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Neoadjuvant chemotherapy with capecitabine combined with oxaliplatin for mid-low locally advanced rectal cancer with negative mesorectal fascia:Long-term outcomes of a prospective trial(PKUCH-R03 trial)

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Chinese Journal of Cancer research 2024年第4期36卷 410-420页

作者： Nan Chen Minghe Zhao Yunfeng Yao Lin Wang Yifan Peng Tingting Sun Tiancheng Zhan Jun Zhao Aiwen Wu Key Laboratory of Carcinogenesis and translational research(Ministry of Education/Beijing) Gastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchGastrointestinal Cancer CenterUnit IIIPeking University Cancer Hospital&InstituteBeijing 100142China

Objective:To evaluate the safety and efficacy of neoadjuvant chemotherapy(NCT)in mid-low locally advanced rectal cancer with negative mesorectal fascia(MRF).Methods:This prospective,single-arm phaseⅡtrial was designed and conducted at Peking University Cancer *** patients who provided consent received 3 months of NCT(capecitabine and oxaliplatin,CapOX)followed by total mesorectal excision(TME).The primary endpoint was the rate of pathological complete response(pCR).Results:From January 2019 through December 2021,a total of 53 patients were enrolled,7.5%of whom experienced grade 3-4 adverse events during *** pCR rate was 17.0%for the entire cohort,and the overall rate of postoperative complications was 37.7%(1.9%of gradeⅢa patients).The 3-year disease-free survival rate was 91.4%,and 23.5%(12/51)of the patients suffered from major low anterior resection syndrome(LARS).Postoperative complications were independently associated with major ***:For patients with mid-low rectal cancer with negative MRF,3 months of NCT were found to yield a favorable tumor response with acceptable *** fair long-term survival,the NCT regimen could be associated with low rates of perioperative complications as well as acceptable anal function.

关键词： Neoadjuvant chemotherapy rectal cancer mesorectal fascia disease-free survival anal function

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Advances in MET tyrosine kinase inhibitors in gastric cancer

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Cancer Biology & Medicine 2024年第6期21卷 484-498页

作者： Yifan Zhang Lin Shen Zhi Peng Key Laboratory of Carcinogenesis and translational research(Ministry of Education) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China

Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths *** gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics,the management of gastric cancer calls for better-defined,biomarker-guided,molecular-based treatment *** is a receptor tyrosine kinase mediating important physiologic processes,such as embryogenesis,tissue regeneration,and wound ***,mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types,including gastric cancer,and is associated with poor patient *** such,MET-targeting therapies are being actively developed and promising progress has been demonstrated,especially with MET tyrosine kinase *** review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib,tepotinib,capmatinib,and *** on current knowledge,this review further discusses existing challenges in MET alterations testing,possible resistance mechanisms to MET inhibitors,and future directions of MET-targeting therapies.

关键词： Gastric cancer MET alterations MET tyrosine kinase inhibitors savolitinib MET testing

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Baicalin Prevents Colon Cancer by Suppressing CDKN2A Protein Expression

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Chinese Journal of Integrative Medicine 2024年第11期30卷 1007-1017页

作者： LI Gang-gang CHU Xiu-feng XING Ya-min XUE Xia Ihtisham Bukhari LIANG Xin-feng XU Ji-xuan MI Yang ZHENG Peng-yuan Henan Key Laboratory of Helicobacter pylori Microbiota and Gastrointestinal Cancers Marshall Medical Research Center Fifth Affiliated Hospital of Zhengzhou University

Objective:To observe the therapeutic effects and underlying mechanism of baicalin against colon ***:The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and *** were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network ***,molecular docking and drug affinity responsive target stability（DARTS）analysis were performed to confirm the interaction between potential targets and ***,the mechanisms predicted by in silico analyses were experimentally verified in-vitro and ***:Baicalin significantly inhibited proliferation,invasion,migration,and induced apoptosis in MC38 and CT26 cells（all P<0.01）.Additionally,baicalin caused cell cycle arrest at the S phase,while the G0/G1phase was detected in the tiny portion of the *** network pharmacology analysis identified 6 therapeutic targets associated with baicalin,which potentially affect various pathways including 39 biological processes and 99 sugnaling *** addition,molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A（CDKN2A）,protein kinase B（AKT）,caspase 3,and mitogen-activated protein kinase（MAPK）.In vitro,the expressions of CDKN2A,MAPK,and p-AKT were suppressed by baicalin in MC38 and CT26 *** vivo,baicalin significantly reduced the tumor size and weight（all P<0.01） in the colon cancer mouse model via inactivating p-AKT,CDKN2A,cyclin dependent kinase 4,cyclin dependent kinase 2,interleukin-1,tumor necrosis factor α,and activating caspase 3 and mouse double minute 2 homolog signaling（all P<0.05）.Conclusion:Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.

关键词： CDKN2A apoptosis baicalin cell cycle colon cancer network pharmacology

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Nab-paclitaxel plus capecitabine as first-line treatment for advanced biliary tract cancers:An open-label,non-randomized,phase II clinical trial

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World Journal of Gastroenterology 2024年第30期30卷 3564-3573页

作者： Ling-Xiao Xu Jia-Jia Yuan Ran Xue Jun Zhou Department of gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND Biliary tract cancers(BTCs)are a heterogeneous group of tumors with high malignancy,poor prognosis,and limited treatment *** To explore the efficacy and safety of nab-paclitaxel plus capecitabine as first-line treatment for advanced and metastatic *** This open-label,non-randomized,double-center,phase II clinical trial recruited systemic therapy-naive patients with unresectable or metastatic BTCs between April 2019 and June 2022 at Beijing Cancer Hospital and the First Hospital of China Medical *** patients were administered nab-paclitaxel(150 mg/m^(2),day 1)and capecitabine(2000 mg/m^(2),twice daily,days 1-7)in 14-day cycles until experiencing intolerable toxicity or disease *** primary outcome was the objective response rate(ORR).The secondary outcomes included the disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and *** A total of 44 patients successfully completed the trial,with a median age of 64.00 years(interquartile range,35.00-76.00),and 26(59.09%)were *** response assessment was impeded for one patient due to premature demise from tumor *** the remaining 43 patients undergoing at least one imaging assessment,the ORR was 23.26%[95%confidence interval(CI):11.80%-38.60%],and the DCR was 69.77%(95%CI:53.90%-82.80%).The median OS was 14.1 months(95%CI:8.3-19.9),and the median PFS was 4.4 months(95%CI:2.5-6.3).A total of 41 patients(93.18%)experienced at least one adverse event(AE),with 10 patients(22.73%)encountering grade≥3 AEs,and the most frequent AEs of any grade were alopecia(79.50%),leukopenia(54.55%),neutropenia(52.27%),and liver dysfunction(40.91%),and no treatment-related deaths were *** Nab-paclitaxel plus capecitabine may be an effective and safe first-line treatment strategy for patients with advanced or metastatic BTCs.

关键词： Nab-paclitaxel Capecitabine Biliary tract cancer Objective response rate Phase II clinical trial

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Surgical management of metastatic neuroendocrine tumors:beyond the realm of evidence-based medicine

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 551-553页

作者： Jonathan R.Strosberg Taymeyah Al-Toubah Department of gastrointestinal Oncology Moffitt Cancer Center&Research InstituteUniversity of South FloridaTampaFLUSA

How strong is the evidence supporting surgery for patients with metastatic neuroendocrine tumors(NETs)?This is the chief question from ***’comprehensive and balanced literature analysis on the surgical treatment of metastatic pancreatic NETs(1).No matter how many non-randomized studies demonstrate a survival advantage for patients undergoing cytoreductive hepatic surgery or resection of the primary pancreatic tumor,the methodological biases remain constant(2-9).Patients undergoing surgery tend to be younger and healthier,and their tumors tend to be lower grade,less aggressive,and fewer in number than patients undergoing other systemic or liver-directed *** other words,the survival advantage begins when the patient is selected as a surgical candidate and before the scalpel even touches the *** multivariate analyses can control for some confounding variables,it is impossible to control for *** a simple concept such as tumor burden is challenging to standardize:a patient with a few large tumors confined to a single hepatic lobe may have a vastly different prognosis than a patient with a similar burden of miliary tumors scattered throughout the liver(2).

关键词： Neuroendocrine tumor(NET) cytoreduction debulking surgery transplantation

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Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

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Chinese Journal of Cancer research 2024年第1期36卷 78-89页

作者： Changsong Qi Xiaoyi Chong Ting Zhou Mingyang Ma Jifang Gong Miao Zhang Jian Li Jun Xiao Xiaohui Peng Zhen Liu Zonghai Li Lin Shen Xiaotian Zhang State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and translational research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China CARsgen Therapeutics Co. LtdShanghai 200231China CARsgen Life Sciences Co. LtdShanghai 200131China

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in ***: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression ***: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of *** death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of ***18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive ***: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

关键词： Gastric cancer claudin18.2 CT041 PD-L1 immunotherapy

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Prognostic significance of grade of malignancy based on histopathological differentiation and Ki-67 in pancreatic ductal adenocarcinoma

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Cancer Biology & Medicine 2024年第5期21卷 416-432页

作者： Yuexiang Liang Guannan Sheng Yu Guo Yiping Zou Hanhan Guo Zhifei Li Shaofei Chang Quan Man Song Gao Jihui Hao Department of Pancreatic Cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of gastrointestinal Oncology The First Affiliated Hospital of Hainan Medical UniversityHaikou 570102China Department of gastrointestinal Pancreatic Surgery Shanxi Provincial People’s HospitalTaiyuan 030012China

Objective:Tumor cell malignancy is indicated by histopathological differentiation and cell ***-67,an indicator of cellular proliferation,has been used for tumor grading and classification in breast cancer and neuroendocrine ***,its prognostic significance in pancreatic ductal adenocarcinoma(PDAC)remains ***:Patients who underwent radical pancreatectomy for PDAC were retrospectively enrolled,and relevant prognostic factors were *** of malignancy(GOM),a novel index based on histopathological differentiation and Ki-67,is proposed,and its clinical significance was ***:The optimal threshold for Ki-67 was determined to be 30%.Patients with a Ki-67 expression level>30%rather than≤30%had significantly shorter 5-year overall survival(OS)and recurrence-free survival(RFS).In multivariate analysis,both histopathological differentiation and Ki-67 were identified as independent prognostic factors for OS and *** GOM was used to independently stratify OS and RFS into 3 tiers,regardless of TNM stage and other established prognostic *** tumor-nodemetastasis-GOM stage was used to stratify survival into 5 distinct tiers,and surpassed the predictive performance of TNM stage for OS and ***:Ki-67 is a valuable prognostic indicator for *** of the GOM in the TNM staging system may potentially enhance prognostic accuracy for PDAC.

关键词： Pancreatic ductal adenocarcinoma prognosis Ki-67 differentiation TNM stage

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2024年

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital &Institute Department of gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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Role of albumin-bilirubin score in non-malignant liver disease

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World Journal of Gastroenterology 2024年第9期30卷 999-1004页

作者： Shi-Xue Xu Fan Yang Nan Ge Jin-Tao Guo Si-Yu Sun Department of Gastroenterology Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

The albumin-bilirubin(ALBI)score,which was proposed to assess the prognosis of patients with hepatocellular carcinoma,has gradually been extended to other liver diseases in recent years,including primary biliary cholangitis,liver cirrhosis,hepatitis,liver transplantation,and liver *** ALBI score is often compared with classical scores such as the Child-Pugh and model for end-stage liver disease scores or other noninvasive prediction *** is widely employed because of its immunity to subjective evaluation indicators and ease of obtaining detection *** increasing number of studies have confirmed that it is highly accurate for assessing the prognosis of patients with chronic liver disease;additionally,it has demonstrated good predictive performance for outcomes beyond survival in patients with liver diseases,such as decompensation *** article presents a review of the application of ALBI scores in various non-malignant liver diseases.

关键词： Albumin-bilirubin score Liver cirrhosis Primary biliary cholangitis Hepatitis Liver transplantation Liver injury

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From macroautophagy to mitophagy:Unveiling the hidden role of mitophagy in gastrointestinal disorders

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World Journal of Gastroenterology 2024年第23期30卷 2934-2946页

作者： Duo-Lun Gao Meng-Ran Lin Nan Ge Jin-Tao Guo Fan Yang Si-Yu Sun Department of Gastroenterology Engineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

In this editorial,we comment on an article titled“Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases”,which was published in a recent issue of the World Journal of *** focused on the statement that“autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal cells”.With advancing research,autophagy,and particularly the pivotal role of the macroautophagy in maintaining cellular equilibrium and stress response in the gastrointestinal system,has garnered extensive ***,the significance of mitophagy,a unique selective autophagy pathway with ubiquitin-dependent and independent variants,should not be *** recent decades,mitophagy has been shown to be closely related to the occurrence and development of gastrointestinal diseases,especially inflammatory bowel disease,gastric cancer,and colorectal *** interplay between mitophagy and mitochondrial quality control is crucial for elucidating disease mechanisms,as well as for the development of novel treatment *** the pathogenesis behind gastrointestinal diseases and providing individualized and efficient treatment for patients are subjects we have been *** article reviews the potential mechanism of mitophagy in gastrointestinal diseases with the hope of providing new ideas for diagnosis and treatment.

关键词： Mitophagy gastrointestinal diseases Parkin Autophagic receptor Colorectal cancer Gastric cancer Inflammatory bowel disease

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