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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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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(P<0.05).Conclusions:In a mouse orthotopic 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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Gastrointestinal stromal tumors in a cohort of Chinese patients in Hong Kong

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World Journal of Gastroenterology 2006年第14期12卷 2223-2228页

作者： Kam Hoi Chan Chun wing Chan Wai Hung Chow Wai Keung Kwan Chi Kwan Kong Ka Fung mak Miu Yi Leung Lin Kiu Lau Department of Medicine Yan Chai Hospital Tsuen Wan Hong Kong SAR China Department of Surgery Yan Chai Hospital Tsuen Wan Hong Kong SAR China Department of Radiology Yah Chai Hospital Tsuen Wan Hong Kong SAR Chin Department of Pathology Yah Chai Hospital Tsuen Wan Hong Kong SAR China

AIM： To investigate the prevalence and clinical pattern of gastrointestinal stromal tumors （GISTs） in Hong Kong Chinese, and to assess the impact of introduction of CD117 on the disease incidence. METHODS： From the database of the Department of Pathology of yan Chai Hospital, 47 patients, with GISTs from September 1995 to December 2003 were included in this study. Ten GISTs were diagnosed before the introduction of CD117. The clinical features, tumor characteristics, and treatment were analyzed. Factors predicting tumor related death or recurrence were studied with Cox proportional hazard model. RESULTS： The patients included 26 males and 21 females, with a mean age of 66.6 years （SD 13.1, range 29-87 years）. The estimated prevalence of GISTs was 13.4-15.6 per 100 000 people, with an annual inddence of 1.68-1.96 per 100 000 people. The annual incidence of GISTs before and after the introduction of CD117 was 1.1 per 100 000 people and 2.1 per 100 000 people respectively. Stomach （34 patients, 72.3%） was the most common location for the tumor, followed by the small intestine （8 patients, 17.0%）, esophagus （2 patients, 4.3%）, omentum （2 patients, 4.3%） and colon （1 patient, 2.1%）. Thirty-one patients （66%） had complete tumor resection. Eleven out of 16 deaths （23%） were tumor-related. The median survival time was 26 too. Five-year survival rate was 61.3%. The significant factors associated with tumor-related death or recurrence were incomplete resection, tumor size 5 cm or above, invasion to the adjacent organ or presence of metastasis, CONCLUSION： The incidence of GIST in Hong Kong is comparable to that in the United States but lower than that in Finland. The true incidence of GISTs could be underestimated before the introduction of CD117. Incomplete resection, tumor size 5 cm or above, invasion to the adjacent organ or presence of metastasis are factors predicting tumor-related death or recurrence.

关键词： Gastrointestinal tumor GIST Prognostic factors, Clinical features Incidence

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Molecular basis of von Hippel-Lindau syndrome in Chinese patients

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Chinese Medical Journal 2011年第2期000卷 237-241页

作者： SIU Wai-kwan MA Ronald Ching-wan LAM Ching-wan mak Chloe Miu YUEN Yuet-ping LO Fai-man Ivan CHAN Kin-wan LAM Siu-fung LING Siu-cheung TONG Sui-fan SO wing-yee CHOW Chun-chung TANG Mary Hoi-yin TAM wing-hung CHAN Albert yan-wo Department of Pathology Princess Margaret Hospital Hong Kong China Department of Medicine & Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China Department of Pathology Li Ka Shing Faculty of Medicine The University of Hong Kong Queen Mary Hospital Hong Kong China Clinical Genetic Service Department of Health Hong Kong China Department of Medicine and Geriatrics Princess Margaret Hospital Hong Kong China Department of Paediatrics and Adolescent Medicine Princess Margaret Hospital Hong Kong China Department of Obstetrics & Gynaecology Tsan Yuk Hospital Hong Kong China Department of Obstetrics & Gynaecology The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong China

Background Von Hippel-Lindau （VHL） syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various *** genetic basis of VHL in Southern Chinese is largely *** this study,we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese *** Nine probands with clinical features of VHL,two symptomatic and eight asymptomatic family members were included in this *** diagnosis was performed twice for one *** probands had only isolated bilateral *** VHL gene was screened for mutations by polymerase chain reaction,direct sequencing and multiplex ligation-dependent probe amplification （MLPA）.Results The nine probands and the two symptomatic family members carried heterozygous germline *** different VHL mutations were identified in the nine *** splicing mutation,NM_000551.2：c.463＋1G〉T,was *** other seven VHL mutations,c.233A〉G [***78Ser],c.239G〉T [***80lle],c.319C〉G [***107Gly],c.481C〉T [***161X],c.482G〉A [***161GIn],c.499C〉T [***167Trp] and an exon 2 deletion,had been previously *** asymptomatic family members were positive for the mutation and the other five tested *** prenatal diagnosis,the fetuses were positive for the *** Genetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary *** detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their ***-based diagnosis can have an important impact on clinical management for VHL families.

关键词： von Hippel-Lindau syndrome VHL gene Chinese VHL mutations

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