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Preoperative lymphocyte to C-reactive protein ratio as a new prognostic indicator in patients with resectable gallbladder cancer

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Hepatobiliary & Pancreatic diseases International 2022年第3期21卷 267-272页

作者： Wen-Yan Yao Xiang-Song Wu Shi-Lei Liu Zi-You Wu Ping Dong Wei Gong Department of General Surgery Xinhua HospitalAffiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Laboratory of Biliary Tract Disease Research Shanghai 200092China

Background:Inflammation is often related to cancer,and several inflammatory scores have been established to predict the prognosis of various types of cancer.Our study aimed to determine the prognostic value of the preoperative lymphocyte to C-reactive protein ratio(LCR)for predicting postoperative outcomes in patients with resectable gallbladder cancer(GBC).Methods:A retrospective analysis of 104 GBC patients who received curative surgery at Xinhua Hospital,Affiliated to shanghai Jiao Tong University School of Medicine from January 2000 to December 2016 was performed.A time-dependent receiver operating characteristic curve was constructed to evaluate the accuracy of different markers.Univariate and multivariate Cox proportional hazard models were used to define factors associated with overall survival.Results:Among the assessed variables,the preoperative LCR showed the highest accuracy in predicting the overall survival of GBC patients(AUC:0.736).Decreased preoperative LCR was significantly associated with advanced tumor stage,including tumor invasion(P=0.018),lymph node metastasis(P=0.011)and TNM stage(P=0.022).A low preoperative LCR(cutoff threshold=145.5)was an independent risk factor for overall survival in patients with resectable GBC(P<0.001).Conclusions:The preoperative LCR is a novel and valuable prognostic indicator of postoperative survival in patients with resectable GBC.

关键词： Gallbladder neoplasms Inflammation Lymphocyte to C-reactive protein ratio Overall survival

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Advances in immunotherapy for biliary tract cancers

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Chinese Medical Journal 2024年第5期137卷 524-532页

作者： Yuhao Zhao Mao Yang Jiayi Feng Xu’an Wang Yingbin Liu Department of biliary–Pancreatic Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China shanghai Cancer Institute State Key Laboratory of Oncogenes and Related GenesShanghai 200127China shanghai key laboratory of biliary tract disease Shanghai 200082China

biliary tract cancers(BTC),a heterogeneous disease with poor prognosis,including gallbladder cancer(GBC),intrahepatic cholangiocarcinoma(ICC),and extrahepatic cholangiocarcinoma(ECC).Although surgery is currently the primary regimen to treat BTC,most BTC patients are diagnosed at an advanced stage and miss the opportunity of surgical eradication.As a result,non-surgical therapy serves as the main intervention for advanced BTC.In recent years,immunotherapy has emerged as one of the most promising therapies in a number of solid cancers,and it includes immune checkpoint inhibitors(ICIs)monotherapy or combined therapy,tumor vaccines,oncolytic virus immunotherapy,adoptive cell therapy(ACT),and cytokine therapy.However,these therapies have been practiced in limited clinical settings in patients with BTC.In this review,we focus on the discussion of latest advances of immunotherapy in BTC and update the progress of multiple current clinical trials with different immunotherapies.

关键词： Immunotherapy biliary tract cancers Immune checkpoint inhibitors Cholangiocarcinoma Gallbladder cancer

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Hepatopancreatoduodenectomy for advanced biliary malignancies

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Chinese Medical Journal 2022年第23期135卷 2851-2858页

作者： Xiangsong Wu Maolan Li Wenguang Wu Xu’an Wang Huaifeng Li Runfa Bao Yijun Shu Jun Shen Jun Gu Xuefeng Wang Wei Gong Shuyou Peng Yingbin Liu Department of General Surgery Xinhua HospitalAffiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of biliary-Pancreatic Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China State key laboratory of Oncogenes and Related Genes Shanghai 200092China Shanghai Key Laboratory of Biliary Tract Disease Research Shanghai 200092China shanghai research Center of biliary tract disease Shanghai 200092China Department of General Surgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejing 310009China

Background:Hepatopancreatoduodenectomy(HPD)has been considered the only curative treatment for metastatic cholangiocarcinoma and some locally advanced gallbladder cancers(GBCs).However,HPD has not yet been included in treatment guidelines as a standard surgical procedure in consideration of its morbidity and mortality rates.The aim of this study was to evaluate the safety and effectiveness of HPD in treating biliary malignancies.Methods:The medical records of 57 patients with advanced biliary cancer undergoing HPD from January 2009 to December 2019 were retrospectively retrieved.A case-control analysis was conducted at our department.Patients with advanced GBC who underwent HPD(HPD-GBC group)were compared with a control group(None-HPD-GBC group).Baseline characteristics,preoperative treatments,tumor pathologic features,operative results,and prognosis were assessed.Results:Thirteen patients with cholangiocarcinoma and 44 patients with GBC underwent HPD at our department.Significant postoperative complications(grade III or greater)and postoperative pancreatic fistula were observed in 24(42.1%)and 15(26.3%)patients,respectively.One postoperative death occurred in the present study.Overall survival(OS)was longer in patients with advanced cholangiocarcinoma than in those with GBC(median survival time[MST],31 months vs.11 months;P<0.001).In the subgroup analysis of patients with advanced GBC,multivariate analysis demonstrated that T4 stage tumors(P=0.012),N2 tumors(P=0.001),and positive margin status(P=0.004)were independently associated with poorer OS.Patients with either one or more prognostic factors exhibited a shorter MST than patients without those prognostic factors(P<0.001).Conclusion:HPD could be performed with a relatively low mortality rate and an acceptable morbidity rate in an experienced highvolume center.For patients with advanced GBC without an N2 or T4 tumor,HPD can be a preferable treatment option.

关键词： Hepatectomy Hepatopancreatoduodenectomy Gallbladder cancer Cholangiocarcinoma

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Drosophila P75 safeguards oogenesis by preventing H3K9me2 spreading

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Journal of Genetics and Genomics 2020年第4期47卷 187-199页

作者： Kun Dou Yanchao Liu Yingpei Zhang Chenhui Wang Ying Huang ZZ Zhao Zhang Department of Embryology Carnegie Institution for ScienceBaltimoreMD21218USA School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State key laboratory of Molecular Biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China State key laboratory of Oncogenes and Related Genes Shanghai Key Laboratory of Biliary Tract Disease ResearchShanghai Research Center of Biliary Tract DiseaseDepartment of General SurgeryXinhua HospitalShanghai Jiao Tong University School of MedicineShanghai200092China Department of Pharmacology and Cancer Biology Duke University School of MedicineDurhamNC27710USA Regeneration Next Duke UniversityDurhamNC27710USA

Serving as a host factor for human immunodeficiency virus(HIV)integration,LEDGF/p75 has been under extensive study as a potential target for therapy.However,as a highly conserved protein,its physiological function remains to be thoroughly elucidated.Here,we characterize the molecular function of dP75,the Drosophila homolog of LEDGF/p75,during oogenesis.dP75 binds to transcriptionally active chromatin with its PWWP domain.The C-terminus integrase-binding domain-containing region of dP75 physically interacts with the histone kinase Jil-1 and stabilizes it in vivo.Together with Jil-1,dP75 prevents the spreading of the heterochromatin mark-H3 K9 me2-onto genes required for oogenesis and piRNA production.Without dP75,ectopical silencing of these genes disrupts oogenesis,activates transposons,and causes animal sterility.We propose that dP75,the homolog of an HIV host factor in Drosophila,partners with and stabilizes Jil-1 to ensure gene expression during oogenesis by preventing ectopic heterochromatin spreading.

关键词： Drosophila LEDGF/p75 Jil-1 H3K9me2

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Topological reorganization and functional alteration of distinct genomic components in gallbladder cancer

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Frontiers of Medicine 2024年第1期18卷 109-127页

作者： Guoqiang Li Peng Pu Mengqiao Pan Xiaoling Weng Shimei Qiu Yiming Li Sk Jahir Abbas Lu Zou Ke Liu Zheng Wang Ziyu Shao Lin Jiang Wenguang Wu Yun Liu Rong Shao Fatao Liu Yingbin Liu Department of biliary-Pancreatic Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China State key laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai200127China shanghai key laboratory of biliary tract disease Shanghai200082China Department of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai200082China shanghai Tenth People’s Hospital of Tongji University Shanghai200072China Department of General Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200082China Department of Pharmacology Shanghai Jiao Tong University School of MedicineShanghai200025China

Altered three-dimensional architecture of chromatin influences various genomic regulators and subsequent gene expression in human cancer.However,knowledge of the topological rearrangement of genomic hierarchical layers in cancer is largely limited.Here,by taking advantage of in situ Hi-C,RNA-sequencing,and chromatin immunoprecipitation sequencing(ChIP-seq),we investigated structural reorganization and functional changes in chromosomal compartments,topologically associated domains(TADs),and CCCTC binding factor(CTCF)-mediated loops in gallbladder cancer(GBC)tissues and cell lines.We observed that the chromosomal compartment A/B switch was correlated with CTCF binding levels and gene expression changes.Increased inter-TAD interactions with weaker TAD boundaries were identified in cancer cell lines relative to normal controls.Furthermore,the chromatin short loops and cancer unique loops associated with chromatin remodeling and epithelial–mesenchymal transition activation were enriched in cancer compared with their control counterparts.Cancer-specific enhancer–promoter loops,which contain multiple transcription factor binding motifs,acted as a central element to regulate aberrant gene expression.Depletion of individual enhancers in each loop anchor that connects with promoters led to the inhibition of their corresponding gene expressions.Collectively,our data offer the landscape of hierarchical layers of cancer genome and functional alterations that contribute to the development of GBC.

关键词： 3D genome cancer TADs loop gene regulation

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Modified FOLFIRINOX for unresectable locally advanced or metastatic gallbladder cancer,a comparison with GEMOX regimen

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Hepatobiliary Surgery and Nutrition 2021年第4期10卷 498-506页

作者： Xu-Ya Cui Xue-Chuan Li Jiu-Jie Cui Xiang-Song Wu Lu Zou Xiao-Ling Song Tai Ren Yi-Di Zhu Huai-Feng Li Yang Yang Ke Liu Xu-Sheng Han Zi-Yao Jia Wen-Guang Wu Xu-An Wang Wei Gong Li-Wei Wang Mao-Lan Li Ying-Bin Liu Department of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of biliary-Pancreatic Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Biliary Tract Disease Research ShanghaiChina State key laboratory of Oncogenes and Related Genes ShanghaiChina shanghai research Center of biliary tract disease ShanghaiChina shanghai Cancer Institute ShanghaiChina Department of Medical Oncology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background:The first-line chemotherapy regimen for advanced gallbladder cancer(GBC)is gemcitabine plus platinum(GP),despite its efficacy is limited.The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX(mFOLFIRINOX)and gemcitabine plus oxaliplatin(GEMOX)as the first-line chemotherapy for unresectable locally advanced or metastatic GBC.Methods:The data of patients with unresectable locally advanced or metastatic GBC,who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to shanghai Jiaotong University School of Medicine,were retrieved.This retrospective study evaluated the clinical characteristics,survival outcomes and adverse events.Results:A total of 44 patients(n=25 in mFOLFIRINOX,n=19 in GEMOX)were included.There were no significant differences between groups in baseline characteristics.The median progression free survival(mPFS)was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group[P=0.021;hazard ratio(HR),0.499;95%CI,0.266 to 0.937].The median overall survival(mOS)was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group(P=0.019;HR,0.471;95%CI,0.239 to 0.929).disease control rate(DCR)was 76.0%in the mFOLFIRINOX group and 47.4%in the GEMOX group(P=0.051).The rate of grade 3-4 adverse events was 48%in the mFOLFIRINOX group and 36.8%in the GEMOX group(P=0.459).The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group,while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group.Conclusions:mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC,and the results need to be further verified by prospective clinical studies.

关键词： Gallbladder cancer(GBC) modified FOLFIRINOX(mFOLFIRINOX) gemcitabine plus oxaliplatin(GEMOX) chemotherapy

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Overview of current targeted therapy in gallbladder cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 530-548页

作者： Xiaoling Song Yunping Hu Yongsheng Li Rong Shao Fatao Liu Yingbin Liu Department of General Surgery and laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine1665 Kongjiang Road200092 ShanghaiChina Shanghai Key Laboratory of Biliary Tract Disease Research 1665 Kongjiang Road200092 ShanghaiChina State key laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteSchool of MedicineShanghai Jiao Tong University200127 ShanghaiChina Department of biliary-Pancreatic Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong University200127 ShanghaiChina Department of Pharmacology Shanghai Jiao Tong University School of Medicine200025 ShanghaiChina

Gallbladder cancer(GBC)is rare,but is the most malignant type of biliary tract tumor.Unfortunately,only a small population of cancer patients is acceptable for the surgical resection,the current effective regimen;thus,the high mortality rate has been static for decades.To substantially circumvent the stagnant scenario,a number of therapeutic approaches owing to the creation of advanced technologic measures(e.g.,next-generation sequencing,transcriptomics,proteomics)have been intensively innovated,which include targeted therapy,immunotherapy,and nanoparticle-based delivery systems.In the current review,we primarily focus on the targeted therapy capable of specifically inhibiting individual key molecules that govern aberrant signaling cascades in GBC.Global clinical trials of targeted therapy in GBC are updated and may offer great value for novel pathologic and therapeutic insights of this deadly disease,ultimately improving the efficacy of treatment.

关键词： targeted cancer mortality

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Identification of two migratory colon ILC2 populations differentially expressing IL-17A and IL-5/IL-13

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Science China(Life Sciences) 2023年第1期66卷 67-80页

作者： Hongzhi Liu Liang Li Yanyun Hao Jialu Li Zhaoyuan Liu Jingjing Qi Jingjing Zhang Ningbo Wu Dandan Wu Caixia Gao Lei Chen Lei Shen Jinke Cheng Bing Su shanghai Institute of Immunology Department of Immunology and Microbiologythe Ministry of Education Key Laboratory of Cell Death and DifferentiationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Biochemistry and Molecular Cell Biology Shanghai Key Laboratory for Tumor Microenvironment and InflammationShanghai Jiao Tong University School of MedicineShanghai 200025China State key laboratory for Oncogenes and Related Genes Key Laboratory of Gastroenterology and HepatologyMinistry of HealthDivision of Gastroenterology and HepatologyShanghai Institute of Digestive DiseaseRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Cancer InstituteShanghai Institute of Digestive DiseaseShanghai 200001China Department of biliary and Pancreatic Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Group 2 innate lymphoid cells(ILC2s)play important tissue resident roles in anti-parasite immunity,allergic immune response,tissue homeostasis,and tumor immunity.ILC2s are considered tissue resident cells with little proliferation at steady state.Recent studies have shown that a subset of small intestinal ILC2s could leave their residing tissues,circulate and migrate to different organs,including lung,liver,mesenteric LN and spleen,upon activation.However,it remains unknown whether other ILC populations with migratory behavior exist.In this study,we find two major colon ILC2 populations with potential to migrate to the lung in response to IL-25 stimulation.One subset expresses IL-17A and resembles inflammatory ILC2s(iILC2s)but lacks CD27 expression,whereas the other expresses CD27 but not IL-17A.In addition,the IL-17A^(+)ILC2s express lower levels of CD127,CD25,and ST2 than CD27^(+)ILC2s,which express higher levels of IL-5 and IL-13.Surprisingly,we found that both colon ILC2 populations still maintained their colonic features of preferential expression of IL-17A and CD27,IL-5/IL-13,respectively.Together,our study identifies two migratory colon ILC2 subsets with unique surface markers and cytokine profiles which are critical in regulating lung and colon immunity and homeostasis.

关键词： colon ILC2s IL-17A CD27 iILC2 lung inflammation

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QKI-5 regulates the alternative splicing of cytoskeletal gene ADD3 in lung cancer

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Journal of Molecular Cell Biology 2021年第5期13卷 347-360页

作者： Jin-Zhu Wang Xing Fu Zhaoyuan Fang Hui Liu Feng-Yang Zong Hong Zhu Yan-Fei Yu Xiao-Ying Zhang Shen-Fei Wang Ying Huang jingyi Hui State key laboratory of Molecular Biology Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China shanghai Center for Plant Stress Biology Chinese Academy of SciencesShanghai 201602China key laboratory of Systems Biology Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China Department of General Surgery Shanghai Key Laboratory of Biliary Tract Disease ResearchState Key Laboratory of Oncogenes and Related GenesXinhua HospitalShanghai Jiao Tong UniversityShanghai 200092China

Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer develop-ment and progression.The RNA-binding protein QKI-5 is frequently downregulated and exhibits anti-tumor activity in lung cancer.Howeve-r,little is known about the functional targets and regulatory mechanism of QKI-5.Here,we report that upregulation of exon 14 inclusion of cytoskeletal gene Adducin 3(ADD3)significantly correlates with a poor prognosis in lung cancer.QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14.Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis,we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner.By binding to multiple sites in an upstream intron region,QKI-5 represses the splicing of ADD3 exon 14.We also identified several QKI mutations in tumors,which cause dysregulation of the splicing of QKI targets ADD3 and NUMB.Taken together,our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event,which underlies in part the tumor suppressor function of QKI.

关键词： ADD3t alternative splicing RNA-binding protein QKI lung cancer

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Application of single balloon enteroscopy-assisted therapeutic endoscopic retrograde cholangiopancreatography in patients after bilioenteric Roux-en-Y anastomosis: Experience of multi-disciplinary collaboration

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World Journal of Gastroenterology 2019年第36期25卷 5505-5514页

作者： Wen-Guang Wu Lu-Cui Qin Xiao-Ling Song Ming-Ning Zhao Wen-Jie Zhang Jun Gu Hao Weng Ying-Bin Liu Yi Zhang Chun-Ying Qu Lei-Ming Xu Xue-Feng Wang Department of General Surgery and laboratory of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200092 China Department of Operating Room Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200092 China Shanghai Key Laboratory of Biliary Tract Disease Research Shanghai 200092 China Department of Gastroenterology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200092 China

BACKGROUND Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.

关键词： Bilioenteric Roux-en-Y anastomosis Single balloon enteroscopy Multidisciplinary cooperation Hepaticojejunostomy Pancreaticoduodenectomy

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