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Immunobiology and immunotherapy of HCC:spotlight on innate and innate-like immune cells

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Cellular & Molecular Immunology 2021年第1期18卷 112-127页

作者： Benjamin Ruf Bernd Heinrich Tim F.Greten gastrointestinal Malignancy Section Thoracic and Gastrointestinal Malignancies BranchCentre for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA NCI CCR Liver Cancer Program National Institutes of HealthBethesdaMD 20892USA

Immune-based therapies such as immune checkpoint inhibitors have revolutionized the systemic treatment of various cancer *** therapeutic application of monoclonal antibodies targeting inhibitory pathways such as programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)and CTLA-4 to cells of the adaptive immune system has recently been shown to generate meaningful improvement in the clinical outcome of hepatocellular carcinoma(HCC).Nevertheless,current immunotherapeutic approaches induce durable responses in only a subset of HCC *** immunologic mechanisms such as chronic inflammation due to chronic viral hepatitis or alcoholic and nonalcoholic fatty liver disease play a crucial role in the initiation,development,and progression of HCC,it is important to understand the underlying mechanisms shaping the unique tumor microenvironment of liver *** liver is an immunologic organ with large populations of innate and innate-like immune cells and is exposed to bacterial,viral,and fungal antigens through the gut-liver ***,we summarize and highlight the role of these cells in liver cancer and propose strategies to therapeutically target *** also discuss current immunotherapeutic strategies in HCC and outline recent advances in our understanding of how the therapeutic potential of these agents might be enhanced.

关键词： HCC immunotherapy innate immunity tumor microenvironment

Endoscopic ultrasound staging for early esophageal cancer: Are we denying patients neoadjuvant chemo-radiation?

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World Journal of Gastroenterology 2017年第46期23卷 8193-8199页

作者： Carrie Luu Marisa Amaral Jason Klapman Cynthia Harris Khaldoun Almhanna Sarah Hoffe Jessica Frakes Jose M Pimiento Jacques P Fontaine Department of thoracic oncology H. Lee Moffitt Cancer Center and Research Institute Department of gastrointestinal oncology H. Lee Moffitt Cancer Center and Research Institute Department of Radiation oncology H. Lee Moffitt Cancer Center and Research Institute

AIM To evaluate the accuracy of endoscopic ultrasound(EUS) in early esophageal cancer(EC) performed in a highvolume tertiary cancer center. METHODS A retrospective review of patients undergoing esophagectomy was performed and patients with c T1 N0 and c T2 N0 esophageal cancer by EUS were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. EUS staging was compared to surgical pathology to determine accuracy of EUS. Descriptive statistics was used to describe the cohort. Student's t test and Fisher's exact test or χ~2 test was used to compare variables. Logistic regression analysis was used to determine if clinical variables such as tumor location and tumor histology were associated with EUS *** Between 2000 and 2015, 139 patients with clinical stage Ⅰ or Ⅱ?A esophageal cancer undergoing esophagectomy were identified. There were 25(18%) female and 114(82%) male patients. The tumor location included the middle third of the esophagus in 11(8%) and lower third and gastroesophageal junction in 128(92%) patients. Ninety-three percent of patients had adenocarcinoma. Preoperative EUS matched the final surgical pathology in 73/139 patients for a concordance rate of 53%. Twenty-nine patients(21%) were under-staged by EUS; of those, 19(14%) had unrecognized nodal disease. Positron emission tomography(PET) was used in addition to EUS for clinical staging in 62/139 patients. Occult nodal disease was only found in 4 of 62 patients(6%) in whom both EUS and PET were negative for nodal involvement. CONCLUSION EUS is less accurate in early EC and endoscopic mucosal resection might be useful in certain settings. The addition of PET to EUS improves staging accuracy.

关键词： Esophageal cancer Endoscopic ultrasound Staging Early esophageal cancer Endoscopic mucosal resection

Immunotherapy of hepatocellular carcinoma with infection of hepatitis B or C virus

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Hepatoma Research 2020年第10期6卷 22-35页

作者： Cecilia Monge Bonilla Nicole A.McGrath Jianyang Fu Changqing Xie thoracic and gastrointestinal Malignancies branch Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA

Hepatocellular carcinoma(HCC)has one of highest mortalities globally amongst cancers,but has limited therapeutic options once in the advanced *** B or C virus infection are the most common drivers for HCC carcinogenesis,triggering chronic liver inflammation and adding to the complexity of the immune microecosystem of *** emergence of immunotherapy has afforded a new avenue of therapeutic options for patients with advanced HCC with a history of hepatitis B or C virus *** article reviews the change of immunity elicited by hepatitis B or C virus infection,the immune feature of HCC,and the clinical evidence for immunotherapy in advanced HCC and discusses future directions in this field.

关键词： Hepatocellular carcinoma hepatitis B virus hepatitis C virus immunotherapy

Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

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World Journal of gastrointestinal oncology 2025年第1期17卷 39-51页

作者： Si-Yun Lin Hou Huang Jin-Jie Yu Feng Su Tian Jiang Shao-Yuan Zhang Lu Lv Tao Long Hui-Wen Pan Jun-Qing Qi Qiang Zhou Wei-Feng Tang Guo-Wen Ding Li-Ming Wang Li-Jie Tan Jun Yin Department of thoracic Surgery Zhongshan Hospital Affiliated to Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Clinical Geriatric Medicine Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China Department of Cardiothoracic Surgery The Affiliated People's Hospital of Jiangsu UniversityZhenjiang 212002Jiangsu ProvinceChina Department of thoracic Surgery Sichuan Cancer Hospital&InstituteChengdu 610042Sichuan ProvinceChina Department of Cardiothoracic Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210000Jiangsu ProvinceChina Department of Respiratory and Critical Care Medicine Shanghai Xuhui Central HospitalShanghai 200032China

BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and *** A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent *** To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han *** In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were *** SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction ***-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were *** Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male *** the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to *** ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

关键词： Activin A receptor type 1C Single nucleotide polymorphisms Esophageal squamous cell carcinoma Genetic susceptibility Hospital-based cohort study

Verteporfin synergizes the efflcacy of anti-PD-1 in cholangiocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2022年第5期21卷 485-492页

作者： Jianyang Fu Nicole A McGrath Jihye Lee Xin Wang Gagandeep Brar Changqing Xie thoracic and gastrointestinal Malignancies branch Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Sandra and Edward Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA

Background:Cholangiocarcinoma(CCA)is one of the primary hepatobiliary malignant neoplasms with only 10%of 5-year survival *** immunotherapy with the blockade of immune checkpoints has no clear benefit in *** inhibition of YAP1 signaling by verteporfin has shown encouraging results by inhibiting cell proliferation and inducing *** study aimed to evaluate the potential benefit of the combination of verteporfin and anti-programmed cell death 1(PD-1)in CCA mouse ***:We assessed the cytotoxicity of verteporfin in human CCA cell lines in vitro,including both intrahepatic CCA and extrahepatic CCA *** examined the in vitro effect of verteporfin on cell proliferation,apoptosis,and *** evaluated the in vivo efflcacy of verteporfin,anti-PD-1,and a combination of both in subcutaneous CCA mouse ***:Our study showed that verteporfin reduced tumor cell growth and enhanced apoptosis of human CCA tumor cells in vitro in a dose-dependent ***,verteporfin impaired stemness evidenced by reduced spheroid formation and colony formation,decreased numbers of cells with aldehyde dehydrogenase activity and positive cancer stem cell markers(all P<0.05).The combination of verteporfin and anti-PD-1 reduced tumor burden in CCA subcutaneous SB1 tumor model compared to either agent ***:Verteporfin exhibits antitumor effects in both intrahepatic and extrahepatic CCA cell lines and the combination with anti-PD-1 inhibited tumor growth.

关键词： Verteporfin YAP1 Anti-programmed cell death-1 Immunotherapy Cholangiocarcinoma

Percutaneous hepatic perfusion with melphalan for unresectable liver metastasis

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Hepatoma Research 2016年第1期2卷 197-202页

作者： Humair S.Quadri Eden C.Payabyab David J.Chen William Figg Marybeth S.Hughes thoracic and gastrointestinal oncology branch National Cancer InstituteBethesdaMD 20892USA Genitourinary Malignancies branch National Cancer InstituteBethesdaMD 20892USA

Percutaneous hepatic perfusion(PHP)is an investigative technique for treating patients with diffuse unresectable metastatic liver *** technique has been clinically evaluated and shows great treatment potential for regional therapy to the *** advantage of PHP lies in its minimally invasive approach and ability to be repeated when compared to isolated hepatic *** a literature search,135 publications were screened and 16 of these publications,including clinical trials and reviews,contributed to this review of PHP with *** is an alkylating agent that,when used as the chemotherapeutic agent in PHP,has shown potential for significant control of tumor burden in the liver,especially in metastatic ocular *** the current landscape of liver directed therapy,PHP is a viable option for those with unresectable metastatic disease to the *** article will focus on the technical aspects of PHP and describe the current data available from clinical trials,including outcomes of patients treated with this minimally invasive approach.

关键词： Percutaneous hepatic perfusion melphalan unresectable liver metastasis metastatic melanoma to the liver ocular melanoma

Docetaxel, cisplatin, and 5-fluorouracil compared with epirubicin,cisplatin, and 5-fluorouracil regimen for advanced gastric cancer:A systematic review and meta-analysis

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World Journal of Clinical Cases 2019年第5期7卷 600-615页

作者： Bo Li Lian Chen Hong-Liang Luo Feng-Ming Yi Yi-Ping Wei Wen-Xiong Zhang Department of thoracic Surgery The Second Affiliated Hospital of Nanchang University Jiangxi Medical College Nanchang University Department of gastrointestinal Surgery The Second Affiliated Hospital of Nanchang University Department of Digestive oncology The Second Affiliated Hospital of Nanchang University

BACKGROUND As the first-line regimens for the treatment of advanced gastric cancer, both docetaxel, cisplatin, and 5-fluorouracil(DCF) and epirubicin, cisplatin, and 5-fluorouracil(ECF) regimens are commonly used in clinical practice, but there is still controversy about which is *** To compare the efficacy and safety of DCF and ECF regimens by conducting this *** Computer searches in PubMed, EMBASE, Ovid MEDLINE, Science Direct, Web of Science, The Cochrane Library and Scopus were performed to find the clinical studies of all comparisons between DCF and ECF regimens. We used progression-free survival(PFS), overall survival(OS), objective response rate(ORR), disease control rate(DCR), and adverse effects(AEs) as endpoints for *** Our meta-analysis included seven qualified studies involving a total of 598 patients. The pooled hazard ratios between the DCF and ECF groups were comparable in PFS(95%CI: 0.58-1.46, P = 0.73), OS(95%CI: 0.65-1.10, P = 0.21),and total AEs(95%CI: 0.93-1.29, P = 0.30). The DCF group was significantly better than the ECF group in terms of ORR(95%CI: 1.13-1.75, P = 0.002) and DCR(95%CI: 1.03-1.41, P = 0.02). However, the incidence rate of grade 3-4 AEs was also greater in the DCF group than in the ECF group(95%CI: 1.16-1.88, P = 0.002),especially for neutropenia and febrile *** With better ORR and DCR values, the DCF regimen seems to be more suitable for advanced gastric cancer than the ECF regimen. However, the higher rate of AEs in the DCF group still needs to be noticed.

关键词： Gastric cancer Chemotherapy Docetaxel Epirubicin Cisplatin 5-fluorouracil

Unexpected guests in the tumor microenvironment:microbiome in cancer

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Protein & Cell 2021年第5期12卷 426-435页

作者： Abigail Wong-Rolle Haohan Karen Wei Chen Zhao Chengcheng Jin thoracic and gastrointestinal Malignancies branch National Cancer InstituteNational Institutes of Health4 Memorial DriveBethesdaMD 20892USA Department of Cancer Biology Perelman School of MedicineUniversity of Pennsylvania421 Curie Blvd.PhiladelphiaPA 19104USA

Although intestinal microbiome have been established as an important biomarker and regulator of cancer development and therapeutic response, less is known about the role of microbiome at other body sites in cancer. Emerging evidence has revealed that the local microbiota make up an important part of the tumor microenvironment across many types of cancer, especially in cancers arising from mucosal sites, including the lung, skin and gastrointestinal tract. The populations of bacteria that reside specifically within tumors have been found to be tumor-type specific, and mechanistic studies have demonstrated that tumor-associated microbiota may directly regulate cancer initiation, progression and responses to chemo- or immuno-therapies. This review aims to provide a comprehensive review of the important literature on the microbiota in the cancerous tissue, and their function and mechanism of action in cancer development and treatment.

关键词： microbiome tumor lung cancer immune system tumor-associated microbiota cancer immunotherapy

SHR-A1811(antibody-drug conjugate)in advanced HER2-mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2 study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming Li Zhengbo Song Wei Hong Nong Yang Yongsheng Wang Hong Jian Zibin Liang Sheng Hu Min Peng Yan Yu Yan Wang Zicong Jiao Kaijing Zhao Ke Song You Li Wei Shi Shun Lu Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China Phase I Clinical Trial Ward Zhejiang Cancer HospitalHangzhou 310000China Department of thoracic oncology Zhejiang Cancer HospitalHangzhou 310000China Department of Lung&gastrointestinal oncology Hunan Cancer HospitalChangsha 410031China thoracic oncology Ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China Department of thoracic oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China Department of Medical oncology Hubei Cancer HospitalWuhan 43000China Department of oncology Renmin Hospital of Wuhan UniversityWuhan 430200China Department of thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Medical oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui Pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2 study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had HER2-mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 29(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.

关键词： SHR HER2 doses