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Exosome secretion from hypoxic cancer cells reshapes the tumor microenvironment and mediates drug resistance

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cancer Drug Resistance 2022年第3期5卷 577-594页

作者： Kenneth K.W.To william c.s.cho school of Pharmacy Faculty of MedicineThe Chinese University of Hong KongHong Kong SARChina Department of clinical Oncology Queen Elizabeth HospitalHong Kong SARChina

Hypoxia is a common phenomenon in solid tumors as the poorly organized tumor vasculature cannot fulfill the increasing oxygen demand of rapidly expanding tumors.Under hypoxia,tumor cells reshape their microenvironment to sustain survival,promote metastasis,and develop resistance to therapy.Exosomes are extracellular vesicles secreted by most eukaryotic cells,including tumor cells.They are enriched with a selective collection of nucleic acids and proteins from the originating cells to mediate cell-to-cell communication.Accumulating evidence suggests that exosomes derived from tumor cells play critical roles in modulating the tumor microenvironment(TME).Hypoxia is known to stimulate the secretion of exosomes from tumor cells,thereby promoting intercellular communication of hypoxic tumors with the surrounding stromal tissues.Exosome-mediated signaling pathways under hypoxic conditions have been reported to cause angiogenesis,invasion,metastasis,drug resistance,and immune escape.Recently,the programmed cell death ligand-1(PD-L1)has been reported to reside as a transmembrane protein in tumor exosomes.Exosomal PD-L1 was shown to suppress T cell effector function in the TME and cause drug resistance to immune checkpoint therapy.This review provides an update about the pivotal role of tumor-derived exosomes in drug resistance to chemotherapy and immunotherapy,particularly under hypoxic conditions.Emerging strategies that target the exosomes in the hypoxic TME to enhance the antitumor efficacy are discussed.

关键词： Hypoxia drug resistance exosome tumor microenvironment immunotherapy non-coding RNA

中草药对治疗癌症恶病质动物模型有效性的系统性回顾（英文）

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2019年第1期20卷 9-22页

作者： Bongki PARK sooseong YOU william c.s.cho Jun-Yong choI Myeong soo LEE Liver and Immunology Research center Oriental College Daejeon University clinical Medicine Division Korea Institute of Oriental Medicine Department of clinical Oncology Queen Elizabeth Hospital Department of Korean Internal Medicine School of Korean Medicine Pusan National University

本综述总结利用中草药治疗癌症恶病质的临床前研究及其潜在的机制,是首个针对中草药治疗癌症恶病质动物模型成效进行系统性回顾评价的研究。本文通过检索PubMed、EMBAsE、Allied and complementary Medicine Database以及Web of scienc... 详细信息

本综述总结利用中草药治疗癌症恶病质的临床前研究及其潜在的机制,是首个针对中草药治疗癌症恶病质动物模型成效进行系统性回顾评价的研究。本文通过检索PubMed、EMBAsE、Allied and complementary Medicine Database以及Web of science四大代表性的资料库(检索时间至2016年12月),就中草药治疗癌症恶病质的随机对照动物试验进行系统性回顾分析,并采用cAMARADE评分清单进行质量评价。分析结果显示:在十四项中草药及其化合物中,除了姜黄素外其他如黄连、黄连素、病得灵、清暑益气汤、黄芩、补中益气汤、六君子汤、橙皮苷、苍术呋喃烃、十全大补汤、小柴胡汤、知母及黄柏等都已被证实可以通过抗炎、调节神经内分泌途径、调节泛素蛋白酶体系统或蛋白质合成来改善癌症恶病质的症状。因此,利用中草药治疗癌症恶病质是一种有效的方法。然而该结论尚需要有更详细的分子机制和活性化合物的实验研究验证。

关键词：癌症恶病质中草药传统东亚医学系统性回顾

Disease Biomarkers for Precision Medicine:challenges and Future Opportunities

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Genomics, Proteomics & Bioinformatics 2017年第2期15卷 57-58页

作者： Edwin Wang william c.s.cho s.c.cesar Wong siqi Liu center for Health Genomics and Informatics University of Calgary Cumming School of Medicine Department of clinical Oncology Queen Elizabeth Hospital Department of Health Technology and Informatics Faculty of Health and Social Sciences Hong Kong Polytechnic University cAs Key Laboratory of Genome sciences and Information Beijing Institute of Genomics Chinese Academy of Sciences

Most of the human diseases are complex diseases,which could be caused by many genetic pathways.This means that for a given phenotype(i.e.,a complex disease),there are multiple potential genes which could be genomically or epigenetically changed(i.e.,mutations,copy number variations,epigenetic modifications,and so on).Therefore,it is understandable that different individuals who share the same phenotype/diseases may have different causal genes and thus,may have different drug targets.For example,mutated genes are rarely common between the cancer patients of the same cancer type[1];furthermore,for a given drug,only 10%-30% of the patients

关键词： data Disease Biomarkers for Precision Medicine:challenges and Future Opportunities

MicroRNAs: Mechanisms, Functions and Progress

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Genomics, Proteomics & Bioinformatics 2012年第5期10卷 237-238页

作者： Tongbin Li william c.s.cho *** Research Group LC SciencesHoustonTX 77054USA Department of clinical Oncology Queen Elizabeth HospitalHong Kong SARChina

In 1993 when Ambros and co-workers [1] discovered that a mysterious caenorhabditis elegans gene, lin-4, does not encode a protein, but acts in the form of a small RNA and represses the expression of its target gene, lin-14, through base-pairing with its 3＇ untranslated region （3tUTR）, nobody would imagine that 20 years later, this category of small RNAs - now widely known as microR- NAs （or miRNAs）, has ～2000 known members in the human genome （and counting）, and that miRNA-mediated gene regulation is deeply involved in virtually all important biological processes in animals and plants.

关键词： caenorhabditis elegans biological processes gene regulation human genome target gene small RNA form of

Thematic Trends in complementary and Alternative Medicine Applied in cancer-Related symptoms

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Journal of Data and Information science 2018年第2期3卷 1-19页

作者： jose a.moral-munoz manuel arroyo-morales barbara f.piper antonio i.cuesta-vargas lourdes díaz-rodríguez william c.s.cho enrique herrera-viedma manuel j.cobo dept.nursing and physiotherapy university of cádizCadizSpain institute of research and innovation in biomedical sciences of the province of cádiz(ini bica) university of cádizCadizSpain dept.physical therapy university of granadaGranadaSpain dept.nursing school of health and human servicesnational universitysan diegocausa school clinical science queensland university of technologyBrisbaneQLDAustralia instituto biosanitario(ibs) university of granadaGranadaSpain hospital authority Hong KongChina dept.computer science and artificial intelligence university of granadaGranadaSpain dept.of computer science and engineering university of cádizCadizSpain

Purpose： The main goal of this study is to discover the scientific evolution of cancer-Related symptoms in complementary and Alternative Medicine research area, analyzing the articles indexed in the Web of science database from 1980 to 2013.Design/Methodology/Approach： A co-word science mapping analysis is performed under a longitudinal framework（1980 to 2013）. The documental corpus is divided into two subperiods,1980–2008 and 2009–2013. Thus, the performance and impact rates, and conceptual evolution of the research field are shown.Findings： According to the results, the co-word analysis allows us to identify 12 main thematic areas in this emerging research field： anxiety, survivors and palliative care,meditation, treatment, symptoms and cancer types, postmenopause, cancer pain, low back pain, herbal medicine, children, depression and insomnia, inflammation mediators, and lymphedema. The different research lines are identified according to the main thematic areas,centered fundamentally on anxiety and suffering prevention. The scientific community can use this information to identify where the interest is focused and make decisions in different ways.Research limitation： several limitations can be addressed： 1） some of the complementary and Alternative Medicine therapies may not have been included; 2） only the documents indexed in Web of science are analyzed; and 3） the thematic areas detected could change if another dataset was considered.Practical implications： The results obtained in the present study could be considered as an evidence-based framework in which future studies could be built.Originality/value： currently, there are no studies that show the thematic evolution of this research area.

关键词： cancer-related symptoms complementary and Alternative Medicine Bibliometrics science mapping analysis Thematic evolution H-index

Proteomics Technologies and challenges

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Genomics, Proteomics & Bioinformatics 2007年第2期5卷 77-85页

作者： william c.s. cho Department of clinical Oncology Queen Elizabeth Hospital

Proteomics is the study of proteins and their interactions in a cell. With the completion of the Human Genome Project, the emphasis is shifting to the protein compliment of the human organism. Because proteome reflects more accurately on the dynamic state of a cell, tissue, or organism, much is expected from proteomics to yield better disease markers for diagnosis and therapy monitoring. The advent of proteomics technologies for global detection and quantitation of proteins creates new opportunities and challenges for those seeking to gain greater understanding of diseases. High-throughput proteomics technologies combining with advanced bioinformatics are extensively used to identify molecular signatures of diseases based on protein pathways and signaling cascades. Mass spectrometry plays a vital role in proteomics and has become an indispensable tool for molecular and cellular biology. While the potential is great, many challenges and issues remain to be solved, such as mining low abundant proteins and integration of proteomics with genomics and metabolomics data. Nevertheless, proteomics is the foundation for constructing and extracting useful knowledge to biomedical research. In this review, a snapshot of contemporary issues in proteomics technologies is discussed.

关键词： proteomics mass spectrometry, protein chip

MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside

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World Journal of Gastroenterology 2018年第27期24卷 2949-2973页

作者： Kenneth KW To christy Ws Tong Mingxia Wu william cs cho school of Pharmacy Faculty of Medicine the Chinese University of Hong Kong Department of clinical Oncology Queen Elizabeth Hospital

MicroRNAs(miRNAs) are small, single-stranded, noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes. Dysregulated expression of many miRNAs have been shown to mediate the signaling pathways critical in the multistep carcinogenesis of colorectal cancer(cRc). MiR NAs are stable and protected from RNase-mediated degradation, thereby enabling its detection in biological fluids and archival tissues for biomarker studies. This review focuses on the role and application of miRNAs in the prognosis and therapy of cRc. While stage Ⅱ cRc is potentially curable by surgical resection, a significant percentage of stage Ⅱ cRc patients do develop recurrence. MiRNA biomarkers may be used to stratify such high-risk population for adjuvant chemotherapy to provide better prognoses. Growing evidence also suggests that miRNAs are involved in the metastatic process of cRc. certain of these miRNAs may thus be used as prognostic biomarkers to identify patients more likely to have micro-metastasis, who could be monitored more closely after surgery and/or given more aggressive adjuvant chemotherapy. Intrinsic and acquired resistance to chemotherapy severely hinders successful chemotherapy in cRc treatment. Predictive miRNA biomarkers for response to chemotherapy may identify patients who will benefit the most from a particular regimen and also spare the patients from unnecessary side effects. selection of patients to receive the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Lastly, forced expression of tumor suppressor miRNA or silencing of oncogenic miRNA in tumors by gene therapy can also be adopted to treat cRc alone or in combination with other chemotherapeutic drugs.

关键词： microRNA colorectal cancer multidrug resistance prognosis therapeutic target apoptosis metastasis recurrence risk stratification

探索microRNAs在人类癌症中的治疗潜能

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中国肺癌杂志 2012年第8期15卷 501-505页

作者： william cs cho 丁燕 Department of clinical Oncology Queen Elizabeth Hospital 天津医科大学总医院天津市肺癌研究所天津市肺癌转移与肿瘤微环境重点实验室

大量研究表明microRNAs(miRNAs)的异常调节与癌症的发生和进展相关。新近研究发现了若干在各种人类癌症中具有可作为治疗靶标巨大潜能的miRNAs。这些肿瘤miRNAs的抑制或过表达可调节相关基因的表达,从而抑制各种癌症的增殖或转移。一些m... 详细信息

大量研究表明microRNAs(miRNAs)的异常调节与癌症的发生和进展相关。新近研究发现了若干在各种人类癌症中具有可作为治疗靶标巨大潜能的miRNAs。这些肿瘤miRNAs的抑制或过表达可调节相关基因的表达,从而抑制各种癌症的增殖或转移。一些miRNAs可逆转上皮-间质转化的表型,有些则可用于增强细胞对抗癌药物的敏感性。它们大部分的抗癌作用均已在临床前动物模型中得到验证。miRNA治疗的一个优点是它可靶向作用于不同信号通路中的许多基因,但同时亦伴有许多未知的脱靶效应的缺点。此外,对于有效的miRNA治疗来说,成功转运也是一个主要的挑战。然而,新近研究的发现及药物转运系统的高速发展为该领域的飞跃展现了一个乐观的前景。

关键词：癌症 microRNA miRNA 肿瘤miRNA 治疗靶标

癌症相关遗传变异的新进展及其在诊断研发中的意义

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中国肺癌杂志 2011年第1期14卷 79-83页

作者：南娟(翻译) 曹志成(校对) william cs cho 天津医科大学总医院、天津市肺癌研究所、天津市肺癌转移与肿瘤微环境重点实验室香港特别行政区伊利沙伯医院临床肿瘤科 Department of clinical Oncology Queen Elizabeth Hospital Hong Kong

＂了解更多癌症相关的遗传变异可能有助于癌症的预防和早期诊断,以及为癌症个体化诊断和治疗方案开辟新途径。＂

关键词：癌症诊断拷贝数目变异(copy number variant,cNV) 遗传变异全基因组关联(genome-wide association,GWA) 小分子RNA(microRNA,miRNA) 罕见变异单核苷酸多态性(single nucleotide polymorphism,sNP)