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HM30181A,a potent P-glycoprotein inhibitor,potentiates the absorption and in vivo antitumor efficacy of paclitaxel in an orthotopic brain tumor model

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Cancer Biology & Medicine 2020年第4期17卷 986-1001页

作者： Wu Zeng Betty Yuen Kwan Law Vincent kam Wai Wong Denise So Bik Chan Simon Wing Fai Mok Joyce Jia Ying Gao rebecca ka yan ho Xu Liang Jia Hao Li Ming Tsung Lee Weng Li Yoon Michael P Smolinski Johnson Yiu Nam Lau Christopher Wai Kei Lam Manson Fok State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina At he nex hong Kong Irmo vative Limited Hong Kong China Faculty of Medici ne Macao Un iversity of Science and TechnologyMacaoChina Athenex Inc. New York 14203USA

Objective:Delivery of chemotherapeutic drugs to the brain has remained a major obstacle in the treatment of glioma,owing to the presence of the blood-brain barrier and the activity of P-gp,which pumps its substrate back into the systemic *** aim of the present study was to develop an intravenous formulation of HM30181 A(HM)to inhibit P-gp in the brain to effectively deliver paclitaxel(PTX)for the treatment of malignant ***:Two formulations of solubilized HM were designed on the basis of different solid dispersion strategies:i)spray-drying[polyvinlypyrrolidone(PVP)-HM]and ii)solvent evaporation[HP-β-cyclodextrin(cyclodextrin)-HM].The P-gp inhibition of these 2 formulations was assessed on the basis of rhodamine 123 uptake in cancer *** and brain pharmacokinetic parameters were also determined,and the antitumor effect of cyclodextrin-HM with PTX was evaluated in an orthotopic glioma xenograft mouse ***:Although both PVP-HM and cyclodextrin-HM formulations showed promising P-gp inhibition activity in vitro,cyclodextrin-HM had a higher maximum tolerated dose in mice than did *** study of cyclodextrin-HM revealed a plasma concentration plateau at 20 mg/kg,and the mice began to lose weight at doses above this ***-HM(10 mg/kg)administered with PTX at 10 mg/kg showed optimal antitumor activity in a mouse model,according to both tumor volume measurement and survival time(Photopic brain tumor model,the intravenous co-administration of cyclodextrin-HM with PTX showed potent antitumor effects and therefore may have potential for glioma therapy in humans.

关键词： HM30181A glioma pharmacokinetics paclitaxel P-glycoprotein

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Inferior vena cava reconstruction in extended right hepatectomy

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 533-534页

作者： karin KY ho Sui Ling Sin Kin Pan Au Henry HY Lee Daniel TL Chan Albert Chan Department of Surgery The University of Hong Kong102 Pok Fu Lam RoadHong KongChina Department of Surgery Yan Chai Hospital7 Yan Chai StreetHong KongChina State Key Laboratory of Liver Research(Li ka Shing Faculty of Medicine The University of Hong Kong)102 Pok Fu Lam RoadHong KongChina

To the Editor : Barcelona Clinic Liver Cancer(BCLC) Stage C hepatocellular carcinoma(HCC) with vascular invasion has been considered unresectable. however, the curative rate from systemic treatment is rather dismal. Even with the use of immunotherapy, complete remission is less than 10% [ 1 ]. On the contrary, recent advances in transplant oncology, especially in the application of liver transplant-related surgical techniques in complex liver resections, make the operation possible for patients with locally advanced HCC who were previously considered to be unresectable [ 2 ]. We hereby present the surgical management of a patient with giant HCC in right liver lobe with inferior vena cava(IVC) invasion.

关键词： invasion vena Liver

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Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

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世界胃肠病学杂志:英文版 2023年第33期29卷 4942-4961页

作者： Joyce Wing yan Mak Alvin Wing Hin Law Kimmy Wan Tung Law Rita ho Carmen ka Man Cheung Man Fai Law Department of Medicine and Therapeutics Prince of Wales HospitalHong Kong 852China West Island School Hong Kong 852China Department of Medicine North District HospitalHong Kong 852China

Hepatitis due to hepatitis B virus(HBV)reactivation can be serious and potentially fatal,but is *** reactivation is most commonly reported in patients receiving chemotherapy,especially rituximab-containing therapy for hematological malignancies and those receiving stem cell *** with inactive and even resolved HBV infection still have persistence of HBV genomes in the *** expression of these silent genomes is controlled by the immune *** or ablation of immune cells,most importantly B cells,may lead to reactivation of seemingly resolved HBV ***,all patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core *** found to be positive for HBsAg should be given prophylactic antiviral *** patients with resolved HBV infection,there are two *** first is pre-emptive therapy guided by serial HBV DNA monitoring,and treatment with antiviral therapy as soon as HBV DNA becomes *** second approach is prophy-lactic antiviral therapy,particularly for patients receiving high-risk therapy,especially anti-CD20 monoclonal antibody or hematopoietic stem cell *** and tenofovir are the preferred antiviral *** new effective therapies for hematological malignancies have been introduced in the past decade,for example,chimeric antigen receptor(CAR)-T cell therapy,novel monoclonal antibodies,bispecific antibody drug conjugates,and small molecule inhibitors,which may be associated with HBV *** there is limited evidence to guide the optimal preventive measures,we recommend antivi-ral prophylaxis in HBsAg-positive patients receiving novel treatments,including Bruton’s tyrosine kinase inhibitors,B-cell lymphoma 2 inhibitors,and CAR-T cell *** studies are needed to determine the risk o

关键词： Hepatitis B Hematologic neoplasms Chimeric antigen receptor-T cell therapy Monoclonal antibodies Bruton’s tyrosine kinase inhibitors Antiviral agents

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A machine learning model for colorectal liver metastasis post-hepatectomy prognostications

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Hepatobiliary Surgery and Nutrition 2023年第4期12卷 495-506,I0007-I0016页

作者： Cynthia Sin Nga Lam Alina Ashok Bharwani Evelyn Hui Yi Chan Vernice Hui yan Chan howard Lai ho Au Margaret kay ho Shireen Rashed Bernard Ming hong Kwong Wentao Fang ka Wing Ma Chung Mau Lo Tan To Cheung Li ka Shing Faculty of Medicine The University of Hong KongHong Kong SARChina Department of Surgery Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Background:Currently,surgical resection is the mainstay for colorectal liver metastases(CRLM)management and the only potentially curative treatment *** tools can support patient selection for surgical resection to maximize therapeutic *** study aimed to develop a survival prediction model using machine learning based on a multicenter patient sample in hong ***:Patients who underwent hepatectomy for CRLM between 1 January 2009 and 31 December 2018 in four hospitals in hong Kong were included in the *** analysis was performed using Cox proportional hazards(CPH).A stepwise selection on Cox multivariable models with Least Absolute Shrinkage and Selection Operator(LASSO)regression was applied to a multiply-imputed dataset to build a prediction *** model was validated in the validation set,and its performance was compared with that of Fong Clinical Risk Score(CRS)using concordance ***:A total of 572 patients were included with a median follow-up of 3.6 *** full models for overall survival(OS)and recurrence-free survival(RFS)consist of the same 8 established and novel variables,namely colorectal cancer nodal stage,CRLM neoadjuvant treatment,Charlson Comorbidity Score,pre-hepatectomy bilirubin and carcinoembryonic antigen(CEA)levels,CRLM largest tumor diameter,extrahepatic metastasis detected on positron emission-tomography(PET)-scan as well as KRAS *** CRLM Machine-learning Algorithm Prognostication model(CMAP)demonstrated better ability to predict OS(C-index=0.651),compared with the Fong CRS for 1-year(C-index=0.571)and 5-year OS(C-index=0.574).It also achieved a C-index of 0.651 for ***:We present a promising machine learning algorithm to individualize prognostications for patients following resection of CRLM with good discriminative ability.

关键词： Machine-learning colorectal liver metastasis(CRLM) prognostic model survival analysis hepatectomy outcome

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Efficacy of vasopressin, steroid, and epinephrine protocol for in-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis

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Journal of Geriatric Cardiology 2022年第9期19卷 705-711页

作者： Danish Iltaf Satti yan Hiu Athena Lee Keith Sai Kit Leung Jeremy Man ho Hui Thompson ka Ming Kot Arslan Babar Gauranga Mahalwar Abraham KC Wai Tong Liu Leonardo Roever Gary Tse Jeffrey Shi kai Chan International Health Informatics Study(IHIS)Network Cardiovascular Analytics Group Hong KongChina-UK Collaboration Emergency Medicine Unit Li Ka Shing Fac-ulty of MedicineThe University of Hong KongHong KongChina Aston Medical School Faculty of Health&Life SciencesAston UniversityBirminghamUnited Kingdom Li ka Shing Faculty of Medicine The University of Hong KongHong KongChina Department of Anaesthesia and Pain Service Princess Margaret HospitalLai Chi KokKowloonHong KongChina Department of Medicine Cleveland Clinic FoundationClevelandUSA Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease Department of CardiologyTianjin Institute of Cardi-ologySecond Hospital of Tianjin Medical UniversityTianjinChina Department of Clinical Research Federal Uni-versity of UberlândiaUberlândiaBrazil Kent and Medway Medical School CanterburyKentUnited Kingdom 不详

OBJECTIVES To assess the effect of vasopressin,steroid and epinephrine(VSE)combination therapy on return of spontan-eous circulation(ROSC)after in-hospital cardiac arrest(IHCA),and test the conclusiveness of evidence using trial sequential ana-lysis(TSA).METhoDS The systematic search included PubMed,EMBASE,Scopus,and Cochrane Central Register of Controlled *** controlled trials(RCTs)that included adult patients with IHCA,with at least one group receiving combined VSE therapy were *** was extracted independently by two *** main outcome of interest was *** out-comes included survival to hospital discharge or survival to 30 and 90 days,with good neurological *** We included a total of three RCTs(n=869).Results showed that VSE combination therapy increased ROSC(risk ra-tio=1.41;95%CI:1.25-1.59)as compared to *** demonstrated that the existing evidence is *** was also validated by the alpha-spending adjusted relative risk(1.32[1.16,1.49],Phould evaluate survival to hospital discharge,neurological function and long-term survival.

关键词： resuscitation analysis return

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Liver Transplantation for Hepatitis B Virus-related Hepatocellular Carcinoma in hong Kong

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Journal of Clinical and Translational Hepatology 2018年第3期6卷 283-288页

作者： ka Wing Ma Kenneth Siu ho Chok James yan Yue Fung Chung Mau Lo Department of Surgery The University of Hong KongHong KongChina State Key Laboratory for Liver Research The University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina

Hepatocellular carcinoma(HCC)is the fifth most common cancer and the third most common cause of cancer-related deaths *** resection is frequently limited in hong Kong by hepatitis B virus-related cirrhosis,and liver transplantation is the treatment of *** transplanta-tion has been shown to produce superior oncological benefits,when compared to hepatectomy for *** developments in the context of patient selection criteria,modification of organ allocation,bridging therapy,salvage liver transplanta-tion and pharmaceutical breakthrough have improved the survival of HCC *** this article,we will share our experience in transplanting hepatitis B virus-related HCC patients in hong Kong and discuss the recent progress in several areas of liver transplantation.

关键词： Liver transplantation Hepatitis B Hepatocel ular carcinoma Review

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Pandemic of the aging society—sporadic cerebral small vessel disease

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Chinese Medical Journal 2021年第2期134卷 143-150页

作者： Alexander Yuk Lun Lau Bonaventure Yiu Ming Ip ho Ko Bonnie Yin ka Lam Lin Shi karen ka yan Ma Lisa Wing Chi Au yannie Oi yan Soo Thomas Wai hong Leung Adrian Wong Vincent Chung Tong Mok Division of Neurology Department of Medicine and TherapeuticsThe Faculty of MedicineThe Chinese University of Hong KongHong KongChina Gerald Choa Neuroscience Centre Faculty of MedicineLui Che Woo Institute of Innovative MedicineThe Chinese University of Hong KongHong KongChina Faculty of Medicine School of Biomedical SciencesLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina Margaret Cheung K.L.Cheung Research Centre for Management of Parkinsonism Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Imaging and Interventional Radiology The Chinese University of Hong KongHong KongChina Shenzhen Research Institute The Chinese University of Hong KongShenzhenGuangdongChina.

Age-related sporadic cerebral small vessel disease(CSVD)has gained increasing attention over the past decades because of its increasing prevalence associated with an aging *** widespread application of and advances in brain magnetic resonance imaging in recent decades have significantly increased researchers’understanding in the in vivo evolution of CSVD,its impact upon the brain,its risk factors,and the mechanisms that explain the various clinical manifestation associated with sporadic *** this review,we aimed to provide an update on the pathophysiology,risk factors,biomarkers,and the determinants and spectrum of the clinical manifestation of sporadic CSVD.

关键词： Cerebral small vessel disease Clinical spectrum Pathophysiology

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Are newborn rat-derived neural stem cells more sensitive to lead neurotoxicity?

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Neural Regeneration Research 2013年第7期8卷 581-592页

作者： yan ho Chan Mingyong Gao Wutian Wu Department of Anatomy Li Ka Shing Faculty of Medicine the University of Hong Kong Department of Spine Surgery Renmin Hospital of Wuhan University State Key Laboratory of Brain and Cognitive Sciences Li Ka Shing Faculty of Medicine The University of Hong Kong Research Center of Reproduction Development and Growth Li Ka Shing Faculty of Medicine the University of Hong Kong GHM Institute of Central Nervous System Regeneration Jinan University

Lead ion （Pb2＋） has been proven to be a neurotoxin due to its neurotoxicity on mammalian nervous system, especially for the developing brains of juveniles. however, many reported studies involved the negative effects of Pb2＋ on adult neural cells of humans or other mammals, only few of which have examined the effects of Pb2＋ on neural stem cells. The purpose of this study was to reveal the biological effects of Pb2＋from lead acetate [Pb （0H30OO）2] on viability, proliferation and differentiation of neural stem cells derived from the hippocampus of newborn rats aged 7 days and adult rats aged 90 days, respectively. This study was carried out in three parts. In the first part, 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay （MTT viability assay） was used to detect the effects of Pb2＋ on the cell viability of passage 2 hippocampal neural stem cells after 48-hour exposure to 0-200 pM Pb2＋. In the second part, 10 pM bromodeoxyuridine was added into the culture medium of passage 2 hippocampal neural stem cells after 48-hour exposure to 0- 200 pM Pb2＋, followed by immunocytochemical staining with anti-bromodeoxyuridine to demonstrate the effects of Pb2＋ on cell proliferation. In the last part, passage 2 hippocampal neural stem cells were allowed to grow in the differentiation medium with 0-200 pM Pb2＋. Immunocytochemical staining with anti-microtubule-associated protein 2 （a neuron marker）, anti-glial fibrillary acidic protein （an astrocyte marker）, and anti-RIP （an oligodendrocyte marker） was performed to detect the differentiation commitment of affected neural stem cells after 6 days. The data showed that Pb2~ inhibited not only the viability and proliferation of rat hippocampal neural stem cells, but also their neuronal and oligodendrocyte differentiation in vitro. Moreover, increased activity of astrocyte differentiation of hippocampal neural stem cells from both newborn and adult rats was observed after exposure to high concentration of lead ion in v

关键词： neural regeneration stem cells neural stem cells adult neonate mammals Pb2+ neurotoxicity viability proliferation hippocampus photographs-containing paper neuroregeneration

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Validated model for prediction of recurrent hepatocellular carcinoma after liver transplantation in Asian population

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World Journal of Gastrointestinal Oncology 2019年第4期11卷 322-334页

作者： ka Wing Ma Wong hoi She Albert Chi yan Chan Tan To Cheung James yan Yue Fung Wing Chiu Dai Chung Mau Lo Kenneth Siu ho Chok Department of Surgery the University of Hong Kong Department of Surgery and State Key Laboratory for Liver Research the University of Hong Kong Department of Medicine and State Key Laboratory for Liver Research The University of Hong Kong

BACKGROUND Liver transplantation(LT) is regarded as the best treatment for both primary and recurrent hepatocellular carcinoma(HCC). Post-transplant HCC recurrence rate is relatively low but significant, ranging from 10%-30% according to different series. When recurrence happens, it is usually extrahepatic and associated with poor prognosis. A predictive model that allows patient stratification according to recurrence risk can help to individualize post-transplant surveillance protocol and guidance of the use of anti-tumor immunosuppressive *** To develop a scoring system to predict HCC recurrence after LT in an Asian *** Consecutive patients having LT for HCC from 1995 to 2016 at our hospital were recruited. They were randomized into the training set and the validation set in a60:40 ratio. Multivariable Cox regression model was used to identity factors associated with HCC recurrence. A risk score was assigned to each factor according to the odds ratio. Accuracy of the score was assessed by the area under the receiver operating characteristic *** In total, 330 patients were eligible for analysis(183 in training and 147 invalidation). Recurrent HCC developed in 14.2% of them. The median follow-up duration was 65.6 mo. The 5-year disease-free and overall survival rates were78% and 80%, respectively. On multivariate analysis, alpha-fetoprotein > 400 ng/mL [P = 0.012, hazard ratio(HR) 2.92], sum of maximum tumor size and number(P = 0.013, HR 1.15), and salvage LT(P = 0.033, HR 2.08) were found to be independent factors for disease-free survival. A risk score was calculated for each patient with good discriminatory power(c-stat 0.748 and 0.85, respectively,in the training and validation sets). With the derived scores, patients were classified into low-(0–9), moderate-(> 9–14), and high-risk groups(> 14), and the risk of HCC recurrence in the training and validation sets was 10%, 20%, 54%(cstat 0.67) and 4%, 22%, 62%(c-stat 0.811), accordin

关键词： Hepatocellular carcinoma Liver transplantation Post-transplant recurrence Predictive model

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Liver transplantation:would it be the best and last chance of cure for hepatocellular carcinoma with major venous invasion?

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Hepatobiliary Surgery and Nutrition 2021年第3期10卷 308-314页

作者： ka Wing Ma Albert Chi yan Chan Kenneth Siu ho Chok Wong hoi She Tan To Cheung Wing Chiu Dai James yan Yue Fung Chung Mau Lo Department of Surgery The University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina

Background:Hepatocellular carcinoma(HCC)with portal vein tumour thrombus(PVTT)signifies advanced disease,whether LT confers any survival superiority over resection remains ***:A propensity score matched(PSM)analysis of liver transplantation(LT)and liver resection(LR)for HCC with PVTT was ***:A consecutive series of 88 patients who received either LT(10 DDLTs and 3 LDLTs)or LR(n=75)respectively were *** PSM,the LT group has a higher MELD score(17.3 vs.7.8,Phould be considered.

关键词： Liver transplantation(LT) portal vein tumour thrombus liver resection(LR)

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