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Signal Transduction and Targeted Therapy 2021年第12期6卷 3740-3754页

作者： Jinhong Chen Zhifei Lin Lu Liu Rui Zhang Yan Geng Minghao Fan Wenwei Zhu Ming Lu Lu Lu Huliang Jia Jubo Zhang lun-xiu qin Department of General Surgery Huashan HospitalCancer Metastasis InstituteFudan University12 Urumqi Road(M)Shanghai 200040China Department of Infectious Diseases Huashan HospitalFudan University12 Urumqi Road(M)Shanghai 200040China

The immunosuppressive microenvironment plays an important role in tumor progression and immunotherapy *** membrane protein 1(GOLM1)is correlated to hepatocellular carcinoma(HCC)progression and ***,little is known about the role of GOLM1 in regulating the immunosuppressive environment and its impact on immunotherapeutic efficacy in *** this study,GOLM1 was positively correlated with infiltrating tumor-associated macrophages(TAMs)expressed high levels of programmed death-ligand 1(PD-L1)and CD8^(+)T cell suppression in HCC *** gain-and loss-of-function studies determined a close correlation between GOLM1 and *** the mechanism,GOLM1 promoted COP9 signalosome 5-mediated PD-L1 deubiquitination in HCC cells and increased the transport of PD-L1 into exosomes via suppression of Rab27b ***,co-culture with exosomes derived from HCC cells upregulated the expression of PD-L1 on *** acid in combination with anti-PD-L1 therapy reduced PD-L1^(+)TAMs infiltration and alleviated CD8^(+)T cell suppression,resulting in tumor growth inhibition in the mouse HCC ***,our study unveils a mechanism by which GOLM1 induces CD8^(+)T cells suppression through promoting PD-L1 stabilization and transporting PD-L1 into TAMs with exosome *** PD-L1^(+)TAM could be a novel strategy to enhance the efficacy of anti-PD-L1 therapy in HCC.

关键词： hepatocellular transport metastasis

Properties and feasibility of using cancer stem cells in clinical cancer treatment

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Cancer Biology & Medicine 2016年第4期13卷 489-495页

作者： Xiao-Mei Gao Rui Zhang Qiong-Zhu Dong lun-xiu qin Institutes of Biomedical Sciences Fudan University Department of General Surgery Huashan Hospital and Cancer Metastasis Institute Fudan University

Cancer treatment failure, drug resistance, or metastatic recurrence are thought to be caused mainly by the existence of a very small number of cancer stem cells(CSCs). The characteristics of this subgroup of cells include self-renewal, tumorigenesis, multiple differentiation and high invasiveness, metastasis, and drug resistance potential. Many studies have demonstrated that CSCs play important roles in tumor growth, spread and metastatic relapse after treatment, and are closely related to the prognosis of *** a therapeutic viewpoint, deep insights into the CSCs biology, development of specific therapeutic strategies for targeting CSCs, and characterization of their microenvironment could be an ideal way to combat cancer.

关键词： Cancer stem cells cancers treatment failure metastasis cancer therapy

The application of real-time indocyanine green fluorescence cholangiography in laparoscopic living donor left lateral sectionectomy

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 575-585,I0001页

作者： Lu Lu Wen-Wei Zhu Cong-Huan Shen Yi-Feng Tao Zheng-Xin Wang Jin-Hong Chen lun-xiu qin Hepatobiliary Surgery Center Department of General SurgeryHuashan HospitalFudan UniversityShanghaiChina Liver Transplantation Center Department of General SurgeryHuashan HospitalFudan UniversityShanghaiChina

Background:The judgment of the division point of the bile duct has always been one of the difficulties of laparoscopic left lateral sectionectomy(LLLS).The purpose of this study was to assess the effects of indocyanine green(ICG)fluorescence cholangiography during LLLS on the occurrence of biliary complications in both donors and *** optimal dose and injection time of ICG were also ***:This is a retrospective cohort *** October 2016 to December 2022,the clinical data of 103 donors who underwent LLLS and relevant recipients were retrospectively *** to whether ICG fluorescence cholangiography was used,they were divided into a non-ICG group(n=46)and an ICG group(n=57).Biliary complications were observed and the optimal dose and injection time of ICG were ***:Three donors in the non-ICG group suffered from bile *** grafts had multiple bile duct openings and biliary complications were observed in the relevant recipients who received these grafts in the non-ICG *** recipients had bile leakage,and the other two had biliary *** was no biliary complications both in donors and recipients in the ICG *** fluorescence intensity of the liver was 108.1±17.6 at a dose of 0.004 mg/kg 90 minutes after injection,significantly weaker than that at 0.05 mg/kg 30 minutes(200.3±17.6,P=0.001)and 90 minutes after injection(140.2±15.4,P=0.001).The fluorescence intensity contrast value at a dose of 0.004 mg/kg was stronger than that at 0.05 mg/kg,both measured 90 minutes after injection(0.098±0.032 vs.0.078±0.022,P=0.021).Conclusions:ICG fluorescence cholangiography is safe and feasible in *** reduces biliary complications in both donors and *** optimal ICG dose was 0.004 mg/kg,and 90 minutes after injection was the best observation *** fluorescence cholangiography is recommended for routine use in LLLS.

关键词： Laparoscopic living donor hepatectomy(LLDH) living donor liver transplantation(LDLT) real-time indocyanine green fluorescence cholangiography(real-time ICG fluorescence cholangiography)

Chromosomal aberrations related to metastasis of human solid tumors

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World Journal of Gastroenterology 2002年第5期8卷 769-776页

作者： lun-xiu qin Liver Cancer Institute and Zhongshan Hospital,Fudan University,Shanghai,China Liver Cancer Institute Zhongshan Hospital Fudan University Shanghai China. lxqin@***

The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic *** does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor *** the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have *** is still controversial with the association between

关键词：染色体变异实质肿瘤肿瘤转移综述

The combination of PD-1 blockade with interferon-αhas a synergistic effect on hepatocellular carcinoma

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Cellular & Molecular Immunology 2022年第6期19卷 726-737页

作者： Ying Zhu Mo Chen Da Xu Tian-En Li Ze Zhang Jian-Hua Li Xiang-Yu Wang Xin Yang Lu Lu Hu-Liang Jia Qiong-Zhu Dong lun-xiu qin Department of General Surgery Huashan HospitalCancer Metastasis InstituteFudan University12 Urumqi Road(M)Shanghai 200040China institutes of Biomedical Sciences Fudan University131 Dong An RoadShanghai 200032China

Background The efficacy of immune checkpoint inhibitors(ICIs),such as programmed cell death protein-1(PD-1)or its ligand 1(PD-L1)antibody,in hepatocellular carcinoma(HCC)is limited,and it is recommended that they be combined with other *** evaluated the combination of pegylated interferon-α(Peg-IFNα)with PD-1 blockade in HCC mouse *** We analyzed the effects of Peg-IFNαon tumor-infiltrating immune cells and PD-1 expression in the HCC immune microenvironment and examined the underlying mechanism of its unique effect on the PD-1 *** in vivo efficacy of anti-PD-1 and Peg-IFNαwas evaluated in both subcutaneous and orthotopic mouse models of *** The combination of Peg-IFNαwith PD-1 blockade dramatically enhanced T-cell infiltration,improved the efficacy of PD-1 antibody and prolonged mouse survival compared with PD-1 antibody ***,Peg-IFNαcould recruit cytotoxic CD8+T cells to infiltrate the HCC microenvironment by inducing tumor cells to secrete the chemokine ***,the HCC microenvironment quickly overcame the immune responses by upregulating PD-1 expression in CD8+T cells via the IFNα-IFNAR1-JAK1-STAT3 signaling *** combination of PD-1 blockade with Peg-IFNαcould restore the cytotoxic capacity of CD8+T cells and exerted a significant synergistic effect on *** These results indicate that in addition to initiating the antitumor immune response itself,Peg-IFNαcan also generate a microenvironment favoring PD-1 ***,the combination of Peg-IFNαand PD-1 blockade can be a promising strategy for HCC.

关键词： Hepatocellular carcinoma Tumor microenvironment PD-1 Pegylated interferon-α T-cell exhaustion

The prognostic significance of clinical and pathological features in hepatocellular carcinoma

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World Journal of Gastroenterology 2002年第2期8卷 193-199页

作者： lun-xiu qin Zhao-You Tang,Liver Cancer Institute and Zhongshan Hospital,Fudan University,Shanghai,China Liver Cancer Institute Zhongshan Hospital 136 Yi Xue Yuan Road Shanghai 200032 China.

The prognosis of patients with HCC still remains dismal. The life expectancy of HCC patients is hard to predict because of the high possibility of postoperative recurrence. Many factors, such as patient's general conditions, macroscopic tumor morphology, as well as tumor histopathology features, have been proven of prognostic significance. Female HCC patient often has a better prognosis than male patient, which might be due to the receptor of sex hormones. Younger patients often have tumors with higher invasiveness and metastatic potentials, and their survival and prognosis are worse than the older ones. Co-existing hepatitis status and hepatic functional reserve have been confirmed as risk factors for recurrence. Serum alpha-fetoprotein (AFP) is useful not only for diagnosis, but also as a prognostic indicator for HCC patients. AFP mRNA has been proposed as a predictive marker of HCC cells disseminated into the circulation and for metastatic recurrence. Many pathologic features, such as tumor size, number, capsule state, cell differentiation, venous invasion, intrahepatic spreading, and advanced pTNM stage, are the best-established risk factors for recurrence and important aspects affecting the prognosis of patients with HCC. Marked inflammatory cell infiltration in the tumor could predict a better prognosis. Clinical stage is still the most important factor influencing on the prognosis. Extratumor spreading and lymph nodal metastasis are independent predictors for poor outcome. Some new predictive systems have recently been proposed. Different strategies of treatment might have significant different effects on the patients' prognosis. To date, surgical resection is still the only potentially curative treatment for HCC, including localized postoperative recurrences. Extent of resection, blood transfusion, occlusion of porta hepatis, and blood loss affect the survival and prognosis of HCC patients. Regional therapies provide alternative ways to improve the prognosis

关键词： Age Factors Carcinoma, Hepatocellular Hepatitis Humans Liver Cirrhosis Liver Neoplasms Neoplasm Staging Prognosis Recurrence Sex Factors alpha-Fetoproteins

The prognostic molecular markers in hepatocellular carcinoma

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World Journal of Gastroenterology 2002年第3期8卷 385-392页

作者： lun-xiu qin Zhao-You Tang,Liver Cancer Institute and Zhongshan Hospital,Fudan University,Shanghai,China Liver Cancer Institute and Zhongshan Hospital Fudan university 136 Yi Xue Yuan Road Shanghai 200032 China.

The prognosis of hepatocellular carcinoma (HCC) still remains dismal, although many advances in its clinical study have been made. It is important for tumor control to identify the factors that predispose patients to death. With new discoveries in cancer biology, the pathological and biological prognostic factors of HCC have been studied quite extensively. Analyzing molecular markers (biomarkers) with prognostic significance is a complementary method. A large number of molecular factors have been shown to associate with the invasiveness of HCC, and have potential prognostic significance. One important aspect is the analysis of molecular markers for the cellular malignancy phenotype. These include alterations in DNA ploidy, cellular proliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, and CSE1L/CAS protein), nuclear morphology, the p53 gene and its related molecule MD M2, other cell cycle regulators (cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenes and their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members), apoptosis related factors (Fas and FasL), as well as telomerase activity. Another important aspect is the analysis of molecular markers involved in the process of cancer invasion and metastasis. Adhesion molecules (E-cadherin, catenins, serum intercellular adhesion molecule-1, CD44 variants), proteinases involved in the degradation of extracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAI), as well as other molecules have been regarded as biomarkers for the malignant phenotype of HCC, and are related to prognosis and therapeutic outcomes. Tumor angiogenesis is critical to both the growth and metastasis of cancers including HCC, and has drawn much attention in recent years. Many angiogenesis-related markers, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived endothelial cell growth factor (PD-ECGF), thrombospondin (TSP), angiogenin, pleiotrophin, and endostatin (ES) leve

关键词： Apoptosis Carcinogens Carcinoma, Hepatocellular Cell Adhesion Cell Division Cell Nucleus Extracellular Matrix Genes, p53 Humans Liver Neoplasms Neovascularization, Pathologic Ploidies Prognosis Proteome Telomerase Tumor Markers, Biological

Risk factors for postoperative complications after liver resection

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Hepatobiliary & Pancreatic Diseases International 2005年第3期4卷 370-374页

作者： Hui-Chuan Sun, lun-xiu qin, Lu Wang, qin-Hai Ye, Zhi-Quan Wu, Jia Fan and Zhao-You Tang Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai 200032, China Liver Cancer Institute and Zhongshan Hospital Fudan University Shanghai 200032 China. sunhc@***

Liver resection is still a complicated operation with a high risk of postoperative morbidity. This study was undertaken to analyze the risk factors for postoperative complications after liver resection. METHODS:From 2001 to 2004, a total of 146 patients underwent liver resection for malignant or benign lesions. Postoperative complications after the resection were classified as surgical and medical, their incidences were analyzed *** risk factors for both surgical and medical complications were analyzed. To increase the safety of liver resection, surgical techniques were modified after April 2003, including control of inflow or outflow and intra- operative test with methylene blue. RESULTS:Before April 2003, a series of 58 patients received liver resection. Modified surgical techniques were used in liver resections for 88 patients after April 2003.A total of 36 patients (24.7%) had postoperative complications. Surgical and medical complications occurred in 24 and 13 patients respectively (One patient had both surgical and medical complications). Perioperative blood transfusion was related to a higher risk of surgical complications (P<0.05). Patients with diabetes mellitus were associated with a higher risk of medical complications (P<0.05). Surgical complications and postoperative hospitalization were decreased after the use of modified surgical techniques (P<0.05). CONCLUSION:Postoperative surgical complications can be decreased by modified surgical techniques, and careful selection of patients for liver resection may help to decrease postoperative medical complications also.

关键词： hepatocellular carcinoma resection complications

Circulating DNA level is negatively associated with the long-term survival of hepatocellular carcinoma patients

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World Journal of Gastroenterology 2006年第24期12卷 3911-3914页

作者： Ning Ren qing-Hai Ye lun-xiu qin Bo-Heng Zhang Yin-Kun Liu Zhao-YouTang Liver Cancer Institute and Zhongshan Hospital Fudan University 180 Feng Lin Road Shanghai 200032 China

AIM： To quantify the circulating DNA in plasma from patients with hepatocellular carcinoma （HCC） and to evaluate its prognostic value. METHODS： Blood samples were collected from 79 patients with HCC before operation, 20 patients with liver cirrhosis, and 20 healthy volunteers. Circulating DNA was extracted from plasma and quantified. The association between circulating DNA level and prognosis of HCC patients was evaluated. RESULTS： Compared with the healthy volunteers （17.6 ± 9.5 ng/mL）, a significant higher circulating DNA level was found in the patients with HCC （47.1 ± 43.7 ng/ mL, P = 0.000） or with liver cirrhosis （30.0 ± 13.3 ng/ mL, P = 0.002）. The circulating DNA level was closely associated with tumor size （P = 0.008） and TNM stage （P = 0.040）, negatively associated with the 3-year diseasefree survival （DFS）（P = 0.017） and overall survival （OS）（P = 0.001）. CONCLUSION： Large or invasive tumor may release more circulating DNA, and higher level of circulating DNA may be associated with poor prognosis of HCC patients.

关键词： Hepatocellular carcinoma Prognosis Circulating DNA

The molecular biology of pancreatic adenocarcinoma:translational challenges and clinical perspectives

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2348-2370页

作者： Shun Wang Yan Zheng Feng Yang Le Zhu Xiao-Qiang Zhu Zhe-Fang Wang Xiao-Lin Wu Cheng-Hui Zhou Jia-Yan Yan Bei-Yuan Hu Bo Kong De-Liang Fu Christiane Bruns Yue Zhao lun-xiu qin Qiong-Zhu Dong Department of General Surgery Huashan HospitalCancer Metastasis InstituteFudan UniversityShanghaiChina Department of Pancreatic Surgery Pancreatic Disease InstituteHuashan HospitalFudan UniversityShanghaiChina School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina General Visceral and Cancer SurgeryUniversity Hospital of CologneCologneGermany Department of Biliary-Pancreatic Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Surgery Klinikum rechts der IsarSchool of MedicineTechnical University of Munich(TUM)MunichGermany Key laboratory of whole-period monitoring and precise intervention of digestive cancer Shanghai Municipal Health Commission(SMHC)ShanghaiChina

Pancreatic cancer is an increasingly common cause of cancer mortality with a tight correspondence between disease mortality and ***,it is usually diagnosed at an advanced stage with a very dismal *** to the high heterogeneity,metabolic reprogramming,and dense stromal environment associated with pancreatic cancer,patients benefit little from current conventional *** insight into the biology and genetics of pancreatic cancer has supported its molecular classification,thus expanding clinical therapeutic *** this review,we summarize how the biological features of pancreatic cancer and its metabolic reprogramming as well as the tumor microenvironment regulate its development and *** further discuss potential biomarkers for pancreatic cancer diagnosis,prediction,and surveillance based on novel liquid *** also outline recent advances in defining pancreatic cancer subtypes and subtype-specific therapeutic responses and current preclinical therapeutic ***,we discuss prospects and challenges in the clinical development of pancreatic cancer therapeutics.

关键词： clinical mortality diagnosis