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Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression

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Frontiers of Medicine 2024年第3期18卷 430-445页

作者： Yue Ma Hongwei Lv Fuxue Xing Wei Xiang Zixin Wu Qiyu Feng Hongyang Wang Wen Yang Cancer Research Center First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230027China National Center for Liver Cancer Naval Medical University(Second Military Medical University)Shanghai201805China international Co-operation laboratory on signal transduction Eastern Hepatobiliary Surgery HospitalNaval Medical University(Second Military Medical University)Shanghai200438China Shanghai Key laboratory of Hepato-biliary Tumor Biology Shanghai200438China Key laboratory of signaling Regulation and Targeting Therapy of Liver Cancer Ministry of EducationShanghai200438China

Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression.A tumor subpopulation called liver cancer stem cells(CSCs)significantly accounts for the initiation,metastasis,therapeutic resistance,and recurrence of liver *** evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy *** review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression,as well as the underlying molecular mechanisms after presenting an overview of liver CSCs characteristic and their ***,we discuss the potential application of liver CSCs-targeted immunotherapy for liver cancer treatment.

关键词： liver cancer cancer stem cell immune cell immunotherapy

Infection with SARS-CoV-2 can cause pancreatic impairment

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signal transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie Zhao Xiuqin Zhang Yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin NHC Key laboratory of Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing Key laboratory of Cardiometabolic Molecular Medicine Peking UniversityBeijing 100871China State Key laboratory of Biomembrane and Membrane Biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of Engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China international Co-operation laboratory on signal transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China National laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping National laboratory(CPNL) Beijing 102206China State Key laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of ***,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 ***-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and *** and limited phenotypic and histopathological changes were observed in adult *** proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio ***,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic *** contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

HCCDB v2.0:Decompose Expression Variations by Single-cell RNA-seq and Spatial Transcriptomics in HCC

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 131-142页

作者： Ziming Jiang Yanhong Wu Yuxin Miao Kaige Deng Fan Yang Shuhuan Xu Yupeng Wang Renke You Lei Zhang Yuhan Fan Wenbo Guo Qiuyu Lian Lei Chen Xuegong Zhang Yongchang Zheng Jin Gu Eight-Year Program of Clinical Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100006China MOE Key laboratory of Bioinformatics BNRIST Bioinformatics DivisionInstitute for Precision Medicine&Department of AutomationTsinghua UniversityBeijing 100084China Department of Liver surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Fuzhou Institute for Data Technology Fuzhou 350207China University of Michigan-Shanghai Jiao Tong University Joint Institute Shanghai Jiao Tong UniversityShanghai 200240China Department of Automation Shanghai Jiao Tong UniversityShanghai 200240China international cooperation laboratory on signal transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438China National Center for Liver Cancer Shanghai 201805China

Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma(HCC).Integrated 15 transcriptomic datasets of HCC clinical samples,the first version of HCC database(HCCDB v1.0)was released in *** the meta-analysis of differentially expressed genes and prognosis-related genes across multiple datasets,it provides a systematic view of the altered biological processes and the inter-patient heterogeneities of HCC with high reproducibility and *** four years having passed,the database now needs integration of recently published ***,the latest single-cell and spatial transcriptomics have provided a great opportunity to decipher complex gene expression variations at the cellular level with spatial ***,we present HCCDB v2.0,an updated version that combines bulk,single-cell,and spatial transcriptomic data of HCC clinical *** dramatically expands the bulk sample size by adding 1656 new samples from 11 datasets to the existing 3917 samples,thereby enhancing the reliability of transcriptomic meta-analysis.A total of 182,832 cells and 69,352 spatial spots are added to the single-cell and spatial transcriptomics sections,respectively.A novel single-cell level and 2-dimension(sc-2D)metric is proposed as well to summarize cell type-specific and dysregulated gene expression *** are all graphically visualized in our online portal,allowing users to easily retrieve data through a user-friendly interface and navigate between different *** extensive clinical phenotypes and transcriptomic data in the database,we show two applications for identifying prognosis-associated cells and tumor *** v2.0 is available at http://***/database/hccdb2.

关键词： Hepatocellular carcinoma Database Integrative analysis Single-cell RNA sequencing Spatial transcriptomics

Cancer prevention and control: alarming challenges in China

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National Science Review 2016年第1期3卷 117-127页

作者： Ann M.Bode Zigang Dong Hongyang Wang The Hormel Institute University of Minnesota National Center for Liver Cancer international cooperation laboratory on signal transduction Eastern Hepatobiliary Surgery Hospital

China is geographically the third largest country in the world and the most populated low-to-middle-income country. Cancer incidence and mortality rates for some cancers in the USA and European countries have steadily decreased over the last decades, whereas the incidence and mortality of certain cancers in China have been increasing at an alarming speed. Rapid industrialization and urbanization in China have been accompanied by incredible changes in lifestyle and environment combined with an aging population. Mortality caused by lung, colorectal and breast cancers has been steadily increasing, whereas cancer mortality from gastric, esophageal and cervical tumors has tended to decrease. Similar to what has occurred in the United States, unhealthy lifestyles in China, including heavy smoking and poor diet combined with pollution, have contributed to increased cancer risk. China is facing many challenges in cancer treatment and prevention for the general population. The major areas that need to be addressed in the control of cancer in China include cancers associated with environmental pollution,tobacco use, occupational carcinogens, infection, excessive alcohol consumption, dietary deficiencies and obesity. In this perspective, we review the problems in each area and suggest ideas for future directions in cancer research and strategies and actions to reduce the incidence of cancer in China.

关键词： cancer incidence environmental pollution tobacco use and control occupational carcinogens infection-caused cancers alcohol dietary deficiencies obesity cancer prevention

Cloning and expression of MXR7 gene in human HCC tissue

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World Journal of Gastroenterology 2000年第1期6卷 57-60页

作者： Zhou XP Wang HY Yang GS Chen ZJ Li BA Wu MC The international cooperation laboratory on signal transduction Eastern Hepatobiliary Surgery Hospitalthe Second Military Medical UniversityShanghai 200438China

AIM To clone and identify the whole cDNA ofMXR7 gene and to find out its expression inhuman HCC,and normal *** The DNA primers were designed andsynthesized according to the whole cDNAsequence of MXR? *** cDNA of humanHCC was taken as the template while the cDNA ofMXR7 gene was synthesized by polymerasechain reaction（PCR）.Recombinant DNAconforming to reading frame was constructed byconnecting purified PCR product of the cDNA ofMXR? gene with expression vector pGEX-5X-1 offusion *** plasmid MXRT/pGEX-5X-1was identified by *** 32p labeledMXR? cDNA as probe,MXR7 mRNA expressionwas detected by Northern blot analysis in 12different human normal tissues,7 preoperativelyuntreated non-liver tumor tissues,30preoperatively untreated HCC,theparacancerous liver tissues and 12 normal livertissues *** Restriction enzyme and sequenceanalysis confirmed that the insertion sequence invector pGEX-5X-1 was the same as the cDNAsequence of MXR7 *** blot analysisshowed no expression of MXR? mRNA in 12 kindsof normal human tissues including liver,7 tumortissues in other sites and 12 normal livertissues,the frequencies of MXR7 mRNA expression in HCC and paracancerous livertissues were 76.6% and 13.3%,*** frequency of MXR7 mRNA expression in HCCwithout elevation of serum AFP and in HCC<5cm was 90%（9/10）and 83.3%（5/6）,*** MXR7 mRNA is highly expressedin human HCC,which is specific and occurs at anearly stage of HCC,suggesting MXR7 mRNA canbe a tumor biomarker for *** detection ofMXR7 mRNA expression in the biopsied livertissue is helpful in discovering early subclinicalliver cancer in those with negative serum AFP.

关键词： Subject headings human HCC tissues MXR7 gene gene expression cDNA mRNA

From cell signaling to cancer therapy

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Acta Pharmacologica Sinica 2007年第9期28卷 1494-1498页

作者： Jin DING Yun FENG Hong-yang WANG The international cooperation laboratory on signal transduction,eastern hepatobiliary surgery Institute,Second Military Medical University,Shanghai 200438,China The international cooperation laboratory on signal transduction Eastern Hepatobiliary Surgery Institute Second Military Medical University Shanghai China

Cancer has been seriously threatening the health and life of humans for a *** the intensive effort put into revealing the underlying mechanismsof cancer,the detailled machinery of carcinogenesis is still far from fully *** studies have illustrated that cell signaling is extensively involved intumor initiation,promotion and ***,targeting the key mol-ecules in the oncogenic signaling pathway might be one of the most promisingways to conquer *** targeted drugs,such as imatinib mesylate (Gleevec),herceptin,gefitinib (Iressa),sorafenib (Nexavar) and sunitinib (Sutent),whichevolve from monotarget drug into multitarget ones,have been developed withencouraging effects.

关键词： cell signaling cancer therapy chemotherapy

Experimental study on enhancement of the metastatic potential of portal vein tumor thrombus-originated hepatocellular carcinoma cells using portal vein serum

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Chinese Journal of Cancer Research 2014年第5期26卷 588-595页

作者： Yufu Tang Hongming Yu Long Zhang Kang Wang Weixing Guo Jie Shi Shupeng Liu Mengchao Wu Hongyang Wang Shuqun Cheng eastern hepatobiliary surgery hospital Second Military Medical University Department of hepatobiliary surgery General Hospital of Shenyang Military Area Command Changhai hospital Second Military Medical University international cooperation laboratory on signal transduction of eastern hepatobiliary surgery Institute Second Military Medical University

Objective： Portal vein metastasis of hepatocellular carcinoma（HCC） results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus（PVTT） is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.Methods： Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits. Results： Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis（P〈0.01）, significantly enhanced cell metastasis and invasion（P〈0.01）, whereas cell proliferation and the stages of the cell cycle did not differ significantly（P〉0.05）. A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum（P〈0.05）, while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly（P〈0.05）. Conclusions： Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell metasta

关键词： Hepatocellular carcinoma(HCC) portal vein portal vein tumor thrombus(PVTT) metastasis

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Reduced expression of P120 catenin in cholangiocarcinoma correlated with tumor clinicopathologic parameters

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World Journal of Gastroenterology 2008年第23期14卷 3739-3744页

作者： Bo Zhai He-Xin Yan Shu-Qin Liu Lei Chen Meng-Chao Wu Hong-Yang Wang Department of Ultrasonic Intervention Eastern Hepatobiliary Surgery Hospital Second Military Medical University Shanghai 200438 China international cooperation laboratory on signal transduction Eastern Hepatobilliary Surgery Institute Second Military Medical University Shanghai 200438 China

AIM： To investigate the relationship between the expression of P120 and the clinicopathologic parameters in intrahepatic cholangiocarcinoma （ICC）. METHODS： An immunohistochemical study of E-cadherin and P120 catenin was performed on 42 specimens of ICC with a Dako Envision kit. RESULTS： The expression of E-cadherin and P120 was reduced in 27 cases （64.3%） and 31 cases （73.8%）, respectively. Both E-cadherin and P120 expressions were significantly correlated with the tumor histological grade （χ^2 = 9.333, P = 009 and χ^= 11.71, P = 0.003）, TNM stage （χ^= 8.627, P = 0.035 and χ^= 13.123, P = 0.004）, intrahepatic metastasis （χ^= 7.292, P = 0.007 and χ^= 4.657, P = 0.041, respectively） and patients′ survival （χ^= 6.351, P = 0.002 and χ^= 4.023, P = 0.000, respectively）. In addition, the expression of P120 was in concordance with that of E-cadherin （χ^ = 13.797, P = 0.000）, indicating that the expression of P120 may be dependent on that of E-cadherin. Finally, only P120 expression was found to be an independent prognostic factor in Cox regression model （r = 0.088, P = 0.049）. CONCLUSION： Down-regulated expression of E-cadherin and P120 occurs frequently in ICC and contributes to the progression and development of tumor. Both of them may be valuable biologic markers for predicting tumor invasion, metastasis and patients′ survival, but only P120 is an independent prognostic factor for ICC.

关键词： P120 Intrahepatic cholangiocarcinoma Clinicopathologic feature Invasion and metastasis Survival

Structural basis of interaction between protein tyrosine phosphatase PCP-2 and β-catenin

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Science China(Life Sciences) 2005年第2期48卷 163-167页

作者： HE Yaqin YAN Hexin DONG Hui ZHANG Peng TANG Liang QIU Xiuhua WU Mengchao WANG Hongyang international Co-operation laboratory on signal transduction Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghai 200438China

PCP-2 is a member of receptor-like protein tyrosine phosphatase of the MAM do-main *** investigate which part of PCP-2 was involved in its interaction withβ-catenin,we constructed various deletion mutants of *** PCP-2 mutants and wild-type PCP-2 were co-transfected into BHK-21 cells withβ-catenin *** in vivo binding assay revealed that the expression of wild-type PCP-2,PCP-2?C1C2(deleted PCP-2 without both PTP domains)and PCP-2?C2(deleted PCP-2 without the second PTP domain)could be immunoprecipitated by anti-catenin antibody in every co-transfection,but PCP-2 EXT(deleted PCP-2 without the juxtamembrane region and both PTP domains)was missing,which implied that PCP-2 andβ-catenin could associate directly and the juxtamembrane region in PCP-2 was sufficient for the process.

关键词： PCP-2 β-catenin protein tyrosine phosphatase interaction.

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