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

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World Journal of Gastroenterology 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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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)Submitted Aug 10,2019.Accepted for publication Oct 15,2019.

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Impact of small-for-size liver grafts on medium-term and long-term graft survival in living donor liver transplantation: A meta-analysis

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World Journal of Gastroenterology 2019年第36期25卷 5559-5568页

作者： ka Wing Ma Kelly Hiu Ching Wong Albert Chi yan Chan Tan To Cheung Wing Chiu Dai James yan Yue Fung Wong hoi She Chung Mau Lo Kenneth Siu ho Chok Department of Surgery Queen Mary Hospital Hong Kong China Li ka Shing Faculty of Medicine The University of Hong Kong Hong Kong China Department of Surgery The University of Hong Kong Hong Kong China Department of Medicine Queen Mary Hospital Hong Kong China

BACKGROUND Small-for-size grafts (SFSGs) in living donor liver transplantation (LDLT) could optimize donor postoperative outcomes and also expand the potential donor pool. Evidence on whether SFSGs would affect medium-term and long-term recipient graft survival is lacking. AIM To evaluate the impact of small-for-size liver grafts on medium-term and longterm graft survival in adult to adult LDLT. METhoDS A systematic review and meta-analysis were performed by searching eligible studies published before January 24, 2019 on PubMed, EMBASE, and Web of Science databases. The primary outcomes were 3-year and 5-year graft survival. Incidence of small-for-size syndrome and short term mortality were also extracted. RESULTS This meta-analysis is reported according to the guidelines of the PRISMA 2009 Statement. Seven retrospective observational studies with a total of 1821 LDLT recipients were included in the meta-analysis. SFSG is associated with significantly poorer medium-term graft survival. The pooled odds ratio for 3-year graft survival was 1.58 [95% confidence interval 1.10-2.29, P = 0.014]. On the other hand, pooled results of the studies showed that SFSG had no significant discriminatory effect on 5-year graft survival with an odds ratio of 1.31 (95% confidence interval 0.87-1.97, P = 0.199). Furthermore, incidence of small-for-size syndrome detected in recipients of SFSG ranged from 0-11.4% in the included studies. CONCLUSION SFSG is associated with inferior medium-term but not long-term graft survival. Comparable long-term graft survival based on liver graft size shows that smaller grafts could be accepted for LDLT with appropriate flow modulatory measures. Close follow-up for graft function is warranted within 3 years after liver transplantation.

关键词： Living donor liver transplantation Small-for-size grafts Small-for-size syndrome Graft survival

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Intravenous fluid selection rationales in acute clinical management

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World Journal of Emergency Medicine 2018年第1期9卷 13-19页

作者： Wing yan Shirley Cheung Wai Kwan Cheung Chun ho Lam Yeuk Wai Chan Hau Ching Chow ka Lok Cheng Yau Hang Wong Chak Wah kam Accident and Emergency Department Tuen Mun Hospital

BACKGROUND: Intravenous fluid(IVF) is commonly used in acute clinical management. This study aimed to review the choice and primary considerations in IVF prescriptions and to evaluate the adequacy of guidelines and trainings on it in the New Territories West Cluster(NTWC) of hong ***: This is a descriptive study based on data collected from an online survey. Data were processed by SPSS for statistical analysis. This study focused on a general description and doctor-nurse between group comparison. Participants were asked the choice of IVF for nine acute clinical scenarios and provide reason. A 1–10 scale was used to assess the sufficiency of guideline, training and information, and time for revision on IVF ***: 0.9% sodium chloride was the most familiar IVF(36%), followed by 5% Dextrose solution(26%). In the nine scenarios, the most chosen IVF was 0.9% sodium chloride(37%–61%). There was significant difference in the choice of IVF between doctors and nurses in 7 cases. The second most chosen IVF for doctors was Plasma-Lyte A while that for nurses was Gelofusine. Departmental practice was the most chosen reason to account for the prescription. The adequacy of guideline, information and training, and time for revision was rated 5. Doctors had significantly more time at work than nurses to update knowledge in IVF prescription(5.41 versus 4.57).CONCLUSION: 0.9% sodium chloride was mostly chosen. The choice of IVF was mainly based on departmental practice. Adequacy of guideline, information and training, and time for revision on IVF prescription were average, indicating significant training deficit.

关键词： Intravenous fluid Acute care Resuscitation

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Impressive near-infrared brightness and singlet oxygen generation from strategic lanthanide-porphyrin double-decker complexes in aqueous solution

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Light(Science & Applications) 2019年第1期8卷 766-775页

作者： Jing-Xiang Zhang Wai-Lun Chan Chen Xie yan Zhou ho-Fai Chau Partha Maity George T.Harrison Aram Amassian Omar F.Mohammed Peter A.Tanner Wai-Kwok Wong ka-Leung Wong Department of Chemistry Hong Kong Baptist UniversityKowloon TongHong Kong S.A.R.China Hanshan Normal University ChaozhouGuangdong ProvinceChina Department of Biology Hong Kong Baptist UniversityKowloon TongHong Kong S.A.R.China kaUST Solar Center Division of Physical Science and EngineeringKing Abdullah University of Science and Technology(KAUST)Thuwal 23955-6900Saudi Arabia

Although lanthanide double-decker complexes with hetero-macrocyclic ligands as functional luminescent and magnetic materials have promising properties,their inferior water solubility has negated their biomedical ***,four water-soluble homoleptic lanthanide(Ln=Gd,Er,Yb and La)sandwiches with diethylene-glycoldisubstituted porphyrins(DD)are reported,with their structures proven by both quantum chemical calculations and scanning tunneling *** findings demonstrate that the near-infrared emission intensity and singlet oxygen(1O2)quantum yields of YbDD and GdDD in aqueous media are higher than those of the reported capped lanthanide monoporphyrinato analogues,YbN and GdN;the brightness and luminescence lifetime in water of YbDD are greater than those of *** work provides a new dimension for the future design and development of molecular theranostics-based water-soluble double-decker lanthanide bisporphyrinates.

关键词： lanthanide porphyrin complexes

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What do we know about housing supply?The case of hong Kong SAR

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Economic and Political Studies 2020年第1期8卷 6-20页

作者： Charles ka Yui Leung Joe Cho Yiu Ng Edward Chi ho Tang Department of Economics and Finance City University of Hong KongHong Kong SARChina Department of Economics and Finance Hong Kong Shue Yan UniversityHong Kong SARChina

The house price in the hong Kong SAR of China is well-known to be‘unaffordable’.This paper relates the macroeconomy with the housing market of hong Kong and argues that the housing supply plays a vital role in explaining the *** paper also shows that there are some practical challenges in understanding the housing supply of hong Kong,including the potentially complicated ownership structure of real estate *** the discussion centres on the situation of hong Kong,its lesson may also apply to housing markets in other small open economies.

关键词： New housing supply oligopolistic market structure ownership structure real estate development real estate developers

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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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