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Cancer Communications 2020年第2期40卷 119-121页

作者： Luo Huang Melvin L.K.Chua Division of Radiation Oncology National Cancer Centre SingaporeSingapore 169610 Division of Radiation Oncology Chongqing University Cancer Hospital and InstituteChongqing 400030P.R.China Division of medical Sciences National Cancer Centre SingaporeSingapore 169610 Oncology Academic Clinical Programme Duke-National University of Singapore Medical SchoolSingapore 169857

Radiotherapy(RT)has an unassailable track record as the backbone of treatment in nasopharyngeal carcinoma(NPC).Several reasons explain its *** to human papilloma virus-associated oropharyngeal squamous cell carcinoma,Epstein-Barr virus(EBV)-associated NPC is exquisitely sensitive to ***,huge leaps with technological advances in RT delivery over the past decades have led to substantial improvements in tumor control,while reducing debilitating late RT-induced complications[1,2].Innovations in this space continue to drive the enhancement of the therapeutic ratio of RT,with the goal of enhancing the quality of life(QoL)among long-term survivors[3].Therefore,there has not been any compelling reason to disrupt this timehonored convention of employing RT as the standard of care in NPC.

关键词： Early stage nasopharyngeal carcinoma resection surgery toxicities

Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis:A meta-analysis

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World Journal of Hepatology 2022年第6期14卷 1248-1257页

作者： Jing Hong Loo Wen Xin Flora Xu Jun Teck Low Wei Xuan Tay Le Shaun Ang Yew Chong Tam Prem Harichander Thurairajah Rahul Kumar Yu Jun Wong Yong Loo Lin School of Medicine National University of SingaporeSingapore 119077Singapore Education Resource Center Medical BoardSingapore General HospitalSingapore 100059Singapore Department of Gastroenterology and Hepatology National University HospitalSingapore 119077Singapore Department of Gastroenterology and Hepatology Changi General HospitalSingapore 529889Singapore Duke-NUS Medicine Academic Clinical Program Singapore 100059Singapore

BACKGROUND Hepatitis C virus(HCV)is a leading cause of liver cirrhosis and hepatocellular carcinoma ***/velpatasvir(SOF/VEL)is an effective pangenotypic direct-acting antiviral combination for treatment of chronic HCV *** the addition of ribavirin(RBV)to SOF/VEL improved sustained virological response(SVR12)in genotype 3(GT3)decompensated cirrhosis patients,the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains *** To evaluate the efficacy and safety of SOF/VEL,with or without RBV in GT3 compensated cirrhosis *** We searched four electronic databases(PubMed/Medline,Embase,Cochrane Library and Web of Science)from inception up to June 2021 using both free text and MeSH *** was no restriction on language,geography,publication dates and publication status(full text or abstracts).All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL,with or without RBV,were included,regardless of age,gender or prior treatment *** primary outcome was sustained virological response 12-wk posttreatment(SVR12).The secondary outcome was treatment-related adverse events,as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/*** pooled relative risk(RR),95%CI and heterogeneity(I^(2))were estimated using Review Manager version *** From 1752 citations,a total of seven studies(2 randomized controlled trials,5 cohort studies)with 1088 subjects were *** SVR12 was similar in GT3 compensated cirrhosis patients,regardless of the use of RBV,for both the intention-to-treat RR 1.03,95%CI:0.99-1.07;I^(2)=0%)and the per-protocol analysis(RR:1.03,95%CI:0.99-1.07;I^(2)=48%).The overall pooled rate of treatment-related adverse events was 7.2%.Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL(RR:4.20,95%CI:1.29-13.68;I^(2)=0%).Subgroup analysis showed that RBV wa

关键词： Direct-acting antiviral Hepatitis C Cirrhosis Sofosbuvir/velpatasvir

^(68)Gallium-labelled PSMA-PET/CT as a diagnostic and clinical decision-making tool in Asian prostate cancer patients following prostatectomy

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Cancer Biology & Medicine 2019年第1期16卷 157-165页

作者： Janice S.H.Tan Charles X.Y.Goh Yen Sin Koh Youquan Li Jeffrey K.L.Tuan Eu Tiong Chua Terence W.K.Tan Michael L.C.Wang Lui Shiong Lee Kae Jack Tay Ravindran Kanesvaran Chee Keong Toh Aaron K.T.Tong Winnie W.C.Lam Melvin L.K.Chua Division of Radiation Oncology National Cancer Centre Singapore Department of Nuclear Medicine and Molecular Imaging Singapore General Hospital Radiological Sciences Academic Clinical Programme Duke-NUS Medical School Oncology Academic Clinical Programme Duke-NUS Medical School Department of Urology Singapore General Hospital Department of Surgery Sengkang General Hospital Division of medical Oncology National Cancer Centre Singapore Division of medical Sciences National Cancer Centre Singapore

Objective: Prostate cancers(PCa) in Asian individuals are molecularly distinct from those found in their Caucasian *** is no risk stratification tool for Asian men with rapid biochemical recurrence(BCR) following radical prostatectomy(Rad P). This study aims to assess the detection rate of ^(68)Ga-prostate-specific membrane antigen-positron emission tomography/computed tomography(PSMA-PET/CT) for diagnosis of clinical recurrence and as a treatment decision making tool in Asian patients with BCR post-Rad ***: ^(68)Ga PSMA-PET and CT body with/without bone scan [conventional workup(CWU)] were performed in 55 Asian patients with BCR within 36 months post-Rad P. Two blinded reviewers assessed the images. Detection rates of ^(68)Ga PSMAPET/CT were evaluated, and impact on management was reviewed by comparison with ***: Median time to BCR post-Rad P was 8.1 months. Detection rate for ^(68)Ga PSMA-PET/CT was 80%(44/55). A positive scan was significantly associated with increasing prostate-specific antigen(PSA) level [odds ratio(OR) = 1.13(95% CI 1.05–1.30), P =0.017], but not with higher Gleason grade or shorter PSA doubling time. Compared to CWU, ^(68)Ga PSMA-PET/CT detected an additional 106 lesions in 33/44 patients with a positive scan, resulting in a change in management in 25/44(56.8%) patients: 10 to hormonal therapy(HT) and whole pelvis radiotherapy(RT) in addition to bed RT, and 15 to palliative HT ***: In the present report, we demonstrated the diagnostic and treatment decision utility of ^(68)Ga PSMA-PET/CT in Asian men with rapid BCR. Detection of small volume nodal and systemic recurrences at low PSA levels(< 1.0 ng/mL) highlights the role of the tool in assigning patients to treatment intensification with HT-RT or palliative HT in polymetastatic disease.

关键词： ^68Ga PSMA PET/CT prostate cancer Asian diagnostic recurrence prostatectomy salvage radiotherapy

A cellular and proteomic approach to assess proteins extracted from cryopreserved human amnion in the cultivation of corneal stromal keratocytes for stromal cell therapy

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Eye and Vision 2019年第1期6卷 247-260页

作者： Beau J.Fenner Nur Zahirah B.M.Yusoff Matthias Fuest Lei Zhou Francisco Bandeira Howard ***-Uy H.K.Tan Jodhbir S.Mehta Gary H.F.Yam Tissue Engineering and Stem Cell Group Singapore Eye Research Institute20 College RoadThe AcademiaDiscovery Tower Level 6Singapore 169856Singapore Singapore national Eye Centre SingaporeSingapore Department of Ophthalmology RWTH Aachen UniversityAachenGermany Eye-Academic Clinical Programme Duke-NUS Graduate Medical SchoolSingaporeSingapore Proteomics Platform Singapore Eye Research InstituteSingaporeSingapore Federal University of São Paulo Sao PauloBrazil Singapore Eye Bank SingaporeSingapore Department of Obstetrics and Gynaecology Singapore General HospitalSingaporeSingapore

Background:Human corneal stromal keratocytes propagated in culture media supplemented with human amnion extract(AME)can correct early corneal haze in an animal *** application of cultivated keratocytes is limited by infectious disease screening before amnion products can be used in *** remains unclear if AME from cryopreserved versus fresh human amnion can support human keratocyte propagation,and which components of the extract promote keratocyte ***:Three placentas were collected for the preparation of fresh and cryopreserved amnion tissues followed by homogenization and protein *** protein profiles were studied using isobaric tagging for relative and absolute quantitation(iTRAQ)*** gene ontology(GO)terms and functional classes were *** human keratocytes from 4 donor corneas were cultured in media supplemented with fresh AME(F-AME)or cryopreserved AME(C-AME).Cell viability,proliferation and keratocyte marker expression were examined by confocal immunofluorescence and flow ***:AME proteomics revealed 1385 proteins with similar expression levels(between 0.5-and 2-fold)between Fand C-AME,while 286 proteins were reduced(less than 0.5-fold)in *** GO term and biological pathway analysis showed that those proteins with comparable expression between F-AME and C-AME were involved in cell metabolism,epithelial-mesenchymal transition,focal adhesion,cell-extracellular matrix interaction,cell stress regulation and complement *** corneal stromal keratocytes cultured with F-AME or C-AME showed similar morphology and viability,while cell proliferation was mildly suppressed with C-AME(P>0.05).Expression of aldehyde dehydrogenase 3A1(ALDH3A1)and CD34 was similar in both ***:AME from cryopreserved amnion had limited influence on keratocyte *** is feasible to use protein extract from cryopreserved amnion to propagate human keratocytes for potential translati

关键词： Amnion extract Proteomics Corneal stromal keratocytes Marker expression

JUPITER-02 trial: advancing survival for recurrent metastatic nasopharyngeal carcinoma and next steps

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Cancer Communications 2022年第1期42卷 56-59页

作者： Laura Ling Ying Tan Quynh-Thu Le Nancy Ying Ying Lee Melvin Lee Kiang Chua Ministry of Health Holdings Singapore 099253Singapore Department of Radiation Oncology Stanford UniversityCalifornia 94305USA Department of Radiation Oncology Memorial Sloan Kettering Cancer CenterNew York 10065USA Department of Head and Neck and Thoracic Cancers Division of Radiation Oncology and Division of Medical SciencesNational Cancer Centre SingaporeSingapore 169610Singapore Oncology Academic Clinical Programme Duke-NUS Medical SchoolSingapore 169857Singapore

Nasopharyngeal carcinoma(NPC)is a disease with unique *** is endemic in Southern China,Southeast Asia,and North Africa,and typically affects males more than females in the 30-60 years age group[1].Globally,133,354 NPC cases were diagnosed in 2020 with 80,008;deaths in the same year[2].While the survival rates of early-stage NPC after radiotherapy(RT)are high,dis-ease recurrences are common in locoregionally-advanced NPC,with the predominant pattern of failure being dis-tant metastasis[3].In this clinical scenario,palliative chemotherapy is the primary treatment modality。

关键词： epidemiology chemotherapy nasopharyngeal

Transcriptomic analyses of localized prostate cancers of East Asian and North American men reveal race-specific luminal-basal and microenvironmental differences

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Cancer Communications 2023年第10期43卷 1164-1168页

作者： Melvin L.K.Chua Alexander K.Hakansson Enya H.W.Ong Boon Hao Hong Jing Jing Miao Adelene Y.L.Sim Janice S.H.Tan Kah Min Tan Gabrielle C.J.Lee Kar Perng Low Jeffrey K.L.Tuan Terence W.K.Tan Michael L.C.Wang Joe P.S.Yeong Michael C.S.Tan Lui Shiong Lee Ravindran Kanesvaran Xin Zhao Julian Ho Daniel E.Spratt Edward M.Schaeffer Kae-Jack Tay Yang Liu Elai Davicioni Li Yan Khor Division of Radiation Oncology National Cancer Centre SingaporeSingaporeSingapore Duke-NUS medical School SingaporeSingapore Division of medical Sciences National Cancer Centre SingaporeSingaporeSingapore Veracyte IncSan DiegoCAUSA Department of Nasopharyngeal Carcinoma State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapySun Yat-sen University Cancer CenterGuangzhouGuangdongP.R.China Faculty of Medicine Nursing and Health SciencesMonash UniversityVictoriaAustralia Department of Anatomical Pathology Singapore General HospitalSingaporeSingapore Department of Pathology Changi General HospitalSingaporeSingapore Department of Urology Sengkang General HospitalSingaporeSingapore Division of medical Oncology National Cancer Centre SingaporeSingaporeSingapore Department of Radiation Oncology University Hospitals Seidman Cancer CenterCase Comprehensive Cancer CenterClevelandOHUSA Department of Urology Northwestern University Feinberg School of MedicineChicagoILUSA Department of Urology Singapore General HospitalSingaporeSingapore

Dear editor,Prostate cancer(PCa)remains a major healthcare burden in men globally[1].Most patients present with localized disease,and treatment is recommended based on risk classification systems like the national Comprehensive Cancer Network(NCCN)[2].However,these methods are imprecise for estimating metastasis-free survival and prostate cancer-specific mortality and thus biomarkers that can predict tumor aggression are needed[3–5].Several studies have since characterized the molecular landscape of localized PCa in White[4,5]and Black/African-American men[6],but data is lacking in Asian *** Chinese Prostate Cancer Genome and Epigenome Atlas(CPGEA)reported on the genomic and epigenomic landscape of 208 PCa of men from China[7].Comparative analyses between the CPGEA cohort and data from The Cancer Genome Atlas(TCGA)revealed higher frequencies of Forkhead box A1(FOXA1)and chromodomain-helicase DNA-binding 1(CHD1)mutations,and lower frequencies of phosphatase and tensin homolog(PTEN)mutations and transmembrane protease serine 2-E26 transformationspecific related gene(TMPRSS2-ERG)fusion in Chinese compared with White men[7].These preliminary findings highlight the presence of race-specific differences in molecular phenotypes of PCa.

关键词： landscape Atlas editor

Clinical outcomes of coronavirus disease 2019 (COVID-19) in cancer patients with prior exposure to immune checkpoint inhibitors

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Cancer Communications 2020年第8期40卷 374-379页

作者： Qiuji Wu Qian Chu Hongyan Zhang Bin Yang Xudong He Yahua Zhong Xianglin Yuan Melvin L.K.Chua Conghua Xie Department of Radiation and medical Oncology Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071P.R.China Hubei Key Laboratory of Tumor Biological Behaviors Zhongnan Hospital ofWuhan UniversityWuhanHubei 430071P.R.China Hubei Cancer Clinical Study Center Zhongnan Hospital ofWuhan UniversityWuhanHubei 430071P.R.China Department of Oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030P.R.China Department of medical Oncology Hubei Cancer HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430079P.R.China Department of Gastroenterology Dongfeng HospitalHubei University of MedicineShiyanHubei 442000P.R.China Divisions of Radiation Oncology and medical Sciences National Cancer Centre SingaporeSingapore 169610Singapore Oncology Academic Programme Duke-NUS Medical SchoolSingapore 169857Singapore

Dear Editor,The coronavirus disease 2019(COVID-19)pandemic has affected over 6,000,000 people globally[1].Patients with COVID-19 manifest with symptoms of fever,dry cough,dyspnea,and present with radiological changes that are consistent with atypical pneumonia[2].Pathogenetic mechanisms for these abnormalities involve the systemic immune response that is associated with the hyperactivation of peripheral CD8+and CD4+T cells,and a cytokine storm[3].Globally,the reported prevalence of patients with COVID-19 and cancer ranges from 0.5%to 6.0%in the different case series[4].

关键词： patients cancer immune

Optimal sequencing of chemotherapy with chemoradiotherapy based on TNM stage classification and EBV DNA in locoregionally advanced nasopharyngeal carcinoma

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Cancer Communications 2019年第1期39卷 576-578页

作者： Li-Ting Liu Melvin L.K.Chua Yungan Tao Lin-Quan Tang Hai-Qiang Mai Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangzhou 510060GuangdongP.R.China Department of Nasopharyngeal Carcinoma Sun Yat-sen University Cancer Center651 Dongfeng Road EastGuangzhou 510060GuangdongP.R.China Divisions of Radiation Oncology and medical Sciences National Cancer Centre SingaporeSingapore 169610Singapore Oncology Academic Programme Duke-National University of Singapore Medical SchoolSingapore 169857Singapore.5 Institute Gustave-Roussy94800 VillejuifFrance

Main text In the past decades,there have been several studies con-cerning the efficacy of sequencing of chemotherapy on disease control and survival in locoregionally advanced(LA)nasopharyngeal carcinoma(NPC).The addition of concurrent cisplatin to radiotherapy has demonstrated survival improvements that are attributable to both dis-tant metastasis and locoregional *** to the latter,the advent of intensity-modulated radiotherapy has resulted in superior tumor control given the bet-ter dosimetry compared to conventional techniques[1].However,distant recurrence still occurs in 20-30%patients and accounts for the main cause of *** address this,several groups have explored the advantages of adding neoadjuvant chemotherapy(NACT)or adju-vant chemotherapy(ACT)to the backbone of concurrent chemoradiotherapy(CCRT).

关键词： chemotherapy nasopharyngeal metastasis

Endothelial progenitor cells in cardiovascular diseases

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World Journal of Stem Cells 2014年第3期6卷 355-366页

作者： Poay Sian Sabrina Lee Kian Keong Poh Cardiac Departmentnational University Heart Centre National University HealthSystem Singapore Yong Loo Lin School of Medicine Na-tional University of Singapore

Endothelial dysfunction has been associated with the development of atherosclerosis and cardiovascular diseases. Adult endothelial progenitor cells(EPCs) are derived from hematopoietic stem cells and are capable of forming new blood vessels through a process of vas-culogenesis. There are studies which report correlations between circulating EPCs and cardiovascular risk fac-tors. There are also studies on how pharmacotherapies may influence levels of circulating EPCs. In this review, we discuss the potential role of endothelial progenitor cells as both diagnostic and prognostic biomarkers. In addition, we look at the interaction between cardio-vascular pharmacotherapies and endothelial progenitor cells. We also discuss how EPCs can be used directly and indirectly as a therapeutic agent. Finally, we evalu-ate the challenges facing EPC research and how these may be overcome.

关键词： Endothelial progenitor cells Cardiovasculardiseases Hypertension Diabetes Dyslipidemia Therapy Stents

Neutrophil kinetics and function after major trauma:A systematic review

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World Journal of Critical Care Medicine 2021年第5期10卷 260-277页

作者： Liam DB Finlay Andrew Conway Morris Adam M Deane Alexander JT Wood Melbourne medical School University of MelbourneMelbourne 3052VictoriaAustralia Department of Medicine University of CambridgeCambridge 01223United Kingdom Centre for Integrated Critical Care University of MelbourneParkville 3052VictoriaAustralia Intensive Care Unit Royal Melbourne HospitalParkville 3052VictoriaAustralia

BACKGROUND Immune dysfunction following major traumatic injury is complex and strongly associated with significant morbidity and mortality through the development of multiple organ dysfunction syndrome(MODS),persistent inflammation,immunosuppression,and catabolism syndrome and *** are thought to be a pivotal mediator in the development of immune *** To provide a review with a systematic approach of the recent literature describing neutrophil kinetics and functional changes after major trauma in humans and discuss hypotheses as to the mechanisms of the observed neutrophil dysfunction in this *** Medline,Embase and PubMed were searched on January 15,*** were screened by two reviewers and those included had their reference list hand searched for additional papers of *** criteria were adults>18 years old,with an injury severity score>12 requiring admission to an intensive care *** that analysed major trauma patients as a subgroup were *** Of 107 papers screened,48 were included in the *** were heterogeneous and most studies had a moderate to significant risk of bias owing to their observational nature and small sample *** findings included a persistently elevated neutrophil count,stereotyped alterations in cell-surface markers of activation,and the elaboration of heterogeneous and immunosuppressive populations of cells in the *** of these changes correlate with clinical outcomes such as MODS and secondary *** phenotype remains a promising avenue for the development of predictive markers for immune *** Understanding of neutrophil phenotypes after traumatic injury is expanding.A greater emphasis on incorporating functional and clinically significant markers,greater uniformity in study design and assessment of extravasated neutrophils may facilitate risk stratification in patients affected by major trauma.

关键词： Neutrophils Multiple trauma Immunophenotypes Inflammation Systemic inflammatory response syndrome Intensive care units