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Kabatnik S, Zheng X, Pappas G, Steigerwald S, Padula MP, Mann M. Deep visual proteomics reveals DNA replication stress as a hallmark of signet ring cell carcinoma. NPJ Precis Oncol 2025; 9:37. [PMID: 39910169 PMCID: PMC11799539 DOI: 10.1038/s41698-025-00819-7] [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: 07/22/2024] [Accepted: 01/17/2025] [Indexed: 02/07/2025] Open
Abstract
Signet Ring Cell Carcinoma (SRCC) is a rare and highly malignant form of adenocarcinoma with increasing incidence and poor prognosis due to late diagnosis and limited treatment options. We employed Deep Visual Proteomics (DVP), which combines AI-directed cell segmentation and classification with laser microdissection and ultra-high sensitivity mass spectrometry, for cell-type-specific proteomic analysis of SRCC across the bladder, prostate, seminal vesicle, and a lymph node of a single patient. DVP identified significant alterations in DNA damage response (DDR) proteins, particularly within the ATR and mismatch repair (MMR) pathways, indicating replication stress as a crucial factor in SRCC mutagenicity. Additionally, we observed substantial enrichment of immune-related proteins, reflecting high levels of cytotoxic T lymphocyte infiltration and elevated PD-1 expression. These findings suggest that pembrolizumab immunotherapy may be more effective than conventional chemotherapy for this patient. Our results provide novel insights into the proteomic landscape of SRCC, identify potential targets, and open up for personalized therapeutic strategies in managing SRCC.
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Affiliation(s)
- Sonja Kabatnik
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
| | - Xiang Zheng
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Georgios Pappas
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
| | - Sophia Steigerwald
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany
| | - Matthew P Padula
- School of Life Sciences and Proteomics Core Facility, Faculty of Science, University of Technology Sydney, Ultimo, Australia.
| | - Matthias Mann
- Novo Nordisk Foundation Center for Protein Research, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.
- Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
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Su P, Jiang L, Zhang Y, Yu T, Huang H, Chen M, Cao C, Kang W, Liu Y, Yu J. Perioperative chemotherapy versus adjuvant chemotherapy treatment for resectable locally advanced gastric cancer: a retrospective cohort study. Eur J Med Res 2023; 28:409. [PMID: 37814327 PMCID: PMC10563233 DOI: 10.1186/s40001-023-01400-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 09/27/2023] [Indexed: 10/11/2023] Open
Abstract
BACKGROUND Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced gastric cancer (LAGC), but the clinical safety and efficacy are still controversial. This study aims to compare perioperative chemotherapy (PEC) with adjuvant chemotherapy (AC) for resectable LAGC. METHODS Patients who underwent D2 gastrectomy for resectable LAGC were retrospectively reviewed, and divided into NSA group (NAC plus surgery and AC) and SA group (surgery followed by AC). The baseline characteristics and perioperative data were compared. Survival analysis was based on Kaplan-Meier method. Multivariate analyses for prognostic factors were based on the Cox regression. RESULTS A total of 450 patients were eligible for this study. 218 patients received NAC plus surgery and AC, while 232 upfront surgery followed by AC. The baseline characteristics were comparable between the two groups. NSA group showed significant superiority in R0 resection rate (P = 0.014), excised tumor size (P = 0.038), and tumor downstage (all P < 0.001). NAC did not affect postoperative complications or AC-related grade 3/4 adverse events. Patients in NSA group achieved significantly longer OS (P = 0.021) and DFS (P = 0.002). The Cox regression model showed that NAC was independently associated with better OS (HR 0.245, P = 0.039) and DFS (HR 0.591, P = 0.031). CONCLUSIONS Compared with SA, the administration of NSA was considered safe and feasible for achieving higher R0 resection rate without increasing the postoperative complications or AC-related grade 3/4 adverse events, and NAC was independently associated with better OS and DFS for resectable LAGC.
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Affiliation(s)
- Pengfei Su
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Lin Jiang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Yingjing Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Tian Yu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Hongyun Huang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Moxi Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Can Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Weiming Kang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Yuqin Liu
- Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China
| | - Jianchun Yu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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Aiolfi A, Sozzi A, Bonitta G, Lombardo F, Cavalli M, Campanelli G, Bonavina L, Bona D. Short-term outcomes of different esophagojejunal anastomotic techniques during laparoscopic total gastrectomy: a network meta-analysis. Surg Endosc 2023:10.1007/s00464-023-10231-6. [PMID: 37400689 DOI: 10.1007/s00464-023-10231-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 06/17/2023] [Indexed: 07/05/2023]
Abstract
BACKGROUND Different techniques have been described for esophagojejunostomy (EJ) during laparoscopic total gastrectomy (LTG) for gastric cancer. Linear stapled techniques include overlap (OL) and functional end-to-end anastomosis (FEEA) while single staple technique (SST), hemi-double staple technique (HDST), and OrVil® are circular stapled approaches. Nowadays, the choice among techniques for EJ depends on operating surgeon personal preference. PURPOSE To compare short-term outcomes of different EJ techniques during LTG. METHODS Systematic review and network meta-analysis. OL, FEEA, SST, HDST, and OrVil® were compared. Primary outcomes were anastomotic leak (AL) and stenosis (AS). Risk ratio (RR) and weighted mean difference (WMD) were used as pooled effect size measures, whereas 95% credible intervals (CrI) were used to measure relative inference. RESULTS Overall, 3177 patients (20 studies) were included. The technique for EJ was SST (n = 1026; 32.9%), OL (n = 826; 26.5%), FEEA (n = 752; 24.1%), OrVil® (n = 317; 10.1%), and HDST (n = 196; 6.4%). AL was comparable for OL vs. FEEA (RR = 0.82; 95% CrI 0.47-1.49), OL vs. SST (RR = 0.55; 95% CrI 0.27-1.21), OL vs. OrVil® (RR = 0.54; 95% CrI 0.32-1.22), and OL vs. HDST (RR = 0.65; 95% CrI 0.28-1.63). Similarly, AS was similar for OL vs. FEEA (RR = 0.46; 95% CrI 0.18-1.28), OL vs. SST (RR = 0.89; 95% CrI 0.39-2.15), OL vs. OrVil® (RR = 0.36; 95% CrI 0.14-1.02), and OL vs. HDST (RR = 0.61; 95% CrI 0.31-1.21). Anastomotic bleeding, time to soft diet resumption, pulmonary complications, hospital length of stay, and mortality were comparable while operative time was reduced for FEEA. CONCLUSIONS This network meta-analysis shows similar postoperative AL and AS risk when comparing OL, FEEA, SST, HDST, and OrVil® techniques. Similarly, no differences were found for anastomotic bleeding, operative time, soft diet resumption, pulmonary complications, hospital length of stay and 30-day mortality.
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Affiliation(s)
- Alberto Aiolfi
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio Hospital, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Via C. Belgioioso n.173, 20151, Milan, Italy.
| | - Andrea Sozzi
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio Hospital, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Via C. Belgioioso n.173, 20151, Milan, Italy
| | - Gianluca Bonitta
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio Hospital, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Via C. Belgioioso n.173, 20151, Milan, Italy
| | - Francesca Lombardo
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio Hospital, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Via C. Belgioioso n.173, 20151, Milan, Italy
| | - Marta Cavalli
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio Hospital, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Via C. Belgioioso n.173, 20151, Milan, Italy
| | - Giampiero Campanelli
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio Hospital, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Via C. Belgioioso n.173, 20151, Milan, Italy
| | - Luigi Bonavina
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio Hospital, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Via C. Belgioioso n.173, 20151, Milan, Italy
| | - Davide Bona
- I.R.C.C.S. Ospedale Galeazzi - Sant'Ambrogio Hospital, Division of General Surgery, Department of Biomedical Science for Health, University of Milan, Via C. Belgioioso n.173, 20151, Milan, Italy
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Wang M, Yang G, Tian Y, Zhang Q, Liu Z, Xin Y. The role of the gut microbiota in gastric cancer: the immunoregulation and immunotherapy. Front Immunol 2023; 14:1183331. [PMID: 37457738 PMCID: PMC10348752 DOI: 10.3389/fimmu.2023.1183331] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 05/11/2023] [Indexed: 07/18/2023] Open
Abstract
Gastric cancer (GC) is one of the most common cancers, leading to the deaths of millions of people worldwide. Therefore, early detection and effective therapeutic strategies are of great value for decreasing the occurrence of advanced GC. The human microbiota is involved not only in the maintenance of physiological conditions, but also in human diseases such as obesity, diabetes, allergic and atopic diseases, and cancer. Currently, the composition of the bacteria in the host, their functions, and their influence on disease progression and treatment are being discussed. Previous studies on the gut microbiome have mostly focused on Helicobacter pylori (Hp) owing to its significant role in the development of GC. Nevertheless, the enrichment and diversity of other bacteria that can modulate the tumor microenvironment are involved in the progression of GC and the efficacy of immunotherapy. This review provides systematic insight into the components of the gut microbiota and their application in GC, including the specific bacteria of GC, their immunoregulatory effect, and their diagnostic value. Furthermore, we discuss the relationship between the metabolism of microbes and their potential applications, which may serve as a new approach for the diagnosis and treatment of GC.
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Affiliation(s)
- Meiqi Wang
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Ge Yang
- College of Basic Medical Sciences and Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Yuan Tian
- College of Basic Medical Sciences and Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Qihe Zhang
- College of Basic Medical Sciences and Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Zhuo Liu
- Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Ying Xin
- College of Basic Medical Sciences and Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
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Bi JH, Jiang YH, Ye SJ, Wu MR, Yi Y, Wang HX, Wang LM. Investigation of the inhibition effect of 1,2,3,4,6-pentagalloyl-β-D-glucose on gastric cancer cells based on a network pharmacology approach and experimental validation. Front Oncol 2022; 12:934958. [PMID: 35992839 PMCID: PMC9383036 DOI: 10.3389/fonc.2022.934958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 07/07/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundGastric cancer (GC) is ranked as the third leading cause of cancer-related mortality worldwide. 1,2,3,4,6-Pentagalloyl-β-D-glucose (β-PGG) has various pharmacological activities and has been shown to suppress cancer development. However, the mechanism by which β-PGG inhibits gastric cancer has not been elucidated.ObjectiveThis study explored the potential targets and mechanism of β-PGG in GC using the network pharmacology approach combined with in-vitro experiments.MethodsThe PharmMapper software was used to predict the potential targets of β-PGG, and GC-related genes were identified on the GeneCards database. PPI analysis of common genes was performed using the STRING database. The potential regulatory mechanism of β-PGG in GC was explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The binding ability of key genes and target proteins was verified by molecular docking. The effects of β-PGG on genes and proteins were evaluated using the CCK-8 assay, cell cycle analysis, apoptosis assay, real-time fluorescence quantification polymerase chain reaction (qRT-PCR), and Western blotting.ResultsEight hub genes involved in cell cycle progression and apoptosis were identified. Cancer-related signaling pathways were identified using the Cytoscape tool. Some of those genes were significantly enriched in the p53 signaling pathway. The CCK-8 assay showed that β-PGG inhibited the proliferation of GC cells. Cell cycle and apoptosis experiments revealed that β-PGG induced cell cycle arrest and apoptosis of gastric cancer cells. qRT-PCR and Western blot analysis showed that β-PGG inhibited β-PGG cells by modulating the p53 signaling pathway.ConclusionIn the present study, the targets and mechanism of β-PGG in gastric cancer were explored. The results indicate that β-PGG can be used to develop treatments for GC.
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Affiliation(s)
- Jing-hui Bi
- College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China
| | - Yu-han Jiang
- College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China
| | - Shi-jie Ye
- College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China
| | - Min-rui Wu
- College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China
| | - Yang Yi
- College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan, China
| | - Hong-xun Wang
- College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China
| | - Li-mei Wang
- College of Life Science and Technology, Wuhan Polytechnic University, Wuhan, China
- *Correspondence: Li-mei Wang,
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Liu L, Wang C, Li F, Zhang X, Cheng X, Lin S, Liu Y, Yang C, Li W. The safety and efficacy of laparoscopic gastrectomy for patients with locally advanced gastric cancer following neoadjuvant chemotherapy. Sci Rep 2022; 12:10384. [PMID: 35726012 PMCID: PMC9209419 DOI: 10.1038/s41598-022-14717-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Accepted: 06/10/2022] [Indexed: 12/12/2022] Open
Abstract
Limited researches focused on the application of laparoscopic gastrectomy (LG) in locally advanced gastric cancer (LAGC) patients following neoadjuvant chemotherapy (NACT). In this study, we aimed at illustrating the surgical and survival outcome of LG in LAGC patients following NACT. We performed a retrospective study of patients with LAGC who received either LG following NACT or upfront LG at Fujian Provincial Hospital between March 2013 and October 2018. Perioperative parameters, short-term and long-term outcomes were compared. The Kaplan–Meier estimator was used to describe the survival curves, and the differences were examined by the log-rank test. In total, 76 consecutive patients were enrolled into the NACT-LG (41 patients) and LG (35 patients) group. The postoperative hospital stay was significantly longer for LG than for NACT-LG (11.0 vs. 12.0 day, P = 0.031). Significant difference was found in Grade ≥ III severe postoperative complications in two groups (0 vs. 17.1%, P = 0.001). No patient died of postoperative complications in the NACT-LG group, and one patient (1/35, 2.9%) died of postoperative complications in the LG group. A forest plot revealed that most subgroups of LG group were at great risks of postoperative complications. Compared with the LG group, the NACT-LG group had a significantly better DFS (14.4% vs. 5.7%, P = 0.0299) and better OS (34.1% vs. 8.6%, P = 0.0061) at 3 years. NACT increased the safety of LG for patients with LAGC and offer better disease-free and overall survival. For patients with LAGC, LG following NACT should be the priority treatment.
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Affiliation(s)
- Lihang Liu
- Shengli Clinical Medical College, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Chuandong Wang
- Shengli Clinical Medical College, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Feng Li
- Shengli Clinical Medical College, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, China.,Department of Pathology, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Xiaojuan Zhang
- Fuzong Clinical Medical College, Fujian Medical University, Fuzhou, 350001, China
| | - Xuefei Cheng
- Shengli Clinical Medical College, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Shengtao Lin
- Shengli Clinical Medical College, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Yi Liu
- Department of Endoscopy, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, People's Republic of China
| | - Changshun Yang
- Shengli Clinical Medical College, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, China.,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, China
| | - Weihua Li
- Shengli Clinical Medical College, Fujian Medical University, No. 134, East Street, Fuzhou, 350001, China. .,Department of Surgical Oncology, Fujian Provincial Hospital, Fuzhou, 350001, China.
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Wang Z, Fu L, Zhang J, Ge Y, Guo C, Wang R, Deng M, Wang Q, Wang Z. A comprehensive analysis of potential gastric cancer prognostic biomarker ITGBL1 associated with immune infiltration and epithelial-mesenchymal transition. Biomed Eng Online 2022; 21:30. [PMID: 35596183 PMCID: PMC9123716 DOI: 10.1186/s12938-022-00998-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 04/27/2022] [Indexed: 11/17/2022] Open
Abstract
Background Integrin, beta-like 1 (ITGBL1) is involved in a variety of human malignancies. However, the information on the involvement of ITGBL1 in gastric carcinoma (GC) is limited. Hence, this study aimed further to explore the functions and mechanisms of ITGBL1 in GC. Methods First, multiple bioinformatics databases, including Oncomine, Tumor Immune Estimation Resource, UALCAN, and Kaplan–Meier Plotter, were used to predict the expression level and prognostic value of ITGBL1, as well as its association with immune infiltration and epithelial–mesenchymal transition (EMT) in GC. Quantitative reverse transcription–polymerase chain reaction and immunohistochemical analysis were used to detect the expression of ITGBL1 in both GC tissues and cells. Then, targeted silencing of ITGBL1 in GC cells was further used to examine the biological functions of ITGBL1. Results These databases revealed that ITGBL1 was overexpressed and affected the overall survival in GC. Besides, the expression of ITGBL1 positively correlated with immune-infiltrating cells and EMT-related markers. Subsequently, molecular biology experiments verified these predictions. In GC tissues and cells, ITGBL1 was notably overexpressed. Loss-of-function studies showed that the knockdown of ITGBL1 significantly suppressed migration and invasion but promoted apoptosis in MGC803 GC cells. Furthermore, the inhibition of ITGBL1 resulted in remarkably increased protein expression levels of cadherin 1, while the expression of Vimentin, Snail, and transforming growth factor-β1 was downregulated, indicating the initiation and progression of GC caused by ITGBL1 partly via inducing EMT. Conclusions To sum up, the findings indicated that ITGBL1 acted as a valuable oncogenic factor in GC.
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Affiliation(s)
- Zhe Wang
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Putuo District, Shanghai, 200065, People's Republic of China
| | - Liu Fu
- Department of Gastroenterology, Putuo People's Hospital, Tongji University, Shanghai, 200060, People's Republic of China
| | - Junjie Zhang
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Putuo District, Shanghai, 200065, People's Republic of China
| | - Yanli Ge
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Putuo District, Shanghai, 200065, People's Republic of China
| | - Cheng Guo
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Putuo District, Shanghai, 200065, People's Republic of China
| | - Rui Wang
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Putuo District, Shanghai, 200065, People's Republic of China
| | - Min Deng
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People's Republic of China
| | - Qizhi Wang
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233004, People's Republic of China
| | - Zhirong Wang
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Putuo District, Shanghai, 200065, People's Republic of China.
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Capdevila J, Grande E, García-Carbonero R, Simó M, del Olmo-García MI, Jiménez-Fonseca P, Carmona-Bayonas A, Pubul V. Position Statement on the Diagnosis, Treatment, and Response Evaluation to Systemic Therapies of Advanced Neuroendocrine Tumors, With a Special Focus on Radioligand Therapy. Oncologist 2022; 27:e328-e339. [PMID: 35380724 PMCID: PMC8982404 DOI: 10.1093/oncolo/oyab041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Accepted: 10/08/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The aim of this study was to provide a guidance for the management of neuroendocrine tumors (NETs) in clinical practice. MATERIAL AND METHODS Nominal group and Delphi techniques were used. A steering committee of 8 experts reviewed the current management of NETs, identified controversies and gaps, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a panel of 26 experts, was selected to test agreement with the statements through 2 Delphi rounds. Items were scored on a 4-point Likert scale from 1 = totally agree to 4 = totally disagree. The agreement was considered if ≥75% of answers pertained to Categories 1 and 2 (consensus with the agreement) or Categories 3 and 4 (consensus with the disagreement). RESULTS Overall, 132 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) progression and treatment response criteria; (3) advanced gastro-enteric NETs; (4) advanced pancreatic NETs; (5) advanced NETs in other locations; (6) re-treatment with radioligand therapy (RLT); (7) neoadjuvant therapy. After 2 Delphi rounds, only 4 statements lacked a clear consensus. RLT was not only recommended in the sequencing of different NETs but also as neoadjuvant treatment, while several indications for retreatment with RLT were also established. CONCLUSION This document sought to pull together the experts' attitudes when dealing with different clinical scenarios of patients suffering from NETs, with RLT having a specific role where evidence-based data are limited.
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Affiliation(s)
- Jaume Capdevila
- Department of Medical Oncology, Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO), IOB-Quiron-Teknon Barcelona, Barcelona, Spain
| | - Enrique Grande
- Department of Medical Oncology, MD Anderson Cancer Center, Madrid, Spain
| | | | - Marc Simó
- Department of Nuclear Medicine and Molecular Imaging, Hospital Universitari Vall d’Hebron, Barcelona, Spain
| | - Mª Isabel del Olmo-García
- Department of Endocrinology, Hospital Universitario y Politécnico la Fe de Valencia, Valencia, Spain
| | - Paula Jiménez-Fonseca
- Department of Medical Oncology, Hospital Universitario Central de Asturias, ISPA, Madrid, Spain
| | - Alberto Carmona-Bayonas
- Department of Hematology and Medical Oncology, Hospital General Universitario Morales Meseguer, University of Murcia, IMIB, CP13/00126, PI17/0050 (ISCIII & FEDER) and Fundación Séneca (04515/GERM/06), Murcia, Spain
| | - Virginia Pubul
- Department of Nuclear Medicine Department and Molecular Imaging Research Group, University Hospital and Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
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9
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Chen J, Liu W, Du J, Wang P, Wang J, Ye K. Comprehensive Genomic and Epigenomic Analyses on Transcriptomic Regulation in Stomach Adenocarcinoma. Front Genet 2022; 12:778095. [PMID: 35222516 PMCID: PMC8873582 DOI: 10.3389/fgene.2021.778095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 12/28/2021] [Indexed: 12/24/2022] Open
Abstract
Background: DNA methylation (MET)–mediated transcriptomic disturbance and copy number variations (CNVs) exert a significant influence in stimulating the heterogeneous progression of stomach adenocarcinoma (STAD). Nevertheless, the relation of DNA MET with CNVs, together with its impact on tumor occurrence, is still unclear.Methods: The messenger RNA (mRNA) expression (EXP) profiles, DNA MET, and DNA copy numbers, together with STAD mutation data, were collected from the TCGA official data portal. We employed circular binary segmentation algorithm in “DNAcopy.” library of R package for mapping DNA CNV data at genetic level for all samples based on the segmented CNV data. Stable clusters of samples were recognized using negative matrix factorization cluster analysis based on 50 iterations and the “brunet” method using the MET-correlated (METcor) and CNV-correlated (CNVcor) genes. The R package “iCluster” method was utilized to comprehensively analyze the EXP, MET, and DNA CNV profiles.Results: A total of 313 STAD samples were isolated for checking DNA copy numbers and MET and for measuring EXP. In accordance with our results, we discovered obvious co-regulation of CNVcor genes and METcor counterparts. Apart from that, these genes were subject to multi-omics integration. Meanwhile, three subtypes of STAD were detected and confirmed based on independent data. Among them, the subtype with increased aggressiveness was related to decreased mutation frequencies of ARID1A, PIK3CA, ZFHX3, SPECC1, OBSCN, KMT2D, FSIP2, ZBTB20, TTN, and RANBP2, together with the abnormal levels of JPH3, KCNB1, and PLCXD3.Conclusion: According to the results, these aforementioned genes exerted crucial roles in the development of invasive STAD. Our findings on transcriptomic regulation genomically and epigenetically facilitate the understanding of the STAD pathology from different aspects, which help to develop efficient anti-STAD therapy.
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10
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Zhang YX, Liu HD, Chen ZH, Jin T, Hu JK, Yang K. Comparison of Survival and Safety Between Total Omentectomy and Partial Omentectomy for Gastric Cancer: A Meta-Analysis. Front Surg 2022; 8:708545. [PMID: 35004832 PMCID: PMC8739222 DOI: 10.3389/fsurg.2021.708545] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2021] [Accepted: 11/29/2021] [Indexed: 02/05/2023] Open
Abstract
Background: The greater omentum can limit abdominal inflammation and act as a protective cushion, but it is always involved in dissemination of gastric cancer. The purpose of this meta-analysis was to compare the survival and safety between total omentectomy and partial omentectomy for gastric cancer. Methods: Two investigators independently conducted a systematic search of PubMed, Embase, CNKI, and Cochrane Library ranging from January 2000 to November 2020. The pooled odds ratio (ORs) and weighted mean difference (WMD) with the 95% confidence interval (95% CI) were used to assess perioperative and survival parameters. Results: A total of 2,031 patients in 11 studies (574 patients in the partial omentectomy group and 1,457 patients in the total omentectomy group) were included. The results found shorter operation time (WMD = −25.584; P = 0.000) and less intraoperative blood loss (WMD = −47.301; P = 0.050) in the partial omentectomy group, compared to total omentectomy. There were no significant differences in terms of incidence of complications (OR = 0.770; P = 0.164), blood transfusions rates (OR = 0.269; P = 0.161), time to first flatus (WMD = 0.160; P = 0.345), hospital stay (WMD = −1.258; P = 0.087), and number of harvested lymph nodes (WMD = 1.265; P = 0.662). For the disease-free survival (OR = 0.80; P = 0.381) and overall survival, there were no statistical differences between the two procedures. Conclusions: The partial omentectomy could reduce operation time and trended to decrease intraoperative blood loss. And the survival in patients with partial omentectomy seemed to be comparable to that of patients with total omentectomy.
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Affiliation(s)
- Yue-Xin Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.,Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Han-Dong Liu
- Department of Gastrointestinal Surgery, West China Hospital Sichuan University Jintang Hosptial, Chengdu, China
| | - Ze-Hua Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.,Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Tao Jin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.,Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.,Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Kun Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China.,Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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11
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Laparoscopic versus open distal gastrectomy for gastric cancer: A systematic review and meta-analysis. Surgery 2022; 171:1552-1561. [DOI: 10.1016/j.surg.2021.11.035] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 11/13/2021] [Accepted: 11/29/2021] [Indexed: 12/16/2022]
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12
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Dong YP, Cai FL, Wu ZZ, Wang PL, Yang Y, Guo SW, Zhao ZZ, Zhao FC, Liang H, Deng JY. Risk of station 12a lymph node metastasis in patients with lower-third gastric cancer. World J Gastrointest Surg 2021; 13:1390-1404. [PMID: 34950428 PMCID: PMC8649572 DOI: 10.4240/wjgs.v13.i11.1390] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 07/06/2021] [Accepted: 10/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Controversy over the issue that No. 12a lymph node involvement is distant or regional metastasis remains, and the possible inclusion of 12a lymph nodes in D2 lymphadenectomy is unclear. As reported, gastric cancer (GC) located in the lower third is highly related to the metastasis of station 12a lymph nodes. AIM To investigate whether the clinicopathological factors and metastasis status of other perigastric nodes can predict station 12a lymph node metastasis and evaluate the prognostic significance of station 12a lymph node dissection in patients with lower-third GC. METHODS A total of 147 patients with lower-third GC who underwent D2 or D2+ lymphadenectomy, including station 12a lymph node dissection, were included in this retrospective study from June 2003 to March 2011. Survival prognoses were compared between patients with or without station 12a lymph node metastasis. Logistic regression analyses were used to clarify the association between station 12a lymph node metastasis and clinicopathological factors or metastasis status of other perigastric nodes. The metastasis status of each regional lymph node was evaluated to identify the possible predictors of station 12a lymph node metastasis. RESULTS Metastasis to station 12a lymph nodes was observed in 18 patients with lower-third GC, but not in 129 patients. The incidence of station 12a lymph node involvement was reported as 12.2% in patients with lower-third GC. The overall survival of patients without station 12a lymph node metastasis was significantly better than that of patients with station 12a metastasis (P < 0.001), which could also be seen in patients with or without extranodal soft tissue invasion. Station 12a lymph node metastasis and extranodal soft tissue invasion were identified as independent predictors of poor prognosis in patients with lower-third GC. Advanced pN stage was defined as independent risk factor significantly correlated with station 12a lymph node positivity. Station 3 lymph node staus was also proven to be significantly correlated with station 12a lymph node involvement. CONCLUSION Metastasis of station 12a lymph nodes could be considered an independent prognosis factor for patients with lower-third GC. The dissection of station 12a lymph nodes may not be ignored in D2 or D2+ lymphadenectomy due to difficulties in predicting station 12a lymph node metastasis.
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Affiliation(s)
- Yin-Ping Dong
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Feng-Lin Cai
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Zi-Zhen Wu
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Peng-Liang Wang
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Yang Yang
- Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Shi-Wei Guo
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Zhen-Zhen Zhao
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Fu-Cheng Zhao
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Han Liang
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
| | - Jing-Yu Deng
- Department of Gastroenterology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy at Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin 300060, China
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13
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Wang Z, Hou Y, Yao Z, Zhan Y, Chen W, Liu Y. Expressivity of Interleukin-8 and Gastric Cancer Prognosis Susceptibility: A Systematic Review and Meta-Analysis. Dose Response 2021; 19:15593258211037127. [PMID: 34531708 PMCID: PMC8438942 DOI: 10.1177/15593258211037127] [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: 03/29/2021] [Revised: 07/07/2021] [Accepted: 07/09/2021] [Indexed: 12/23/2022] Open
Abstract
Background The relationship between interleukin-8 (IL-8) expression and the prognosis of gastric cancer (GC) patients has been reported, but the results are contradictory. Aim To investigate the effect of IL-8 expression on the prognosis of patients with GC. Method A comprehensive search strategy was used to search the PubMed, Web of Science and Cochrane Library databases. The total survival time was analysed using the RevMan 5.4 software. Through extensive search and meta-analysis of relevant studies, studies examining the relationship between IL-8 expression and prognosis in patients with GC were conducted to obtain more accurate estimates. Findings Eight studies (1843 patients) were included. The combined results of all the studies showed that high expression of IL-8 was a risk factor for poor prognosis in patients with GC (hazard ratio (HR): 2.08; 95% CI: 1.81–2.39). Sensitivity analysis suggested that the pooled HR was stable, and omitting a single study did not change the significance of the pooled HR. Funnel plots revealed no significant publication bias in the meta-analysis. Conclusion High IL-8 expression could be a negative prognostic biomarker for patients with GC.
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Affiliation(s)
- Zhenzhen Wang
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuhan Hou
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhen Yao
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yanyan Zhan
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Wenyue Chen
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yulong Liu
- Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University, Suzhou, China.,State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China.,Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Suzhou, China
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14
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Morgant S, Artru P, Oudjit A, Lourenco N, Pasquer A, Walter T, Gornet JM, Rouquette A, Brezault C, Coriat R. Endoscopic ultrasound efficacy in staging gastric linitis plastica lesion: a retrospective multicentric French study. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:50. [PMID: 33553343 PMCID: PMC7859799 DOI: 10.21037/atm-20-3474] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 09/25/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Endoscopic ultrasound (EUS) is a key imaging technique in gastric cancer (GC). The aim of this study was to evaluate the performance of EUS in the staging of parietal and lymph node involvement in linitis plastica (LP) compared to "classical" GC. METHODS A retrospective multicentric French study was conducted on patients with no metastatic LP and operated by gastrectomy. A 2/1 matching based on pTNM stage and center was performed with GC. RESULTS Forty-three patients were included, sixteen patients in the LP group and 27 in the control group. Sensitivity and specificity of EUS for diagnosis of T3-T4 parietal invasion were 77% and 100% respectively in the LP group and 89% and 56% respectively in the control group. Sensitivity and specificity of EUS for diagnosis of lymph node involvement were 73% and 80%, respectively in the LP group and 88% and 50%, respectively in the control group. Patients from LP group had significantly more advanced histological lesion, and frequent undiagnosed peritoneal carcinomatosis. CONCLUSIONS This study evaluated for the first time in a European population, the preoperative EUS performance in LP. Our study identified a similar sensitivity and specificity of the EUS in LP compared to "classical" GC paving for a broader use of EUS in preoperative settings.
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Affiliation(s)
- Stephanie Morgant
- Gastroenterology and digestive oncology unit, Hôpital Cochin, Paris, France
| | - Pascal Artru
- Gastroenterology and Digestive Unit, Jean Mermoz Clinic, Lyon, France
| | - Ammar Oudjit
- Radiology Unit, Cochin Teaching Hospital, Paris, France
| | - Nelson Lourenco
- Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France
| | - Arnaud Pasquer
- Digestive Surgery Unit, Edouard Herriot Teaching Hospital, Lyon, France
| | - Thomas Walter
- Oncology Unit, Edouard Herriot Teaching Hospital, Lyon, France
| | - Jean-Marc Gornet
- Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France
| | | | - Catherine Brezault
- Gastroenterology and digestive oncology unit, Hôpital Cochin, Paris, France
| | - Romain Coriat
- Gastroenterology and digestive oncology unit, Hôpital Cochin, Paris, France
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15
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Peng D, Cheng YX, Zhang W. Does Roux-en-Y Construction Really Bring Benefit of Type 2 Diabetes Mellitus Remission After Gastrectomy in Patients with Gastric Cancer? A Systematic Review and Meta-Analysis. Diabetes Ther 2020; 11:2863-2872. [PMID: 33006131 PMCID: PMC7644734 DOI: 10.1007/s13300-020-00934-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 09/16/2020] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION To evaluate whether the extent of gastrectomy or the reconstruction method brings benefit of type 2 diabetes mellitus (T2DM) remission after gastrectomy in patients with gastric cancer. METHODS PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library were searched to find eligible studies published from inception to July 31, 2020. RESULTS A total of nine studies (1424 patients) were included. At the first year and the end of follow-up time after gastrectomy, the total gastrectomy group had better T2DM remission than the subtotal gastrectomy group, and the Roux-en-Y reconstruction (R-Y) group had better T2DM remission compared with the non-R-Y group. There was no difference between R-Y and non-R-Y in terms of subtotal gastrectomy (OR 1.08, 95% CI 0.63-1.84, P = 0.78). However, total gastrectomy with R-Y had better T2DM remission than subtotal gastrectomy with R-Y (OR 2.75, 95% CI 1.19-6.35, P = 0.02). CONCLUSION Total gastrectomy with R-Y had better T2DM remission. The extent of gastrectomy rather than the reconstruction method might play an important role in T2DM remission after gastrectomy in patients with gastric cancer.
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Affiliation(s)
- Dong Peng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu-Xi Cheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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16
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Xu T, Shen G, Cheng M, Wu X, Xu Y, Hu S. Upregulated β-arrestin1 predicts poor prognosis and promotes metastasis via AKT/ERK signaling pathway in gastric cancer. Pathol Res Pract 2020; 216:153262. [PMID: 33129195 DOI: 10.1016/j.prp.2020.153262] [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: 07/10/2020] [Revised: 10/16/2020] [Accepted: 10/17/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND β-Arrestins have been found to regulate cell proliferation, invasion and migration; transmit anti-apoptotic survival signals; and affect other characteristics of tumours. However, their role in gastric cancer (GC) is not clear. We investigated the role and mechanism of β-arrestins in the regulation of GC. METHODS We first examined β-arrestins mRNA levels in 17 pairs of GC tissues by qRT-PCR. We also used immunohistochemistry to further examine the expression of β-arrestins in 60 paraffin-embedded primary GC tissues and 20 normal gastric tissues. Then, the function of β-arrestin1 was investigated in vitro and in vivo. RESULTS β-Arrestin1 was upregulated in GC tissue and was associated with tumour stage, lymph node metastasis, invasion depth and patient sex. High expression of β-arrestin1 expression predicted poor prognosis in GC. β-Arrestin1 promoted GC cell proliferation, migration and invasion, and it suppressed E-cadherin expression and upregulated Vimentin expression via AKT/ERK signalling pathway. The in vivo metastasis assays showed that knockdown of β-arrestin1 reduced lung metastasis and inhibited EMT. CONCLUSION The upregulation of β-arrestin1 predicts poor prognosis and promotes metastasis and epithelial-mesenchymal transition in GC through AKT/ERK signalling pathway. This study may provide therapeutic advances for the treatment and early diagnosis of patients with metastatic GC.
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Affiliation(s)
- Tingjuan Xu
- Gerontology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People's Republic of China; Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, Anhui 230001, People's Republic of China
| | - Guodong Shen
- Gerontology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People's Republic of China; Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, Anhui 230001, People's Republic of China
| | - Min Cheng
- Gerontology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People's Republic of China; Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, Anhui 230001, People's Republic of China
| | - Xinchun Wu
- Gerontology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People's Republic of China; Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, Anhui 230001, People's Republic of China
| | - Yayuan Xu
- Agro-products Processing Research Institute, Anhui Academy of Agricultural Sciences, Hefei, Anhui 230031, People's Republic of China
| | - Shilian Hu
- Gerontology Institute, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, People's Republic of China; Anhui Provincial Key Laboratory of Tumor Immunotherapy and Nutrition Therapy, Hefei, Anhui 230001, People's Republic of China.
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17
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Rahimi AM, Nabavizadeh F, Ashabi G, Halimi S, Rahimpour M, Vahedian J, Panahi M. Probiotic Lactobacillus rhamnosus Supplementation Improved Capecitabine Protective Effect against Gastric Cancer Growth in Male BALB/c Mice. Nutr Cancer 2020; 73:2089-2099. [PMID: 33955797 DOI: 10.1080/01635581.2020.1832237] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
The gastric cancer (GC) is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Herein, we studied the effects of probiotics (Lactobacillus rhamnosus) on subcutaneous implantation of xenograft GC. Moreover, the effect of probiotics (L. rhamnosus) was compared with the capecitabine drug as known used drug against GC. Human GC tissue was obtained from patients with gastric adenocarcinoma and grafted into mice armpit. Probiotic (L. rhamnosus) was given to animals by gavage 2 weeks prior to GC and 4 weeks after GC induction. Also, capecitabine was orally added through feeding tube at the last week of treatment procedure. All grafted animals received cyclosporine a day before the surgery and during the study period to prevent graft rejection. Capecitabine-probiotic complex reduced the size of the axillary implanted GC when compared with control group. Furthermore, combination of capecitabine and probiotic increased apoptotic and necrotic responses in the grafted tumor, blood cells (red blood cells, white blood cells, and platelet counts) in comparison with capecitabine. Probiotic (L. rhamnosus) administration effectively improved the therapeutic index and outcomes, and also, improved the therapeutic effects of the capecitabine.
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Affiliation(s)
- Ahmad Mustafa Rahimi
- Department of Physiology, Medical school, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Nabavizadeh
- Department of Physiology, Medical school, Tehran University of Medical Sciences, Tehran, Iran.,Electrophysiology Research Center, Neurosciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ghorbangol Ashabi
- Department of Physiology, Medical school, Tehran University of Medical Sciences, Tehran, Iran.,Electrophysiology Research Center, Neurosciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahnaz Halimi
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Milad Rahimpour
- Department of Physiology, Medical school, Tehran University of Medical Sciences, Tehran, Iran
| | - Jalal Vahedian
- Department of Surgery, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mahshid Panahi
- Department of Pathology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
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18
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Qiu HB. Safety and efficacy of tislelizumab plus chemotherapy for first-line treatment of advanced esophageal squamous cell carcinoma and gastric/gastroesophageal junction adenocarcinoma. Thorac Cancer 2020; 11:3419-3421. [PMID: 33043992 PMCID: PMC7705902 DOI: 10.1111/1759-7714.13690] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 09/20/2020] [Indexed: 11/30/2022] Open
Affiliation(s)
- Hai-Bo Qiu
- Department of Gastric Surgery, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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19
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Zhang Y, Ma S, Niu Q, Han Y, Liu X, Jiang J, Chen S, Lin H. Features of alternative splicing in stomach adenocarcinoma and their clinical implication: a research based on massive sequencing data. BMC Genomics 2020; 21:580. [PMID: 32831016 PMCID: PMC7443856 DOI: 10.1186/s12864-020-06997-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 08/17/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Alternative splicing (AS) offers a main mechanism to form protein polymorphism. A growing body of evidence indicates the correlation between splicing disorders and carcinoma. Nevertheless, an overall analysis of AS signatures in stomach adenocarcinoma (STAD) is absent and urgently needed. RESULTS 2042 splicing events were confirmed as prognostic molecular events. Furthermore, the final prognostic signature constructed by 10 AS events gave good result with an area under the curve (AUC) of receiver operating characteristic (ROC) curve up to 0.902 for 5 years, showing high potency in predicting patient outcome. We built the splicing regulatory network to show the internal regulation mechanism of splicing events in STAD. QKI may play a significant part in the prognosis induced by splicing events. CONCLUSIONS In our study, a high-efficiency prognostic prediction model was built for STAD patients, and the results showed that AS events could become potential prognostic biomarkers for STAD. Meanwhile, QKI may become an important target for drug design in the future.
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Affiliation(s)
- Yuanyuan Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
| | - Shengling Ma
- Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qian Niu
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yun Han
- Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xingyu Liu
- Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Jie Jiang
- Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Simiao Chen
- Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Haolong Lin
- Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
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20
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Canale M, Casadei-Gardini A, Ulivi P, Arechederra M, Berasain C, Lollini PL, Fernández-Barrena MG, Avila MA. Epigenetic Mechanisms in Gastric Cancer: Potential New Therapeutic Opportunities. Int J Mol Sci 2020; 21:E5500. [PMID: 32752096 PMCID: PMC7432799 DOI: 10.3390/ijms21155500] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer (GC) is one of the deadliest malignancies worldwide. Complex disease heterogeneity, late diagnosis, and suboptimal therapies result in the poor prognosis of patients. Besides genetic alterations and environmental factors, it has been demonstrated that alterations of the epigenetic machinery guide cancer onset and progression, representing a hallmark of gastric malignancies. Moreover, epigenetic mechanisms undergo an intricate crosstalk, and distinct epigenomic profiles can be shaped under different microenvironmental contexts. In this scenario, targeting epigenetic mechanisms could be an interesting therapeutic strategy to overcome gastric cancer heterogeneity, and the efforts conducted to date are delivering promising results. In this review, we summarize the key epigenetic events involved in gastric cancer development. We conclude with a discussion of new promising epigenetic strategies for gastric cancer treatment.
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Affiliation(s)
- Matteo Canale
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy; (M.C.); (P.U.)
| | - Andrea Casadei-Gardini
- Department of Oncology and Hematology, Division of Oncology, University of Modena and Reggio Emilia, 41125 Modena, Italy
| | - Paola Ulivi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 Meldola, Italy; (M.C.); (P.U.)
| | - Maria Arechederra
- Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (M.A.); (C.B.); (M.G.F.-B.)
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
| | - Carmen Berasain
- Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (M.A.); (C.B.); (M.G.F.-B.)
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), 28029 Madrid, Spain
| | - Pier-Luigi Lollini
- Laboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40126 Bologna, Italy;
| | - Maite G. Fernández-Barrena
- Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (M.A.); (C.B.); (M.G.F.-B.)
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), 28029 Madrid, Spain
| | - Matías A. Avila
- Program of Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain; (M.A.); (C.B.); (M.G.F.-B.)
- IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain
- National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Carlos III Health Institute), 28029 Madrid, Spain
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Xu J, Bai Y, Xu N, Li E, Wang B, Wang J, Li X, Wang X, Yuan X. Tislelizumab Plus Chemotherapy as First-line Treatment for Advanced Esophageal Squamous Cell Carcinoma and Gastric/Gastroesophageal Junction Adenocarcinoma. Clin Cancer Res 2020; 26:4542-4550. [PMID: 32561664 DOI: 10.1158/1078-0432.ccr-19-3561] [Citation(s) in RCA: 72] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 04/13/2020] [Accepted: 06/16/2020] [Indexed: 12/24/2022]
Affiliation(s)
- Jianming Xu
- Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.
| | - Yuxian Bai
- Harbin Medical University Cancer Hospital, Harbin, China
| | - Nong Xu
- The First Affiliated Hospital of Zhejiang University, Hangzhou, China
| | - Enxiao Li
- First Affiliated Hospital of Xi'an Jiao Tong University, Xi'an, China
| | - Buhai Wang
- Northern Jiangsu People's Hospital, Yangzhou, China
| | - Jin Wang
- BeiGene (Beijing) Co., Ltd., Beijing, China
| | - Xiang Li
- BeiGene (Beijing) Co., Ltd., Beijing, China
| | - Xin Wang
- BeiGene (Beijing) Co., Ltd., Beijing, China
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22
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Xiao AT, Tong YX, Xu XS, Zhou Y, Zhang S. Preoperative Nutritional Status Contributes to the Development of Neutropenia Event in Patients With Gastric Cancer Receiving CAPEOX Adjuvant Chemotherapy. Front Oncol 2020; 10:692. [PMID: 32426291 PMCID: PMC7204396 DOI: 10.3389/fonc.2020.00692] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2019] [Accepted: 04/14/2020] [Indexed: 11/17/2022] Open
Abstract
Purpose: The aim of this study is to evaluate the risk factors for ≥ grade 3 neutropenia in gastric cancer patients receiving postoperative adjuvant chemotherapy. Methods: This is a retrospective study from a single tertiary referral hospital. Patients diagnosed with gastric cancer who met the inclusion criteria were included in this study. Baseline and clinicopathological characteristics of the patients were collected. Patients were followed-up for 12 months and the incidence of neutropenia were recorded. Factors associated with neutropenia of chemotherapy in cycle 1 were investigated. Results: A total of 202 patients with gastric cancer were included. All patients received oxaliplatin plus oral capecitabine (CAPEOX) as the adjuvant chemotherapy. The incidence of ≥ grade 3 neutropenia is 11.9% (24/202) in cycle 1 among all patients. In multivariate analysis, independent risk factors for ≥ grade 3 neutropenia were serum prealbumin level (p = 0.041), prognostic nutritional index (PNI) (p = 0.049) and pre-cycle neutrophil count (p = 0.007). Conclusions: Our findings for the first time showed that nutritional parameter as prealbumin level and PNI are independent risk factors for neutropenia in gastric cancer patients receiving adjuvant chemotherapy. This may provide evidence for further investigation on prophylaxis use of granulocyte colony-stimulating factor in selected high-risk patients to prevent sever neutropenia in cycle 1 of adjuvant chemotherapy.
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Affiliation(s)
| | | | | | | | - Sheng Zhang
- Department of Gastrointestinal Surgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China
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23
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Ahmadzadeh A, Seyedian SS, Valizadeh A, Soleimani M, Nazari P, Hamidi H. The Efficacy and Safety of Modified Docetaxel, Cisplatin, and 5-Fluorouracil Vs. Epirubicin, Oxaliplatin, and Capecitabine Regimen in the Advanced Gastric Cancer: A Randomized Controlled Clinical Trial. Asian Pac J Cancer Prev 2020; 21:727-732. [PMID: 32212800 PMCID: PMC7437336 DOI: 10.31557/apjcp.2020.21.3.727] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Indexed: 12/11/2022] Open
Abstract
INTRODUCTION One of the major challenges of advanced gastric cancer treatment is the lack of a standard regimen for patients. However, several clinical trials have shown that modified docetaxel, cisplatin, and 5-fluorouracil (m-DCF) and epirubicin, oxaliplatin, and capecitabine (EOX) regimens are superior to other regimens. METHODS This randomized, single-center clinical trial was performed on 40 patients with advanced gastric cancer. The first group received the m-DCF regimen as follows: docetaxel (40 mg/m2) on the first day; cisplatin (40 mg/m2) on the first and second days; and 5-fluorouracil (400 mg/m2) from the first to fourth day. The second group received the EOX regimen, including epirubicin (50 mg/m2) and oxaliplatin (130 mg/m2) i.v on the first day and capecitabine at a twice-daily dose of 625 mg/m2 p.o for 21 days. Treatment was applied every three weeks for a total of eight cycles in both groups. In each group, the overall and progression-free survival rates and toxicity were assessed. RESULTS A total of 40 patients were enrolled in this study (21 samples in the m-DCF group and 19 samples in the EOX group), 62.5% of whom were male. The median survival rate was 14.00 (95% CI: 11.82-16.18) months in the m-DCF group and 15.00 (95% CI: 9.56-20.43) months in the EOX group; however, differences between the groups were not significant. The progression-free survival rate was higher in the EOX group, although there was no significant difference between the two groups. Also, there was no significant difference regarding the side effects (e.g., toxicity) or need for supportive care between the groups. CONCLUSION It seems that both m-DCF and EOX regimens are similar in terms of survival and toxicity and are recommended as first-line treatment for advanced gastric cancer with respect to the patient's status.
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Affiliation(s)
- Ahmad Ahmadzadeh
- Research Center of Thalassemia and Hemoglobinopathy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Saeid Seyedian
- Alimentary Tract Research Center, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
| | - Armita Valizadeh
- Department of Anatomy, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
| | - Mahin Soleimani
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Pedram Nazari
- Cancer Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hossein Hamidi
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Downregulated Expression of hsa_circ_0005556 in Gastric Cancer and Its Clinical Significance. DISEASE MARKERS 2019; 2019:2624586. [PMID: 31827632 PMCID: PMC6885797 DOI: 10.1155/2019/2624586] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Revised: 09/09/2019] [Accepted: 09/30/2019] [Indexed: 12/24/2022]
Abstract
Background Gastric cancer (GC) has a poor prognosis due to the lack of ideal tumor markers. Circular RNAs (circRNAs) are a novel type of noncoding RNA related to the occurrence of GC. Among our research, we investigated the role of hsa_circ_0005556 in GC. Materials and Methods The expression of hsa_circ_0005556 of 100 paired GC tissues and adjacent normal tissues was detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was established to evaluate the diagnostic value of hsa_circ_0005556. The correlation between the expression of hsa_circ_0005556 and corresponding clinicopathological characteristic was explored. Results hsa_circ_0005556 was significantly downregulated in GC tissues contrasted with adjacent normal tissues (n = 100, p < 0.001). The areas under the ROC curve (AUC) of hsa_circ_0005556 were up to 0.773, while 64% sensitivity and 82% specificity, respectively. Moreover, its expression levels were significantly associated with differentiation (p = 0.001), TNM stage (p = 0.013), and lymphatic metastasis (p = 0.039). GC patients of high hsa_circ_0005556 levels had a longer overall survival (OS) than those of the low group (p = 0.047). Conclusion hsa_circ_0005556 is a potential biomarker for GC, which may guide judgment of the indication of endoscopic treatment for early gastric cancer (EGC).
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25
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Luo SS, Liao XW, Zhu XD. Genome-wide analysis to identify a novel microRNA signature that predicts survival in patients with stomach adenocarcinoma. J Cancer 2019; 10:6298-6313. [PMID: 31772663 PMCID: PMC6856753 DOI: 10.7150/jca.33250] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 08/30/2019] [Indexed: 12/22/2022] Open
Abstract
Objective: Using genome-wide screening, this study was aimed at identifying prognostic microRNA (miRNA) in those patients suffering from stomach adenocarcinoma (STAD). Methods: A genome-wide miRNA sequencing dataset and relevant STAD clinical information was obtained via The Cancer Genome Atlas (TCGA). Prognostic miRNA selection was carried out through a whole genome multivariate Cox regression model in order to establish a prognostic STAD signature. Results: Eleven miRNAs (hsa-mir-509-2, hsa-mir-3917, hsa-mir-495, hsa-mir-653, hsa-mir-3605, hsa-mir-2115, hsa-mir-1292, hsa-mir-137, hsa-mir-6511b-1, hsa-mir-145, and hsa-mir-138-2) were recognized as prognostic and used for the construction of a STAD prognostic signature. This signature exhibited good performance in predicting prognosis (adjusted P<0.0001, adjusted hazard ratio= 3.047, and 95% confidence interval=2.148-4.323). The time-dependent receiver operating characteristic examination exhibited area under curve values of 0.711, 0.697, 0.716, 0.733, 0.805, and 0.805, for 1-, 2-, 3-, 4-, 5-, and 10-year overall survival (OS) estimation, respectively. Comprehensive survival analysis suggests that the 11-miRNA prognostic signature acts as an independent feature of STAD prognosis and exhibits superior performance in OS prediction when compared to traditional clinical parameters. Furthermore, fourteen miRNA target genes were linked to STAD OS. These included SERPINE1, MLEC, ANGPT2, C5orf38, FZD7, MARCKS, PDGFD, DUSP6, IRS1, PSAT1, TENM3, TMEM127, BLMH, and TIRAP. Functional and gene set enrichment analysis suggested that target genes and the 11-miRNA prognostic signature were both participate in various biological processes and pathways, including the growth factor beta, Wnt, and Notch signaling pathways. Conclusions: By means of a genome-wide analysis, an 11-miRNA expression signature that may serve as an underlying prognostic indicator for those patients suffering from STAD has been identified and described here.
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Affiliation(s)
- Shan-Shan Luo
- Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Xi-Wen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
| | - Xiao-Dong Zhu
- Department of Radiation Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Cancer Institute of Guangxi Zhuang Autonomous Region, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China
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26
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Lin C, He H, Liu H, Li R, Chen Y, Qi Y, Jiang Q, Chen L, Zhang P, Zhang H, Li H, Zhang W, Sun Y, Xu J. Tumour-associated macrophages-derived CXCL8 determines immune evasion through autonomous PD-L1 expression in gastric cancer. Gut 2019; 68:1764-1773. [PMID: 30661053 DOI: 10.1136/gutjnl-2018-316324] [Citation(s) in RCA: 259] [Impact Index Per Article: 43.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Revised: 11/26/2018] [Accepted: 12/10/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Our previous studies have identified CXCL8 as the crucial chemokine responsible for gastric cancer metastasis mediated by loss of RACK1. However, the regulatory effect of CXCL8 on immune surveillance in gastric cancer remains obscure. DESIGN Flow cytometry analyses were performed to examine major source of CXCL8 and phenotypes of immune cells in fresh tumour tissues from 76 patients with gastric cancer. Real-time PCR was performed to analyse CXCL8 mRNA level in gastric cancer tissues. For immunohistochemical analyses, a total of 420 patients with gastric cancer undergoing curative resection were enrolled. In vitro culture of fresh tumour tissue was performed to evaluate the potential therapeutic effect of blocking CXCL8 pathway in gastric cancer. RESULTS Increased level of CXCL8 indicates poor clinical outcome and tumour progression in patients with gastric cancer. In gastric cancer tissues, CXCL8 is predominantly secreted by macrophages and colony stimulating factor 2 (CSF-2) facilitates macrophage-derived CXCL8 secretion. High level of CXCL8 is associated with decreased CD8+ T cells infiltration and Ki67+ CD8+ T cells proportion. Moreover, CXCL8 also inhibits CD8+ T cells function by inducing the expression of PD-L1 on macrophages. Finally, we show that a small-molecule CXCR2 inhibitor, reparixin, drives the decreased programmed death-ligand 1 (PD-L1+) macrophages and promotes antitumour immunity. Accordingly, high levels of CXCL8+ macrophages are positively correlated with poor prognosis in patients with gastric cancer. CONCLUSIONS CXCL8 is predominantly secreted by macrophages and contributes to the immunosuppressive microenvironment by inducing PD-L1+ macrophages in gastric cancer. CXCL8 inhibitors may drive antitumour response, providing potential therapeutic effects for patients with gastric cancer.
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Affiliation(s)
- Chao Lin
- Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China
| | - Hongyong He
- Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China
| | - Hao Liu
- Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China
| | - Ruochen Li
- Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China
| | - Yifan Chen
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yangyang Qi
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Qi Jiang
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Lingli Chen
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peipei Zhang
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Heng Zhang
- Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China
| | - He Li
- Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China
| | - Weijuan Zhang
- Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital Fudan University, Shanghai, China
| | - Jiejie Xu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
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Yang W, Wu B, Ma N, Wang Y, Guo J, Zhu J, Zhao S. BATF2 reverses multidrug resistance of human gastric cancer cells by suppressing Wnt/β-catenin signaling. In Vitro Cell Dev Biol Anim 2019; 55:445-452. [DOI: 10.1007/s11626-019-00360-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Accepted: 04/15/2019] [Indexed: 12/26/2022]
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Two-dimensional versus three-dimensional laparoscopic gastrectomy in surgical efficacy for gastric cancer: a systematic review and meta-analysis. Clin Transl Oncol 2019; 22:122-129. [DOI: 10.1007/s12094-019-02116-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 04/11/2019] [Indexed: 01/04/2023]
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Wang Z, Ma K, Pitts S, Cheng Y, Liu X, Ke X, Kovaka S, Ashktorab H, Smoot DT, Schatz M, Wang Z, Meltzer SJ. Novel circular RNA circNF1 acts as a molecular sponge, promoting gastric cancer by absorbing miR-16. Endocr Relat Cancer 2019; 26:265-277. [PMID: 30576282 PMCID: PMC6545167 DOI: 10.1530/erc-18-0478] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 12/14/2018] [Indexed: 12/17/2022]
Abstract
Circular RNAs (circRNAs) are a new class of RNA involved in multiple human malignancies. However, limited information exists regarding the involvement of circRNAs in gastric carcinoma (GC). Therefore, we sought to identify novel circRNAs, their functions and mechanisms in gastric carcinogenesis. We analyzed next-generation RNA sequencing data from GC tissues and cell lines, identifying 75,201 candidate circRNAs. Among these, we focused on one novel circRNA, circNF1 , which was upregulated in GC tissues and cell lines. Loss- and gain-of-function studies demonstrated that circNF1 significantly promotes cell proliferation. Furthermore, luciferase reporter assays showed that circNF1 binds to miR-16, thereby derepressing its downstream target mRNAs, MAP7 and AKT3. Targeted silencing or overexpression of circNF1 had no effect on levels of its linear RNA counterpart, NF1. Taken together, these results suggest that circNF1 acts as a novel oncogenic circRNA in GC by functioning as a miR-16 sponge.
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Affiliation(s)
- Zhe Wang
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China
- Division of Gastroenterology, Department of Medicine, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Ke Ma
- Division of Gastroenterology, Department of Medicine, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Steffie Pitts
- Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Yulan Cheng
- Division of Gastroenterology, Department of Medicine, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Xi Liu
- Department of Pathology, The First Affiliated Hospital of Xi’ an Jiaotong University, No. 277 Yanta West Road, Xi’ an, 710061, Shaanxi, China
| | - Xiquan Ke
- Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China
| | - Samuel Kovaka
- Department of Computer Science, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA
| | - Hassan Ashktorab
- Cancer Center, Howard University School of Medicine, Washington, D.C
| | - Duane T. Smoot
- Department of Medicine, Meharry Medical College, Nashville, TN
| | - Michael Schatz
- Department of Computer Science, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, 21205, USA
| | - Zhirong Wang
- Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200092, China
| | - Stephen J. Meltzer
- Division of Gastroenterology, Department of Medicine, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
- Correspondence: Stephen J. Meltzer, MD, The Johns Hopkins University School of Medicine, 1503 East Jefferson Street, Room 112, Baltimore, Maryland 21287, , Tel.: (410) 502-6071, Fax: (410) 502-1329
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Elghali MA, Fadhl H, Hamila F, Mestiri S, Jarrar MS, Letaief R. Colon Metastasis, 8 years after Gastrectomy, for Stage I Gastric Cancer. J Gastrointest Cancer 2019; 50:127-129. [PMID: 28660526 DOI: 10.1007/s12029-017-9976-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Mohamed Amine Elghali
- Department of General Surgery, Farhat Hached University Hospital, Sousse, Tunisia.
- University of Medicine, Sousse, Tunisia.
| | - Houssem Fadhl
- Department of General Surgery, Farhat Hached University Hospital, Sousse, Tunisia
- University of Medicine, Sousse, Tunisia
| | - Fehmi Hamila
- Department of General Surgery, Farhat Hached University Hospital, Sousse, Tunisia
- University of Medicine, Sousse, Tunisia
| | - Sarra Mestiri
- Department of Anatomopathologie, Farhat Hached University Hospital, Sousse, Tunisia
| | | | - Rached Letaief
- Department of General Surgery, Farhat Hached University Hospital, Sousse, Tunisia
- University of Medicine, Sousse, Tunisia
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Barchi LC, Ramos MFKP, Dias AR, Yagi OK, Ribeiro-Júnior U, Zilberstein B, Cecconello I. TOTAL OMENTECTOMY IN GASTRIC CANCER SURGERY: IS IT ALWAYS NECESSARY? ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2019; 32:e1425. [PMID: 30758473 PMCID: PMC6368152 DOI: 10.1590/0102-672020180001e1425] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/27/2018] [Accepted: 11/22/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND Traditionally, total omentectomy is performed along with gastric resection and extended lymphadenectomy in gastric cancer (GC) surgery. However, solid evidences regarding its oncologic benefit is still scarce. AIM To evaluate the incidence of metastatic omental lymph nodes (LN) in patients undergoing curative gastrectomy for GC, as well as its risk factors and patients' outcomes. METHODS All consecutive patients submitted to D2/modified D2 gastrectomy due to gastric adenocarcinoma from March 2009 to April 2016 were retrospectively reviewed from a prospective collected database. RESULTS Of 284 patients included, five (1.8%) patients had metastatic omental LN (one: pT3N3bM0; two: pT4aN3bM0; one: pT4aN2M0 and one pT4bN3bM0). Four of them deceased and one was under palliative chemotherapy due relapse. LN metastases in the greater omentum significantly correlated with tumor's size (p=0.018), N stage (p<0.001), clinical stage (p=0.022), venous invasion growth (p=0.003), recurrence (p=0.006), site of recurrence (peritoneum: p=0.008; liver: p=0.023; ovary: p=0.035) and death (p=0.008). CONCLUSION The incidence of metastatic omental LN of patients undergoing radical gastrectomy due to GC is extremely low. Total omentectomy may be avoided in tumors smaller than 5.25 cm and T1/T2 tumors. However, the presence of lymph node metastases in the greater omentum is associated with recurrence in the peritoneum, liver, ovary and death.
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Affiliation(s)
- Leandro Cardoso Barchi
- Discipline of Digestive Surgery, Department of Gastroenterology, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
| | | | - André Roncon Dias
- Discipline of Digestive Surgery, Department of Gastroenterology, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
| | - Osmar Kenji Yagi
- Discipline of Digestive Surgery, Department of Gastroenterology, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
| | - Ulysses Ribeiro-Júnior
- Discipline of Digestive Surgery, Department of Gastroenterology, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
| | - Bruno Zilberstein
- Discipline of Digestive Surgery, Department of Gastroenterology, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
| | - Ivan Cecconello
- Discipline of Digestive Surgery, Department of Gastroenterology, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil
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Liu G, Xu M, Gao T, Xu L, Zeng P, Bo H, Li F, Zhang W, Wang Z. Surgical Compliance and Outcomes in Gastric Cancer: a population-based cohort study. J Cancer 2019; 10:779-788. [PMID: 30854083 PMCID: PMC6400806 DOI: 10.7150/jca.29073] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 01/09/2019] [Indexed: 12/12/2022] Open
Abstract
Background: Surgical resection is one of curative treatment for gastric cancer (GC), however, a set of patients show poor surgical compliance in the USA. We aimed to identify the risk factors associated with surgical compliance and investigate the difference in survival. Methods: GC patients diagnosed between 1973 and 2014 were identified from the Surveillance Epidemiology and End Results (SEER) databases. Based on different surgical compliance and treatment regimen, patients were classified into three subgroups: surgical compliance group, surgical noncompliance group, and non-surgical group. Multivariable Logistic regression analysis was adopted to identify the factors related to surgical compliance; Multivariable Cox regression was used to investigate the prognostic factors. Overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan-Meier estimator method. Results: Of 79374 GC patients who were recommended for surgical therapy, 15201(19.2%) cases did not perform surgery. Poor compliance of surgery was related to old age, American Indian/Alaska Native race, poor grading/late staging, single/widowed status, lower socioeconomic status and earlier time of diagnosis. As expected, GC patients of surgical compliance group showed significantly more favorable survival than the other two groups (P<0.0001); notably, the outcome of surgical noncompliance group came close to that of non-surgical group. Conclusion: GC patients of poor surgical compliance demonstrated adverse survival, which was comparable to that of non-surgical patients. The poor surgical compliance was associated with older age, American Indian/Alaska Native race, poor tissue differentiation/advanced stage of tumor, single/widowed status, lower socioeconomic status and earlier time of diagnosis.
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Affiliation(s)
- Guihua Liu
- Department of General Practice, Zhongshan Street Community Health Center of Songjiang District, Shanghai, 201600, China
| | - Ming Xu
- Department of General Surgery, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China
| | - Tingting Gao
- Department of General Practice, Zhongshan Street Community Health Center of Songjiang District, Shanghai, 201600, China
| | - Lingying Xu
- Department of General Practice, Zhongshan Street Community Health Center of Songjiang District, Shanghai, 201600, China
| | - Peijun Zeng
- Department of General Practice, Zhongshan Street Community Health Center of Songjiang District, Shanghai, 201600, China
| | - Haiying Bo
- Department of General Practice, Zhongshan Street Community Health Center of Songjiang District, Shanghai, 201600, China
| | - Fang Li
- Department of General Practice, Zhongshan Street Community Health Center of Songjiang District, Shanghai, 201600, China
| | - Wei Zhang
- Department of General Practice, Zhongshan Street Community Health Center of Songjiang District, Shanghai, 201600, China
| | - Zhengting Wang
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200001, China
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Jiao Y, Yang H, Qian J, Gong Y, Liu H, Wu S, Cao L, Tang L. miR‑3664‑5P suppresses the proliferation and metastasis of gastric cancer by attenuating the NF‑κB signaling pathway through targeting MTDH. Int J Oncol 2019; 54:845-858. [PMID: 30628643 PMCID: PMC6365029 DOI: 10.3892/ijo.2019.4680] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 11/16/2018] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) is one of the most common and fatal types of cancers worldwide and the specific mechanism has not been completely elucidated. microRNA (miR)‑3664‑5P has rarely been studied and the aim of the present study was to assess an association between miR‑3664‑5P and GC. Differences in miR‑3664‑5P expression in 100 GC (0.1846±0.08276) and paired normal tissues (0.4382±0.1595) were detected using reverse transcription‑quantitative polymerase chain reaction assays (P<0.001). 5‑Ethynyl‑2‑deoxyuridine, Cell Counting Kit‑8, transwell and flow cytometry assays were performed in vitro and the results were further verified using a mouse xenotransplantation and a lung metastasis model in vivo. miR‑3664‑5P was significantly downregulated in GC tissues when compared with normal tissues and positively associated with the prognosis of patients with GC (P<0.001). Overexpression of miR‑3664‑5P suppressed and miR‑3664‑5P knockdown promoted the proliferation and metastasis of GC cells in vitro and in vivo. Following the application of bioinformatic algorithms and luciferase reporter assays, metadherin (MTDH) was confirmed as the target gene of miR‑3664‑5P. miR‑3664‑5P reduced MTDH expression and downregulated the nuclear factor (NF)‑κB signaling pathway. Rescue experiments demonstrated that suppression of MTDH restored the effect of miR‑3664‑5P inhibitors on GC cell lines. The results suggested that miR‑3664‑5P suppressed the proliferation and metastasis of GC cells by attenuating the NF‑κB signaling pathway via MTDH targeting. Consequently, miR‑3664‑5P may have potential to be an independent prognostic factor and biomarker in GC.
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Affiliation(s)
- Yuwen Jiao
- Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
| | - Haojun Yang
- Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
| | - Jun Qian
- Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
| | - Yu Gong
- Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
| | - Hanyang Liu
- Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
| | - Siyuan Wu
- Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
| | - Liang Cao
- Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
| | - Liming Tang
- Department of Gastrointestinal Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, P.R. China
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Wang X, Li Z, Chen M, Wu C, Fu Y. Minimally invasive and open gastrectomy for gastric cancer: A protocol for systematic review and network meta-analysis. Medicine (Baltimore) 2018; 97:e13419. [PMID: 30508949 PMCID: PMC6283097 DOI: 10.1097/md.0000000000013419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND The aim of this study is to find the better treatment for gastric cancer by comparing robotic gastrectomy, laparoscopic gastrectomy, and open gastrectomy using Bayesian network meta-analysis. METHODS We will search PubMed, Embase, and the Cochrane Library for eligible studies published before 1 September 2018. There will be no language restrictions. Randomized clinical trials that compare robotic gastrectomy, laparoscopic gastrectomy, or open gastrectomy for patients with gastric cancer will be included. The risk of bias of included studies will be assessed by the Cochrane Collaboration's tool for assessing risk of bias in randomized trial. The outcomes of the study include operation time, estimated blood loss, time of ambulation, times to first flatus, time of oral intake, hospitalization, and the occurrence of complication. If sufficient data is collected and adequate clinical homogeneity is established among studies, we will conduct pairwise meta-analyses and Bayesian network meta-analyses for all related outcome measures. ETHICS AND DISSEMINATION The study does not involve human subjects and does not need ethical approval and patient consent. The results of the network meta-analysis will be disseminated in a peer-reviewed journal for publication.
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Affiliation(s)
- Xixiong Wang
- Department of Surgical Oncology, Boao Evergrande International Hospital, Qionghai
| | - Zhiqiang Li
- Department of Gastrointestinal Surgery, Sanya People's Hospital, Sanya, China
| | - Meizhu Chen
- Department of Gastrointestinal Surgery, Sanya People's Hospital, Sanya, China
| | - Chenming Wu
- Department of Gastrointestinal Surgery, Sanya People's Hospital, Sanya, China
| | - Yexiang Fu
- Department of Gastrointestinal Surgery, Sanya People's Hospital, Sanya, China
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Ren DF, Zheng FC, Zhao JH, Shen GS, Ahmad R, Zhang SS, Zhang Y, Kan J, Dong L, Wang ZY, Zhao FX, Zhao JD. Adjuvant chemotherapy with S-1 plus oxaliplatin improves survival of patients with gastric cancer after D2 gastrectomy: A multicenter propensity score-matched study. World J Clin Cases 2018; 6:373-383. [PMID: 30283800 PMCID: PMC6163137 DOI: 10.12998/wjcc.v6.i10.373] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 08/22/2018] [Accepted: 08/28/2018] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the safety and efficacy of S-1 plus oxaliplatin (SOX) as an adjuvant chemotherapy regimen in gastric cancer (GC) after D2 dissection.
METHODS GC Patients who underwent D2 gastrectomy from September 2009 to December 2011 in four Chinese institutions were enrolled. Patients with stage IB-IIIC GC, who received adjuvant SOX treatment were matched by propensity scores with those who underwent surgery alone and those who conducted capecitabine plus oxaliplatin (XELOX) regimen. Disease-free survival (DFS) and overall survival (OS) were compared among the groups. In addition, adverse events in SOX patients were analyzed.
RESULTS Of 1944 GC patients who underwent D2 dissection, 867 were included for analysis. One hundred and seventeen patients treated with SOX were matched to 234 patients who conducted surgery alone. Fifty-seven patients treated with SOX were matched to 57 patients who received XELOX. The estimated five-year DFS was 57.5% in the adjuvant SOX group which was higher than that (44.6%) in the surgery alone group (P = 0.001); and the estimated five-year OS was 68.3% which was higher than that (45.8%) of surgery alone group (P < 0.001). Survival benefit was also revealed in stage III and > 60 years old subgroups (P < 0.001 and P = 0.015, respectively). Compared with XELOX regimen, SOX showed no significant difference in DFS (P = 0.340) and OS (P = 0.361). The most common ≥ 3 grade adverse events of SOX regimen were neutropenia (22.6%), leukopenia (8.9%) and thrombocytopenia (5.6%).
CONCLUSION Compared with surgery alone, SOX regimen significantly improves the long-term survival and has acceptable toxicity in patients with stage IB-IIIC GC after D2 dissection. It may be a novel adjuvant chemotherapy regimen in GC patients.
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Affiliation(s)
- Deng-Feng Ren
- Department of Medical Oncology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Fang-Chao Zheng
- Department of Medical Oncology, Shouguang Hospital of Traditional Chinese Medicine, Weifang 262700, Shandong Province, China
| | - Jun-Hui Zhao
- Department of Medical Oncology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Guo-Shuang Shen
- Department of Surgical Oncology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Raees Ahmad
- Department of Medical Oncology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Shui-Sheng Zhang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yu Zhang
- Department of Medical Oncology, Qinghai Red Cross Hospital, Xining 810000, Qinghai Province, China
| | - Jie Kan
- Department of Medical Oncology, People’s Hospital of Qinghai Province, Xining 810000, Qinghai Province, China
| | - Li Dong
- Institutes of Biomedical Sciences, Shanxi University, Taiyuan 030006, Shanxi Province, China
| | - Zi-Yi Wang
- Department of Medical Oncology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Fu-Xing Zhao
- Department of Medical Oncology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining 810000, Qinghai Province, China
| | - Jiu-Da Zhao
- Department of Medical Oncology, Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining 810000, Qinghai Province, China
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Morgant S, Artru P, Oudjit A, Lourenco N, Pasquer A, Walter T, Gornet JM, Rouquette A, Lledo G, Brezault C, Coriat R. Computed tomography scan efficacy in staging gastric linitis plastica lesion: a retrospective multicentric French study. Cancer Manag Res 2018; 10:3825-3831. [PMID: 30288113 PMCID: PMC6161744 DOI: 10.2147/cmar.s163141] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Computed tomography (CT) scan is a key imaging technique in the staging of gastric adenocarcinoma and therapeutic management of patients. The aim of this study was to evaluate the performance of CT scan in the staging of parietal and metastatic invasion in gastric linitis plastica group. Methods A retrospective multicentric French study was conducted from January 2006 to December 2015 on patients with no metastatic gastric linitis plastica and operated by gastrec-tomy. A 2/1 matching based on pTNM stage and center was performed. Results Fifty patients were included in the linitis plastica group and 100 in the control group. Patients from the linitis group were significantly different from those from the control group with a lower age at diagnosis, a more advanced histological lesion, a more frequent undiagnosed peritoneal carcinomatosis, and a higher risk of R1 resection. Sensitivity and specificity of CT scan for the diagnosis of lymph node involvement were 44% and 75%, respectively, in the linitis plastica group and 55% and 60%, respectively, in the control group. The sensitivity and specificity of CT scan for the T3–T4 parietal invasion were 26% and 100%, respectively, in the linitis group and 40% and 72%, respectively, in the control group. Conclusion CT scan has an equal sensitivity and specificity for the evaluation of lymph node and parietal involvement in gastric adenocarcinoma, including linitis plastica. CT scan remains the cornerstone of preoperative evaluation in gastric adenocarcinoma, including linitis plastica. However, CT presents a lack of sensitivity to diagnose low-volume peritoneal carcinomatosis.
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Affiliation(s)
- Stéphanie Morgant
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, Paris, France,
| | - Pascal Artru
- Gastroenterology and Digestive Unit, Jean Mermoz Clinic, Lyon, France
| | - Ammar Oudjit
- Radiology Unit, Cochin Teaching Hospital, Paris, France
| | - Nelson Lourenco
- Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France
| | - Arnaud Pasquer
- Digestive Surgery Unit, Edouard Herriot Teaching Hospital, Lyon, France
| | - Thomas Walter
- Oncology Unit, Edouard Herriot Teaching Hospital, Lyon, France
| | - Jean-Marc Gornet
- Gastroenterology Unit, Saint-Louis Teaching Hospital, Paris, France
| | | | - Gérard Lledo
- Gastroenterology and Digestive Unit, Jean Mermoz Clinic, Lyon, France
| | - Catherine Brezault
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, Paris, France,
| | - Romain Coriat
- Gastroenterology and Digestive Oncology Unit, Cochin Teaching Hospital, Paris, France,
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Cai Z, Yin Y, Zhao Z, Xin C, Cai Z, Yin Y, Shen C, Yin X, Wang J, Chen Z, Zhou Y, Zhang B. Comparative Effectiveness of Neoadjuvant Treatments for Resectable Gastroesophageal Cancer: A Network Meta-Analysis. Front Pharmacol 2018; 9:872. [PMID: 30127746 PMCID: PMC6087755 DOI: 10.3389/fphar.2018.00872] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2018] [Accepted: 07/19/2018] [Indexed: 02/05/2023] Open
Abstract
Background: Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence. Method: We searched relevant databases for randomized controlled trials of neoadjuvant treatments for resectable gastroesophageal cancer which compared two or more of the following treatments: surgery alone, perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT), and neoadjuvant treatments listed in National Comprehensive Cancer Network guideline. Then we performed a NMA to summarize the direct and indirect evidence to estimate the relative efficacy for outcomes including overall survival (OS), progression-free survival and R0 resection rate. We calculated odds ratio (OR) and hazard ratio (HR) with 95% credible intervals (CrI) for dichotomous data and time-to-event data, respectively. We also calculated the surface under the cumulative ranking curve (SUCRA) value of each intervention to obtain a hierarchy of treatments. Result: Eight eligible trials (2434 patients) were included in our NMA. The treatment with the highest probability of benefit on OS as compared with surgery alone was perioperative FLOT [HR = 0.58 with 95% CrI: (0.43, 0.78), SUCRA = 93%], followed by preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC) [HR = 0.68 with 95% CrI: (0.53, 0.87), SUCRA = 72%], perioperative cisplatin with fluorouracil (CF) [HR = 0.70 with 95% CrI: (0.51, 0.95), SUCRA = 68%], and perioperative epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) [HR = 0.75 with 95% CrI: (0.60, 0.94), SUCRA = 56%]. Conclusion: Compared with surgery alone, perioperative CF, perioperative ECF/ECX, perioperative FLOT, and preoperative RT/PC significantly improved survival. Perioperative FLOT is likely to be the most effective neoadjuvant treatment for the disease. Further clinical studies are needed and justified.
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Affiliation(s)
- Zhaolun Cai
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Yiqiong Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhou Zhao
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chunyu Xin
- West China College of Public Health, Sichuan University, Chengdu, China
| | - Zhaohui Cai
- Department of Infectious Disease, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- The First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Chaoyong Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Jian Wang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Zhixin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ye Zhou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
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Cai Z, Cai Z, He T, Zhao Z, Yin Y, Shen C, Yin X, Chen Z, Dan C, Zhang B. Comparative effectiveness of hyperthermic intraperitoneal chemotherapy for gastric cancer: A systematic review and network meta-analysis protocol. Medicine (Baltimore) 2018; 97:e11949. [PMID: 30113499 PMCID: PMC6112913 DOI: 10.1097/md.0000000000011949] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 07/27/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Comparative efficacy and safety of different hyperthermic intraperitoneal chemotherapies (HIPEC) in patients with advanced gastric cancer who underwent gastrectomy is unclear. To investigate this question, we conduct a systematic review and network meta-analysis. METHODS The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. PubMed, Embase, and the Cochrane Library will be searched systematically for eligible randomized controlled trials without language restriction. The primary outcome is overall survival. The second outcomes are postoperative complications. The surface under the cumulative ranking curve value will be calculated to establish a hierarchy of the treatments. RESULTS The results will provide useful information about the effectiveness and safety of HIPEC regimens in patients with resected gastric cancer. CONCLUSION The findings of the study will be disseminated through peer-reviewed journal.
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Affiliation(s)
- Zhaolun Cai
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Zhaohui Cai
- Department of Infectious Disease, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine
- The First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing
| | - Tao He
- Department of Breast Surgery, West China Hospital
| | - Zhou Zhao
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Chaoyong Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Zhixin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Cao Dan
- Department of Medical Oncology, Cancer Center of West China Hospital, Sichuan University, Chengdu, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
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Cai Z, Zhou Y, Wang C, Yin Y, Yin Y, Shen C, Yin X, Chen Z, Zhang B. Optimal reconstruction methods after distal gastrectomy for gastric cancer: A systematic review and network meta-analysis. Medicine (Baltimore) 2018; 97:e10823. [PMID: 29768387 PMCID: PMC5976285 DOI: 10.1097/md.0000000000010823] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 04/26/2018] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The choice of anastomosis methods including Billroth I, Billroth II, and Roux-en-Y after a distal gastrectomy is still controversial. The conventional meta-analyses assessing 2 alternative treatments were not powered to compare differences in clinical outcomes. To guide treatment decisions in patients with gastric cancer (GC) after distal gastrectomy, we did a systematic review and network meta-analysis to identify the best reconstruction method. METHODS We systematically searched PubMed, EMBASE, the Cochrane Library for randomized controlled trials comparing the outcomes of Billroth I, Billroth II, or Roux-en-Y reconstruction after distal subtotal gastrectomy for patients with GC, then we performed a direct meta-analysis and Bayesian network meta-analysis to pooled odds ratios (OR) or weighted mean differences (WMD) with 95% credible intervals (CrI) with random effects model. The node-splitting method was used to assess the inconsistency. We estimated the potential ranking probability of treatments by calculating the surface under the cumulative ranking curve for each intervention. RESULTS Nine studies involving 1161 patient were included in the network meta-analysis. Statistical significance was reached for the comparisons of Roux-en-Y versus Billroth I reconstruction (WMD 37, 95% Crl: 22-51) and Billroth II versus Billroth I reconstruction (WMD 25, 95% Crl: 5.8-43) for operation time; and Roux-en-Y versus Billroth I reconstruction (WMD 26, 95% Crl: 2.1-68) for intraoperative blood loss; and Roux-en-Y versus Billroth I reconstruction (OR 3.4, 95% Crl: 1.1-13) for delayed gastric emptying. Roux-en-Y reconstruction was superior to Billroth I and Billroth II reconstruction in terms of frequency of bile reflux (OR 0.095, 95% Crl: 0.010-0.63; OR 0.064, 95% Crl: 0.0037-0.84, respectively) and the incidence of remnant gastritis (OR 0.33, 95% Crl: 0.16-0.58; OR 0.40, 95% Crl: 0.17-0.92, respectively). CONCLUSION Roux-en-Y reconstruction is superior to Billroth I and Billroth II reconstruction in terms of preventing bile reflux and remnant gastritis, Billroth I and Billroth II anastomosis could be considered as the substitute in consideration of technical simplicity. As for postoperative morbidity and the advantage of physiological food passage, Billroth I method is the choice.
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Affiliation(s)
- Zhaolun Cai
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Ye Zhou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai
| | - Chenxiao Wang
- West China School of Preclinical Medicine and Forensic Medicine, Sichuan University, Chengdu, Sichuan, China
| | - Yiqiong Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Yuan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Chaoyong Shen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Xiaonan Yin
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Zhixin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan
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Du C, Yang S, Zhao X, Dong H. Pathogenic roles of alterations in vitamin D and vitamin D receptor in gastric tumorigenesis. Oncotarget 2018; 8:29474-29486. [PMID: 28206978 PMCID: PMC5438745 DOI: 10.18632/oncotarget.15298] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2016] [Accepted: 01/20/2017] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer is currently the second leading cause of cancer-related death worldwide, especially in Japan, Korea and China, and the 5-year survival rate of gastric cancer is less than 30%. Thus, it is important to shed more lights on novel agents to prevent gastric cancer or to improve survival rate of the patients. Vitamin D not only maintains calcium and bone homeostasis, but also mostly inhibits tumor genesis, invasion, and metastasis through activation of vitamin D receptor. Although epidemiological results are not consistent, accumulating evidence from gastric cancer cells, animal models, and clinical trials suggest that vitamin D deficiency may increase the risk and mortality of gastric cancer, but vitamin D supplement might be a safe and economical way to prevent or treat gastric cancer. Here, we reviewed the current studies on vitamin D and its receptor and focused on the pathogenic roles of their alterations in gastric tumorigenesis.
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Affiliation(s)
- Chao Du
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.,Department of Gastroenterology and Hepatology, Chengdu Military General Hospital, Sichuan Province, China
| | - Shiming Yang
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Xiaoyan Zhao
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Hui Dong
- Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.,Division of Gastroenterology, Department of Medicine, School of Medicine, University of California, San Diego, California, USA
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Hu Y, Yu K, Wang G, Zhang D, Shi C, Ding Y, Hong D, Zhang D, He H, Sun L, Zheng JN, Sun S, Qian F. Lanatoside C inhibits cell proliferation and induces apoptosis through attenuating Wnt/β-catenin/c-Myc signaling pathway in human gastric cancer cell. Biochem Pharmacol 2018; 150:280-292. [DOI: 10.1016/j.bcp.2018.02.023] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 02/16/2018] [Indexed: 02/06/2023]
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Short-term outcomes in minimally invasive versus open gastrectomy: the differences between East and West. A systematic review of the literature. Gastric Cancer 2018; 21:19-30. [PMID: 28730391 PMCID: PMC5741797 DOI: 10.1007/s10120-017-0747-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Accepted: 07/06/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Minimally invasive surgical techniques for gastric cancer are gaining more interest worldwide. Several Asian studies have proven the benefits of minimally invasive techniques over the open techniques. Nevertheless, implementation of this technique in Western countries is gradual. The aim of this systematic review is to give insight in the differences in outcomes and patient characteristics in Asian countries in comparison to Western countries. METHODOLOGY An extensive systematic search was conducted using the Medline, Embase, and Cochrane databases. Analysis of the outcomes was performed regarding operative results, postoperative recovery, complications, mortality, lymph node yield, radicality of the resected specimen, and survival. A total of 12 Asian and 8 Western studies were included. RESULTS Minimally invasive gastrectomy shows faster postoperative recovery, fewer complications, and similar outcomes regarding mortality in both the Eastern and Western studies. However, patient characteristics such as age and BMI differ between these populations. Comparison of overall outcomes in minimally invasive and open procedures between East and West showed differences in complications, mortality, and number of resected lymph nodes in favor of the Asian population. CONCLUSION Improved outcomes are observed following minimally invasive gastrectomy in comparison to open procedures in both Western and Asian studies. There are differences in patient characteristics between the Western and Asian populations. Overall outcomes seem to be in favor of the Asian population. These differences may fade with centralization of care for gastric cancer patients in the West and increasing surgical experience.
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Zhang Q, Qu H, Sun G, Li Z, Ma S, Shi Z, Zhao E, Zhang H, He Q. Early postoperative tumor marker responses provide a robust prognostic indicator for N3 stage gastric cancer. Medicine (Baltimore) 2017; 96:e7560. [PMID: 28796039 PMCID: PMC5556205 DOI: 10.1097/md.0000000000007560] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The clinical significance of tumor markers after radical gastrectomy has not been well characterized. The purpose of this study is to evaluate the prognostic value of early postoperative tumor marker normalization in N3 stage gastric cancer (GC) patients. A total of 259 N3 stage GC patients with preoperatively elevated carcinoembryonic antigen (CEA, >5 ng/mL) or carbohydrate antigen 19-9 (CA19-9, >37 U/mL) levels underwent radical gastrectomy were analyzed retrospectively. Early postoperative tumor marker response was considered as a normalization of CEA or CA19-9 levels 4 weeks after surgery. The disease-free survival (DFS) and overall survival (OS) were analyzed. N3 stage GC patients were divided into N3a (n = 157) and N3b (n = 102) groups according to the 8th TNM stage system. Early tumor marker response was identified in 96 of 157 N3a patients (61.15%) and 57 of 102 N3b patients (55.88%). In N3 stage GC patients with a tumor marker response, significant increase was observed in both DFS (25.2 months vs 12.5 months, P < .001) and OS (32.5 months vs 18.5 months, P < .001) compared with those without tumor marker response. N3b patients with a tumor marker response showed more favorable DFS (19.2 months vs 13.6 months, P = .019) and OS (25.8 months vs 19.0 months, P = .013) compared with N3a patients lacking a tumor marker response. Multivariate analysis revealed that early tumor marker response was an independent factor for DFS and OS in N3 stage GC, as well as for depth of invasion and metastatic lymph node rate (P < .05). Early postoperative CEA or CA19-9 normalization serves as a strong prognostic indicator in N3 stage GC. Both N3a and N3b patients with increased early postoperative tumor marker levels showed poor outcomes.
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Affiliation(s)
| | - Hui Qu
- Department of General Surgery
| | | | | | - Shuzhen Ma
- Department of Chemotherapy, Shandong University Qilu Hospital, Jinan
| | - Zhenxing Shi
- Department of General Surgery, The People's Hospital of Laoling, Dezhou, China
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Wang G, Sun J, Liu G, Fu Y, Zhang X. Bradykinin Promotes Cell Proliferation, Migration, Invasion, and Tumor Growth of Gastric Cancer Through ERK Signaling Pathway. J Cell Biochem 2017; 118:4444-4453. [PMID: 28464378 DOI: 10.1002/jcb.26100] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Accepted: 04/28/2017] [Indexed: 01/06/2023]
Abstract
Bradykinin (BK) has been reported to be involved in the progression of diverse types of cancer. In the present study, we investigated the possible role of BK in cell proliferation, migration, invasion, and tumor growth of gastric cancer (GC). Cell proliferation was evaluated by MTT assays. Cell migration and invasion were assessed by Transwell assays. Tumor growth of nude mice was detected by establishing subcutaneous xenograft tumor model. Silencing of bradykinin B1 receptor (B1R) and the bradykinin B2 receptor (B2R) was performed by transfecting cells with si-B1R and si-B2R, respectively. The protein expression levels of phospho-ERK1/2 (p-ERK1/2), matrix metalloproteinase (MMP)-2, MMP-9, and E-Cadherin were examined by Western blot. Data revealed that BK promoted cell proliferation, migration, invasion, and the in vivo tumor growth of GC cells SGC-7901 and HGC-27. Furthermore, BK elevated the protein levels of p-ERK1/2, MMP-2, and MMP-9, but reduced E-Cadherin. In addition, by repressing B2R using si-B2R or inhibiting ERK signaling pathway using PD98059, BK-mediated promotion of cell proliferation, migration, and invasion and upregulation of p-ERK1/2, MMP-2/9, as well as downregulation of E-Cadherin were attenuated. Taken together, the present study demonstrated that BK promoted cell proliferation, migration, invasion, and tumor growth by binding to B2R via ERK signaling pathway. Our findings may provide promising options for the further treatment of GC. J. Cell. Biochem. 118: 4444-4453, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Guojun Wang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China
| | - Junfeng Sun
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China
| | - Guanghui Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China
| | - Yang Fu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China
| | - Xiefu Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China
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Ji X, Yan Y, Bu ZD, Li ZY, Wu AW, Zhang LH, Wu XJ, Zong XL, Li SX, Shan F, Jia ZY, Ji JF. The optimal extent of gastrectomy for middle-third gastric cancer: distal subtotal gastrectomy is superior to total gastrectomy in short-term effect without sacrificing long-term survival. BMC Cancer 2017; 17:345. [PMID: 28526077 PMCID: PMC5437661 DOI: 10.1186/s12885-017-3343-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 05/11/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND The optimal extent of gastrectomy for middle-third gastric cancer remains controversial. In our study, the short-term effects and longer-term survival outcomes of distal subtotal gastrectomy and total gastrectomy are analysed to determine the optimal extent of gastrectomy for middle-third gastric cancer. METHODS We retrospectively collect and analyse clinicopathologic data and follow-up outcomes from a prospectively collected database at the Peking University Cancer Hospital. Patients with middle-third gastric adenocarcinoma who underwent curative resection are enrolled in our study. RESULTS We collect data of 339 patients between January 2005 and October 2011. A total of 144 patients underwent distal subtotal gastrectomy, and 195 patients underwent total gastrectomy. Patients in the total gastrectomy group have longer operative duration (P < 0.001) and postoperative hospital stay (P = 0.001) than those in the distal subtotal gastrectomy group. In the total gastrectomy group, more lymph nodes are harvested (P < 0.001). Meanwhile, the rate of postoperative complications is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (8% vs 15%, P = 0.047). Further analysis demonstrates that the rate of anastomosis leakage is lower in the distal subtotal gastrectomy group than in the total gastrectomy group (0% vs 4%, P = 0.023). Kaplan-Meier (log rank test) analysis shows a significant difference in overall survival between the two groups. The 5-year overall survival rates in the distal subtotal gastrectomy and total gastrectomy groups are 65% and 47%, respectively (P < 0.001). Further stage-stratified analysis reveals that no statistical significance exists in 5-year survival rate between the distal subtotal gastrectomy and total gastrectomy groups at the same stage. Multivariate analysis shows that age (P = 0.046), operation duration (P < 0.001), complications (P = 0.037), usage of neoadjuvant chemotherapy (P < 0.001), tumor size (P = 0.012), presence of lymphovascular invasion (P = 0.043) and N stage (P < 0.001) are independent prognostic factors for survival. CONCLUSIONS For patients with middle-third gastric cancer, distal subtotal gastrectomy shortens the operation duration and postoperative hospital stay and reduces postoperative complications. Meanwhile, the long-term survival of patients with distal subtotal gastrectomy is similar to that of those with total gastrectomy at the same stage. The extent of gastrectomy for middle-third gastric cancer is not an independent prognostic factor for survival.
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Affiliation(s)
- Xin Ji
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Yan Yan
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Endoscopy, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhao-De Bu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Zi-Yu Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Ai-Wen Wu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Lian-Hai Zhang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Xiao-Jiang Wu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Xiang-Long Zong
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Shuang-Xi Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Fei Shan
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Zi-Yu Jia
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
| | - Jia-Fu Ji
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52 Fucheng Road, Haidian District, Beijing, 100142 China
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Suda K, Kitagawa Y. How Do We Bridge the West and the East in the Treatment for Gastric Cancer? Ann Surg Oncol 2017; 24:864-865. [PMID: 27783165 DOI: 10.1245/s10434-016-5647-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2016] [Indexed: 08/29/2023]
Affiliation(s)
- Koichi Suda
- Cancer Center/Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
| | - Yuko Kitagawa
- Cancer Center/Department of Surgery, School of Medicine, Keio University, Tokyo, Japan
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Franklyn J, George SV, Yacob M, Abraham V, Chandran S, Sebastian T, Samarasam I. Surgical Outcomes Associated with Operable Gastric Cancer in a Tertiary Care Indian Hospital. J Gastric Cancer 2017; 17:63-73. [PMID: 28337364 PMCID: PMC5362835 DOI: 10.5230/jgc.2017.17.e7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 02/09/2017] [Accepted: 02/20/2017] [Indexed: 12/14/2022] Open
Abstract
Purpose Data on operable gastric cancer from India is sparse. The purpose of this study was to investigate the clinical details, histopathological demographics, and 5-year overall survival (OS) and disease free survival (DFS) associated with operable, non-metastatic gastric cancer in a dedicated upper gastrointestinal (GI) surgical unit in India. Materials and Methods Data for patients diagnosed with operable gastric cancer between January 2006 and December 2014 were retrospectively analyzed. Data were collected from electronic hospital records in addition to mail and telephonic interviews when possible. Results A total of 427 patients were included. The tumor was located in the pyloro-antral region in 263 patients (61.7%). Subtotal gastrectomy was performed in 291 patients and total gastrectomy in 136 patients. Tumor stage classification revealed 43 patients (10.0%) with stage I, 40 patients (9.4%) with stage IIA, 59 patients (13.9%) with stage IIB, 76 patients (17.8%) with stage IIIA, 96 patients (22.5%) with stage IIIB, and 113 patients (26.4%) with stage IIIC disease. Follow-up data were available for 71.6% of the patients with a mean duration of 32.4 months. Five-year DFS and OS were 39% and 59%, respectively. Conclusions Despite presenting at an advanced stage, the 5-year DFS and OS of patients with operable gastric cancer treated at a dedicated upper GI unit of a tertiary care center in India was good.
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Affiliation(s)
- Joshua Franklyn
- Upper GI Surgery Unit, Department of General Surgery Unit 3, Christian Medical College, Vellore, India
| | - Sam V George
- Upper GI Surgery Unit, Department of General Surgery Unit 3, Christian Medical College, Vellore, India
| | - Myla Yacob
- Upper GI Surgery Unit, Department of General Surgery Unit 3, Christian Medical College, Vellore, India
| | - Vijay Abraham
- Upper GI Surgery Unit, Department of General Surgery Unit 3, Christian Medical College, Vellore, India
| | - Sudhakar Chandran
- Upper GI Surgery Unit, Department of General Surgery Unit 3, Christian Medical College, Vellore, India
| | - Tunny Sebastian
- Upper GI Surgery Unit, Department of General Surgery Unit 3, Christian Medical College, Vellore, India
| | - Inian Samarasam
- Upper GI Surgery Unit, Department of General Surgery Unit 3, Christian Medical College, Vellore, India
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Tsai CY, Liu YY, Liu KH, Hsu JT, Chen TC, Chiu CT, Yeh TS. Comprehensive profiling of virus microRNAs of Epstein-Barr virus-associated gastric carcinoma: highlighting the interactions of ebv-Bart9 and host tumor cells. J Gastroenterol Hepatol 2017; 32:82-91. [PMID: 27144885 DOI: 10.1111/jgh.13432] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 03/23/2016] [Accepted: 04/27/2016] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIM Epstein-Barr virus (EBV) is suggested to actively utilize its ebv-microRNAs (miRNAs) to manipulate viral and cellular functions during neoplasia transformation. A systemic profiling of ebv-miRNAs expressed in EBV-associated gastric carcinoma (EBVa GC) helps understand its epigenetic regulation of carcinogenesis. METHODS A total of 1039 patients with gastric cancer were screened for EBVa GC using EBV-encoded RNAs in situ hybridization. A comprehensive profiling of ebv-miRNAs expressed in EBVa GC was constructed using stem-loop quantitative polymerase chain reaction. Functional assay of specific ebv-miRNA was conducted. Expression of epithelial-to-mesenchymal transition (EMT) markers among EBVa GC and non-EBVa GC was compared. RESULTS The prevalence of EBVa GC was 5.0% (52 out of 1039) in our series. The most abundant ebv-miRNAs of EBVa GC were Bart4, followed by Bart11, Bart2, Bart6, Bart9, and Bart18, in the decreasing order. Of them, Bart9 exhibited the same seed sequence as to hsa miR-200a and miR-141. Expression of E-cadherin of EBV-positive SNU-719 was increased after BART9 knockdown. Depleting endogenous Bart9 of SNU-719 induced a surged expression of miR-200a and miR-141, accompanied by decreased proliferative and invasive ability. Expression of mesenchymal markers in EBVa GC was increased compared with those of non-EBVa GC, albeit the two cohorts exhibited a comparable long-term survival. CONCLUSIONS We constructed a comprehensive profiling of ebv-miRNAs in EBVa GC. BART9 plays an important role during carcinogenesis through EMT. Inherent mesenchymal phenotype of EBVa GC represents a unique virus-induced morphology and microenvironment rather than being able to predict the prognosis.
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Affiliation(s)
- Chun-Yi Tsai
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yu Yin Liu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Keng-Hao Liu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Jun-Te Hsu
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Tse-Ching Chen
- Department of Pathology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Cheng-Tang Chiu
- Department of Gastroenterology, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Ta-Sen Yeh
- Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan
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Toiyama Y, Yasuda H, Ohi M, Yoshiyama S, Araki T, Tanaka K, Inoue Y, Mohri Y, Kusunoki M. Clinical impact of preoperative albumin to globulin ratio in gastric cancer patients with curative intent. Am J Surg 2017; 213:120-126. [DOI: 10.1016/j.amjsurg.2016.05.012] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2015] [Revised: 05/07/2016] [Accepted: 05/31/2016] [Indexed: 02/08/2023]
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Abstract
Gastric cancer is one of the leading causes of cancer-related death worldwide. Many patients have inoperable disease at diagnosis or have recurrent disease after resection with curative intent. Gastric cancer is separated anatomically into true gastric adenocarcinomas and gastro-oesophageal-junction adenocarcinomas, and histologically into diffuse and intestinal types. Gastric cancer should be treated by teams of experts from different disciplines. Surgery is the only curative treatment. For locally advanced disease, adjuvant or neoadjuvant therapy is usually implemented in combination with surgery. In metastatic disease, outcomes are poor, with median survival being around 1 year. Targeted therapies, such as trastuzumab, an antibody against HER2 (also known as ERBB2), and the VEGFR-2 antibody ramucirumab, have been introduced. In this Seminar, we present an update of the causes, classification, diagnosis, and treatment of gastric cancer.
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Affiliation(s)
- Eric Van Cutsem
- Department of Gastroenterology/Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium.
| | - Xavier Sagaert
- Department of Pathology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
| | - Baki Topal
- Department of Abdominal Surgery, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
| | - Karin Haustermans
- Department of Radiation Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
| | - Hans Prenen
- Department of Gastroenterology/Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium
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