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IFN-γ^(+) cytotoxic CD4^(+) T lymphocytes are involved in thepathogenesis of colitis induced by IL-23 and the foodcolorant Red 40

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Cellular & Molecular Immunology 2022年第7期19卷 777-790页

作者： Lili Chen Zhengxiang He Bernardo S.Reis Jesse D.Gelles Jerry Edward Chipuk Adrian T.Ting Julie A.Spicer Joseph A.Trapani Glaucia C.Furtado Sergio A.Lira Precision Immunology institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Laboratory of Mucosal Immunology The Rockefeller UniversityNew YorkNY 10065USA Department of Oncological Sciences Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA The tisch cancer institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA The Diabetes Obesityand Metabolism InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA Department of Immunology Mayo ClinicRochesterMN 55905USA Auckland cancer Society Research Centre Faculty of Medical and Health SciencesThe University of AucklandPrivate Bag 92019Auckland 1142New Zealand cancer Immunology Program Peter MacCallum Cancer Centre305 Grattan StreetMelbourneVIC 3000Australia

The food colorant Red 40 is an environmental risk factor for colitis development in mice with increased expression of interleukin(IL)-23.This immune response is mediated by CD4^(+)T cells,but mechanistic insights into how these CD4^(+)T cells trigger andperpetuate colitis have remained elusive.Here,using single-cell transcriptomic analysis,we found that several CD4^(+)T-cell subsetsare present in the intestines of colitic mice,including an interferon(IFN)-γ-producing subset.In vivo challenge of primed mice withRed 40 promoted rapid activation of CD4^(+)T cells and caused marked intestinal epithelial cell(IEC)apoptosis that was attenuated bydepletion of CD4^(+)cells and blockade of IFN-γ.Ex vivo experiments showed that intestinal CD4^(+)T cells from colitic mice directlypromoted apoptosis of IECs and intestinal enteroids.CD4^(+)T cell-mediated cytotoxicity was contact-dependent and required FasL,which promoted caspase-dependent cell death in target IECs.Genetic ablation of IFN-γconstrained IL-23-and Red 40-inducedcolitis development,and blockade of IFN-γinhibited epithelial cell death in vivo.These results advance the understanding of themechanisms regulating colitis development caused by IL-23 and food colorants and identify IFN-γ^(+)cytotoxic CD4^(+)T cells as a newpotential therapeutic target for colitis.

关键词： Allura Red IL23 Cytotoxic CD4^(+)T cells CD4^(+)CTL Inflammation Epithelium damage Colitis

Examining heterogeneity of stromal cells in tumor microenvironment based on pan-cancer single-cell RNA sequencing data

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cancer Biology & Medicine 2022年第1期19卷 30-42页

作者： Wenhui Wang Li Wang Junjun She Jun Zhu Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA Sema4 a Mount Sinai ventureStamfordCT 06902USA First Affiliate Hospital of Xi’an Jiaotong University Xi’an 710061China tisch cancer institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA

Tumor tissues contain both tumor and non-tumor cells,which include infiltrated immune cells and stromal cells,collectively called the tumor microenvironment(TME).Single-cell RNA sequencing(sc RNAseq)enables the examination of heterogeneity of tumor cells and TME.In this review,we examined sc RNAseq datasets for multiple cancer types and evaluated the heterogeneity of major cell type composition in different cancer types.We further showed that endothelial cells and fibroblasts/myofibroblasts in different cancer types can be classified into common subtypes,and the subtype composition is clearly associated with cancer characteristic and therapy response.

关键词： Stromal cells tumor microenvironment pan-cancer single-cell RNA sequencing data

Circulating and non-circulating proteins and nucleic acids as biomarkers and therapeutic molecules in ovarian cancer

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Genes & Diseases 2023年第3期10卷 1005-1018页

作者： Kumar Utkarsh Abhishek Kumar Aditi Azhar Khan Ashima Nayyar Shabirul Haque Shams Iqbal Department of Microbiology and Biotechnology Shoolini UniversitySolanHimachal Pradesh 173229India Faculty of Applied Science and Biotechnology Shoolini UniversitySolanHimachal Pradesh 173229India tisch cancer institute Icahn School of MedicineMt.SinaiNY 10029USA Department of Autoimmune Diseases Feinstein Institute for Medical ResearchNorthwell HealthManhassetNY 11030USA Vascular Interventional Radiology Department of RadiologyMassachusetts General HospitalHarvard Medical SchoolBostonMA 02115USA

Ovarian cancer is the second most fatal gynecological cancer. For the last decade or so significant use of non-circulating and circulating biomarkers has been highlighted. However, the study of such biomarkers at nanovesicle technology such as exosomes, proteomic and genomics studies could further contribute to better identification of anomalous protein and networks which could act as potential targets for biomarker and immunotherapy development. This review provides an overview of the circulating and non-circulating biomarkers with the aim of addressing the current challenges and potential biomarkers that could lead to early ovarian cancer diagnosis and better management. By means of this review we also lay a hypothesis that characterization of exosomal protein, nucleic acid content from body fluids (serum, plasma, urine, etc.) can decode the secret of disease and potentially improve diagnostic sensitivity which could further lead to more effective screening and early detection of the disease.

关键词： Biomarker Circulating protein Exosomes Extracellular vesicles Ovarian cancer Proteonnics

Treatment of unresectable malignant pleural mesothelioma in 2021: emerging standards in immunotherapy

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Journal of cancer Metastasis and Treatment 2021年第1期7卷 737-747页

作者： Bailey G.Fitzgerald Lee M.Krug tisch cancer institute Icahn School of Medicine at Mount SinaiNew YorkNY 10029USA AstraZeneca GaithersburgMD 20878USA

Patients with unresectable malignant pleural mesothelioma(MPM)have historically poor outcomes and treatment,and their treatments have been limited to palliative chemotherapy.Recent efforts to improve prognosis for these patients by adding angiogenesis inhibitors to chemotherapy led to significant benefits.However,the emergence of immunotherapy combinations for the front-line treatment has upended the standard of care and has led to the first new FDA approvals for the treatment of MPM in nearly two decades.This review aims to cover the main clinical trials in unresectable MPM with VEGF inhibitors and immunotherapy which have led to paradigm shifts in current practice.Ongoing clinical trials exploring the combination of chemo and immunotherapies show a great deal of promise,and continued support for ambitious,large-scale well-designed trials remain vital for defining the future outcomes of patients diagnosed with MPM.

关键词： Malignant pleural mesothelioma VEGF chemotherapy immunotherapy PD-L1 CTLA-4

The metastatic castration-resistant prostate cancer treatment paradigm： more choices, more questions

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Asian Journal of Andrology 2014年第3期16卷 331-333页

作者： Evan Y Yu William K Oh Department of Medicine Division of Medical Oncology University of Washington Seattle WA 98109 USA Division of Hematology and Medical Oncology Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York NY 10029 USA.

The world of prostate cancer has dramatically changed in the last few years. The original paradigm that metastatic castration-resistant prostate cancer （mCRPC） is untreatable is clearly wrong.

关键词： prostate cancer castration-resistant treatment

Attributable Causes of cancer in China:Fruit and Vegetable

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Chinese Journal of cancer Research 2011年第3期23卷 171-176页

作者： Hui-juan Xiao Hao Liang Jian-bing Wang Cheng-Yu Huang Wen-qiang Wei Mathieu Boniol You-lin Qiao Paolo Boffetta Department of Nutrition and Food Hygiene West China School of Public Health Sichuan University Chengdu 610041 China Departments of cancer Epidemiolo gy Cancer Institute Chinese Academy of Medical Sciences Beijing 100021 China Department of Epidemiology and Statistics Institute of Basic Medical Sciences Chinese Academy of Medical Sciences ＆School of Basic Medicine Peking Union Medical College Beijing 100005 China International Prevention Research institute Lyon 69008 France The tisch cancer institute Mount Sinai School of Medicine New York NY 10029 USA Nutrition Department Tianjin Third Central Hospital Tianjin 300170 China

Objective：To provide an evidence-based and consistent assessment of the burden of cancer attributable to inadequate fruit and vegetable intake in China in 2005.Methods：The proportions of cancers attributable to low consumption of vegetable and fruit were calculated separately to estimate the burden of related cancers for the year 2005 in China.Data on the prevalence of exposure were derived from a Chinese nutrition and health survey.Data on relative risks were mainly derived from meta-analysis.Attributable fractions were calculated based on the counterfactual scenario which was a shift in the exposure distribution.Results：The total cancer burden attributable to inadequate consumption of fruit was up to 233,000 deaths （13.0% of all cancers） and 300,000 cases （11.6% of all cancers） in 2005.Increasing consumption of vegetable to the highest quintile could avoid total cancer deaths and cases by 3.6% （64,000 persons） and 3.4% （88,000 persons）.The contributions to cancer burden were higher in rural areas than in urban areas.They have greater influence on men than on women.The largest proportions of cancer burden attributable to low fruit and vegetable intake were for oral and pharyngeal cancers.Conclusion：This study showed that inadequate intake of fruit and vegetable makes a significant contribution to the cancer burden.Increasing consumption of fruit and vegetable could prevent many cancer deaths and save many lives.Promoting the consumption of fruit and vegetable is an important component in diet-based strategies for preventing cancer.

关键词： Fruit Vegetable cancer Population attributable fraction China

Attributable Causes of Breast cancer and Ovarian cancer in China:Reproductive Factors,Oral Contraceptives and Hormone Replacement Therapy

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Chinese Journal of cancer Research 2012年第1期24卷 9-17页

作者： Li Li Jia JI Jian-bing Wang Mayineur Niyazi You-lin Qiao Paolo Boffettas Deportment of Gynecology the People's Hospitul of Xinjiung Uygur Autonomous RegionUrumqi 830011China Department of cancer Epidemiology Cancer InstituteChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China Division of Pharmaceutics College of Pharmacythe Ohio State UniversityColumbusOH 43210USA Department of Epidemiology and Statistics Institute of Basic Medical SciencesChinese Academy of Medical Sciences&School of Basic MedicinePeking Union Medical CollegeBeijing 100730China The tisch cancer institute Mount Sinai School of MedicineNew YorkNY 10029USA International Prevention Research institute Lyon 69006France

Objective： To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors （RFs, including nulliparity, mean number of children, age at first birth and breastfeeding）, use of oral contraceptives （OCs, restricted to the age group of 15-49 years）, and hormone replacement therapy （HRT）, as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005. Methods： We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure. Results： Exposure of RFs in 2002 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer （712 cases, 294 deaths）. The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction （PAF） of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths. Conclusion： RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.

关键词： Reproductive factors Oral contraceptives Hormone replacement therapy cancer Population attributable fraction

Novel Non-Protein Biomarkers for Early Detection of Hepatocellular Carcinoma

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Engineering 2021年第10期7卷 1369-1374页

作者： Ghassan K.Abou-Alfa Lin Wu Augusto Villanueva Memorial Sloan Kettering cancer Center New York CityNY 10065USA Weill Medical College Cornell UniversityNew York CityNY 10065USA Berry Oncology Corporation Beijing 102200China Division of Liver Diseases Division of Hematology/Medical OncologyLiver Cancer ProgramDepartment of MedicineTisch Cancer InstituteIcahn School of Medicine at Mount SinaiNew York CityNY 10029USA

Early detection of hepatocellular carcinoma(HCC)while in its early stages is critical for reducing HCC mortality in high-risk patients.However,highly sensitive and specific surveillance biomarkers for early-stage HCC detection are still lacking.In recent years,great efforts have been made to research tumor-derived molecular features that are detectable in circulation,such as circulating tumor deoxyribonucleic acid and circulating tumor ribonucleic acid,in order to explore their potential as noninvasive biomarker candidates in many tumor types.In this review,we summarize current studies on these new approaches and their application in early HCC detection.

关键词： Hepatocellular carcinoma Early detection Biomarkers Liquid biopsy

Biomarkers for therapy selection in metastatic urothelial cancer

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Journal of cancer Metastasis and Treatment 2022年第1期8卷 579-606页

作者： Tomi Jun Jonathan Anker Matthew D.Galsky Division of Hematology and Medical Oncology Tisch Cancer InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA Medical Sciences Sema4StamfordCT 06902USA

The treatment of metastatic urothelial cancer(mUC)has been transformed by recent progress in clinical trials and drug development.There are now three therapeutic classes with proven benefits in mUC:chemotherapy,immunotherapy,and targeted therapy.The optimal sequence and combination of these classes remain to be defined.Biomarker development is essential to guide treatment selection at each therapeutic juncture.Two biomarkers,programmed death-ligand 1 expression and fibroblast growth factor receptor alterations,have been incorporated into the mUC treatment paradigm thus far.This review discusses predictive biomarkers in development and their potential to influence mUC treatment selection moving forward.

关键词： Metastatic urothelial cancer biomarkers immunotherapy chemotherapy targeted therapy antibody-drug conjugates