| | - Zev Wainburg
- Department of Medicine, University of California Los Angeles Medical Centre, Los Angeles, CA, USA
| | - Bo Chuan Tan
- Department of Upper Gastrointestinal Surgery, Clinic for Digestive Surgery, Singapore, Singapore
| | - Guowei Kim
- Department of Upper Gastrointestinal Surgery, Crest Surgical Practice, Singapore, Singapore
| | - Koichi Suda
- Department of Surgery, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, Japan
| | - Simon Law
- Division of Esophageal and Upper Gastrointestinal Surgery, Department of Surgery, The University of Hong Kong, Hong Kong, China
| | - Takeshi Sano
- Gastroenterological Center, The Cancer Institute Hospital, Tokyo, Japan
| | - Ramesh Gurunathan
- Department of Surgery, Sunway Medical Centre, Subang, Selangor, Malaysia
| | - Philip Chiu
- Division of Upper GI and Metabolic Surgery, Department of Surgery, Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R, China
| | - Emile Woo
- Department of Surgery, University of British Columbia, Vancouver, BC, Canada
| | - Cuong Duong
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia
| | | | - Vo Duy Long
- Gastro-Intestinal Surgery Department, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Hyung Ho Kim
- Comprehensive Cancer Center, Seoul National University Bundang Hospital, Seongnam, South Korea
| | | | - Hyuk Joon Lee
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Inian Samarasam
- Upper Gastrointestinal Surgery Unit, Department of General Surgery Unit 3, Christian Medical College, Vellore, India
| | - Takuji Gotoda
- Department of Gastroenterology, Cancer Institute Hospital of JFCR, Tokyo, Japan
| | - Reis Liew
- Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, National University Hospital, Singapore, Singapore
| | - Asim Shabbir
- Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, National University Hospital, Singapore, Singapore
| | - Myint Oo Aung
- Upper Gastrointestinal & Bariatric Surgery Service, Department of General Surgery, Tan Tock Seng Hospital, Singapore, Singapore
| | - Masanori Terashima
- Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Monagakubo, Nagaizumi-Cho, Sunto-Gun, Nagaizumi, Shizuoka, Japan
| | - Edward Cheong
- Department of Upper Gastrointestinal Surgery, PanAsia Surgery, Singapore, Singapore
| | - Jimmy So
- Division of General Surgery (Upper Gastrointestinal Surgery), Department of Surgery, National University Hospital, Singapore, Singapore.
- Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.
- Division of Surgical Oncology, National University Cancer Institute of Singapore (NCIS), 5 Lower Kent Ridge Road, Singapore, 119074, Singapore.
| | - Jeremy Tan
- Department of Upper Gastrointestinal & Bariatric Surgery, Division of Surgery, Singapore General Hospital, Singapore, Singapore
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Wang B, Han X, Zhang Z, Song H, Song Y, Liu R, Li Z, Liu S. Longitudinal CT Radiomics to Predict Progression-free Survival in Patients with Locally Advanced Gastric Cancer After Neoadjuvant Chemotherapy. Acad Radiol 2025; 32:2618-2629. [PMID: 39732617 DOI: 10.1016/j.acra.2024.11.068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Revised: 11/24/2024] [Accepted: 11/28/2024] [Indexed: 12/30/2024]
Abstract
RATIONALE AND OBJECTIVES To develop and validate a radiomics signature, utilizing baseline and restaging CT, for preoperatively predicting progression-free survival (PFS) after neoadjuvant chemotherapy (NAC) in locally advanced gastric cancer (LAGC). METHODS A total of 316 patients with LAGC who received NAC followed by gastrectomy were retrospectively included in this single-center study; these patients were split into two cohorts, one for training (n = 243) and the other for validation (n = 73), based on the different districts of our hospital. A total of 1316 radiomics features were extracted from the volume of interest of the gastric-cancer lesion on venous phase CT images. Four radiomics signatures were built for predicting PFS based on baseline CT (Pre-Rad), restaging CT (Post-Rad), delta radiomics (Delta-Rad) and multi-time radiomics (PrePost-Rad), respectively. Then the PrePost-Rad was combined with clinical factors to establish a nomogram (Rad-clinical model). Kaplan-Meier survival curves with log-rank tests were used to assess the prognostic usefulness of the Rad-clinical model. RESULTS All baseline characteristics were not statistically different between the two cohorts. The PrePost-Rad achieved improved predictive value by a C-index of 0.724 (95% CI: 0.639-0.809) in the validation cohort [Pre-Rad: 0.715 (0.632-0.798); Post-Rad: 0.632 (0.538-0.725), Delta-Rad: 0.549 (0.447-0.651)]. In terms of clinical benefit, calibration capability, and prediction efficacy, the Rad-clinical model performed well for PFS prediction, with a C-index of 0.754 (95% CI: 0.707-0.800) and 0.719 (95% CI: 0.639-0.800) in the training and validation cohorts, respectively, superior to the clinical model (cN stage and CA199) but comparable to the PrePost-Rad. Moreover, the Rad-clinical model could accurately classify gastric-cancer patients after NAC into three PFS risk groups in both training and validation cohorts. The risk stratification also performed well in most subgroups (good responders, poor responders, ypTNM Ⅱ, and ypTNM Ⅲ/Ⅳ). CONCLUSIONS The Rad-clinical model integrating longitudinal radiomics score and clinical factors performed well in preoperatively predicting PFS of LAGC patients after NAC and surgery.
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Affiliation(s)
- Bo Wang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China (B.W., X.H., Z.Z., Z.L., S.L.)
| | - Xiaomeng Han
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China (B.W., X.H., Z.Z., Z.L., S.L.)
| | - Zaixian Zhang
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China (B.W., X.H., Z.Z., Z.L., S.L.)
| | - Hongzheng Song
- Department of Radiology, Qingdao Municipal Hospital, Shandong Province, Qingdao, Shandong Province, China (H.S.)
| | - Yaolin Song
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China (Y.S.)
| | - Ruiqing Liu
- Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China (R.L.)
| | - Zhiming Li
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China (B.W., X.H., Z.Z., Z.L., S.L.)
| | - Shunli Liu
- Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China (B.W., X.H., Z.Z., Z.L., S.L.).
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Liang Q, Wang S, Wang B, Hong Y. Efficacy and safety of post-discharge oral nutritional supplements for patients with gastric cancer undergoing gastrectomy: a meta-analysis of randomized controlled trials. Front Nutr 2025; 11:1488054. [PMID: 39877540 PMCID: PMC11772097 DOI: 10.3389/fnut.2024.1488054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 11/26/2024] [Indexed: 01/31/2025] Open
Abstract
Objectives To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluated the efficacy and safety of post-discharge oral nutritional supplements (ONS) for patients with gastric cancer undergoing gastrectomy. Design Systematic review and meta-analysis. Eligibility criteria for selecting studies RCT which evaluated the efficacy and/or safety of post-discharge ONS for patients with gastric cancer undergoing gastrectomy. Data sources We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April, 2023 for relevant RCTs. Data analysis Outcomes of meta-analysis included absolute change of body weight, % change of body weight, absolute change of body composition, absolute change of laboratory parameters and adverse events. All the relevant data were analyzed by Review Manager 5.4.1 and Stata 15.1. Results 5 RCTs including 1,586 patients (804 in ONS group versus 782 in control group) were included for meta-analysis. The two groups were comparable in age, gender (male), weight at baseline, BMI at baseline, albumin at baseline, and hemoglobin at baseline. Meta-analysis revealed a significant lower absolute body weight loss (WMD: 0.75; 95% CI: 0.11, 1.40; p = 0.02) and % body weight loss (WMD: 1.15; 95% CI: 0.20, 2.11; p = 0.02) in the ONS group compared with the control (regular diet/dietary advice) group. Moreover, this study did not observe a significant difference between the two groups for adverse events rate (RR: 1.11; 95% CI: 0.81, 1.53; p = 0.52). Conclusion ONS was significantly effective and safe in improving postoperative weight loss for patients with gastric cancer undergoing gastrectomy. Systematic review registration Identifier, CRD42023414678, https://www.crd.york.ac.uk/PROSPERO/.
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Affiliation(s)
- Qiuman Liang
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Siyi Wang
- School of Nursing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Beibei Wang
- School of Elderly Care Services and Management, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yanyan Hong
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Gao P, Xiao Q, Tan H, Song J, Fu Y, Xu J, Zhao J, Miao Y, Li X, Jing Y, Feng Y, Wang Z, Zhang Y, Yao E, Xu T, Mei J, Chen H, Jiang X, Yang Y, Wang Z, Gao X, Zheng M, Zhang L, Jiang M, Long Y, He L, Sun J, Deng Y, Wang B, Zhao Y, Ba Y, Wang G, Zhang Y, Deng T, Shen D, Wang Z. Interpretable multi-modal artificial intelligence model for predicting gastric cancer response to neoadjuvant chemotherapy. Cell Rep Med 2024; 5:101848. [PMID: 39637859 PMCID: PMC11722130 DOI: 10.1016/j.xcrm.2024.101848] [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: 08/28/2024] [Revised: 10/15/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024]
Abstract
Neoadjuvant chemotherapy assessment is imperative for prognostication and clinical management of locally advanced gastric cancer. We propose an incremental supervised contrastive learning model (iSCLM), an interpretable artificial intelligence framework integrating pretreatment CT scans and H&E-stained biopsy images, for improved decision-making regarding neoadjuvant chemotherapy. We have constructed and tested iSCLM using retrospective data from 2,387 patients across 10 medical centers and evaluated its discriminative ability in a prospective cohort (132 patients; ChiCTR2300068917). iSCLM achieves areas under receiver operating characteristic curves of 0.846-0.876 across different test cohorts. Computed tomography (CT) and pathological attention heatmaps from Shapley additive explanations and global sort pooling illustrate additional benefits for capturing morphological features through supervised contrastive learning. Specifically, pathological top-ranked tiles exhibit decreased distances to tumor-invasive borders and increased inflammatory cell infiltration in responders compared with non-responders. Moreover, CD11c expression is elevated in responders. The developed interpretable model at the molecular pathology level accurately predicts chemotherapy efficacy.
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Affiliation(s)
- Peng Gao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Qiong Xiao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Hui Tan
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Jiangdian Song
- School of Health Management, China Medical University, Shenyang 110122, China
| | - Yu Fu
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Jingao Xu
- Neusoft Research of Intelligent Healthcare Technology, Co. Ltd., Shenyang 110169, China
| | - Junhua Zhao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Yuan Miao
- Department of Pathology, The First Hospital of China Medical University, Shenyang 110001, China
| | - Xiaoyan Li
- Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Shenyang 110042, China
| | - Yi Jing
- Neusoft Research of Intelligent Healthcare Technology, Co. Ltd., Shenyang 110169, China
| | - Yingying Feng
- The School of Computer Science and Engineering, Northeastern University, Shenyang 110167, China
| | - Zitong Wang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Yingjie Zhang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Enbo Yao
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Tongjia Xu
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Jipeng Mei
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Hanyu Chen
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China
| | - Xue Jiang
- Department of Radiology, The First Hospital of China Medical University, Shenyang 110001, China
| | - Yuchong Yang
- Department of GI Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300202, China
| | - Zhengyang Wang
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
| | - Xianchun Gao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Minwen Zheng
- Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Liying Zhang
- Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
| | - Min Jiang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China
| | - Yuying Long
- Department of Pathology, Shenyang Fifth People Hospital, Shenyang 110001, China
| | - Lijie He
- Department of Oncology, People's Hospital of Liaoning Province, People's Hospital of China Medical University, Shenyang 110000, China
| | - Jinghua Sun
- Department of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian 116021, China
| | - Yanhong Deng
- The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China
| | - Bin Wang
- Department of Gastroenterology & Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China; School of Medicine, Chongqing University, Chongqing 400000, China; Institute of Pathology and Southwest Cancer Center, and Key Laboratory of Tumor Immunopathology of Ministry of Education of China, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China
| | - Yan Zhao
- Department of Stomach Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, The Liaoning Provincial Key Laboratory of Interdisciplinary Research on Gastrointestinal Tumor Combining Medicine with Engineering, Shenyang 110042, China
| | - Yi Ba
- Cancer Medical Center & Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Guan Wang
- Department of Radiology, The First Hospital of China Medical University, Shenyang 110001, China.
| | - Yong Zhang
- Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Cancer Hospital of Dalian University of Technology, Shenyang 110042, China.
| | - Ting Deng
- Department of GI Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300202, China.
| | - Dinggang Shen
- School of Biomedical Engineering & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China; Shanghai United Imaging Intelligence Co., Ltd., Shanghai 201807, China; Shanghai Clinical Research and Trial Center, Shanghai 201210, China.
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110001, China.
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Lin Y, Zhang L, Zhang X, Wei X, Liu X, Xie Y, Han G. Preliminary report on the short-term efficacy and safety of SAPO-S1 therapy for locally advanced gastric cancer with a deep learning perspective. Biotechnol Genet Eng Rev 2024; 40:2704-2719. [PMID: 37078530 DOI: 10.1080/02648725.2023.2202513] [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: 02/16/2023] [Accepted: 04/10/2023] [Indexed: 04/21/2023]
Abstract
The neoadjuvant therapeutic effects of various chemotherapeutic drugs on gastric cancer have reached the corresponding plateau. Whether the combination of sindilizumab and albumin-bound paclitaxel+oxaliplatin+S-1 chemotherapy (SAPO-S1 therapy) regimen can bring better efficacy and observe the incidence of adverse reactions in the neoadjuvant treatment of Gastric Cancer (GC) may be the direction of our research. This study aimed to evaluate the efficacy of S1 chemotherapy regimen combined with multiple chemotherapy drugs sindilizumab (PD-1 inhibitor), albumin-bound paclitaxel and oxaliplatin) for neoadjuvant therapy in locally advanced Gastric Cancer (LA-GC). The patients were given 4 cycles of sindilizumab combined with albumin paclitaxel+oxaliplatin+S-1 chemotherapy (SAPO-S1) before surgery. The R0 resection rate, surgical complications, pathologic complete response, complete pathologic response (pCR) the main pathological response rates (residual tumor cells≤10%, major pathological response) were observed. MPR and postoperative pathological tumor regression grade (TRG), using the response evaluation criteria in solid tumors (RECIST1.1) to evaluate the efficacy of new adjuvant therapy and record the short-term adverse events (adverse event, AE) of patients after medication to evaluate safety. The overall response rate (ORR) was achieved to 53.3% and disease control rate (DCR) was achieved in 28 patients (93.3%), and the descending phase was achieved in 17 patients (56.7%). The tumor resolution grades of TRG 0, TRG 1, TRG 2 and TRG 3 were 16.7%, 13.3%, 43.3% and 16.7%, respectively. The pCR rate was 16.7%, the MPR rate was 30.0%, and the R0 resection rate was 90.0%. In addition, SAPO-S1 therapy has fewer side effects. Overall, SAPO-S1 therapy has a good therapeutic effect and safety in LA-GC.
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Affiliation(s)
- Yecheng Lin
- First Department of Gastrointestinal Surgery, Cangzhou Central Hospital, Cangzhou, China
| | - Lei Zhang
- Department of Clinical Laboratory, Cangzhou Central hospital, Cangzhou, China
| | - Xiaoling Zhang
- Department of Pathology, Cangzhou Central Hospital, Cangzhou, China
| | - Xiaonan Wei
- First Department of Gastrointestinal Surgery, Cangzhou Central Hospital, Cangzhou, China
| | - Xu Liu
- First Department of Gastrointestinal Surgery, Cangzhou Central Hospital, Cangzhou, China
| | - Yanchao Xie
- First Department of Gastrointestinal Surgery, Cangzhou Central Hospital, Cangzhou, China
| | - Guoda Han
- First Department of Gastrointestinal Surgery, Cangzhou Central Hospital, Cangzhou, China
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Zhu C, Da M, Li Y, Peng L. Case report: pathological complete response after S-1/oxaliplatin regimen combined with trastuzumab and tislelizumab in patients with locally advanced gastric cancer. Front Oncol 2024; 14:1425572. [PMID: 39301541 PMCID: PMC11410570 DOI: 10.3389/fonc.2024.1425572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 08/21/2024] [Indexed: 09/22/2024] Open
Abstract
Background The efficacy of a regimen combining Tegafur, Gimeracil and Oteracil Potassium Capsules (S-1), oxaliplatin (SOX) with trastuzumab and tislelizumab chemotherapy for advanced gastric cancer (GC) has not been reported. Case summary A 56-year-old male was diagnosed with GC combined with peripheral lymph node metastasis. The patient received neoadjuvant chemotherapy, including SOX, tislelizumab and trastuzumab. After 4 cycles of chemotherapy, the tumor shrank significantly, and radical surgery was performed with good clinical results. To date, the patient has been followed up for 6 months with no significant side effects. Conclusion In this study, the patient received combination chemotherapy with SOX trastuzumab and tislelizumab and successfully underwent radical surgery with good clinical outcomes. Combined SOX with trastuzumab and tislelizumab may be an effective neoadjuvant chemotherapy regimen.
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Affiliation(s)
- Chenglou Zhu
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Mingxu Da
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, China
| | - Yaoqi Li
- Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, China
| | - Lingzhi Peng
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
- Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou, China
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Wang Y, Lei X, Shan F, Li S, Jia Y, Miao R, Xue K, Li Z, Ji J, Li Z. Long-term outcomes of laparoscopic versus open total gastrectomy in patients with advanced gastric cancer after neoadjuvant chemotherapy: a retrospective cohort study. BMC Cancer 2024; 24:1074. [PMID: 39215275 PMCID: PMC11365285 DOI: 10.1186/s12885-024-12669-w] [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: 02/20/2024] [Accepted: 07/22/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND This study was conducted to investigate the long-term outcomes of laparoscopic total gastrectomy (LTG) versus open total gastrectomy (OTG) in patients with advanced gastric cancer (AGC) after neoadjuvant chemotherapy (NACT). METHODS Patients with AGC who received NACT before surgery were enrolled in either the LTG or OTG group. Propensity score matching (PSM) (1:2) was performed between the two groups based on the propensity score using a 0.15 calliper width. Three-year overall survival (OS) and disease-free survival (DFS) were compared between these two groups before and after PSM. OS and DFS rates were calculated by the Kaplan‒Meier method, and any differences in survival were evaluated with a log-rank test. Univariate and multivariate Cox proportional hazards analyses were used to estimate the simultaneous effects of prognostic factors on survival and the hazard ratio (HR) between LTG and OTG patients. RESULTS A total of 144 patients completed the follow-up, with 24 patients in the LTG group and 120 patients in the OTG group. After a mean follow-up of 64.40 months, there were no significant differences in the 3-year OS or DFS rates between the two groups before (P = 0.453 and P = 0.362, respectively) or after PSM (P = 0.972 and P = 0.884, respectively). Multivariate Cox proportional hazards analysis indicated that ypN stage was an independent risk factor for worse OS (P = 0.013). CONCLUSIONS This study showed that LTG with D2 lymphadenectomy performed by an experienced surgical team resulted in comparable 3-year OS and DFS compared with OTG in patients with AGC after NACT. TRIAL REGISTRATION This study is not registered.
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Affiliation(s)
- Yinkui Wang
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xiaokang Lei
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Fei Shan
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Shuangxi Li
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Yongning Jia
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Rulin Miao
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Kan Xue
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Zhemin Li
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Jiafu Ji
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Ziyu Li
- Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, Beijing, China.
- Key Laboratory of Carcinogenesis and Translational Research, (Ministry of Education/Beijing), Gastrointestinal Cancer Center, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
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8
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Gu T, Wang Y, Wu Z, He N, Li Y, Shan F, Li Z, Ji J. Feasibility and long-term survival of proximal gastrectomy after neoadjuvant therapy for locally advanced proximal gastric cancer: A propensity-score-matched analysis. Chin Med J (Engl) 2024:00029330-990000000-01165. [PMID: 39090777 DOI: 10.1097/cm9.0000000000003232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Indexed: 08/04/2024] Open
Abstract
BACKGROUND Neoadjuvant therapy enhances the possibility of achieving radical resection and improves the prognosis for locally advanced gastric cancer (GC). However, there is a lack of evidence regarding the optimal extent of resection for locally advanced proximal GC after neoadjuvant therapy. METHODS In this study, 330 patients underwent resection in Peking University Cancer Hospital, with curative intent after neoadjuvant therapy for histologically confirmed proximal GC from January 2009 to December 2022. Among them, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). RESULTS In this study, 45 patients underwent proximal gastrectomy (PG), while 285 underwent total gastrectomy (TG). After propensity-score matching, 110 patients (71 TG and 39 PG) were included in the analysis. No significant differences between PG and TG regarding short-term outcomes and long-term prognosis were found. Specifically, PG demonstrated comparable overall survival to TG (P = 0.47). Subgroup analysis revealed that although not statistically significant, PG showed a potential advantage over TG in overall survival for patients with tumor-long diameters less than 4 cm (P = 0.31). However, for those with a long diameter larger than 4 cm, TG had a better survival probability (P = 0.81). No substantial differences were observed in baseline characteristics, surgical safety, postoperative recovery, and postoperative complications. CONCLUSION For locally advanced proximal GC with objective response to neoadjuvant therapy (long diameter <4 cm), PG is an alternative surgical procedure. Further research and prospective studies are warranted to validate these findings and guide clinical decision-making.
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Affiliation(s)
- Tingfei Gu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yinkui Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Translational Research, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhouqiao Wu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ning He
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yingai Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Fei Shan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Ziyu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Jiafu Ji
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, Beijing 100142, China
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9
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Chen Z, Chen G, Li Y, Kou S, Wang T, Zhang L, Cao Y, Liu L. Comparison of totally laparoscopic and laparoscopic-assisted approach in gastrectomy with D2 lymphadenectomy for advanced gastric cancer after neoadjuvant chemotherapy: a retrospective comparative study. Ann Surg Treat Res 2024; 106:218-224. [PMID: 38586555 PMCID: PMC10995841 DOI: 10.4174/astr.2024.106.4.218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Revised: 01/12/2024] [Accepted: 01/30/2024] [Indexed: 04/09/2024] Open
Abstract
Purpose Neoadjuvant chemotherapy is strongly recommended for advanced gastric cancer due to good local control and a high rate of R0 dissection with this strategy. Minimally invasive techniques such as laparoscopy-assisted or total laparoscopic approaches is becoming more and more acceptable in the treatment for gastric cancer. However, the safety and efficiency of total laparoscopic D2 gastrectomy (TLG) for advanced gastric cancer after neoadjuvant chemotherapy have not been well evaluated. Methods A retrospective study in a single center from 2014 to 2016 was conducted. A total of 65 locally advanced gastric cancers were treated by laparoscopy-assisted gastrectomy (LAG) or TLG. Parameters which include operation time, blood loss, complications, hospital stay, 3-year overall survival, and 3-year disease-free survival were used for comparison. Results The time of operation in the TLG group was shorter than in the LAG group (P = 0.013), blood loss was less (P = 0.002) and time to first flatus was shorter (P = 0.039) in the TLG group than that in the LLG group. Intraoperative and postoperative complications were comparable in both groups. No significant difference was found in 3-year overall and disease-free survival. Conclusion For patients with locally advanced gastric cancer after neoadjuvant chemotherapy, laparoscopic D2 gastrectomy can be considered as a safe and efficient alternative. A further multicenter prospective randomized controlled study is needed to elucidate the applicability of this technique for advanced gastric cancer.
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Affiliation(s)
- Zhenyu Chen
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu, China
| | - Guangyu Chen
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu, China
| | - Yan Li
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu, China
| | - Sha Kou
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu, China
| | - Tao Wang
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu, China
| | - Lin Zhang
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu, China
| | - Yongkuan Cao
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu, China
| | - Liye Liu
- General Surgery Center, The General Hospital of Western Theater Command, Chengdu, China
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10
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Yang GY, Peng YY, Hu M, Ma YT. Letter to the Editor on "Programmed 'seven-step method' mode in the clinical application of laparoscopic radical resection of distal gastric cancer". Asian J Surg 2024; 47:742-744. [PMID: 37891116 DOI: 10.1016/j.asjsur.2023.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 10/06/2023] [Indexed: 10/29/2023] Open
Affiliation(s)
- Guo-Yuan Yang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China
| | - Yi-Yun Peng
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China; General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China
| | - Ming Hu
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China; The First Ward of General Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Yun-Tao Ma
- General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou, China; NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China; The First Ward of General Surgery, Gansu Provincial Hospital, Lanzhou, China.
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11
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Nie W, Hu L, Yan Z, Wang Y, Shi Q, He S, Wang Q, Yang F. A potential therapeutic approach for gastric cancer: inhibition of LACTB transcript 1. Aging (Albany NY) 2023; 15:15213-15227. [PMID: 38149985 PMCID: PMC10781463 DOI: 10.18632/aging.205345] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 11/03/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND This study sought to investigate the role of LACTB transcript 1 in regulating adaptive immune resistance and stemness in gastric cancer and its potential as a therapeutic target for precision medicine. METHODS Bioinformatics analysis and RT-qPCR were used to analyze the expression level of LACTB and its transcripts in gastric cancer cells. The effects of LACTB transcript 1 on adaptive immune resistance and stemness were evaluated using in vitro cell experiments and western blotting experiments. RESULTS Our study findings revealed that LACTB transcript 1 modulated adaptive immune resistance and inhibited the stemness of gastric cancer cells. Knocking down the expression level of LACTB transcript 1 activated autophagy and inhibited EMT. As expected, overexpression of LACTB transcript 1 yielded the opposite findings. The expression level of LACTB transcript 1 in the peripheral blood of gastric cancer patients was consistent with the bioinformatics analysis, suggesting its potential as a biomarker of gastric cancer. CONCLUSIONS LACTB transcript 1 is a promising therapeutic target for precision medicine in gastric cancer by modulating immune evasion mechanisms and stemness. These findings provide insights into leveraging long non-coding RNAs (lncRNAs) in immunotherapy, radiotherapy, and chemotherapy to enhance cancer therapy efficacy, particularly in the context of targeting tumor heterogeneity and stemness.
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Affiliation(s)
- Wei Nie
- Center of Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Lihua Hu
- Department of Basic Clinical Laboratory and Hematology, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, China
| | - Zhiqiang Yan
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Yang Wang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Qianyun Shi
- Department of Basic Clinical Laboratory and Hematology, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, China
| | - Shui He
- Department of Basic Clinical Laboratory and Hematology, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, China
| | - Qian Wang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Fang Yang
- Center of Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- Department of Basic Clinical Laboratory and Hematology, School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, China
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12
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Chen H, Hu Y, Zhuang Z, Wang D, Ye Z, Jing J, Cheng X. Advancements and Obstacles of PARP Inhibitors in Gastric Cancer. Cancers (Basel) 2023; 15:5114. [PMID: 37958290 PMCID: PMC10647262 DOI: 10.3390/cancers15215114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 11/15/2023] Open
Abstract
Gastric cancer (GC) is a common and aggressive cancer of the digestive system, exhibiting high aggressiveness and significant heterogeneity. Despite advancements in improving survival rates over the past few decades, GC continues to carry a worrisome prognosis and notable mortality. As a result, there is an urgent need for novel therapeutic approaches to address GC. Recent targeted sequencing studies have revealed frequent mutations in DNA damage repair (DDR) pathway genes in many GC patients. These mutations lead to an increased reliance on poly (adenosine diphosphate-ribose) polymerase (PARP) for DNA repair, making PARP inhibitors (PARPi) a promising treatment option for GC. This article presents a comprehensive overview of the rationale and development of PARPi, highlighting its progress and challenges in both preclinical and clinical research for treating GC.
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Affiliation(s)
- Hongjie Chen
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; (H.C.); (Y.H.); (D.W.)
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
| | - Yangchan Hu
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; (H.C.); (Y.H.); (D.W.)
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
| | - Zirui Zhuang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
- School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences (UCAS), Hangzhou 310024, China
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
| | - Dingyi Wang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China; (H.C.); (Y.H.); (D.W.)
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
| | - Zu Ye
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
- Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Hangzhou 310022, China
| | - Ji Jing
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
- Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Hangzhou 310022, China
| | - Xiangdong Cheng
- Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China;
- Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Hangzhou 310022, China
- Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou 310022, China
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Chu Z, Zhu M, Luo Y, Hu Y, Feng X, Wang H, Sunagawa M, Liu Y. PTBP1 plays an important role in the development of gastric cancer. Cancer Cell Int 2023; 23:195. [PMID: 37670313 PMCID: PMC10478210 DOI: 10.1186/s12935-023-03043-0] [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: 03/23/2023] [Accepted: 08/25/2023] [Indexed: 09/07/2023] Open
Abstract
BACKGROUND Polypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation. METHODS We used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis. RESULTS Through bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC. CONCLUSIONS Our study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC.
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Affiliation(s)
- Zewen Chu
- The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
- The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, China
| | - Miao Zhu
- The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
- The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, China
| | - Yuanyuan Luo
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
- The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, China
| | - Yaqi Hu
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
- The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, China
| | - Xinyi Feng
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China
- The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, China
| | - Haibo Wang
- The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.
- The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, China.
| | - Masataka Sunagawa
- Department of physiology, School of Medicine, Showa University, Tokyo, Japan.
| | - Yanqing Liu
- The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
- Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, China.
- The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou, China.
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Shen K, Ke S, Chen B, Zhang T, Wang H, Lv J, Gao W. Identification and validation of biomarkers for epithelial-mesenchymal transition-related cells to estimate the prognosis and immune microenvironment in primary gastric cancer by the integrated analysis of single-cell and bulk RNA sequencing data. MATHEMATICAL BIOSCIENCES AND ENGINEERING : MBE 2023; 20:13798-13823. [PMID: 37679111 DOI: 10.3934/mbe.2023614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/09/2023]
Abstract
BACKGROUND The epithelial-mesenchymal transition (EMT) is associated with gastric cancer (GC) progression and immune microenvironment. To better understand the heterogeneity underlying EMT, we integrated single-cell RNA-sequencing (scRNA-seq) data and bulk sequencing data from GC patients to evaluate the prognostic utility of biomarkers for EMT-related cells (ERCs), namely, cancer-associated fibroblasts (CAFs) and epithelial cells (ECs). METHODS scRNA-seq data from primary GC tumor samples were obtained from the Gene Expression Omnibus (GEO) database to identify ERC marker genes. Bulk GC datasets from the Cancer Genome Atlas (TCGA) and GEO were used as training and validation sets, respectively. Differentially expressed markers were identified from the TCGA database. Univariate Cox, least-absolute shrinkage, and selection operator regression analyses were performed to identify EMT-related cell-prognostic genes (ERCPGs). Kaplan-Meier, Cox regression, and receiver-operating characteristic (ROC) curve analyses were adopted to evaluate the prognostic utility of the ERCPG signature. An ERCPG-based nomogram was constructed by integrating independent prognostic factors. Finally, we evaluated the correlations between the ERCPG signature and immune-cell infiltration and verified the expression of ERCPG prognostic signature genes by in vitro cellular assays. RESULTS The ERCPG signature was comprised of seven genes (COL4A1, F2R, MMP11, CAV1, VCAN, FKBP10, and APOD). Patients were divided into high- and low-risk groups based on the ERCPG risk scores. Patients in the high-risk group showed a poor prognosis. ROC and calibration curves suggested that the ERCPG signature and nomogram had a good prognostic utility. An immune cell-infiltration analysis suggested that the abnormal expression of ERCPGs induced the formation of an unfavorable tumor immune microenvironment. In vitro cellular assays showed that ERCPGs were more abundantly expressed in GC cell lines compared to normal gastric tissue cell lines. CONCLUSIONS We constructed and validated an ERCPG signature using scRNA-seq and bulk sequencing data from ERCs of GC patients. Our findings support the estimation of patient prognosis and tumor treatment in future clinical practice.
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Affiliation(s)
- Kaiyu Shen
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Shuaiyi Ke
- Department of Internal Medicine, XianJu People's Hospital, XianJu 317399, China
| | - Binyu Chen
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Tiantian Zhang
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China
| | - Hongtai Wang
- Department of General Surgery, XianJu People' Hospital, XianJu 317399, China
| | - Jianhui Lv
- Department of General Surgery, XianJu People' Hospital, XianJu 317399, China
| | - Wencang Gao
- Department of Oncology, Zhejiang Chinese Medical University, Hangzhou 310005, China
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Guo X, Gao Y, Song Q, Wei J, Wu J, Dong J, Chen L, Xu S, Wu D, Yang X, Chen L, Li X, Ji G, Lv X, Wei B. Early assessment of circulating exosomal lncRNA-GC1 for monitoring neoadjuvant chemotherapy response in gastric cancer. Int J Surg 2023; 109:1094-1104. [PMID: 37222716 PMCID: PMC10389467 DOI: 10.1097/js9.0000000000000249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 01/22/2023] [Indexed: 05/25/2023]
Abstract
BACKGROUND The timing of surgery for patients with gastric cancer (GC) who undergo neoadjuvant chemotherapy (neoCT) was mainly guided by serial radiologic imaging. However, an earlier assessment was indispensable to avoid delayed treatment for nonresponders and excessive toxicity for responders. Our previous study has identified circulating extracellular vesicles-derived lncRNA-GC1 as a biomarker for early detection and monitoring progression of GC. However, the potential role of neoCT remains poorly understood. METHODS In this explorative biomarker analysis, we conducted a multi-cohort study to examine longitudinal levels of circulating extracellular vesicles-derived lncRNA-GC1 in 798 patients enrolled in the RESONANCE study (NCT01583361). Both circulating extracellular vesicles-derived lncRNA-GC1 and traditional gastrointestinal biomarkers were assessed at defined time nodes. Computed tomography (CT) scans were performed before treatment and 8-10 weeks and assessed based on the RECIST criteria. RESULTS Circulating extracellular vesicles-derived lncRNA-GC1 could be detected in 96.3% of patients at baseline, and significant reductions were observed before cycle 2 (P<0.0001). Levels of circulating extracellular vesicles-derived lncRNA-GC1 showed a stronger correlation with tumor burden and exhibited earlier dynamic changes than the traditional gastrointestinal biomarkers during the first cycle of neoCT. Strong agreement was observed between circulating extracellular vesicles-derived lncRNA-GC1 response (reduction >50%) and radiographic response (Cohen's κ, 0.704). Importantly, circulating extracellular vesicles-derived lncRNA-GC1 maintained predictive value in two external cohorts. Patients with circulating extracellular vesicles-derived lncRNA-GC1 response showed superior disease-free survival [hazard ratio (HR), 0.6238; 95% CI, 0.4095-0.9501; P=0.0118] and overall survival (HR, 0.6131; 95% CI, 0.4016-0.9358; P=0.0090). CONCLUSION Circulating extracellular vesicles-derived lncRNA-GC1 is an early marker of neoCT efficacy and predicts superior survival in GC patients treated with neoCT.
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Affiliation(s)
- Xin Guo
- Department of Digestive Surgery
- Department of Endoscopic Surgery, Air Force 986th Hospital, Fourth Military Medical University, Xian
- Department of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | - Yunge Gao
- Department of Gynecology and Obstetrics
| | - Qiying Song
- Department of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | | | | | - Jian Dong
- Department of Gynecology and Obstetrics
| | | | - Shenhui Xu
- Department of Pathology, Xijing Hospital
| | - Di Wu
- Department of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China
| | | | - Lubin Chen
- Department of Digestive Surgery
- Department of Endoscopic Surgery, Air Force 986th Hospital, Fourth Military Medical University, Xian
| | | | - Gang Ji
- Department of Digestive Surgery
| | | | - Bo Wei
- Department of General Surgery, Chinese PLA General Hospital, Beijing, People’s Republic of China
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16
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Zhu L, Ma M, Zhang L, Wang S, Guo Y, Ling X, Lin H, Lai N, Lin S, Du L, Dong Q. System Analysis Based on Lipid-Metabolism-Related Genes Identifies AGT as a Novel Therapy Target for Gastric Cancer with Neoadjuvant Chemotherapy. Pharmaceutics 2023; 15:810. [PMID: 36986671 PMCID: PMC10051152 DOI: 10.3390/pharmaceutics15030810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Revised: 02/20/2023] [Accepted: 02/24/2023] [Indexed: 03/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common causes of cancer-related deaths worldwide, and chemotherapy is still a standard strategy for treating patients with advanced GC. Lipid metabolism has been reported to play an important role in the carcinogenesis and development of GC. However, the potential values of lipid-metabolism-related genes (LMRGs) concerning prognostic value and the prediction of chemotherapy responsiveness in GC remains unclear. A total of 714 stomach adenocarcinoma patients were enrolled from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Using univariate Cox and LASSO regression analyses, we developed a risk signature based on LMRGs that can distinguish high-GC-risk patients from low-risk patients with significant differences in overall survival. We further validated this signature prognostic value using the GEO database. The R package "pRRophetic" was applied to calculate the sensitivity of each sample from high- and low-risk groups to chemotherapy drugs. The expression of two LMRGs, AGT and ENPP7, can predict the prognosis and response to chemotherapy in GC. Furthermore, AGT significantly promoted GC growth and migration, and the downregulation of AGT enhanced the chemotherapy response of GC both in vitro and in vivo. Mechanistically, AGT induced significant levels of epithelial-mesenchymal transition (EMT) through the PI3K/AKT pathway. The PI3K/AKT pathway agonist 740 Y-P can restore the EMT of GC cells impaired by AGT knockdown and treatment with 5-fluorouracil. Our findings suggest that AGT plays a key role in the development of GC, and targeting AGT may help to improve the chemotherapy response of GC patients.
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Affiliation(s)
- Le Zhu
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Ming Ma
- Gastroenterology Department of Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Lumin Zhang
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Shun Wang
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Yu Guo
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Xinxin Ling
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Hanchao Lin
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Nannan Lai
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Shengli Lin
- Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University & Shanghai Collaborative Innovation Center of Endoscopy, Shanghai 200032, China
| | - Ling Du
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
| | - Qiongzhu Dong
- Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital, Fudan University, Shanghai 201199, China
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17
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Xu Y, Yu X, Guo W, He Y. Emerging role of interaction between m6A and main ncRNAs in gastrointestinal (GI) cancers. Front Immunol 2023; 14:1129298. [PMID: 36875073 PMCID: PMC9982029 DOI: 10.3389/fimmu.2023.1129298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 02/06/2023] [Indexed: 02/19/2023] Open
Abstract
As a prevalent epigenetic modification, the role of m6A has been increasingly highlighted in the alteration of numerous RNAs implicated with multiple biological processes, such as formation, export, translation, and degradation. With further the understanding of m6A, accumulating evidence shows that m6A modification similarly affects metabolic process of non-coding genes. But the specifical interplay of m6A and ncRNAs (non-coding RNAs) in gastrointestinal cancers still lacks complete discussion. Thus, we analyzed and summarized how ncRNAs affect the regulators of m6A and by what means the expression of ncRNAs is altered via m6A in gastrointestinal cancers. We focused on the effect of the interaction of m6A and ncRNAs on the molecular mechanisms of malignant behavior in gastrointestinal cancers, revealing more possibilities of ncRNAs for diagnosis and treatment in term of epigenetic modification.
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Affiliation(s)
- Yating Xu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiao Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuting He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary & Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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18
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Li H, Xue S, Zhang X, Li F, Bei S, Feng L. CircRNA PVT1 modulated cell migration and invasion through Epithelial-Mesenchymal Transition (EMT) mediation in gastric cancer through miR-423-5p/Smad3 pathway. Regen Ther 2022; 21:25-33. [PMID: 35663842 PMCID: PMC9133701 DOI: 10.1016/j.reth.2022.02.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 01/05/2022] [Accepted: 02/19/2022] [Indexed: 02/07/2023] Open
Abstract
Background Gastric cancer (GC) progression is related with gene regulations. Objectives This study explored underlying regulatory axis of circRNA PVT1 (circPVT1) in GC. Methods GC cell lines were detected for circPVT1 expression with the normal mucous epithelial cell GES-1 as control. After regulation of circPVT1, miR-423-5p and SMAD3 expression through transfection, CCK8 evaluated the cell viability, Transwell measured the migratory and invasive capability of cells. Luciferase verified the paired bindings between miR-423-5p and CircPVT1 or SMAD3. The functions of CircPVT1/miR-423-5p/SMAD3 were evaluated using RT-PCR, CCK8, Transwell assays. Western blot analyzed EMT-related proteins and phosphorylation of Smad3 in GC cells. Immunofluorescence method was used to evaluate the EMT-related proteins as well. Results CircPVT1 displayed higher expression in GC cells and knockdown led to decrease in cell growth, invasion and migration. CircPVT1 was targeted by miR-423-5p as a ceRNA of SMAD3. miR-423-5p upregulation suppressed both cicRNA PVT1 and SMAD3 in GC cells. Decrease in SMAD3 expression suppressed CircPVT1 by releasing miR-423-5p in cells, inhibiting cell growth, invasion and migration and suppressing the EMT process. Conclusion CircPVT1 modulated cell growth, invasion and migration through EMT mediation in gastric cancer through miR-423-5p/Smad3 pathway.
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19
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Di Carlo S, Siragusa L, Fassari A, Fiori E, La Rovere F, Izzo P, Usai V, Cavallaro G, Franceschilli M, Dhimolea S, Sibio S. Laparoscopic versus Open Total Gastrectomy for Locally Advanced Gastric Cancer: Short and Long-Term Results. Curr Oncol 2022; 29:8442-8455. [PMID: 36354725 PMCID: PMC9689079 DOI: 10.3390/curroncol29110665] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 10/30/2022] [Accepted: 11/03/2022] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Laparoscopic gastrectomy for early gastric cancer is widely accepted and routinely performed. However, it is still debated whether the laparoscopic approach is a valid alternative to open gastrectomy in advanced gastric cancer (AGC). The aim of this study is to compare short-and long-term outcomes of laparoscopic (LG) and open (OG) total gastrectomy with D2 lymphadenectomy in patients with AGC. METHODS A retrospective comparative study was conducted on patients who underwent LG and OG for ACG between January 2015 and December 2021. Primary endpoints were the following: recurrence rate, 3-year disease-free survival, 3-year and 5-year overall survival. Univariate and multivariate analysis was conducted to compare variables influencing outcomes and survival. RESULTS Ninety-two patients included: fifty-three OG and thirty-nine LG. No difference in morbidity and mortality. LG was associated with lower recurrence rates (OG 22.6% versus LG 12.8%, p = 0.048). No differences in 3-year and 5-year overall survival; 3-year disease-free survival was improved in the LG group on the univariate analysis but not after the multivariate one. LG was associated with longer operative time, lower blood loss and shorter hospital stay. Lymph node yield was higher in LG. CONCLUSION LG for AGC seems to provide satisfactory clinical and oncological outcomes in medium volume centers, improved postoperative results and possibly lower recurrence rates.
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Affiliation(s)
- Sara Di Carlo
- Department of Surgical Sciences, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy
| | - Leandro Siragusa
- Department of Surgical Sciences, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy
| | - Alessia Fassari
- Department of Surgery “Pietro Valdoni”, Sapienza University of Rome, “Umberto I” University Hospital, Viale del Policlinico 155, 00161 Rome, Italy
| | - Enrico Fiori
- Department of Surgery “Pietro Valdoni”, Sapienza University of Rome, “Umberto I” University Hospital, Viale del Policlinico 155, 00161 Rome, Italy
| | - Francesca La Rovere
- Department of Surgery “Pietro Valdoni”, Sapienza University of Rome, “Umberto I” University Hospital, Viale del Policlinico 155, 00161 Rome, Italy
| | - Paolo Izzo
- Department of Surgery “Pietro Valdoni”, Sapienza University of Rome, “Umberto I” University Hospital, Viale del Policlinico 155, 00161 Rome, Italy
| | - Valeria Usai
- Department of Surgical Sciences, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy
| | - Giuseppe Cavallaro
- Department of Surgery “Pietro Valdoni”, Sapienza University of Rome, “Umberto I” University Hospital, Viale del Policlinico 155, 00161 Rome, Italy
| | - Marzia Franceschilli
- Department of Surgical Sciences, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy
| | - Sirvjo Dhimolea
- Department of Surgical Sciences, University of Rome “Tor Vergata”, Viale Oxford 81, 00133 Rome, Italy
| | - Simone Sibio
- Department of Surgery “Pietro Valdoni”, Sapienza University of Rome, “Umberto I” University Hospital, Viale del Policlinico 155, 00161 Rome, Italy
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20
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Ma Y, Wang B, Maswikiti EP, Wang X, Wang N, Chen H. Pathological complete remission of a locally advanced gastric cancer by neoadjuvant therapy "sandwich" regimen as SOXAP+ fluorescence laparoscopic surgery +SOXAP: Case report. Front Pharmacol 2022; 13:1008755. [PMID: 36408251 PMCID: PMC9666721 DOI: 10.3389/fphar.2022.1008755] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 10/18/2022] [Indexed: 12/23/2022] Open
Abstract
Gastric cancer is an extremely burdensome and challenging malignant tumor with a high incidence and a high mortality rate, which seriously results in a thorny prognosis for oncology patients. Surgical treatment combined with postoperative adjuvant therapy are currently the most regular methods for the treatment of locally advanced gastric cancer (LAGC), but long-term efficacy is not an ideal outcome. Therefore, herein we report a case of a pathologically confirmed complete remission of LAGC treated by the administration of neoadjuvant therapy combined with fluorescence laparoscopic surgery with more significant long-term survival. With that being mentioned, a 60-year-old man was diagnosed as moderately differentiated gastric antrum adenocarcinoma (T3N1M0). Moreover, after three cycles of SOXAP regimen (Oxaliplatin + S-1+Apatinib + Camrelizumab), and it was found out that the gastric lesion was smaller in size than before, total laparoscopic radical resection of the distal gastric cancer was performed at the time. Furthermore, no tumor cells were seen in gross specimen post operatively, achieving complete remission of the case. In addition, he also underwent three cycles of SOXAP regimen postoperatively. Interestingly and assuredly, he was in good health after an almost 2-year follow up period. These results suggest that this therapeutic regimen is a promising treatment modality for the management of locally advanced gastric cancers.
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Affiliation(s)
- Yanling Ma
- Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Bofang Wang
- Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | | | - Xueyan Wang
- Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Na Wang
- Second Clinical Medical College, Lanzhou University, Lanzhou, Gansu, China
| | - Hao Chen
- Department of Cancer Center, Lanzhou University Second Hospital, Lanzhou, China,*Correspondence: Hao Chen,
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21
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Ma D, Zhang Y, Shao X, Wu C, Wu J. PET/CT for Predicting Occult Lymph Node Metastasis in Gastric Cancer. Curr Oncol 2022; 29:6523-6539. [PMID: 36135082 PMCID: PMC9497704 DOI: 10.3390/curroncol29090513] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 08/11/2022] [Accepted: 09/06/2022] [Indexed: 11/28/2022] Open
Abstract
A portion of gastric cancer patients with negative lymph node metastasis at an early stage eventually die from tumor recurrence or advanced metastasis. Occult lymph node metastasis (OLNM] is a potential risk factor for the recurrence and metastasis in these patients, and it is highly important for clinical prognosis. Positron emission tomography (PET)/computed tomography (CT) is used to assess lymph node metastasis in gastric cancer due to its advantages in anatomical and functional imaging and non-invasive nature. Among the major metabolic parameters of PET, the maximum standardized uptake value (SUVmax) is commonly used for examining lymph node status. However, SUVmax is susceptible to interference by a variety of factors. In recent years, the exploration of new PET metabolic parameters, new PET imaging agents and radiomics, has become an active research topic. This paper aims to explore the feasibility and predict the effectiveness of using PET/CT to detect OLNM. The current landscape and future trends of primary metabolic parameters and new imaging agents of PET are reviewed. For gastric cancer patients, the possibility to detect OLNM non-invasively will help guide surgeons to choose the appropriate lymph node dissection area, thereby reducing unnecessary dissections and providing more reasonable, personalized and comprehensive treatments.
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Affiliation(s)
- Danyu Ma
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Ying Zhang
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
- Institute of Cell Therapy, Soochow University, Changzhou 213003, China
| | - Xiaoliang Shao
- Department of Nuclear Medicine, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| | - Chen Wu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
- Institute of Cell Therapy, Soochow University, Changzhou 213003, China
- Correspondence: (C.W.); (J.W.)
| | - Jun Wu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
- Correspondence: (C.W.); (J.W.)
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22
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Liu Z, Zhang Z, Sun J, Li J, Zeng Z, Ma M, Ye X, Feng F, Kang W. Comparison of prognosis between neoadjuvant imatinib and upfront surgery for GIST: A systematic review and meta-analysis. Front Pharmacol 2022; 13:966486. [PMID: 36105195 PMCID: PMC9465640 DOI: 10.3389/fphar.2022.966486] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 07/19/2022] [Indexed: 11/24/2022] Open
Abstract
Background: Significant survival benefit of adjuvant imatinib therapy has been observed in gastrointestinal stromal tumor (GIST). However, the impact of neoadjuvant imatinib on prognosis of GIST remains unclear. This meta-analysis aimed to compare the prognostic impact between upfront surgery and neoadjuvant imatinib plus surgery on GIST. Methods: A comprehensive literature search was performed to identify eligible studies up to 30 Sep 2021, through PubMed, Embase, Web of Science, and Cochrane Library. Studies compared the impact of upfront surgery and neoadjuvant imatinib plus surgery on disease-free (DFS) or overall survival (OS) in patients with GIST were selected. Results: Seven eligible studies with 17,171 patients were included. The reduction rates of tumor size in rectal and mixed site GIST were 33% and 29.8%, respectively. Neoadjuvant imatinib was not significantly associated with DFS compared with no-neoadjuvant therapy in rectal GIST (HR: 0.71, 95% CI: 0.35–1.41). The OS of rectal GIST was significantly improved by neoadjuvant imatinib compared with no-neoadjuvant therapy (HR: 0.36, 95% CI: 0.17–0.75). Conclusion: Neoadjuvant imatinib therapy contributed to tumor shrinkage and R0 resection of rectal GIST. Neoadjuvant imatinib plus surgery significantly improved overall survival of rectal GIST in comparison with upfront surgery.
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Affiliation(s)
- Zhen Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zimu Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Juan Sun
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Li
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ziyang Zeng
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingwei Ma
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xin Ye
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fan Feng
- Division of Digestive Surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi’an, China
| | - Weiming Kang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- *Correspondence: Fan Feng, ; Weiming Kang,
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23
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Zhang M, Jin M, Gao Z, Yu W, Zhang W. High COL10A1 expression potentially contributes to poor outcomes in gastric cancer with the help of LEF1 and Wnt2. J Clin Lab Anal 2022; 36:e24612. [PMID: 35929139 PMCID: PMC9459277 DOI: 10.1002/jcla.24612] [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: 03/24/2022] [Revised: 05/15/2022] [Accepted: 06/13/2022] [Indexed: 11/14/2022] Open
Abstract
Background COL10A1 is a secreted, short‐chain collagen found in several types of cancer. Studies have shown that COL10A1 aberrant expression is considered an oncogenic factor. However, its underlying mechanisms and regulation of gastric cancer remain undefined. Methods The data on the expression of COL10A1, clinicopathological characteristics, and outcome of patients with GC were obtained from The Cancer Genome Atlas. The ALGGEN‐PROMO database defined the related transcription factors. Quantitative real‐time reverse transcription‐polymerase chain reaction and western blotting analysis were used to identify the differential expression levels of COL10A1 and related transcription factors. Results We found that high COL10A1 expression is an independent risk factor for gastric cancer. Upregulation of LEF1 and Wnt2 was also observed in gastric cancer, suggesting a potential correlation between LEF1/COL10A1 regulation in the Wnt2 signaling pathway. Conclusion High COL10A1 expression may contribute to poor outcomes via upregulation of LEF1 and Wnt2 in gastric cancer.
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Affiliation(s)
- Miaozun Zhang
- Department of Gastrointestinal Surgery, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
| | - Ming Jin
- Department of Radiation Oncology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
| | - Zhiqiang Gao
- Department of Gastroenterology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
| | - Weiming Yu
- Department of Gastrointestinal Surgery, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China
| | - Wei Zhang
- Department of Gastroenterology, The HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, China
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24
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Ma L, Chen G, Wang D, Zhang K, Zhao F, Tang J, Zhao J, Røe OD, He S, Liao D, Gu Y, Tao M, Shu Y, Li W, Chen X. A nomogram to predict survival probability of gastric cancer patients undergoing radical surgery and adjuvant chemotherapy. Front Oncol 2022; 12:893998. [PMID: 35992865 PMCID: PMC9389342 DOI: 10.3389/fonc.2022.893998] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 07/07/2022] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) is the third-leading cause of cancer mortality worldwide. The aim of this study was to develop a nomogram that estimates 1-year, 3-year, and 5-year survival probability of GC patients after D2 gastrectomy combined with adjuvant chemotherapy. The results showed that median age is 58 (range: 18-85) years in the training cohort and 59 (range: 32-85) years in the validation cohort. On multivariate analysis, four factors were found to be significantly associated with worse overall survival (OS): late TNM stage, positive resection margin, preoperative carcinoembryonic antigen (CEA) level, and single chemotherapy regimens compared with multiple chemotherapy regimens. All of these findings were validated in the validation cohort. Furthermore, the four factors were included in the final nomogram for the prediction of 1-year, 3-year, and 5-year survival probability, with accurate calibration and reasonable discrimination (C-index = 0.676 for training cohort, and C-index = 0.664 for validation cohort). The AUC values analyzed by the ROC analysis demonstrated a good predictive accuracy of the nomogram for OS (1-year, 3-year, and 5-year OS were 94.43%, 77.42%, and 73.03% in the training cohort, respectively; 96.95%, 81.54%, and 73.41% in the validation cohort, respectively). In conclusion, the proposed nomogram may be used to objectively and accurately predict survival probability of GC patients in a multi-institutional clinical setting.
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Affiliation(s)
- Ling Ma
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing, China
| | - Guosheng Chen
- Pancreatic Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute of Nanjing Medical University, Nanjing, China
| | - Deqiang Wang
- The Cancer Therapy Center, Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Kai Zhang
- Pancreatic Center and Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Fengjiao Zhao
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jie Tang
- Department of Oncology, Liyang People’s Hospital, Liyang, China
| | - Jianyi Zhao
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Oluf Dimitri Røe
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Oncology, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - Shaohua He
- The Key Laboratory of Cancer Prevention and Treatment, Second People's Hospital of Huaihua City, Huaihua, China
| | - Dongcheng Liao
- The Key Laboratory of Cancer Prevention and Treatment, Second People's Hospital of Huaihua City, Huaihua, China
| | - Yanhong Gu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Tao
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Yongqian Shu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Li
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
- *Correspondence: Xiaofeng Chen, ; ; Wei Li,
| | - Xiaofeng Chen
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Xiaofeng Chen, ; ; Wei Li,
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Hani U, Osmani RAM, Yasmin S, Gowda BHJ, Ather H, Ansari MY, Siddiqua A, Ghazwani M, Fatease AA, Alamri AH, Rahamathulla M, Begum MY, Wahab S. Novel Drug Delivery Systems as an Emerging Platform for Stomach Cancer Therapy. Pharmaceutics 2022; 14:1576. [PMID: 36015202 PMCID: PMC9416534 DOI: 10.3390/pharmaceutics14081576] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/14/2022] [Accepted: 07/23/2022] [Indexed: 12/04/2022] Open
Abstract
Cancer has long been regarded as one of the world's most fatal diseases, claiming the lives of countless individuals each year. Stomach cancer is a prevalent cancer that has recently reached a high number of fatalities. It continues to be one of the most fatal cancer forms, requiring immediate attention due to its low overall survival rate. Early detection and appropriate therapy are, perhaps, of the most difficult challenges in the fight against stomach cancer. We focused on positive tactics for stomach cancer therapy in this paper, and we went over the most current advancements and progressions of nanotechnology-based systems in modern drug delivery and therapies in great detail. Recent therapeutic tactics used in nanotechnology-based delivery of drugs aim to improve cellular absorption, pharmacokinetics, and anticancer drug efficacy, allowing for more precise targeting of specific agents for effective stomach cancer treatment. The current review also provides information on ongoing research aimed at improving the curative effectiveness of existing anti-stomach cancer medicines. All these crucial matters discussed under one overarching title will be extremely useful to readers who are working on developing multi-functional nano-constructs for improved diagnosis and treatment of stomach cancer.
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Affiliation(s)
- Umme Hani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia; (M.G.); (A.A.F.); (A.H.A.); (M.R.); (M.Y.B.)
| | - Riyaz Ali M. Osmani
- Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSS AHER), Mysuru 570015, Karnataka, India;
| | - Sabina Yasmin
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University (KKU), Abha 62529, Saudi Arabia; (S.Y.); (H.A.)
| | - B. H. Jaswanth Gowda
- Department of Pharmaceutics, Yenepoya Pharmacy College and Research Centre, Yenepoya (Deemed to Be University), Mangalore 575018, Karnataka, India;
| | - Hissana Ather
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University (KKU), Abha 62529, Saudi Arabia; (S.Y.); (H.A.)
| | - Mohammad Yousuf Ansari
- Department of Pharmaceutical Chemistry, MM College of Pharmacy, Maharishi Markandeshwar (Deemed to Be University ), Mullana, Ambala 133203, Haryana, India;
| | - Ayesha Siddiqua
- Department of Clinical Pharmacy, College of Pharmacy, King Khalid University (KKU), Abha 62529, Saudi Arabia;
| | - Mohammed Ghazwani
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia; (M.G.); (A.A.F.); (A.H.A.); (M.R.); (M.Y.B.)
- Cancer Research Unit, King Khalid University, Abha 62529, Saudi Arabia
| | - Adel Al Fatease
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia; (M.G.); (A.A.F.); (A.H.A.); (M.R.); (M.Y.B.)
| | - Ali H. Alamri
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia; (M.G.); (A.A.F.); (A.H.A.); (M.R.); (M.Y.B.)
| | - Mohamed Rahamathulla
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia; (M.G.); (A.A.F.); (A.H.A.); (M.R.); (M.Y.B.)
| | - M. Yasmin Begum
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia; (M.G.); (A.A.F.); (A.H.A.); (M.R.); (M.Y.B.)
| | - Shadma Wahab
- Department of Pharmacognosy, College of Pharmacy, King Khalid University (KKU), Abha 62529, Saudi Arabia;
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Cui H, Zhang KC, Cao B, Deng H, Liu GB, Song LQ, Zhao RY, Liu Y, Chen L, Wei B. Short and long-term outcomes between laparoscopic and open total gastrectomy for advanced gastric cancer after neoadjuvant chemotherapy. World J Gastrointest Surg 2022; 14:452-469. [PMID: 35734616 PMCID: PMC9160691 DOI: 10.4240/wjgs.v14.i5.452] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 01/17/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NACT) combined with surgery is regarded as an effective treatment for advanced gastric cancer (AGC). Laparoscopic surgery represents the mainstream of minimally invasive surgery. Currently, surgeons focus more on surgical safety and oncological outcomes of laparoscopic gastrectomy after NACT. Thus, we sought to evaluate short- and long-term outcomes between laparoscopic total gastrectomy (LTG) and open total gastrectomy (OTG) after NACT.
AIM To compare the short and long-term outcomes between LTG and OTG for AGC after NACT.
METHODS We retrospectively collected the clinicopathological data of 136 patients who accepted gastrectomy after NACT from June 2012 to June 2019, including 61 patients who underwent LTG and 75 who underwent OTG. Clinicopathological characteristics between the LTG and OTG groups showed no significant difference. SPSS 26.0, R software, and GraphPad PRISM 8.0 were used to perform statistical analyses.
RESULTS Of the 136 patients included, eight acquired pathological complete response, and the objective response rate was 47.8% (65/136). The LTG group had longer operation time (P = 0.015), less blood loss (P = 0.003), shorter days to first flatus (P < 0.001), and shorter postoperative hospitalization days (P < 0.001). LTG spent more surgical cost than OTG (P < 0.001), while total hospitalized cost of LTG was less than OTG (P < 0.001). 21 (28.0%) patients in the OTG group and 14 (23.0%) in the LTG group had 30-d postoperative complications, but there was no significant difference between the two groups (P = 0.503). The 3-year overall survival (OS) rate was 60.6% and 64.6% in the LTG and OTG groups, respectively [hazard ratio (HR) = 0.859, 95% confidence interval (CI): 0.522-1.412, P = 0.546], while the 3-year disease-free survival (DFS) rate was 54.5% and 51.8% in the LTG and OTG group, respectively (HR = 0.947, 95%CI: 0.582-1.539, P = 0.823). Multivariate cox analysis showed that body mass index and pTNM stage were independent risk factors for OS while vascular invasion and pTNM stage were independent risk factors for DFS (P < 0.05).
CONCLUSION After NACT, LTG shows comparable 30-d postoperative morbidity as well as 3-year OS and DFS rate to OTG. We recommend that experienced surgeons select LTG other than OTG for proper AGC patients after NACT.
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Affiliation(s)
- Hao Cui
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Ke-Cheng Zhang
- Department of General Surgery and Institute of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Bo Cao
- Department of General Surgery and Institute of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Medical School, Chinese PLA General Hospital, Beijing 100853, China
| | - Huan Deng
- Department of General Surgery and Institute of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Medical School, Chinese PLA General Hospital, Beijing 100853, China
| | - Gui-Bin Liu
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Li-Qiang Song
- School of Medicine, Nankai University, Tianjin 300071, China
| | - Rui-Yang Zhao
- Department of General Surgery and Institute of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Medical School, Chinese PLA General Hospital, Beijing 100853, China
| | - Yi Liu
- Department of General Surgery and Institute of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Lin Chen
- Department of General Surgery and Institute of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Bo Wei
- Department of General Surgery and Institute of General Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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A Network Pharmacology Approach for Uncovering the Antitumor Effects and Potential Mechanisms of the Sijunzi Decoction for the Treatment of Gastric Cancer. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2022; 2022:9364313. [PMID: 35463069 PMCID: PMC9019414 DOI: 10.1155/2022/9364313] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 02/11/2022] [Accepted: 03/15/2022] [Indexed: 12/15/2022]
Abstract
Background Sijunzi decoction (SJZD), a classic Chinese formula, has been clinically used for the treatment of gastrointestinal disorders. However, few studies have uncovered its antitumor effects and its potential mechanisms against gastric cancer (GC). Therefore, this work aimed to identify the active compounds and putative targets of the SJZD and to further explore the potential mechanisms involved in the treatment of GC. Materials and Methods The active compounds and potential targets of the SJZD and related genes for GC treatment were collected from a public database. Traditional Chinese medicine (TCM)-compound-target-disease networks, Venn diagrams, protein–protein interactions (PPIs), gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to obtain the bioactive compounds, key targets, and potential pathways. Next, the human gastric adenocarcinoma cell line NUGC-4 was inoculated subcutaneously into the right flank of NCG mice to build a tumor-bearing mouse model to further verify the findings. Results There were 117 compounds in the SJZD in total. The SJZD and GC had 161 and 3288 potential targets, respectively, among which 123 targets overlapped. The network analysis showed that quercetin, kaempferol formononetin, ginsenoside, atractylenolide III, etc., were bioactive molecules. The tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), transcription factor AP-1 (JUN), and vascular endothelial growth factor A (VEGFA) were potential targets. A KEGG pathway enrichment analysis revealed 110 pathways involved in the pathways for cancer, including the PI3K-AKT signaling pathway. Validation experiments showed that the SJZD inhibited tumor growth and induced apoptosis in tumor cells. In addition, the SJZD downregulated expressions of VEGFA, iNOS, COX-2, and Bax/Bcl2 and inhibited the expressions of p-PI3K and p-AKT. Conclusion The SJZD treats GC by inhibiting blood vessel hyperplasia and inducing cell apoptosis by regulating the PI3K/AKT pathway.
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Huang T, Wang Y, Li M, Wang W, Qi Z, Li J. Circular RNA hsa_circ_0119412 contributes to tumorigenesis of gastric cancer via the regulation of the miR-1298-5p/zinc finger BED-type containing 3 (ZBED3) axis. Bioengineered 2022; 13:5827-5842. [PMID: 35200111 PMCID: PMC8974131 DOI: 10.1080/21655979.2022.2036406] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Circular RNAs (circRNAs) are associated with the progression of gastric cancer (GC). This study investigates the regulation of the circular RNA, hsa_circ_0119412 in GC and its effects on GC cells. The expression of hsa_circ_0119412, microRNA (miR)-1298-5p, and zinc finger BED-type containing 3 (ZBED3) were measured by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK-8) assay, flow cytometry, transwell, and animal assays were performed to identify the roles of hsa_circ_0119412, miR-1298-5p, and ZBED3 in the viability, apoptosis, invasion, and growth of GC cells. The relationship between hsa_circ_0119412, miR-1298-5p, and ZBED3 was confirmed by luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. Our data revealed that hsa_circ_0119412 and ZBED3 expression was upregulated in GC, while miR-1298-5p expression was downregulated. Both the knockdown of hsa_circ_0119412/ZBED3 and miR-1298-5p overexpression inhibited GC cell growth and invasion, and enhanced cell apoptosis, while miR-1298-5p interference or ZBED3 overexpression showed the opposite trend. Mechanistically, hsa_circ_0119412 sponges miR-1298-5p, which regulates ZBED3 expression. Silencing hsa_circ_0119412 inhibits the progression of GC, at least in part, by targeting the miR-1298-5p/ZBED3 axis.
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Affiliation(s)
- Ting Huang
- Department of Oncology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yacheng Wang
- Department of Oncology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Miao Li
- Department of Oncology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wenjie Wang
- Department of Oncology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhaozhen Qi
- Department of Oncology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jun Li
- Department of Oncology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Zhang L, Hu D, Huangfu S, Zhou J, Wang W, Liu S, Tang H, Pan J, Pan Y. DNA Repair and Replication-Related Gene Signature Based on Tumor Mutation Burden Reveals Prognostic and Immunotherapy Response in Gastric Cancer. JOURNAL OF ONCOLOGY 2022; 2022:6469523. [PMID: 35058980 PMCID: PMC8766186 DOI: 10.1155/2022/6469523] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 12/01/2021] [Indexed: 12/16/2022]
Abstract
The genomic variant features (mutations, deletions, structural variants, etc.) within gastric cancer impact its evolution and immunogenicity. The tumor has developed several coping strategies to respond to these changes by DNA repair and replication (DRR). However, the intrinsic relationship between the associated DRR-related genes and gastric cancer progression remained unknown. This study selected DRR-related genes with tumor mutation burden based on the TCGA (The Cancer Genome Atlas) database of gastric cancer transcriptome and mutation data. The prognosis model of seven genes (LAMA2, CREB3L3, SELP, ABCC9, CYP1B1, CDH2, and GAMT) was constructed by a univariate and LASSO regression analysis and divided into high-risk and low-risk groups with the median risk score. Survival analysis showed that overall survival (OS) was lower in the high-risk group than that in the low-risk group. Moreover, patients with gastric cancer in the high-risk group have worse survival in different subgroups, including age, gender, histological grade, and TNM stage. The nomogram that included risk scores for DRR-related genes could accurately foresee OS of patients with gastric cancer. Interestingly, the tumor mutation burden score was higher in the low-risk group than that in the high-risk group, and the risk score for DRR-related genes was negatively correlated with tumor mutation burden in gastric cancer. Next, we further combined the risk score and tumor mutation burden to evaluate the prognosis of gastric cancer patients. The low-risk cohort had a better prognosis than the high-risk cohort in the high tumor mutation burden subgroup. The number of mutation types in the high-risk group was lower than that in the low-risk group. In the immune microenvironment of gastric cancer, more naïve B cells, memory resting CD4+ T cells, Treg cells, monocytes cells, and resting mast cells were infiltrated in the high-risk group. At last, PD-L1 and IAP expressions were negatively correlated with the risk scores; patients with gastric cancer in the low-risk group showed better immunotherapy outcomes than those in the high-risk group. Overall, the DRR-related gene signature based on tumor mutation burden is a novel biomarker for prognostic and immunotherapy response in patients with gastric cancer.
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Affiliation(s)
- Lei Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Department of Oncology Surgery, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province 233080, China
| | - Dahai Hu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Clinical Medicine Research Institute, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- International School, Jinan University, Guangzhou, Guangdong 510632, China
| | - Shuchen Huangfu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
| | - Jiaxin Zhou
- International School, Jinan University, Guangzhou, Guangdong 510632, China
| | - Wei Wang
- Department of Oncology Surgery, The Second Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province 233080, China
| | - Shijin Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
| | - Hui Tang
- Clinical Medicine Research Institute, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
- Jiangmen Maternity and Child Health Care Hospital, Huizhou 52900, China
| | - Jinghua Pan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
| | - Yunlong Pan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China
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Zhu Y, Zhou B, Hu X, Ying S, Zhou Q, Xu W, Feng L, Hou T, Wang X, Zhu L, Jin H. LncRNA LINC00942 promotes chemoresistance in gastric cancer by suppressing MSI2 degradation to enhance c-Myc mRNA stability. Clin Transl Med 2022; 12:e703. [PMID: 35073459 PMCID: PMC8785984 DOI: 10.1002/ctm2.703] [Citation(s) in RCA: 80] [Impact Index Per Article: 26.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 12/20/2021] [Accepted: 12/29/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND Chemoresistance to cisplatin (DDP) remains a major challenge in advanced gastric cancer (GC) treatment. Although accumulating evidence suggests an association between dysregulation of long non-coding RNAs (lncRNAs) and chemoresistance, the regulatory functions and complexities of lncRNAs in modulating DDP-based chemotherapy in GC remain under-investigated. This study was designed to explore the critical chemoresistance-related lncRNAs in GC and identify novel therapeutic targets for patients with chemoresistant GC. METHODS Chemoresistance-related lncRNAs were identified through microarray and verified through a quantitative real-time polymerase chain reaction (qRT-PCR). Proteins bound by lncRNAs were identified through a human proteome array and validated through RNA immunoprecipitation (RIP) and RNA pull-down assays. Co-immunoprecipitation and ubiquitination assays were performed to explore the molecular mechanisms of the Musashi2 (MSI2) post-modification. The effects of LINC00942 (LNC942) and MSI2 on DDP-based chemotherapy were investigated through MTS, apoptosis assays and xenograft tumour formation in vivo. RESULTS LNC942 was found to be up-regulated in chemoresistant GC cells, and its high expression was positively correlated with the poor prognosis of patients with GC. Functional studies indicated that LNC942 confers chemoresistance to GC cells by impairing apoptosis and inducing stemness. Mechanically, LNC942 up-regulated the MSI2 expression by preventing its interaction with SCFβ-TRCP E3 ubiquitin ligase, eventually inhibiting ubiquitination. Then, LNC942 stabilized c-Myc mRNA in an N6-methyladenosine (m6 A)-dependent manner. As a potential m6 A recognition protein, MSI2 stabilized c-Myc mRNA with m6 A modifications. Moreover, inhibition of the LNC942-MSI2-c-Myc axis was found to restore chemosensitivity both in vitro and in vivo. CONCLUSIONS These results uncover a chemoresistant accelerating function of LNC942 in GC, and disrupting the LNC942-MSI2-c-Myc axis could be a novel therapeutic strategy for GC patients undergoing chemoresistance.
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Affiliation(s)
- Yiran Zhu
- Laboratory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang ProvinceCancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityHangzhouChina
| | - Bingluo Zhou
- Laboratory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang ProvinceCancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityHangzhouChina
| | - Xinyang Hu
- Laboratory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang ProvinceCancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityHangzhouChina
| | - Shilong Ying
- Laboratory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang ProvinceCancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityHangzhouChina
| | - Qiyin Zhou
- Department of Medical Oncology, Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouChina
| | - Wenxia Xu
- Laboratory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang ProvinceCancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityHangzhouChina
| | - Lifeng Feng
- Laboratory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang ProvinceCancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityHangzhouChina
| | - Tianlun Hou
- Department of Clinical MedicineWenzhou Medical UniversityWenzhouChina
| | - Xian Wang
- Department of Medical Oncology, Sir Run Run Shaw Hospital, School of MedicineZhejiang UniversityHangzhouChina
| | - Liyuan Zhu
- Laboratory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang ProvinceCancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityHangzhouChina
| | - Hongchuan Jin
- Laboratory of Cancer Biology, Key Laboratory of Biotherapy in Zhejiang ProvinceCancer Center of Zhejiang University, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang UniversityHangzhouChina
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Hu X, Wang Z, Wang Q, Chen K, Han Q, Bai S, Du J, Chen W. Molecular classification reveals the diverse genetic and prognostic features of gastric cancer: A multi-omics consensus ensemble clustering. Biomed Pharmacother 2021; 144:112222. [PMID: 34607103 DOI: 10.1016/j.biopha.2021.112222] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2021] [Revised: 09/15/2021] [Accepted: 09/16/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Globally, gastric cancer (GC) is the fifth most common tumor. It is necessary to identify novel molecular subtypes to guide patient selection for specific target therapeutic benefits. METHODS Multi-omics data, including transcriptomics RNA-sequencing (mRNA, LncRNA, miRNA), DNA methylation, and gene mutations in the TCGA-STAD cohort were used for the clustering. Ten classical clustering algorithms were executed to recognize patients with different molecular features using the "MOVICS" package in R. The activated signaling pathways were evaluated using the single-sample gene set enrichment analysis. The differential distribution of gene mutations, copy number alterations, and tumor mutation burden was compared, and potential responses to immunotherapy and chemotherapy were also assessed. RESULTS Two molecular subtypes (CS1 and CS2) were recognized by ten clustering algorithms with consensus ensembles. Patients in the CS1 group had a shorter average overall survival time (28.5 vs. 68.9 months, P = 0.016), and progression-free survival (19.0 vs. 63.9 months, P = 0.008) as compared to those in the CS2 group. Extracellular associated biological process activation was higher in the CS1 group, while the CS2 group displayed the enhanced activation of cell cycle-associated pathways. Significantly higher total mutation numbers and neoantigens were observed in the CS2 group, along with specific mutations in TTN, MUC16, and ARID1A. Higher infiltration of immunocytes was also observed in the CS2 group, reflective of the potential immunotherapeutic benefits. Moreover, the CS2 group could also respond to 5-fluorouracil, cisplatin, and paclitaxel. The similar diversity in clinical outcomes between CS1 and CS2 groups was successfully validated in the external cohorts, GSE62254, GSE26253, GSE15459, and GSE84437. CONCLUSION The findings provided novel insights into the GC subtypes through integrative analysis of five -omics data by ten clustering algorithms. These could provide potential clinical therapeutic targets based on the specific molecular features.
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Affiliation(s)
- Xianyu Hu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, PR China
| | - Zhenglin Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, PR China
| | - Qing Wang
- Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province 515000, PR China
| | - Ke Chen
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, PR China
| | - Qijun Han
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, PR China
| | - Suwen Bai
- Longgang District People's Hospital of Shenzhen & The Third Affiliated Hospital (Provisional) of The Chinese University of Hong Kong, Shenzhen, Shenzhen, Guangdong Province 518172, PR China
| | - Juan Du
- Longgang District People's Hospital of Shenzhen & The Third Affiliated Hospital (Provisional) of The Chinese University of Hong Kong, Shenzhen, Shenzhen, Guangdong Province 518172, PR China; School of Medicine, The Chinese University of Hong Kong, Shenzhen, Shenzhen, Guangdong Province 518172, PR China.
| | - Wei Chen
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province 230022, PR China.
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Jian D, Qian C, Wang D, Ma Q, Wang L, Li C, Xu M, Dai N, Chen Q, He J, Zhang H, Yuan M, Chen R, Chao R, Feng Y. Conversion therapy with tislelizumab for high microsatellite instability, unresectable stage III gastric cancer: a case report. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1489. [PMID: 34734041 PMCID: PMC8506721 DOI: 10.21037/atm-21-4295] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 09/18/2021] [Indexed: 12/20/2022]
Abstract
Gastric cancer (GC) is the fifth-highest ranked cancer for incidence and second for mortality from cancer worldwide. Conversion therapy has recently emerged as an alternative therapy for advanced/metastatic GC patients who are unable to undergo surgical resection at the time of diagnosis. Herein, we present the case of a patient with unresectable stage III GC of high microsatellite instability (MSI), high tumor mutation burden (TMB), and Epstein-Barr virus (EBV) positive. The patient received conversion therapy involving a combination of chemotherapy and immunotherapy regimens. After 3 courses of chemotherapy combined with tislelizumab, the patient underwent laparoscopic radical total gastrectomy. The pathological examination demonstrated that there was no cancerous tissue at the proximal or distal end of the tumor and no lymph node metastases in the lesser or greater curvature, indicating a pathologic complete response. Thereafter, the patient continued tislelizumab treatment to prevent postoperative carcinoma recurrence and metastasis, and to improve prognosis. In conclusion, our study confirmed that chemotherapy combined with immunotherapy is a promising conversion therapy for GC patients with locally unresectable lesions or distant lymph node metastasis, and these findings warrant large-scale clinical studies. This report highlights the clinical importance of next-generation sequencing technology in investigating therapeutic strategy to provide the maximal clinical benefit for patients with GC.
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Affiliation(s)
- Dan Jian
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Chengyuan Qian
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Dong Wang
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Qiang Ma
- Department of Pathology, Daping Hospital, Army Medical University, Chongqing, China
| | - Li Wang
- Department of Gastric & Colorectal Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Chunxue Li
- Department of Gastric & Colorectal Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Mingfang Xu
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Nan Dai
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Qian Chen
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | - Juan He
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
| | | | | | | | - Rui Chao
- Department of Orthopaedic Surgery, Chongqing Emergency Medical Center, The Fourth People's Hospital of Chongqing, Chongqing University Central Hospital, Chongqing, China
| | - Yan Feng
- Cancer Center, Daping Hospital, Army Medical University, Chongqing, China
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Zhang H, Wu J, Yuan J, Li H, Zhang Y, Wu W, Chen W, Wang C, Meng S, Chen S, Huo M, He Y, Zhang C. Ethaselen synergizes with oxaliplatin in tumor growth inhibition by inducing ROS production and inhibiting TrxR1 activity in gastric cancer. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:260. [PMID: 34412665 PMCID: PMC8375208 DOI: 10.1186/s13046-021-02052-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 02/07/2021] [Indexed: 12/23/2022]
Abstract
Background Oxaliplatin is one of the most commonly used chemotherapeutic agent for the treatment of various cancers, including gastric cancer. It has, however, a narrow therapeutic index due to its toxicity and the occurrence of drug resistance. Hence, it is of great significance to develop novel therapies to potentiate the anti-tumor effect and reduce the toxicity of oxaliplatin. In our previous study, we demonstrated that ethaselen (BBSKE), an inhibitor of thioredoxin reductase, effectively inhibited the growth of gastric cancer cells and promoted apoptosis in vitro. In the present study, we investigated whether BBSKE can potentiate the anti-tumor effect of oxaliplatin in gastric cancer in vivo and vitro. Methods Cellular apoptosis and ROS levels were analyzed by flow cytometry. Thioredoxin reductase 1 (TrxR1) activity in gastric cancer cells, organoid and tumor tissues was determined by using the endpoint insulin reduction assay. Western blot was used to analyze the expressions of the indicated proteins. Nude mice xenograft models were used to test the effects of BBSKE and oxaliplatin combinations on gastric cancer cell growth in vivo. In addition, we also used the combined treatment of BBSKE and oxaliplatin in three cases of gastric cancer Patient-Derived organoid (GC-PDO) to detect the anti-tumor effect. Results We found that BBSKE significantly enhanced oxaliplatin-induced growth inhibition in gastric cancer cells by inhibiting TrxR1 activity. Because of the inhibition of TrxR1 activity, BBSKE synergized with oxaliplatin to enhance the production of ROS and activate p38 and JNK signaling pathways which eventually induced apoptosis of gastric cancer cells. In vivo, we also found that BBSKE synergized with oxaliplatin to suppress the gastric cancer tumor growth in xenograft nude mice model, accompanied by the reduced TrxR1 activity. Remarkably, we found that BBSKE attenuated body weight loss evoked by oxaliplatin treatment. We also used three cases of GC-PDO and found that the combined treatment of BBSKE and oxaliplatin dramatically inhibited the growth and viability of GC-PDO with increased ROS level, decreased TrxR1 activity and enhanced apoptosis. Conclusions This study elucidates the underlying mechanisms of synergistic effect of BBSKE and oxaliplatin, and suggests that the combined treatment has potential value in gastric cancer therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-02052-z.
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Affiliation(s)
- Haiyong Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Jing Wu
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
| | - Jinqiu Yuan
- Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
| | - Huafu Li
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Yawei Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Wang Wu
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Wei Chen
- Department of Pathology, The Seventh Affiliated Hospital, Sun Yat-Sen University, 518107, Shenzhen, Guangdong, China
| | - Chunming Wang
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China
| | - Sijun Meng
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
| | - Songyao Chen
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China
| | - Mingyu Huo
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China.
| | - Yulong He
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China. .,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
| | - Changhua Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital, Sun Yat-sen University, 518107, Shenzhen, Guangdong, China. .,Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China.
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Chen Y, Yang YC, Tang LY, Ge QM, Shi WQ, Su T, Shu HY, Pan YC, Liang RB, Li QY, Shao Y. Risk Factors and Their Diagnostic Values for Ocular Metastases in Gastric Adenocarcinoma. Cancer Manag Res 2021; 13:5835-5843. [PMID: 34326667 PMCID: PMC8315769 DOI: 10.2147/cmar.s311474] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 05/24/2021] [Indexed: 11/30/2022] Open
Abstract
Objective Gastric adenocarcinoma originates from the glands in the superficial layer or mucosa of the stomach. It is prone to metastases, of which ocular metastasis (OM) is rare, but once it occurs the disease is considered more serious. The aim of this study was to investigate the risk factors for OM in gastric adenocarcinoma. Methods Patients with gastric adenocarcinoma were recruited to this study between June 2003 and July 2019. Demographic data and serological indicators (SI) were compared between patients with and without OM, and binary logistic regression was used to explore whether the relevant SI may be risk factors for OM of gastric adenocarcinoma. Receiver operating characteristic (ROC) curves were used to analyze different SIs for OM in gastric cancer patients. Results Chi-square tests showed significant between-groups difference in gender composition (P < 0.05), but not in age or histological grade (P > 0.05). t-test results showed that low-density lipoprotein (LDL) and carbohydrate antigen-724 (CA724) were significantly higher in patients with than without OM (P < 0.05). Binary logistic regression analysis showed that LDL was an independent risk factor for OM (P < 0.001). ROC curve analysis showed that the areas under the curves (AUC) for LDL and CA724 were 0.903 and 0.913 respectively, with higher AUC for combined LDL and CA724 (0.934; P < 0.001). Conclusion LDL and CA724 have value as predictors for OM in patients with gastric adenocarcinoma, with higher predictive value when these factors are combined.
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Affiliation(s)
- Yue Chen
- Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People's Republic of China
| | - Yan-Chang Yang
- Department of Anesthesiology, Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Li-Ying Tang
- Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, 361102, People's Republic of China
| | - Qian-Min Ge
- Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Wen-Qing Shi
- Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People's Republic of China.,Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Ting Su
- Department of Ophthalmology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian Province, 361102, People's Republic of China.,Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, 02114, USA
| | - Hui-Ye Shu
- Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People's Republic of China.,Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Yi-Cong Pan
- Department of Dermatology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangzhou, 518033, People's Republic of China.,Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Rong-Bin Liang
- Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Qiu-Yu Li
- Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
| | - Yi Shao
- Department of Geriatric Medicine and Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People's Republic of China
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Wu J, Xu S, Li W, Lu Y, Zhou Y, Xie M, Luo Y, Cao Y, He Y, Zeng T, Ling H. lncRNAs as Hallmarks for Individualized Treatment of Gastric Cancer. Anticancer Agents Med Chem 2021; 22:1440-1457. [PMID: 34229588 DOI: 10.2174/1871520621666210706113102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 04/16/2021] [Accepted: 04/18/2021] [Indexed: 11/22/2022]
Abstract
Gastric cancer is global cancer with a high mortality rate. A growing number of studies have found the abnormal expression of lncRNA (long noncoding RNA) in many tumors, which plays a role in promoting or inhibiting cancer. Similarly, lncRNA abnormal expression plays an essential biological function in gastric cancer. This article focuses on lncRNA involvement in the development of gastric cancer in terms of cell cycle disorder, apoptosis inhibition, metabolic remodeling, promotion of tumor inflammation, immune escape, induction of angiogenesis, and epithelial mesenchymal transition (EMT). The involvement of lncRNA in the development of gastric cancer is related to drug resistance, such as cisplatin and multi-drug resistance. It can also be used as a potential marker for the diagnosis and prognosis of gastric cancer and a target for the treatment. With an in-depth understanding of the mechanism of lncRNA in gastric cancer, new ideas for personalized treatment of gastric cancer are expected.
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Affiliation(s)
- Jing Wu
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Shan Xu
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Wei Li
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yuru Lu
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yu Zhou
- Shaoyang University, Shaoyang, Hunan 422000, China
| | - Ming Xie
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yichen Luo
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yijing Cao
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Yan He
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
| | - Tiebing Zeng
- Hunan Province Cooperative innovation Center for Molecular Target New Drug Study [Hunan Provincial Education Department document (Approval number: 2014-405], Hengyang, Hunan 421001, China
| | - Hui Ling
- Key Laboratory of Tumor Cellular & Molecular Pathology (University of South China)，College of Hunan Province, Cancer Research Institute, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, China
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Comparison of neoadjuvant chemotherapy followed by surgery vs. surgery alone for locally advanced gastric cancer: a meta-analysis. Chin Med J (Engl) 2021; 134:1669-1680. [PMID: 34397593 PMCID: PMC8318625 DOI: 10.1097/cm9.0000000000001603] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND The neoadjuvant chemotherapy is increasingly used in advanced gastric cancer, but the effects on safety and survival are still controversial. The objective of this meta-analysis was to compare the overall survival and short-term surgical outcomes between neoadjuvant chemotherapy followed by surgery (NACS) and surgery alone (SA) for locally advanced gastric cancer. METHODS Databases (PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar) were explored for relative studies from January 2000 to January 2021. The quality of randomized controlled trials and cohort studies was evaluated using the modified Jadad scoring system and the Newcastle-Ottawa scale, respectively. The Review Manager software (version 5.3) was used to perform this meta-analysis. The overall survival was evaluated as the primary outcome, while perioperative indicators and post-operative complications were evaluated as the secondary outcomes. RESULTS Twenty studies, including 1420 NACS cases and 1942 SA cases, were enrolled. The results showed that there were no significant differences in overall survival (P = 0.240), harvested lymph nodes (P = 0.200), total complications (P = 0.080), and 30-day post-operative mortality (P = 0.490) between the NACS and SA groups. However, the NACS group was associated with a longer operation time (P < 0.0001), a higher R0 resection rate (P = 0.003), less reoperation (P = 0.030), and less anastomotic leakage (P = 0.007) compared with SA group. CONCLUSIONS Compared with SA, NACS was considered safe and feasible for improved R0 resection rate as well as decreased reoperation and anastomotic leakage. While unbenefited overall survival indicated a less important effect of NACS on long-term oncological outcomes.
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Zhai J, Wu J, Wang Y, Fan R, Xie G, Wu F, He Y, Qian S, Tan A, Yao X, He M, Shen L. Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer. Front Cell Dev Biol 2021; 9:680491. [PMID: 34164399 PMCID: PMC8215369 DOI: 10.3389/fcell.2021.680491] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 04/26/2021] [Indexed: 12/27/2022] Open
Abstract
Background Perioperative chemotherapy has been accepted as one of the most common approaches for locally advanced gastric cancer. However, the efficacy of chemotherapy varies among patients, and there is no effective method to predict the chemotherapy efficacy currently. We previously established the first larval zebrafish patient-derived xenografts (zPDXs) of gastric cancer as a platform for the translational research and personalized treatment. The objective of this study was to investigate the feasibility of screening individualized chemotherapeutics using the zPDXs. Methods We further optimized this zPDXs platform including administration route, drug dosing, and rhythm to develop a stable and reliable protocol for chemotherapeutics screening. Using the novel platform, we investigated the chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for gastric cancer patients. Results We showed that the engrafted zebrafish retained the original prominent cell components of the corresponding human tumor tissues, and we successfully obtained the results of chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for 28 patients with locally advanced gastric cancer. These patients underwent radical gastrectomy for curative intent and 27 cases received postoperative adjuvant chemotherapy. We revealed that the chemosensitivity obtained from zPDXs was consistent with the clinical responses in these patients (P = 0.029). More importantly, the responder drug(s) from zPDXs used or not was the only risk factor for early-stage recurrence in these 27 patients (P = 0.003). Conclusion Our study with the largest sample size so far suggests that larval zPDXs help to predict the chemotherapeutics response and to achieve precise chemotherapy for gastric cancer.
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Affiliation(s)
- Jing Zhai
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiaqi Wu
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Yaohui Wang
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Ruoyue Fan
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Guiping Xie
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Fangfang Wu
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Yani He
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Sitong Qian
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Aimin Tan
- Nanjing Amory Biotech Co. Ltd., Nanjing, China
| | - Xuequan Yao
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Mingfang He
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Lizong Shen
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Sato M, Endo K, Harada A, Shijo M. A case of successful conversion surgery for gastric cancer with direct invasion to pancreatic head. J Surg Case Rep 2021; 2021:rjab186. [PMID: 34025973 PMCID: PMC8130874 DOI: 10.1093/jscr/rjab186] [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: 03/26/2021] [Accepted: 04/18/2021] [Indexed: 11/29/2022] Open
Abstract
We experienced the case of successful conversion to distal gastrectomy for gastric cancer with direct invasion to the pancreatic head after the pre-operative chemotherapy. Esophagogastroduodenoscopy in a 66-year-old man revealed a tumor at the gastric antrum. Abdominal computed tomography (CT) showed that the tumor of the antrum was in contact with the pancreatic head. A biopsy of the tumor confirmed an adenocarcinoma and an overexpression of HER2 (3+). Staging laparoscopy showed the direct invasion of the gastric tumor to the pancreatic head. The patient received S-1, oxaliplatin and trastuzumab. After the pre-operative chemotherapy, CT showed a significantly shrinking tumor detached from the pancreatic head. Subsequently, distal gastrectomy was performed. Intra-operative exploration showed that the gastric tumor separated from the pancreatic head. The accumulation of trials for pre-operative chemotherapy for local advanced gastric cancer is expected.
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Affiliation(s)
- Manabu Sato
- Department of Surgery, Shiogama City Hospital, Shiogama, Japan
| | - Koujin Endo
- Department of Surgery, JCHO Sendai South Hospital, Sendai, Japan
| | - Akihiko Harada
- Department of Surgery, JCHO Sendai South Hospital, Sendai, Japan
| | - Masahiro Shijo
- Department of Surgery, JCHO Sendai South Hospital, Sendai, Japan
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Yang F, Yan Z, Nie W, Liu Z, Cheng X, Wang W, Shao C, Fu G, Yu Y. LACTB and LC3 could serve as potential biomarkers of gastric cancer to neoadjuvant chemotherapy with oxaliplatin plus S-1. Oncol Lett 2021; 21:470. [PMID: 33907580 PMCID: PMC8063359 DOI: 10.3892/ol.2021.12731] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 03/17/2021] [Indexed: 01/31/2023] Open
Abstract
The present study investigated and evaluated the correlation between the expression of LACTB and LC3 and the clinical outcomes of patients with advanced gastric cancer treated with oxaliplatin plus S-1 neoadjuvant chemotherapy (NACT). A total of 51 patients with advanced gastric cancer underwent NACT treatment between June 2015 and June 2017. Pathomorphological changes in gastric cancer were analyzed by H&E staining. The expression level and subcellular localization of LACTB and LC3 in paraffin-embedded biopsies were detected by immunohistochemistry and immunofluorescence. The mRNA and protein expression of LACTB were investigated by reverse transcription quantitative polymerase chain reaction and Western blotting, respectively. Statistical analysis was performed to determine the association between the expression of LACTB and LC3 and clinical chemotherapy efficacy of NACT for gastric cancer. Among the 51 patients, 3 (5.88%), 27 (52.94%), 13 (25.49%) and 8 (15.69%) displayed complete remission, partial remission, stable disease and progressive disease, respectively. The rate of decreased LACTB expression was 68.6%, while the rate of increased LC3 expression was 60.8%. Furthermore, there was a significant negative correlation between the expression of LACTB and that of LC3 following NACT (P<0.001). High expression of LC3 (P<0.01) and low expression of LACTB (P<0.01) were associated with a poor response of patients with advanced gastric cancer to NACT. In conclusion, the expression of LACTB and LC3 may serve as a promising novel biomarker for determining the prognosis of patients with advanced gastric cancer receiving NACT, while its potential clinical significance requires further elucidation.
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Affiliation(s)
- Fang Yang
- Department of Pathology, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.,School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China.,Laboratory Department of Guizhou Cancer Hospital, Guiyang, Guizhou 550004, P.R. China
| | - Zhiqiang Yan
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Wei Nie
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Zeying Liu
- Laboratory Department of Guizhou Cancer Hospital, Guiyang, Guizhou 550004, P.R. China
| | - Xingzhen Cheng
- Department of Gastrointestinal Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
| | - Wei Wang
- Laboratory Department of Guizhou Cancer Hospital, Guiyang, Guizhou 550004, P.R. China
| | - Chunyan Shao
- Laboratory Department of Guizhou Cancer Hospital, Guiyang, Guizhou 550004, P.R. China
| | - Gui Fu
- Laboratory Department of Guizhou Cancer Hospital, Guiyang, Guizhou 550004, P.R. China
| | - Yanni Yu
- Department of Pathology, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
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Chen L, Zhou X, Kong X, Su Z, Wang X, Li S, Luo A, Liu Z, Fang Y, Wang J. The Prognostic Significance of Anisomycin-Activated Phospho-c-Jun NH2-Terminal Kinase (p-JNK) in Predicting Breast Cancer Patients' Survival Time. Front Cell Dev Biol 2021; 9:656693. [PMID: 33768099 PMCID: PMC7985183 DOI: 10.3389/fcell.2021.656693] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 02/15/2021] [Indexed: 12/24/2022] Open
Abstract
This study aims to investigate the prognostic significance of p-JNK in breast cancer patients receiving neoadjuvant chemotherapy (NACT) and analyze the relationship between anisomycin, p-JNK. A total of 104 breast cancer patients had NACT were enrolled in this study. The western blot and immunohistochemistry assays were used to determine the protein expressions of p-JNK in human breast cancer cell lines and patients’ cancer tissues. The chi-square test and Fisher’s exact test were adopted to gauge the associations between breast cancer and clinicopathological variables by p-JNK expression, whereas the univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of p-JNK expression. The Kaplan-Meier plots and the log-rank test were adopted to determine patients’ disease-free survival (DFS) and overall survival (OS). Findings indicated that the p-JNK expression had prognostic significance in univariate and multivariate Cox regression survival analyses. Results of log-rank methods showed that: (1) the mean DFS and OS times in patients with high p-JNK expression were significantly longer than those in patients with low p-JNK expression (χ2 = 5.908, P = 0.015 and χ2 = 6.593, P = 0.010, respectively). p-JNK expression is a significant prognostic factor that can effectively predict the survival in breast cancer patients receiving NACT. Treatment with the JNK agonist anisomycin can induce apoptosis, lead to increased p-JNK expression and decreased p-STAT3 expression. Moreover, the p-JNK expression was inversely correlated with p-STAT3 expression.
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Affiliation(s)
- Li Chen
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuantong Zhou
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiangyi Kong
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhaohui Su
- Center on Smart and Connected Health Technologies, Mays Cancer Center, School of Nursing, UT Health San Antonio, San Antonio, TX, United States
| | - Xiangyu Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sen Li
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
| | - Aiping Luo
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhihua Liu
- State Key Lab of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yi Fang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Wang
- Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Huang J, Yao H, Li Y, Dong M, Han C, He L, Huang X, Xia T, Yi Z, Wang H, Zhang Y, He J, Liang C, Liu Z. Development and validation of a CT-based radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma. Chin J Cancer Res 2021; 33:69-78. [PMID: 33707930 PMCID: PMC7941693 DOI: 10.21147/j.issn.1000-9604.2021.01.08] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/22/2020] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES To develop and validate a radiomics nomogram for preoperative prediction of tumor histologic grade in gastric adenocarcinoma (GA). METHODS This retrospective study enrolled 592 patients with clinicopathologically confirmed GA (low-grade: n=154; high-grade: n=438) from January 2008 to March 2018 who were divided into training (n=450) and validation (n=142) sets according to the time of computed tomography (CT) examination. Radiomic features were extracted from the portal venous phase CT images. The Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) regression model were used for feature selection, data dimension reduction and radiomics signature construction. Multivariable logistic regression analysis was applied to develop the prediction model. The radiomics signature and independent clinicopathologic risk factors were incorporated and presented as a radiomics nomogram. The performance of the nomogram was assessed with respect to its calibration and discrimination. RESULTS A radiomics signature containing 12 selected features was significantly associated with the histologic grade of GA (P<0.001 for both training and validation sets). A nomogram including the radiomics signature and tumor location as predictors was developed. The model showed both good calibration and good discrimination, in which C-index in the training set, 0.752 [95% confidence interval (95% CI): 0.701-0.803]; C-index in the validation set, 0.793 (95% CI: 0.711-0.874). CONCLUSIONS This study developed a radiomics nomogram that incorporates tumor location and radiomics signatures, which can be useful in facilitating preoperative individualized prediction of histologic grade of GA.
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Affiliation(s)
- Jia Huang
- Graduate College, Shantou University Medical College, Shantou 515041, China
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Huasheng Yao
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- School of Automation Science and Engineering, South China University of Technology, Guangzhou 510006, China
| | - Yexing Li
- Graduate College, Shantou University Medical College, Shantou 515041, China
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Mengyi Dong
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- Graduate College, Southern Medical University, Guangzhou 510515, China
| | - Chu Han
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Lan He
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Xiaomei Huang
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- Graduate College, Southern Medical University, Guangzhou 510515, China
| | - Ting Xia
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- School of Medicine, South China University of Technology, Guangzhou 510006, China
| | - Zongjian Yi
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou 510006, China
| | - Huihui Wang
- Graduate College, Shantou University Medical College, Shantou 515041, China
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Yuan Zhang
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- Graduate College, Southern Medical University, Guangzhou 510515, China
| | - Jian He
- Graduate College, Shantou University Medical College, Shantou 515041, China
- Department of Interventional Radiology, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Changhong Liang
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Zaiyi Liu
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- Zaiyi Liu, PhD. Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
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Meng Q, Tan S, Jiang Y, Han J, Xi Q, Zhuang Q, Wu G. Post-discharge oral nutritional supplements with dietary advice in patients at nutritional risk after surgery for gastric cancer: A randomized clinical trial. Clin Nutr 2021; 40:40-46. [DOI: 10.1016/j.clnu.2020.04.043] [Citation(s) in RCA: 79] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 04/21/2020] [Accepted: 04/27/2020] [Indexed: 02/06/2023]
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Meng Y, Huang X, Liu J, Chen J, Bu Z, Wu G, Xie W, Jeen F, Huang L, Tian C, Mo X, Tang W. A Novel Nomogram for Individually Predicting of Vascular Invasion in Gastric Cancer. Technol Cancer Res Treat 2021; 20:15330338211004924. [PMID: 33929914 PMCID: PMC8111553 DOI: 10.1177/15330338211004924] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 01/22/2021] [Accepted: 02/25/2021] [Indexed: 02/03/2023] Open
Abstract
PURPOSE Vascular invasion (VI) is associated with recurrence and is an indicator of poor prognosis in gastric cancer (GC). Pre-operative identification of VI may guide the selection of the optimal surgical approach and assess the requirement for neoadjuvant therapy. METHODS A total of 271 patients were retrospectively collected and randomly allocated into the training and validation datasets. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features, and multivariable logistic regression analysis was used to develop the nomogram. RESULTS The nomogram consisted of pre-operative serum complement C3 levels, duration of symptoms, pre-operative computed tomography stage, abdominal distension and undifferentiated carcinoma. The nomogram provided good calibration for both the training and the validation set, with area under the curve values of 0.792 and 0.774. Decision curve analysis revealed that the nomogram was clinically useful. CONCLUSION The present study constructed a nomogram for the pre-operative prediction of VI in patients with GC. The nomogram may aid the identification of high-risk patients and aid the optimization of pre-operative decision-making.
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Affiliation(s)
- Yongsheng Meng
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Xiaoliang Huang
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Jungang Liu
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Jianhong Chen
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Zhaoting Bu
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Guo Wu
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Weishun Xie
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Franco Jeen
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Lingxu Huang
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Chao Tian
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Xianwei Mo
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Weizhong Tang
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
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Wang N, Yu PJ, Liu ZL, Zhu SM, Zhang CW. Malignant acanthosis nigricans with Leser–Trélat sign and tripe palms: A case report. World J Clin Cases 2020; 8:5632-5638. [PMID: 33344554 PMCID: PMC7716325 DOI: 10.12998/wjcc.v8.i22.5632] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 08/17/2020] [Accepted: 10/13/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Acanthosis nigricans (AN), Leser–Trélat sign, and tripe palm are all skin diseases. To date, reports of these appearing as a paraneoplastic syndrome in a gastric cancer patient are quite rare.
CASE SUMMARY We report the case of a 61-year-old man with darkened skin color in the face and torso with no obvious inducement after 1 year of treatment for Riehl’s melanosis. He had 40 brown maculopapular eruptions on his face and the top of his head with obvious itching. Papillary wart-like hyperkeratosis with dark brown pigmentation was also observed on both sides of the areola. He had papilloma-like lesions on the face, around the orbit, and on the neck. His bilateral palms had small, smooth, papillary projections with millet-like appearance. Histopathological examination of the skin showed that the patient was suffering from AN, tripe palms, and Leser–Trélat sign. Gastroscopy showed the patient’s cardia was affected, and pathological biopsy revealed that he had moderate-to-poorly differentiated adenocarcinoma. Computed tomography test results showed that his cardia wall had thickened. Based on these histological and skin characteristics, the patient was diagnosed with gastric cancer with AN, tripe palms, and Leser–Trélat sign.
CONCLUSION Researchers should follow up on patients with malignant AN, Leser–Trélat sign, and tripe palms.
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Affiliation(s)
- Ning Wang
- Graduate School, Qinghai University, Xining 810016, Qinghai Province, China
| | - Peng-Jie Yu
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Zhi-Lin Liu
- Graduate School, Qinghai University, Xining 810016, Qinghai Province, China
| | - Sheng-Mao Zhu
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Cheng-Wu Zhang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Qinghai University, Xining 810000, Qinghai Province, China
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Tang S, Liu F, Li Y, Zhao L, Wang X, Khan SA, Chen Y, Zhang Y. Treatment Selection and Survival Outcomes in Locally Advanced Proximal Gastric Cancer: A National Cancer Data Base Analysis. Front Oncol 2020; 10:537051. [PMID: 33102212 PMCID: PMC7546198 DOI: 10.3389/fonc.2020.537051] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 08/26/2020] [Indexed: 12/16/2022] Open
Abstract
Background: We aimed to assess long-term survival between locally advanced proximal gastric cancer (LAPGC) patients who underwent proximal gastrectomy (PG) and those who underwent total gastrectomy (TG) to evaluate the optimal extent of resection and adjuvant therapy. Materials and Methods: Patients diagnosed with locally advanced proximal gastric adenocarcinoma were selected from the National Cancer Data Base (2004–2015) in America. Survival analysis was performed via Kaplan-Meier and Cox proportional hazards models. Results: A total of 4,381 eligible patients were identified, 1,243 underwent PG and 3,138 underwent TG. Patients in TG group had a poor prognosis (hazard ratio [HR] = 1.13, 95% confidence interval [CI]: 1.03–1.25) compared with those in PG group. Moreover, postoperative chemoradiation therapy was associated with improved overall survival compared to surgery alone (HR = 0.71, 95% CI: 0.53–0.97) in LAPGC patients who had PG, while preoperative chemotherapy (HR = 0.74, 95% CI: 0.59–0.92) was associated with improved survival among patients who had TG. Conclusions: Our study suggested that LAPGC patients underwent PG experienced better long-term outcomes than those underwent TG. It also suggested that multimodality treatment of LAPGC, including preoperative chemotherapy followed by TG or postoperative chemotherapy followed by PG, should be considered to achieve better long-term outcomes.
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Affiliation(s)
- Song Tang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Lanzhou University Second Hospital, Lanzhou, China
| | - Fangfang Liu
- Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yumin Li
- Lanzhou University Second Hospital, Lanzhou, China
| | - Lulu Zhao
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiang Wang
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Lanzhou University Second Hospital, Lanzhou, China
| | - Sajid A Khan
- Department of Surgery, Yale School of Medicine, New Haven, CT, United States
| | - Yingtai Chen
- National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yawei Zhang
- Department of Surgery, Yale School of Medicine, New Haven, CT, United States.,Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT, United States
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Ning K, Shao Y, He Y, Wang F, Cui X, Liu F, Li D, Li F. Histone demethylase Jumonji domain-containing 1A inhibits proliferation and progression of gastric cancer by upregulating runt-related transcription factor 3. Cancer Sci 2020; 111:3679-3692. [PMID: 32762126 PMCID: PMC7541000 DOI: 10.1111/cas.14594] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 07/22/2020] [Accepted: 07/26/2020] [Indexed: 12/24/2022] Open
Abstract
The histone demethylase Jumonji domain‐containing 1A (JMJD1A) is overexpressed in multiple cancers and promotes cancer progression. However, the role and mechanism of JMJD1A in gastric cancer (GC) remains poorly understood. Here, we found that JMJD1A could suppress GC cell proliferation and xenograft tumor growth. Using RNA sequencing, we identified runt‐related transcription factor 3 (RUNX3) as a novel target gene of JMJD1A. Mechanistically, we identified that JMJD1A upregulated RUNX3 through co–activating Ets‐1 and reducing the H3K9me1/2 levels at the RUNX3 promoter in GC cells. Functionally, JMJD1A inhibits the growth of GC cells in vivo, which is partially dependent on RUNX3. Moreover, JMJD1A expression was decreased in GC and low expression of JMJD1A was correlated with an aggressive phenotype and a poor prognosis in patients with GC. Importantly, JMJD1A expression was positively associated with RUNX3 expression in GC samples. These studies indicated that JMJD1A upregulates RUNX3 expression via co–activation of transcription factor Ets‐1 to inhibit proliferation of GC cells. Our findings provide new insight into the mechanism by which JMJD1A regulates RUNX3 transcription and suggest that JMJD1A and/or RUNX3 may be used as a therapeutic intervention for GC.
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Affiliation(s)
- Ke Ning
- Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, Shenyang, China.,Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, Shenyang, China
| | - Yangguang Shao
- Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, Shenyang, China.,Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, Shenyang, China
| | - Yuxin He
- Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, Shenyang, China.,Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, Shenyang, China
| | - Fei Wang
- Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, Shenyang, China.,Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, Shenyang, China
| | - Xi Cui
- Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, Shenyang, China.,Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, Shenyang, China
| | - Furong Liu
- Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, Shenyang, China.,Key Laboratory of Medical Cell Biology, Ministry of Education of the PRC, China Medical University, Shenyang, China
| | - Danni Li
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Feng Li
- Department of Cell Biology, Key Laboratory of Cell Biology, National Health Commission of the PRC, Shenyang, China
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Zhang Z, Li B, Huang J, Huang S, He D, Peng W, Zhang S. A Network Pharmacology Analysis of the Active Components of the Traditional Chinese Medicine Zuojinwan in Patients with Gastric Cancer. Med Sci Monit 2020; 26:e923327. [PMID: 32866138 PMCID: PMC7482508 DOI: 10.12659/msm.923327] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Zuojinwan (ZJW) is a traditional Chinese prescription normally used for gastritis. Several studies indicated that it could fight against gastric cancer. This study was designed to determine the potential pharmacological mechanism of ZJW in the treatment of gastric cancer. MATERIAL AND METHODS Bioactive compounds and potential targets of ZJW and related genes of gastric cancer were retrieved from public databases. Pharmacological mechanisms including crucial ingredients, potential targets, and signaling pathways were determined using protein-protein interaction (PPI) and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Virtual docking was performed to validate the findings. RESULTS Network analysis identified 47 active ZJW compounds, and 48 potential ZJW target genes linked to gastric cancer. Quercetin, beta-sitosterol, isorhamnetin, wogonin, and baicalein were identified as potential candidate agents. Our PPI analysis results combined with previously published results indicated that matrix metalloproteinases family members MMP9, MMP1, and MMP3 may play key roles in the anti-gastric cancer effect of ZJW. Molecular docking analysis showed that these crucial targets had good affinity for the representative components in ZJW. GO and KEGG enrichment analysis showed that ZJW target genes functioned in multiple pathways for treating gastric cancer, including interleukin-17 signaling and platinum drug resistance. CONCLUSIONS Our results illuminate the active ingredients, associated targets, biological processes, and signaling pathways of ZJW in the treatment of gastric cancer. This study enhances our understanding of the potential effects of ZJW in gastric cancer and demonstrates a feasible method for discovering potential drugs from Chinese medicinal formulas.
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Affiliation(s)
- Zheyu Zhang
- Department of Integrated Traditional Chinese and Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
| | - Bin Li
- Department of Gastroenterology, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China (mainland)
| | - Jianhua Huang
- Hunan Academy of Chinese Medicine, Changsha, Hunan, China (mainland)
| | - Siqi Huang
- Department of Integrated Traditional Chinese and Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
| | - Dan He
- Hunan Academy of Chinese Medicine, Changsha, Hunan, China (mainland)
| | - Weijun Peng
- Department of Integrated Traditional Chinese and Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
| | - Sifang Zhang
- Department of Integrated Traditional Chinese and Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China (mainland)
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The Predictive and Prognostic Factors in Patients with Gastric Cancer Accompanied by Gastric Outlet Obstruction. Gastroenterol Res Pract 2020; 2020:6529563. [PMID: 32774358 PMCID: PMC7397385 DOI: 10.1155/2020/6529563] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Accepted: 05/16/2020] [Indexed: 12/29/2022] Open
Abstract
Purpose This study is aimed at evaluating the clinicopathological features and prognostic significance of gastric outlet obstruction (GOO) in patients with distal gastric cancer. Methods A retrospective review of 1564 individuals with distal gastric cancer from 2002 to 2010 was performed. In total, 157 patients had GOO. The clinicopathological features of the patients with GOO were compared with those of the patients without GOO. A Kaplan-Meier survival analysis and Cox proportional hazard model were used to assess the overall survival. Results The patients with distal gastric cancer with GOO generally presented more aggressive pathologic features, a poorer nutritional status, more duodenal infiltration, and peritoneal dissemination than those with cancer without GOO. In the univariate analysis, curability, GOO, age, prealbumin, albumin, hemoglobin (Hb), the tumor size, the macroscopic type, lymph node metastasis, and the depth of invasion had a statistically significant influence on prognosis. The multivariate analysis showed that curability, GOO, the tumor size, lymph node metastasis, and the depth of invasion were independent prognostic factors. Conclusions Gastric cancer with GOO exhibits aggressive biological features and has poor outcomes. The multivariate analysis showed that curability, GOO, the tumor size, lymph node metastasis, and the depth of invasion were independent prognostic factors. The gastric outlet status should be considered in the selection of surgical treatment methods for patients with gastric cancer.
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Ma F, Wang B, Xue L, Kang W, Li Y, Li W, Liu H, Ma S, Tian Y. Neoadjuvant chemotherapy improves the survival of patients with neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma of the stomach. J Cancer Res Clin Oncol 2020; 146:2135-2142. [PMID: 32306127 DOI: 10.1007/s00432-020-03214-w] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 04/07/2020] [Indexed: 12/15/2022]
Abstract
PURPOSE The impact of neoadjuvant chemotherapy (NAC) on patients with neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) of the stomach is unclear. The aim of this retrospective study was to evaluate the effects of NAC on patients with these conditions. METHODS This study included patients with locally advanced NEC or MANEC of the stomach who underwent gastrectomy. Histologic and prognostic effects of NAC were assessed. The overall survival (OS) rate was used to compare treatment efficacies between NAC patients and surgery-first patients. RESULTS Of the 69 patients included in this study, 20 received NAC and 49 underwent surgery first after diagnosis. A total of 13 patients responded to NAC (including 3 with complete remission and 10 with partial remission) and 7 patients acquired stable disease status according to the Response Evaluation Criteria in Solid Tumors version 1.1. One patient (5%) achieved a pathological complete response after NAC. Pathological tumor regression grades 1, 2, 3, 4, and 5 were observed in 1 (5%), 5 (25%), 3 (15%), 10 (50%), and 1 (5%) patient(s) with NAC, respectively. The incidence of postoperative complications was similar in the two groups. Patients in the NAC group demonstrated better OS than did patients in the surgery-first group (P = 0.032). Multivariate analyses showed that NAC, adjuvant chemotherapy, and the clinical N stage were independent factors affecting OS. CONCLUSION In patients with locally advanced NEC and MANEC of the stomach, NAC significantly improved OS.
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Affiliation(s)
- Fuhai Ma
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Bingzhi Wang
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Liyan Xue
- Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Wenzhe Kang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Yang Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Weikun Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Hao Liu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Shuai Ma
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China
| | - Yantao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China.
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Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies. Int J Mol Sci 2020; 21:4012. [PMID: 32512697 PMCID: PMC7312039 DOI: 10.3390/ijms21114012] [Citation(s) in RCA: 820] [Impact Index Per Article: 164.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 05/31/2020] [Accepted: 06/01/2020] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.
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Affiliation(s)
- Julita Machlowska
- Center for Medical Genomics OMICRON, Jagiellonian University Medical College, 31-034 Kraków, Poland;
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Jacek Baj
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Monika Sitarz
- Department of Conservative Dentistry with Endodontics, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Ryszard Maciejewski
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
| | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (J.B.); (R.M.)
- Department of Surgery, Center of Oncology of the Lublin Region St. Jana z Dukli, 20-090 Lublin, Poland
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