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A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance

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Journal of Pharmaceutical Analysis 2023年第5期13卷 514-522页

作者： ying-Qi Song Guo-Dong Li Dou Niu Feng Chen Shaozhen Jing Vincent Kam Wai Wong Wanhe Wang Chung-Hang leung State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao999078China Institute of Medical Research Northwestern Polytechnical UniversityXi'an710072China Dr.Neher's Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao999078China

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical ***,despite its effectiveness,at least 50%of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA *** have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine lesions,is overexpressed in glioblastoma tissues compared to normal ***,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in ***,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic *** a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG *** restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell characteristics,and induced GBM cell cycle ***,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

关键词： Drug screening Alkyladenine DNA glycosylase N3-methyladenine Glioblastoma Temozolomide Sunitinib

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微囊泡包裹溶瘤病毒的制备与鉴定及对Hepa 1-6细胞体外杀伤作用的探究

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微生物学通报 2024年第5期51卷 1754-1765页

作者：吴醒郑婷婷梁莹陶薇伊秦莹樊晓晖广西医科大学基础医学院微生物学教研室广西南宁530021 广西高校区域性疾病基础研究重点实验室广西南宁530021 南昌市洪都中医院检验科江西南昌330006

【背景】溶瘤病毒生物治疗是肿瘤治疗发展的新方向,其中新城疫病毒(Newcastle disease virus, NDV)因具有生物安全及靶向性强等优势备受关注。然而,中和抗体的病毒清除将削弱溶瘤病毒的持续有效发挥的作用。基于肿瘤细胞源性的微囊泡递... 详细信息

【背景】溶瘤病毒生物治疗是肿瘤治疗发展的新方向,其中新城疫病毒(Newcastle disease virus, NDV)因具有生物安全及靶向性强等优势备受关注。然而,中和抗体的病毒清除将削弱溶瘤病毒的持续有效发挥的作用。基于肿瘤细胞源性的微囊泡递送体系有望解决上述瓶颈,因此微囊泡包裹溶瘤病毒的制备具有非常重要的现实意义。【目的】探究建立基于肿瘤细胞源性的新城疫病毒微囊泡递送体系和评估其体外杀瘤效应。【方法】采用差速离心的方法,提取出微囊泡包裹的新城疫病毒(MV@NDV);粒度仪检测MV、NDV、MV@NDV的粒径大小;透射电子显微镜观察MV@NDV中MV和NDV的相对位置;免疫印迹技术(Western blotting, WB)检测MV@NDV的Integrin β-1、Gpc3和Flotillin-1蛋白表达;激光共聚焦显微镜观察MV@NDV感染Hepa1-6细胞24 h,细胞NDV-HN蛋白表达;倒置显微镜和CCK-8法分别检测感染Hepa 1-6细胞24、48、72 h的细胞形态以及活力变化;实时荧光定量PCR(quantitative real-time PCR, qPCR)和免疫印迹技术(WB)分别检测MV@NDV感染Hepa 1-6细胞24 h凋亡相关基因Caspase-3和Caspase-9表达以及凋亡相关蛋白Caspase-3表达。【结果】粒径和透射电子显微镜检测结果表明MV粒径范围为141-342 nm,NDV粒径范围为91-825 nm,MV@NDV粒径范围为164-712 nm。WB结果表明MV@NDV能够表达MV所表达的Integrin β-1、Gpc 3、Flotillin-1蛋白。激光共聚焦显微镜观察结果表明MV@NDV、NDV感染Hepa1-6细胞,出现红色荧光,均表达NDV-HN蛋白。CCK-8结果表明MV@NDV组与NC组相比,Hepa 1-6细胞活力下降(P<0.05)。qPCR结果表明MV@NDV与NC组相比凋亡相关基因Caspase-3和Caspase-9均上调(P<0.05)。WB结果表明MV@NDV与NC组相比凋亡相关蛋白Caspase-3上调(P<0.05)。【结论】成功构建NDV微囊泡递送体系MV@NDV,有望解决治疗型溶瘤新城疫病毒在临床转化上存在的瓶颈,为临床新城疫病毒抗肿瘤方面提供新的思路及依据。

关键词：溶瘤病毒新城疫病毒微囊泡抗肿瘤

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Revisiting oral fluoropyrimidine with cetuximab in metastatic colorectal cancer: Real-world data in Chinese population

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World Journal of Gastrointestinal Oncology 2019年第11期11卷 1031-1042页

作者： Ka-On Lam Man-Chi Fu Kin-Sang Lau Kam-Mo Lam Cheuk-Wai Choi Wan-Hang Chiu Cheng-Man Yuen Lai-Han Kwok Fong-kit Tam Wing-Lok Chan Sum-Yin Chan Pui-ying Ho To-Wai leung Ho-Fun Lee Department of Clinical Oncology LKS Faculty of MedicineThe University of Hong KongHong KongChina Department of Clinical Oncology Queen Mary HospitalHong KongChina Clinical Oncology Centre The University of Hong Kong-Shenzhen HospitalShenzhen 518053Guangdong ProvinceChina Department of Pharmacy Queen Mary HospitalHong KongChina Department of Diagnostic Radiology LKS Faculty of MedicineThe University of Hong KongHong KongChina

BACKGROUND Cetuximab in combination with oral fluoropyrimidine(FP)remains controversial in metastatic colorectal cancer(mCRC).In view of the regional variation in the tolerability of FP,we conducted a retrospective analysis to compare oral FP with infusional FP in combination with cetuximab in Chinese *** To compare the efficacy and safety profile of cetuximab in combination with oral FP and infusional FP in Chinese population in the real-world *** A retrospective cohort study was done to analyse consecutive patients with Kras wild-type mCRC who received first-line treatment with cetuximab and FP-based chemotherapy in our unit from January 2010 to December ***-five eligible patients were *** median follow-up of our cohort was 65.0 *** The median progression-free survival(mPFS)and median overall survival(mOS)of the entire cohort were 9.66 mo(95%CI:7.72–12.5)and 25.8 mo(95%CI:18.7–35.6),*** oral FP and infusional FP,there was no statistical significant difference in the mPFS[9.79 mo(95%CI:7.49–12.7)vs 9.63 mo(95%CI:6.34–13.4);P=0.72]and mOS[25.8 mo(95%CI:15.2–35.6)vs 26.3 mo(95%CI:18.7–41.2);P=0.63].Grade 3 or above adverse events were reported in 28.4%of patients,being similar with oral and infusional FP,and included 10.5%of neutropenia and 2.1%of diarrhoea *** The current analysis demonstrates comparable efficacy and safety profiles of cetuximab in combination with oral and infusional FP in Chinese *** results expand treatment options for Chinese patients and invite revision of existing treatment guidelines to incorporate oral FP-based chemotherapy plus cetuximab.

关键词： Capecitabine 5-Fluorouracil Cetuximab Metastatic colorectal cancer Chinese

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Safety Issues of Chinese Medicine:A Review of Intoxication Cases in Hong Kong

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Chinese Herbal Medicines 2009年第1期1卷 29-39页

作者： NG kit-ying CHENG Chuen-lung Hong Kong Jockey Club Institute of Chinese Medicine

Chinese medicine (CM) has been widely used in Hong Kong for centuries. In fact, CM practitioners currently provide over 20% of the medical consultations in Hong Kong and about 60% of the population has previously used CM. In 1999, the Legislative Council passed the Chinese Medicine Ordinance with aims to govern practice, use, trading, and manufacturing of CM in Hong Kong. While it is usually safe to use CM under proper application and guidance, there have been frequent reports on intoxication and fatalities. The misuse of potent/toxic CM, because of misidentification or overdose, can cause severe aconite, aristolochic acid, anticholinergic, podophyllin, grayanotoxin, pyrrolizidine alkaloids, matrine, gelsemine, teucvin, and strychnine poisoning. In this review, we summarized CM intoxication cases in Hong Kong, concentrating on the discussion of toxic and adverse effects as well as the quality control of CM. By increasing the awareness of CM toxicity, we hope to enhance the regulatory process and stimulate further research on their toxic dose, toxic ingredients, intoxication mechanisms, and quality control.

关键词： chemical marker Chinese medicine (CM) intoxication quality control

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Outcome of severely injured trauma patients at a designated trauma centre in the Hong Kong Special Administrative Region

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Chinese Medical Journal 2010年第10期123卷 1251-1254页

作者： leung Ka kit Gilberto HO Wendy TONG King Hung Daniel YUEN Wai Key Trauma Service Queen Mary Hospital and The University of Hong Kong The Hong Kong Special Administrative Region (HKSAR) China

Background The Hong Kong Special Administrative Region （HKSAR） of the People＇s Republic of China （PRC） has seen significant changes in its trauma service over the last ten years including the implementation of a regional trauma system. The author＇s institution is one of the five trauma centres designated in 2003. This article reports our initial clinical experience. Methods A prospective single-centre trauma registry from January 2004 to December 2008 was reviewed. The primary clinical outcome measure was hospital mortality. The Trauma and Injury Severity Score （TRISS） methodology was used for bench-marking with the North America Major Trauma Outcome Study （MTOS） database. Results There were 1451 patients. The majority （83.9%） suffered from blunt injury. The overall mortality rate was 7.8%. Severe injury, defined as the Injury Severity Score 〉15, occurred in 22.5% of patients, and was associated with a mortality rate of 31.6%. A trend of progressive improvement was noted. The M-statistic was 0.99, indicating comparable case-mix with the MTOS. The Z- and W-statistics of each individual year revealed fewer, but not significantly so, number of survivors than expected. Conclusions Trauma centre designation was feasible in the HKSAR and was associated with a gradual improvement in patient care. Trauma system implementation may be considered in regions equipped with the necessary socio-economic and organizational set-up.

关键词： trauma, nervous system outcome trauma and injury severity score Hong Kong, China

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Portal venous gas and thrombosis in a Chinese patient with fulminant Crohn’s colitis: A case report with literature review

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World Journal of Gastroenterology 2006年第34期12卷 5582-5586页

作者： Simon Siu-Man Ng Raymond ying-Chang Yiu Janet Fung-Yee Lee Jimmy Chak-Man Li Ka-Lau leung Department of Surgery The Chinese University of Hong Kong Prince of Wales Hospital Shatin Hong Kong SAR China

Ever since its earliest reports, portal venous gas (PVG) has been associated with numerous intraabdominal catastrophes and has served as an indication for urgent surgical exploration. It is traditionally regarded to be an ominous finding of impending death, with highest mortality reported in patients with underlying bowel ischemia. Today, computed tomography has demonstrated a wider range of clinical conditions associated with PVG, some of which are ‘benign’ and do not necessarily require surgery, unless when there are signs of intraabdominal catastrophe or systemic toxicity. One of these ‘benign’ conditions is Crohn’s disease. The present report describes a 19-year-old Chinese boy with Crohn’s pancolitis who presented with septic shock associated with PVG and portal vein thrombosis, and was successfully managed surgically. To our knowledge, this is the fi rst report of PVG and portal vein thrombosis associated with Crohn’s disease in a Chinese patient. In addition, we have also reviewed the reports of another 18 Crohn’s patients with PVG previously described in the English literature. Specifi c predisposing factors for PVG were identified in 8 patients, including barium enema, colonoscopy, blunt abdominal trauma, and enterovenous f istula. The patients who developed PVG following barium enema and blunt trauma were all asymptomatic and no specifi c treatment was necessary. Eleven patients (58%) who presented with signs of intraabdominal catastrophe or systemic toxicity required either immediate or eventual surgery. The overall mortality rate among the 19 patients was only 11%. The present literature review has shown that the f inding of PVG associated with Crohn’ s disease does not always mandate surgical intervention. It is the clinical features and the related complications that ultimately determine the treatment approaches. The overall outcome of PVG associated with Crohn’s disease has been favourable.

关键词： Portal venous gas Portal vein thrombosis Pylephlebitis Crohn's disease Chinese

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Room temperature Ⅲ–Ⅴ nanolasers with distributed Bragg reflectors epitaxially grown on(001) silicon-on-insulators

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Photonics Research 2019年第9期7卷 1081-1086页

作者： YU HAN WAI kit NG ying XUE KAM SING WONG KEI MAY LAU Department of Electronic and Computer Engineering Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Department of Physics and William Mong Institute of Nano Science and Technology Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina

Efficient, scalable, bufferless, and compact Ⅲ–V lasers directly grown on(001)-oriented silicon-on-insulators(SOIs) are preferred light sources in Si-photonics. In this article, we present the design and operation of Ⅲ–V telecom nanolaser arrays with integrated distributed Bragg reflectors(DBRs) epitaxially grown on industry-standard(001) SOI wafers. We simulated the mirror reflectance of different guided modes under various mirror architectures, and accordingly devised nanoscale DBR gratings to support high reflectivity around1500 nm for the doughnut-shaped TE01 mode. Building from InP/InGaAs nanoridges grown on SOI, we fabricated subwavelength DBR mirrors at both ends of the nanoridge laser cavities and thus demonstrated room-temperature low-threshold InP/InGaAs nanolasers with a 0.28 μm^2 cross-section and a 20 μm effective cavity length. The direct growth of these bufferless nanoscale Ⅲ–V light emitters on Si-photonics standard(001) SOI wafers opens future options of fully integrated Si-based nanophotonic integrated circuits in the telecom wavelength regime.

关键词： InGaAs InP SOI nanolasers with distributed Bragg reflectors epitaxially grown on Room temperature silicon-on-insulators Bragg

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Ondansetron and Hypothermia Induced Cardiac Arrest in a 97-Year-Old Woman: A Case Report

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Cardiovascular Innovations and Applications 2022年第3期7卷 66-72页

作者： Keith Sai kit leung Faareaha Ahmad Amun Mahmood Yuki Ka Ling Shum Ekta Punj Azam Majeed Riad Hosein Anna Hong Muzaffar Hashmi Faculty of Health and Life Sciences Aston UniversityBirmingham B47ETUnited Kingdom Emergency Department Queen Elizabeth Hospital BirminghamUniversity Hospitals Birmingham NHS Foundation TrustBirmingham B152THUnited Kingdom

Background:Ondansetron and hypothermia are both known to induce bradycardia or QT interval prolongation,thus placing affected patients at risk of cardiac *** Report:Herein,we report the case of a 97-year-old woman who initially presented with confusion and hypothermia,and experienced severe bradycardia and asystolic cardiac arrest after a 4 mg intravenous ondansetron bolus ***:Ondansetron is associated with bradycardia and QTc prolongation,both of which might be further exacerbated by *** should be aware that administering ondansetron in patients with hypothermia might further increase the risk of adverse cardiac events and eventual cardiac arrest.

关键词： Ondansetron Hypothermia Bradycardia QT prolongation Cardiac Arrest

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Proteomic analysis reveals distinctive protein profiles involved in CD8^(+) T cell-mediated murine autoimmune cholangitis

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Cellular & Molecular Immunology 2018年第8期15卷 756-767页

作者： Weici Zhang Ren Zhang Jun Zhang ying Sun Patrick SC leung Guo-Xiang Yang Zongwen Shuai William M Ridgway M Eric Gershwin Division of Rheumatology Allergy and Clinical ImmunologyUniversity of CaliforniaDavisCaliforniaUSA Department of Pathogenic Biology and Immunology Guangzhou University of Chinese MedicineGuangzhou 510006China Center for non-infectious liver diseases Beijing 302 HospitalBeijing 100039China Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Division of Immunology Allergy and RheumatologyUniversity of CincinnatiCincinnatiOH 45267

Autoimmune cholangitis arises from abnormal innate and adaptive immune responses in the liver,and T cells are critical drivers in this ***,little is known about the regulation of their functional behavior during disease *** previously reported that mice with T cell-restricted expression of a dominant negative form of transforming growth factor beta receptor type Ⅱ(dnTGFβ RII)spontaneously develop an autoimmune cholangitis that resembles human primary biliary cholangitis(PBC).Adoptive transfer of CD8^(+) but not CD4^(+) T cells into Rag1^(−/−)mice reproduced the disease,demonstrating a critical role for CD8^(+) T cells in PBC ***,we used SOMAscan technology to perform proteomic analysis of serum samples from dnTGFβRII and B6 control mice at different *** addition,we analyzed CD8 protein profiles after adoptive transfer of splenic CD8^(+) cells into Rag1^(−/−)*** use of the unique SOMAscan aptamer technology revealed critical and distinct profiles of CD8 cells,which are key to biliary *** total,254 proteins were significantly increased while 216 proteins were significantly decreased in recipient hepatic CD8^(+) cells compared to donor splenic CD8^(+) *** contrast to donor splenic CD8^(+) cells,recipient hepatic CD8^(+) cells expressed distinct profiles for proteins involved in chemokine signaling,focal adhesion,T cell receptor and natural killer cell-mediated cytotoxicity pathways.

关键词： autoimmune cholangitis CD8 dnTGFβRII mice proteomic analysis

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Comparison of two emergency medical services in Beijing and Hong Kong, China

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Chinese Medical Journal 2019年第11期132卷 1372-1374页

作者： Fei Shao kit-Ling Fan Colin Robertson Marcus Ong Nan Liu Ling-Pong leung Reynold leung Chun-Sheng Li Departm ent of Emergency Medicine Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China Accident and Emergency Department The Hong Kong University-Shenzhen Hospital Shenzhen Guangdong 518053 China Accident and Emergency Medicine and Surgery University of Edinburgh Scotland UK Department of Emergency Medicine Singapore General Hospital Singapore Health Services Research Centre Singapore Health Services Singapore Emergency Medicine Unit Li Ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China

To Out-of-hospital cardiac arrest (OHCA) is a major issue in emergency care worldwide. The incidence of OHCA is estimated to be 50 to 60 per 100,000 persons *** advances in treatment and technology, survival following OHCA remains low. There are multiple factors affecting the survival outcome. The type of emergency medical service (EMS) system is likely to be one of them. In Asia, the EMS structure and its service capability in terms of dispatch, airway management, and medications vary widely between communities. This study aimed to evaluate the survival outcomes of OHCA in Beijing and Hong Kong (HK), China and the effect of the type of EMS system on the survival outcomes for patients with OHCA.

关键词： Extrahospital cardiac arrest (ohca) cardiac arrest emergency medical service

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