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Luo S.-B.,Wenzhou University | Li C.-B.,Clinical Laboratory of Beijing Hospital | Dai D.-P.,Beijing Institute of Geriatrics | Wang S.-H.,Wenzhou University | And 11 more authors.
Journal of Pharmacological Sciences | Year: 2014

Warfarin is the most frequently prescribed anticoagulant for the long-term treatment in the clinic. Recent studies have shown that polymorphic alleles within the CYP2C9, VKORC1, and CYP4F2 genes are related to the warfarin dosage requirement. In this study, a novel non- synonymous mutation (1009C>A) in CYP2C9 was detected in a warfarin-hypersensitive patient, while the other two candidate genes were both found to be homozygous for the wild-type alleles. The newly identified point mutation results in an amino acid substitution at position 337 of the CYP2C9 protein (P337T) and has been designated as the novel allele CYP2C9*58. When expressed in insect cell microsomes, the relative intrinsic clearance values of the CYP2C9.58 variant for tolbutamide and losartan were quite similar to those of the typical defective variant CYP2C9.3, whereas the clearance value of CYP2C9.58 for diclofenac was slightly higher than that of another typical defective variant CYP2C9.2. These data suggested that when compared with wild-type CYP2C9.1, the enzymatic activity of the novel allelic variant has been greatly reduced by the 1009C>A mutation. If patients carrying this allele take drugs metabolized by CYP2C9, their metabolic rate might be slower than that of wild-type allele carriers and thus much more attention should be paid to their clinical care. © The Japanese Pharmacological Society. Source

Yang H.,Chemotherapy Center | Chen Z.,Laboratory of Clinical Pharmacy | Wu M.,Zhejiang Province Cancer Hospital | Lei T.,Chemotherapy Center | And 2 more authors.
Cancer Biology and Therapy | Year: 2016

Background: Poorly Differentiated Thyroid Carcinoma (PDTC), especially advanced PDTC, is an aggressive disease and displays a much poorer prognosis compared with well differentiated thyroid carcinoma. Surgery is the recommended treatment in the early stage of PDTC, however, no effective treatment modalities are currently available for advanced PDTCMethods: Two advanced PDTC patients with no radioiodine uptake adopted a cytotoxic chemotherapy with liposomal doxorubicin (35 mg/m2, day 1) plus cisplatin (75 mg/m2, day1–3) every 3 weeks. Computer tomography (CT) was performed after 6 cycles (case 1) or 5 cycles (case 2) of chemotherapyResults: Our patients achieved remarkable response with one a Complete Remission (CR) and the other a very good Partial Remission (PR)Conclusion: Our findings indicate that liposomal doxorubicin-based chemotherapy regimens might produce response in PDTC patients, and improve their overall survival and quality of life. Hence we believe this result is very important for oncologists in treating PDTC. © 2016 Taylor & Francis Group, LLC. Source

Zhang C.,Zhejiang University City College | Zhou S.-S.,Zhejiang University City College | Feng L.-Y.,Zhejiang University City College | Zhang D.-Y.,Zhejiang University City College | And 5 more authors.
Acta Pharmacologica Sinica | Year: 2013

Aim:To examine the anti-cancer effects of chamaejasmenin B and neochamaejasmin C, two biflavonones isolated from the root of Stellera chamaejasme L (known as the traditional Chinese herb Rui Xiang Lang Du) in vitro. Methods:Human liver carcinoma cell lines (HepG2 and SMMC-7721), a human non-small cell lung cancer cell line (A549), human osteosarcoma cell lines (MG63, U2OS, and KHOS), a human colon cancer cell line (HCT-116) and a human cervical cancer cell line (HeLa) were used. The anti-proliferative effects of the compounds were measured using SRB cytotoxicity assay. DNA damage was detected by immunofluorescence and Western blotting. Apoptosis and cell cycle distribution were assessed using flow cytometry analysis. The expression of the related proteins was examined with Western blotting analysis. Results:Both chamaejasmenin B and neochamaejasmin C exerted potent anti-proliferative effects in the 8 human solid tumor cell lines. Chamaejasmenin B (the IC 50 values ranged from 1.08 to 10.8 μmol/L) was slightly more potent than neochamaejasmin C (the IC 50 values ranged from 3.07 to 15.97 μmol/L). In the most sensitive A549 and KHOS cells, the mechanisms underlying the anti-proliferative effects were characterized. The two compounds induced prominent expression of the DNA damage marker γ-H2AX as well as apoptosis. Furthermore, treatment of the cells with the two compounds caused prominent G 0/G 1 phase arrest. Conclusion:Chamaejasmenin B and neochamaejasmin C are potential anti-proliferative agents in 8 human solid tumor cell lines in vitro via inducing cell cycle arrest, apoptosis and DNA damage. © 2013 CPS and SIMM All rights reserved. Source

Zhang C.,Zhejiang University City College | Zhou S.-S.,Zhejiang University City College | Li X.-R.,Zhejiang University City College | Wang B.-M.,Zhejiang University City College | And 6 more authors.
Oncology Reports | Year: 2013

The present study showed that the combination of dasatinib and combretastatin A-4 (CA-4) exhibited synergistic cytotoxicity in multiple types of cancer, including ovarian, hepatocellular, lung and prostate carcinoma. The enhanced apoptosis induced by dasatinib plus CA-4 was accompanied by a greater extent of mitochondrial depolarization, caspase-3 activation and PARP cleavage in HO-8910 cells. Furthermore, elevated expression of Mcl-1 led to a reduced apoptosis induced by dasatinib plus CA-4, highlighting that down-regulated Mcl-1 was necessary for the potentiating effect of dasatinib to CA-4-triggered apoptosis. A clear increase in γ-H2AX expression was observed in the dasatinib + CA-4 group compared with the mono-treatment groups, indicating that dasatinib plus CA-4 may induce double-strand breaks (DSBs) in HO-8910 cells. Moreover, the increased anticancer efficacy of dasatinib combined with CA-4 was further validated in a human HO-8910 ovarian cancer xenograft model in nude mice. Our study is the first to show that the combination of dasatinib with CA-4 could be a novel and promising therapeutic approach for the treatment of cancer. Source

Wang L.,Wenzhou University | Wang S.,Laboratory of Clinical Pharmacy | Chen M.,Wenzhou University | Chen X.,Wenzhou University | And 5 more authors.
Drug Development and Industrial Pharmacy | Year: 2015

The aim of this study was to investigate the effect of orally administered ketoconazole and voriconazole on the pharmacokinetics of carvedilol and its metabolites in rats. Fifteen healthy male Sprague-Dawley (SD) rats were randomly divided into three groups: A group (30 mg/kg ketoconazole), B group (30 mg/kg voriconazole) and C group (control group). A single dose of carvedilol was administered orally 30 min after administration of ketoconazole and voriconazole. Carvedilol and its metabolites plasma levels were measured by ultra-high performance liquid chromatography-mass spectrometry method (UPLC-MS/MS), and pharmacokinetic parameters were calculated by DAS 3.0 software. The co-administrated with ketoconazole could significantly increase the maximal plasma concentration (Cmax) and area under the curve (AUC) of carvedilol (p<0.01). And the Cmax of its three metabolites 4′-Hydroxyphenyl carvedilol (4′-HPC), 5′-Hydroxyphenyl carvedilol (5′-HPC) and o-desmethyl carvedilol (o-DMC) decreased drastically by 39.4% (p<0.01), 45.0% (p<0.01) and 40.8% (p<0.05), respectively. Following coadministered with voriconazole, Tmax of carvedilol and o-DMC increased, and the Cmax of 5′-HPC decreased by 27.7% (p<0.05), while other drugs pharmacokinetic parameters performed no significant differences. Therefore, in clinical, when carvedilol was co-administrated with ketoconazole, dose adjustment of carvedilol should be taken into account. © 2014 Informa Healthcare USA, Inc. Source

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