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cancer Biology & Medicine 2024年第1期21卷 65-82页

作者： Sen Wang Benling Xu Yangyang Zhang Guangyu Chen Peng Zhao Quanli Gao Long Yuan department of Gastrointestinal surgery Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China department of Immunotherapy Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450003China

Intestinal flora affects the maturation of the host immune system,serves as a biomarker and efficacy predictor in the immunotherapy of several cancers,and has an important role in the development of colorectal cancer(CRC).Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/d MMR CRC but performed poorly in patients with MSS/p MMR *** recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC *** and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in ***,we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s).We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 *** addition,we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.

关键词： Intestinal flora anti-PD-1/PD-L1 therapy colorectal cancer immune checkpoint inhibitor CD8~+T cell

Circulating RNA ZFR promotes hepatocellular carcinoma cell proliferation and epithelial-mesenchymal transition process through miR-624-3p/WEE1 axis

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 52-63页

作者： Li Zhang Sai He Hao Guan Yao Zhao Di Zhang department of General surgery the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004China department of Breast cancer Shaanxi Provincial Cancer HospitalXi’an 710000China

Background:Hepatocellular carcinoma(HCC),the most common type of primary liver cancer,is the fourth leading cause of cancer-related deaths *** evidence shows that the expression of circulating RNA ZFR(circZFR)is upregulated in HCC ***,the molecular mechanism of circZFR in HCC is ***:Quantitative reverse transcriptase polymerase chain reaction(qRT-PCR)was employed to detect the expression of circZFR,microRNA-624-3p(miR-624-3p)and WEE1 in HCC tissues and *** R assay and actinomycin D treatment assay were used to analyze the characteristics of *** functional analysis,the capacities of colony formation,cell proliferation,cell apoptosis,migration and invasion were assessed by colony formation assay,5-ethynyl-2-deoxyuridine(EdU)assay,flow cytometry assay and transwell *** blot was used to examine the protein levels of WEE1 and epithelial-mesenchymal transition(EMT)-related *** interactions between miR-624-3p and circZFR or WEE1 were validated by dual-luciferase reporter assay and RNA immunoprecipitation(RIP)*** models were established to determine the role of circZFR in ***:circZFR and WEE1 were upregulated,while miR-624-3p expression was reduced in HCC tissues and *** could sponge miR-624-3p,and WEE1 was a downstream gene of *** of circZFR significantly reduced the malignant behaviors of HCC and that co-transfection with miR624-3p inhibitor restored this *** of WEE1 abolished the inhibitory effect of miR624-3p mimic on HCC ***,circZFR acted as a competitive endogenous RNA(ceRNA)to regulate WEE1 expression by targeting ***,in vivo studies have illustrated that circZFR knockdown inhibited tumor ***:circZFR knockdown reduced HCC cell proliferation,migration and invasion and promoted apoptosis by regulating the miR-624-3p/WEE1 axis,suggesting that the circZFR/miR-624-3p/WEE1 axis might

关键词： Hepatocellular carcinoma circZFR miR-624-3p WEE1 Liver cancer

TGF-βsignaling in health,disease,and therapeutics

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1466-1505页

作者： Ziqin Deng Tao Fan Chu Xiao He Tian Yujia Zheng Chunxiang Li Jie He department of Thoracic surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

ransforming growth factor(TGF)-βis a multifunctional cytokine expressed by almost every tissue and cell *** signal transduction of TGF-βcan stimulate diverse cellular responses and is particularly critical to embryonic development,wound healing,tissue homeostasis,and immune homeostasis in *** dysfunction of TGF-βcan play key roles in many diseases,and numerous targeted therapies have been developed to rectify its pathogenic *** the past decades,a large number of studies on TGF-βsignaling have been carried out,covering a broad spectrum of topics in health,disease,and ***,a comprehensive overview of TGF-βsignaling is required for a general picture of the studies in this *** this review,we retrace the research history of TGF-βand introduce the molecular mechanisms regarding its biosynthesis,activation,and signal *** also provide deep insights into the functions of TGF-βsignaling in physiological conditions as well as in pathological ***-β-targeting therapies which have brought fresh hope to the treatment of relevant diseases are *** the summary of previous knowledge and recent updates,this review aims to provide a systematic understanding of TGF-βsignaling and to attract more attention and interest to this research area.

关键词： homeostasis healing wound

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 117-122页

作者： Xin Yang Lu Lu Wen-Wei Zhu Yi-Feng Tao Cong-Huan Shen Jin-Hong Chen Zheng-Xin Wang Lun-Xiu Qin Hepatobiliary surgery and Liver Transplantation Centers Department of General SurgeryHuashan Hospital&Cancer Metastasis InstituteFudan UniversityShanghai 200040China

Hepatectomy is still the major curative treatment for patients with liver ***,it is still a big challenge to remove the tumors in the central posterior area,especially if their location involves the retrohepatic inferior vena cava and hepatic *** vivo liver resection and auto-transplantation(ELRA),a hybrid technique of the traditional liver resection and transplantation,has brought new hope to these patients and therefore becomes a valid alternative to liver *** to its technical difficulty,ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver *** efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases,especially in the advanced alveolar ***,the application of ELRA for liver malignances has gained more ***,standardization of clinical practice norms and international consensus are still *** prognostic impact in these oncologic patients also needs further *** this review,we summarized the principles and recent progresses on ELRA.

关键词： Ex vivo liver resection Liver auto-transplantation Oncology Liver malignancies

Effects of dietary intervention on human diseases:molecular mechanisms and therapeutic potential

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1389-1422页

作者： Yu-Ling Xiao Yue Gong Ying-Jia Qi Zhi-Ming Shao Yi-Zhou Jiang Key Laboratory of Breast cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina department of Oncology Shanghai Medical CollegeFudanUniversityShanghai200032China

Diet,serving as a vital source of nutrients,exerts a profound influence on human health and disease ***,dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases,autoimmune diseases,cardiovascular diseases,and metabolic *** interventions have demonstrated substantial potential in modulating metabolism,disease trajectory,and therapeutic *** reprogramming is a hallmark of malignant progression,and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer *** intake,as a key environmental factor,can influence tumor *** evidence indicates that dietary interventions might affect the nutrient availability in tumors,thereby increasing the efficacy of cancer ***,the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is *** encouraging results,the mechanisms underlying diet-based therapeutic strategies remain largely unexplored,often resulting in underutilization in disease *** this review,we aim to illuminate the potential effects of various dietary interventions,including calorie restriction,fasting-mimicking diet,ketogenic diet,protein restriction diet,high-salt diet,high-fat diet,and high-fiber diet,on cancer and the aforementioned *** explore the multifaceted impacts of these dietary interventions,encompassing their immunomodulatory effects,other biological impacts,and underlying molecular *** review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.

关键词： diseases metabolism potential

Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1281-1295页

作者： Zhe-Han Bao Can Hu Yan-Qiang Zhang Peng-Cheng Yu Yi Wang Zhi-Yuan Xu Huan-Ying Fu Xiang-Dong Cheng department of Interventional Radiology Zhejiang Cancer HospitalHangzhou 310004Zhejiang ProvinceChina department of Gastric surgery Zhejiang Cancer HospitalHangzhou 310022Zhejiang ProvinceChina department of Colonic surgery Jinhua Central HospitalJinhua 321000Zhejiang ProvinceChina department of Breast surgery Lin’an People’s HospitalHangzhou 311300Zhejiang ProvinceChina

BACKGROUND Gastric cancer(GC)is the fifth most common and the fourth most lethal malignant tumour in the *** patients are already in the advanced stage when they are diagnosed,which also leads to poor overall *** effect of posto-perative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local *** To investigate the safety and efficacy of a programmed cell death 1(PD-1)inhibitor combined with oxaliplatin and S-1(SOX)in the treatment of Borrmann large type III and IV *** A retrospective analysis(IRB-2022-371)was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy(NAT)from January 2020 to December *** to the different neoadjuvant treatment regimens,the patients were divided into the SOX group(61 patients)and the PD-1+SOX(P-SOX)group(28 patients).RESULTS The pathological response(tumor regression grade 0/1)in the P-SOX group was significantly higher than that in the SOX group(42.86%vs 18.03%,P=0.013).The incidence of ypN0 in the P-SOX group was higher than that in the SOX group(39.29%vs 19.67%,P=0.05).The use of PD-1 inhibitors was an independent factor affecting tumor regression ***,the use of PD-1 did not increase postoperative complications or the adverse effects of *** A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

关键词： Neoadjuvant therapy Immunotherapy Gastric cancer Borrmann type Tumor regression grade

Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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cancer Biology & Medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu department of Colorectal surgery Fudan University Shanghai Cancer CenterShanghai 200032China department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Precision cancer Medical Center Affiliated with Fudan University Shanghai cancer Center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths *** radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of ***,the transformation of high-throughput sequencing has accelerated the development of precision *** example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in ***,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor

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World Journal of Gastroenterology 2024年第8期30卷 863-880页

作者： Gui-Ming Deng Hai-Bin Song Zhong-Ze Du Ying-Wei Xue Hong-Jiang Song Yuan-Zhou Li department of Gastrointestinal surgery Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina department of Radiology Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina

BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of *** immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be *** We performed a retrospective study of patients who were undergoing immuno-therapy for *** the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral *** was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic *** were developed to predict the PFS and OS of patients on the basis of the results of multivariate *** We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had *** with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these ***,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an *** prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,*** The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

关键词： Gastric cancer Sarcopenia Myosteatosis,Immune checkpoint inhibitor Prognostic factor Overall survival Progression-free survival

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World Journal of Gastroenterology 2024年第9期30卷 1224-1236页

作者： Hai-Yang Li Lin-Lin Zheng Nan Hu Zhi-Hao Wang Chang-Cheng Tao Ya-Ru Wang Yue Liu Zulihumaer Aizimuaji Hong-Wei Wang Rui-Qi Zheng Ting Xiao Wei-Qi Rong department of Hepatobiliary surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China department of Hepatobiliary Hernia surgery Liaocheng Dongcangfu People’s HospitalLiaocheng 252000Shandong ProvinceChina State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two *** To perform a bibliometric analysis to systematically assess the current state of research on HCC-related *** The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were *** employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and *** was utilized to compile and visualize the bibliometric *** A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in *** to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each *** United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and *** the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most *** for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific a

关键词： Telomerase Bibliometric analysis Telomerase reverse transcriptase Prognosis Treatment Hepatocellular carcinoma

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