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Novel biomarkers GEP/ABCB5 regulate response to adjuvant transarterial chemoembolization after curative hepatectomy for hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 524-530页

作者： Charing Ching-Ning Chong Siu Tim Cheung Yue-Sun Cheung anthony wing-hung chan Stephen Lam chan Simon Chun-Ho Yu Paul Bo-San Lai Department of Surgery Prince of Wales HospitalThe Chinese University of Hong Kong4/F Clinical Science Building30-32 Ngan Shing StreetShatinHong KongChina Department of Anatomical and Cellular Pathology State Key Laboratory in Oncology in South ChinaPrince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina Department of Clinical Oncology Prince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina Department of Imaging and Interventional Radiology Prince of Wales HospitalThe Chinese University of Hong Kong30-32 Ngan Shing StreetShatinHong KongChina

Background: Transarterial chemoembolization(TACE) is the most commonly used adjuvant therapy for hepatocellular carcinoma(HCC) after curative resection. Responses to TACE are variable due to tumor and patient heterogeneity. We had previously demonstrated that expression of Granulin-epithelin precursor(GEP) and ATP-dependent binding cassette(ABC)B5 in liver cancer stem cells was associated with chemoresistance. The present study aimed to evaluate the association between GEP/ABCB5 expression and response to adjuvant TACE after curative resection for HCC. Methods: Patients received adjuvant TACE after curative resection for HCC and patients received curative resection alone were identified from a prospectively collected database. Clinical samples were retrieved for biomarker analysis. Patients were categorized into 3 risk groups according to their GEP/ABCB5 status for survival analysis: low(GEP-/ABCB5-), intermediate(either GEP +/ABCB5-or GEP-/ABCB5 +) and high(GEP +/ABCB5 +). Early recurrence(recurrence within 2 years after resection) and disease-free survival were analyzed. Results: Clinical samples from 44 patients who had followed-up for more than 2 years were retrieved for further biomarker analysis. Among them, 18 received adjuvant TACE and 26 received surgery alone. Patients with adjuvant TACE in the intermediate risk group was associated with significantly better overall survival and 2-year disease-free survival than those who had surgery alone( P = 0.036 and P = 0.011, respectively). Adjuvant TACE did not offer any significant differences in the early recurrence rate, 2-year disease-free survival and overall survival for patients in low and high risk groups. Conclusions: Adjuvant TACE can only provide survival benefits for patients in the intermediate risk group(either GEP +/ABCB5-or GEP-/ABCB5 +). A larger clinical study is warranted to confirm its role in patient selection for adjuvant TACE.

关键词： Adjuvant therapy Hepatocellular carcinoma Drug transporter Transarterial chemoembolisation Granulin-epithelin precursor

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Cellular & Molecular Immunology 2021年第4期18卷 1005-1015页

作者： Xuezhen Zeng Jingying Zhou Zhewen Xiong Hanyong Sun Weiqin Yang Myth T.S.Mok Jing Wang Jingqing Li Man Liu Wenshu Tang Yu Feng Hector Kwong-Sang W ang Shun-Wa Tsang King-Lau Chow Philip Chun Yeung John Wong Paul Bo-San Lai anthony wing-hung chan Ka Fai To Stephen Lam chan Qiang Xia Jing Xue Xiao Chen Jun Yu Sui Peng Joseph Jao-Yiu Sung Ming Kuang Alfred Sze-Lok Cheng School of Biomedical Sciences The Chinese University of Hong KongHong Kong SARChina lnstitute of Precision Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Liver Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Pharmacy The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Department of Anatomical and Cellular Pathology The Chinese University of Hong KongHong Kong SARChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Gastroenterology The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Division of Life Science Hong Kong University of Science and TechnologyHong Kong SARChina Department of Surgery The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Translational Oncology The Chinese University of Hong KongHong Kong SARChina Department of Clinical Oncology The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Oncogenes and Related Genes Stem Cell Research CenterRen Ji HospitalSchool of MedicineShanghai Cancer InstituteShanghai Jiao Tong UniversityShanghaiChina Department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong Kong SARChina Clinical Trial Unit The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina Cancer Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina

The liver is an immunologically tolerant organ and a common metastatic site of multiple cancer *** a role for cancer cell invasion programs has been well characterized,whether and how liver-intrinsic factors drive metastatic spread is incompletely ***,we show that aberrantly activated hepatocyte-intrinsic cell cycle-related kinase(CCRK)signaling in chronic liver diseases is critical for cancer metastasis by reprogramming an immunosuppressive *** an inducible liverspecific transgenic model,we found that CCRK overexpression dramatically increased both B16F10 melanoma and MC38 colorectal cancer(CRC)metastasis to the liver,which was highly infiltrated by polymorphonuclear-myeloid-derived suppressor cells(PMNMDSCs)and lacking natural killer T(NKT)*** of PMN-MDSCs in CCRK transgenic mice restored NKT cell levels and their interferon gamma production and reduced liver metastasis to 2.7% and 0.7%(metastatic tumor weights)in the melanoma and CRC models,***,CCRK activated nuclear factor-kappa B(NF-κB)signaling to increase the PMN-MDSC trafficking chemokine C-X-C motif ligand 1(CXCL1),which was positively correlated with liver-infiltrating PMN-MDSC levels in CCRK transgenic ***,CRC liver metastasis patients exhibited hyperaaivation of hepatic CCRK/NF-κB/CXCL1 signaling,which was associated with accumulation of PMN-MDSCs and paucity of NKT cells compared to healthy liver transplantation *** summary,this study demonstrates that immunosuppressive reprogramming by hepatic CCRK signaling undermines antimetastatic *** findings offer new mechanistic insights and therapeutic targets for liver metastasis intervention.

关键词： Cell cycle related kinase liver metastasis liver immune microenvironment myeloid-derived suppressor cell natural killer T cell

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Improving definition of the term “synchronous liver metastases” from colorectal cancer

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Hepatobiliary & Pancreatic Diseases International 2016年第5期15卷 458-460页

作者： anthony KC chan Ajith K Siriwardena Hepatobiliary Surgery Unit Manchester Royal Infirmary 0xford Road Manchester M13 9WL UK

The liver is the most frequent site of metastasis in colorectal cancer with up to a quarter of patients having liver metastases at the time of initial diagnosis and a further third subsequently developing liver *** who present with metastatic liver disease after treatment of the primary(termed metachronous disease)receive care focused on this new metastatic *** contrast,the management of patients who present with colorectal cancer and concurrent liver

关键词： Improving definition of the term synchronous liver metastases from colorectal cancer

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Pluripotent Stem Cells Models for Huntington's Disease:Prospects and Challenges

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Journal of Genetics and Genomics 2012年第6期39卷 253-259页

作者： Richard L. Carter anthony W.S.chan Yerkes National Primate Research Center 954 Gatewood Rd.N.E.AtlantaGA 39329USA Genetic and Molecular Biology Program Graduate Division of Biologieal and Biomedical SciencesEmory UniversityAtlantaGA 30322USA Department of Human Genetics Emory University School of Medicine615 Michael St.AtlantaGA 30322USA

Pluripotent cellular models have shown great promise in the study of a number of neurological disorders. Several advantages of using a stem cell model include the potential for cells to derive disease relevant neuronal cell types, providing a system for researchers to monitor disease progression during neurogenesis, along with serving as a platform for drug discovery. A number of stem cell derived models have been employed to establish in ~,itro research models of Huntington＇s disease that can be used to investigate cellular pathology and screen lk^r drug and cell-based therapies. Although some progress has been made, there are a number of challenges and limitations that must be overcome before the true potential of this research strategy is achieved. In this article we review current stem cell models that have been reported, as well as discuss the issues that impair these studies. We also highlight the prospective application of Huntington＇s disease stem cell models in the development of novel therapeutic strategies and advancement of personalized medicine.

关键词： Stem cell models Huntington's disease Induced pluripotent stem cells Drug discovery

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Expression of multiple glutamate transporter splice variants in the rodent testis

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Asian Journal of Andrology 2011年第2期13卷 254-265页

作者： Aven Lee Ashley R Anderson Amanda C Barnett anthony chan David V Pow Centre for Clinical Research Royal Brisbane and Women＇s Hospital The University of Queensland Brisbane QId 4029 Australia

Glutamate is a regulated molecule in the mammalian testis. Extracellular regulation of glutamate in the body is determined largely by the expression of plasmalemmal glutamate transporters. We have examined by PCR, western blotting and immunocytochemistry the expression of a panel of sodium-dependent plasmalemmal glutamate transporters in the rat testis. Proteins examined included： glutamate aspartate transporter （GLAST）, glutamate transporter 1 （GLT1）, excitatory amino acid carrier 1 （EAAC1）, excitatory amino acid transporter 4 （EAAT4） and EAAT5. We demonstrate that many of the glutamate transporters in the testis are alternately spliced. GLAST is present as exon-3- and exon-9-skipping forms. GLT1 was similarly present as the alternately spliced forms GLT1 b and GLTlc, whereas the abundant brain form （GLTla） was detectable only at the mRNA level. EAAT5 was also strongly expressed, whereas EAAC1 and EAAT4 were absent. These patterns of expression were compared with the patterns of endogenous glutamate localization and with patterns of D-aspartate accumulation, as assessed by immunocytochemistry. The presence of multiple glutamate transporters in the testis, including unusually spliced forms, suggests that glutamate homeostasis may be critical in this organ. The apparent presence of many of these transporters in the testis and sperm may indicate a need for glutamate transport by such cells.

关键词： excitatory amino acid transporter glutamate aspartate transporter glutamate transporter 1 sperm splice variant testis transporter

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International validation of the Chinese University Prognostic Index for staging of hepatocellular carcinoma: a joint United Kingdom and Hong Kong study

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Chinese Journal of Cancer 2014年第10期33卷 481-491页

作者： Stephen L.chan Philip J.Johnson Frankie Mo Sarah Berhane Mabel Teng anthony W.H.chan Ming C.Poon Paul B.S.Lai Simon Yu anthony T.C.chan Winnie Yeo State Key Laboratory in Oncology in South China Sir YK Pao Center for CancerDepartment of Clinical OncologyHong Kong Cancer Institute and Prince of Wales HospitalThe Chinese University of Hong Kong School of Cancer Sciences University of Birmingham the Department of Molecular and Clinical Cancer Medicine Institute of Translational MedicineUniversity of Liverpool Department of Anatomical Cellular and PathologyThe Chinese University of Hong Kong Department of Surgery The Chinese University of Hong Kong Department of Radiology and Organ Imaging The Chinese University of Hong Kong

The outcome of hepatocellular carcinoma(HCC) patients significantly differs between western and eastern population centers. Our group previously developed and validated the Chinese University Prognostic Index(CUPI) for the prognostication of HCC among the Asian HCC patient population. In the current study, we aimed to validate the CUPI using an international cohort of patients with HCC and to compare the CUPI to two widely used staging systems, the Barcelona Clinic Liver Cancer(BCLC) classification and the Cancer of the Liver Italian Program(CLIP). To accomplish this goal, two cohorts of patients were enrolled in the United Kingdom(UK; n = 567; 2006-2011) and Hong Kong(HK; n = 517; 2007-2012). The baseline clinical data were recorded. The performances of the CUPI, BCLC, and CLIP were compared in terms of a concordance index(C-index) and were evaluated in subgroups of patients according to treatment intent. The results revealed that the median follow-up durations of the UK and HK cohorts were 27.9 and 29.8 months, respectively. The median overall survival of the UK and HK cohorts were 22.9 and 8.6 months, respectively. The CUPI stratified the patients in both cohorts into three risk subgroups corresponding to distinct outcomes. The median overall survival of the CUPI low-, intermediate-, and high-risk subgroups were 3.15, 1.24, and 0.29 years, respectively, in the UK cohort and were 2.07, 0.32, and 0.10 years, respectively, in the HK cohort. For the patients who underwent curative treatment, the prognostic performance did not differ between the three staging systems, and all were suboptimal. For those who underwent palliative treatment, the CUPI displayed the highest C-index, indicating that this staging system was the most informative for both cohorts. In conclusion, the CUPI is applicable to both western and eastern HCC patient populations. The performances of the three staging systems differed according to treatment intent, and the CUPI was demonstrated to be opti

关键词：香港英国预后肝癌验证国际大学中国

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Developing Exon-Primed Intron-Crossing （EPIC） markers for population genetic studies in three Aedes disease vectors

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Insect Science 2015年第3期22卷 409-423页

作者： Vanessa Linley White Nancy Margaret Endersby Janice chan Ary anthony Hoffmann Andrew Raymond Weeks Department of Genetics Bio21 Institute the University of Melbourne Victoria 3010 Australia

Aedes aegypti, Aedes notoscriptus, and Aedes albopictus are important vectors of many arboviruses implicated in human disease such as dengue fever. Genetic markers applied across vector species can provide important information on population structure, gene flow, insecticide resistance, and taxonomy, however, robust microsatellite markers have proven difficult to develop in these species and mosquitoes generally. Here we consider the utility and transferability of 15 Ribosome protein （Rp） Exon-Primed Intron- Crossing （EPIC） markers for population genetic studies in these 3 Aedes species. Rp EPIC markers designed for Ae. aegypti also successfully amplified populations of the sister species, Ae. albopictus, as well as the distantly related species, Ae. notoscriptus. High SNP and good indel diversity in sequenced alleles plus support for amplification of the same regions across populations and species were additional benefits of these markers. These findings point to the general value of EPIC markers in mosquito population studies.

关键词： Aedes aegypti Aedes albopictus Aedes notoscriptus Exon-Primed Intron- Crossing (EPIC) indels Ribosome protein (Rp) SNPs

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Accounting Systems in Cultural Context： A Research Framework for China Studies in Global Economy

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Journal of Modern Accounting and Auditing 2017年第2期13卷 45-50页

作者： anthony Moung Yin chan Ryerson University Toronto Canada

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Perspectives on Contemporary Accounting Research

Perspectives on Contemporary Accounting Research

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中国会计学会2006年学术年会

作者： anthony Moung Yin chan School of Business Management Ryerson University

自九十年代起,会计研究在中国越来越重视实证方法,这可能与参照英美国家的会计实证研究趋势有关。但回顾英美国家几十年来的会计研究历史,却发现英美会计学者本身也有很多对实证研究方法的质疑。到了二十一世纪,英美会计研究界也尝试寻...

自九十年代起,会计研究在中国越来越重视实证方法,这可能与参照英美国家的会计实证研究趋势有关。但回顾英美国家几十年来的会计研究历史,却发现英美会计学者本身也有很多对实证研究方法的质疑。到了二十一世纪,英美会计研究界也尝试寻求超越实证研究方法的其他研究进路（尤其是人文诠释研究方法）.从英美国家几十年来的会计研究经验来看,是一个从规范性研究方法到实证研究方法,又从实证研究方法到人文诠释研究方法的过程.这个英美国家的经验（和教训）,对中国也很有参考价值.本文将尝试回顾英美国家本身对会计研究方法的不同观点.

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基于红外相机数据评估华南地区豹猫的种群密度和活动节律

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生物多样性 2022年第9期30卷 89-99页

作者：杨剑焕李敬华杨浩炫欧梓键郑玺 anthony J.Giordano 陈辈乐嘉道理农场暨植物园中国香港999077 Society for the Preservation of Endangered Carnivores&Their International Ecological Study VenturaCA 93006USA

可靠的种群密度数据对野生动物的保护和管理十分重要。豹猫(Prionailurus bengalensis)是中国分布最广且常见的猫科动物,但野生种群密度估算的研究并不多。本研究于2020年6月至2021年5月在香港新界嘉道理农场暨植物园开展红外相机调查,... 详细信息

可靠的种群密度数据对野生动物的保护和管理十分重要。豹猫(Prionailurus bengalensis)是中国分布最广且常见的猫科动物,但野生种群密度估算的研究并不多。本研究于2020年6月至2021年5月在香港新界嘉道理农场暨植物园开展红外相机调查,利用空间标记-重捕法估算当地豹猫的种群密度并用核密度估计方法分析其活动节律。本次调查以网格方式布置红外相机,在约1.5 km^(2)的研究范围之内设置了19个相机位点,每个位点安装2台相机以获取豹猫身体两侧花纹来进行个体识别。连续12个月调查共捕获113次有效的豹猫拍摄事件,当中仅61次事件的照片足够清晰以进行个体识别。基于种群封闭的要求,我们以2个月为单位将12个月的数据分为6个采样期去分析豹猫种群密度,结果显示仅两个采样期的估算值最为准确,分别为0.64±0.31(0.26–1.55)只/km^(2)和0.87±0.48(0.31–2.40)只/km^(2),是已知全球豹猫密度最高的地点之一。结果还发现,雨季研究地点的豹猫并无明显的日活动节律,在旱季则偏夜行-晨昏行性多一些,但也有一定的日间活动;雨季和旱季的日活动节律无显著差异。本研究是首次以个体识别配以空间标记-重捕模型对中国大陆地区豹猫种群密度调查的研究;我们也提出一些关于红外相机架设方法的建议,以提高照片个体识别的准确度并增加重捕次数,最后提高密度估算的准确度。本研究也进一步证明豹猫适应性极强,在活动节律上表现出极高的可塑性,在严格保护下可以恢复健康的种群。

关键词：空间标记-重捕模型种群密度活动节律相机陷阱小型猫科动物食肉目香港

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