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排序方式: 共有568条查询结果,搜索用时 31 毫秒
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Wang H Yu N Chen D Lee KC Lye PL Chang JW Deng W Ng MC Lu T Khoo ML Poulsen A Sangthongpitag K Wu X Hu C Goh KC Wang X Fang L Goh KL Khng HH Goh SK Yeo P Liu X Bonday Z Wood JM Dymock BW Kantharaj E Sun ET 《Journal of medicinal chemistry》2011,54(13):4694-4720
A series of 3-(1,2-disubstituted-1H-benzimidazol-5-yl)-N-hydroxyacrylamides (1) were designed and synthesized as HDAC inhibitors. Extensive SARs have been established for in vitro potency (HDAC1 enzyme and COLO 205 cellular IC(50)), liver microsomal stability (t(1/2)), cytochrome P450 inhibitory (3A4 IC(50)), and clogP, among others. These parameters were fine-tuned by carefully adjusting the substituents at positions 1 and 2 of the benzimidazole ring. After comprehensive in vitro and in vivo profiling of the selected compounds, SB939 (3) was identified as a preclinical development candidate. 3 is a potent pan-HDAC inhibitor with excellent druglike properties, is highly efficacious in in vivo tumor models (HCT-116, PC-3, A2780, MV4-11, Ramos), and has high and dose-proportional oral exposures and very good ADME, safety, and pharmaceutical properties. When orally dosed to tumor-bearing mice, 3 is enriched in tumor tissue which may contribute to its potent antitumor activity and prolonged duration of action. 3 is currently being tested in phase I and phase II clinical trials. 相似文献
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Han Chen Josephine Mun Yee Ko Victor Chun Lam Wong Marko Hyytiainen Jorma Keski-Oja Daniel Chua John M. Nicholls Florence Man Fung Cheung Anne Wing Mui Lee Dora Lai-wan Kwong Pui Man Chiu Eugene R. Zabarovsky Sai Wah Tsao Qian Tao Rebecca Kan Stephen Ho Kin Chan Eric J. Stanbridge Maria Li Lung 《Cancer letters》2012
This study identified LTBP-2 as a pleiotropic tumor suppressor in nasopharyngeal carcinoma, which safeguards against critical malignant behaviors of tumor cells. LTBP-2 expression was significantly decreased or lost in up to 100% of NPC cell lines (7/7) and 80% of biopsies (24/30). Promoter hypermethylation was found to be involved in LTBP-2 silencing. Using a tetracycline-regulated inducible expression system, we unveiled functional roles of LTBP-2 in suppressing colony formation, anchorage-independent growth, cell migration, angiogenesis, VEGF secretion, and tumorigenicity. Three-dimensional culture studies suggested the involvement of LTBP-2 in maintenance of tumor cell dormancy in a growth factor favorable microenvironment. 相似文献
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Tze Guan Tan Ernest Mui Hua Cong William H. Witola Alexandre Montpetit Stephen P. Muench John Sidney Jeff Alexander Alessandro Sette Michael E. Grigg Ajesh Maewal Rima McLeod 《Vaccine》2010
Toxoplasma gondii is an intracellular parasite that causes severe neurologic and ocular disease in immune-compromised and congenitally infected individuals. There is no vaccine protective against human toxoplasmosis. Herein, immunization of Ld mice with HF10 (HPGSVNEFDF) with palmitic acid moieties or a monophosphoryl lipid A derivative elicited potent IFN-γ production from Ld-restricted CD8+ T cells in vitro and protected mice. CD8+ T cell peptide epitopes from T. gondii dense granule proteins GRA 3, 6, 7, and Sag 1, immunogenic in humans for HLA-A02+, HLA-A03+, and HLA-B07+ cells were identified. Since peptide repertoire presented by MHC class I molecules to CD8+ T cells is shaped by endoplasmic reticulum-associated aminopeptidase (ERAAP), polymorphisms in the human ERAAP gene ERAP1 were studied and associate with susceptibility to human congenital toxoplasmosis (p < 0.05). These results have important implications for vaccine development. 相似文献
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Ho Yin Yip Wing Lun A. Mui Joseph W.Y. Lee Winky Wing Ki Fung Jocelyn M.T. Chan G. Chiu Maria Y.Y. Law 《Medical Dosimetry》2013,38(2):184-189
Performances of radiosurgery of intracranial lesions between cone-based Linac system and Tomotherapy-based system were compared in terms of dosimetry and time. Twelve patients with single intracranial lesion treated with cone-based Linac radiosurgery system from 2005 to 2009 were replanned for Tomotherapy-based radiosurgery treatment. The conformity index, homogeneity index (HI), and gradient score index (GSI) of each case was calculated. The Wilcoxon matched-pair test was used to compare the 3 indices between both systems. The cases with regular target (n = 6) and those with irregular target (n = 6) were further analyzed separately. The estimated treatment time between both systems was also compared. Significant differences were found in HI (p = 0.05) and in GSI (p = 0.03) for the whole group. Cone-based radiosurgery was better in GSI whereas Tomotherapy-based radiosurgery was better in HI. Cone-based radiosurgery was better in conformity index (p = 0.03) and GSI (p = 0.03) for regular targets, whereas Tomotherapy-based radiosurgery system performed significantly better in HI (p = 0.03) for irregular targets. The estimated total treatment time for Tomotherapy-based radiosurgery ranged from 24 minutes to 35 minutes, including 15 minutes of pretreatment megavoltage computed tomography (MVCT) and image registration, whereas that for cone-based radiosurgery ranged from 15 minutes for 1 isocenter to 75 minutes for 5 isocenters. As a rule of thumb, Tomotherapy-based radiosurgery system should be the first-line treatment for irregular lesions because of better dose homogeneity and shorter treatment time. Cone-based Linac radiosurgery system should be the treatment of choice for regular targets because of the better dose conformity, rapid dose fall-off, and reasonable treatment time. 相似文献
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Chi‐Kin Chung Wai‐Ka Hung Miranda Chi‐Mui Chan Yvonne Lau Kong‐Ling Mak Andrew Wai‐Chun Yip 《Surgical Practice》2001,5(4):142-145
Objective: Sentinel lymph node biopsy (SLNB) is a minimally invasive staging procedure for breast cancer. Results of the first 30 cases of SLNB performed at Kwong Wah Hospital, Hong Kong, were reviewed. Design: This feasibility study applied and assessed a new procedure in Chinese patients. The study was carried out at the Breast Centre, Kwong Wah Hospital, Hong Kong. Sentinel lymph node biopsy was performed with a blue dye technique alone. All patients had full axillary dissection after SLNB. Patients: Female patients with invasive carcinoma of breast and no clinical palpable axillary lymph node were included. Main outcome measures: Pathological results of both the SLN and the remaining axillary content were compared. Results and Conclusion: Sentinel lymph nodes were successfully biopsied in 83% of cases. Sensitivity was 75% and accuracy was 88%. With experience, sentinel lymph node biopsy is feasible in Chinese patients. 相似文献