西咪替丁的应用进展

综述了近年来国内外报道的H2受体抗拮剂－西咪替丁应用于除治疗消化性溃疡以外的其他疾病的进展情况，以其为临床用药提供参考。     

血清硒浓度与口腔鳞癌相关性研究

分析了１９９４￣１９９５年在浙江医科大学附属第一医院门诊的口腔鳞癌患者的血清的硒浓度，结果表明口腔鳞癌患者血清硒浓度极显著低于正常人群，而手术后患者血清硒浓度又极显著高于手术前患者。     

Synthesis and Crystal Structure of 3,3′-(Hexane-1,6-diyl)bis(1-acetyl-5,5-dimethylhydantoin),a New Inducer of Differentiation

1 INTRODUCTION Hexamethylenebis[acetamide] (HMBA) is an effective agent in phaseⅡclinical trial[1] that induces differentiation of certain types of tumors to nonmalignant phenotypes. In an attempt to discover more efficient inducers, a number of derivatives of HMBA have been synthesized and evaluated in vitro[2, 3]. The results proved that increasing the number of functional groups could enhance the anticancer activity. In addition, it was evident that compounds with six methylene i…     

Toward breast cancer resistance protein (BCRP) inhibitors: design, synthesis of a series of new simplified fumitremorgin C analogues

In this study, we report the design and synthesis of a series of new simplified fumitremorgin C analogues. The preliminary biological study indicated some of these simplified fumitremorgin C might be developed into breast cancer resistance inhibitors.     

2-Deoxy-d-glucose Promotes Buforin IIb-Induced Cytotoxicity in Prostate Cancer DU145 Cells and Xenograft Tumors

Inhibition of the glycolytic pathway is a critical strategy in anticancer therapy because of the role of aerobic glycolysis in cancer cells. The glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) has shown potential in combination with other anticancer agents. Buforin IIb is an effective antimicrobial peptide (AMP) with broad-spectrum anticancer activity and selectivity. The efficacy of combination treatment with 2-DG and buforin IIb in prostate cancer remains unknown. Here, we tested the efficacy of buforin IIb as a mitochondria-targeting AMP in the androgen-independent human prostate cancer cell line DU145. Combining 2-DG with buforin IIb had a synergistic toxic effect on DU145 cells and mouse xenograft tumors. Combination treatment with 2-DG and buforin IIb caused stronger proliferation inhibition, greater G1 cell cycle arrest, and higher apoptosis than either treatment alone. Combination treatment dramatically decreased L-lactate production and intracellular ATP levels, indicating severe inhibition of glycolysis and ATP production. Flow cytometry and confocal laser scanning microscopy results indicate that 2-DG may increase buforin IIb uptake by DU145 cells, thereby increasing the mitochondria-targeting capacity of buforin IIb. This may partly explain the effect of combination treatment on enhancing buforin IIb-induced apoptosis. Consistently, 2-DG increased mitochondrial dysfunction and upregulated Bax/Bcl-2, promoting cytochrome c release to initiate procaspase 3 cleavage induced by buforin IIb. These results suggest that 2-DG sensitizes prostate cancer DU145 cells to buforin IIb. Moreover, combination treatment caused minimal hemolysis and cytotoxicity to normal WPMY-1 cells. Collectively, the current study demonstrates that dual targeting of glycolysis and mitochondria by 2-DG and buforin IIb may be an effective anticancer strategy for the treatment of some advanced prostate cancer.     

BRCA1 mutation screening using restriction endonuclease fingerprinting-single-strand conformation polymorphism in an automated capillary electrophoresis system

Efficient mutation scanning techniques are needed for the rapid detection of novel disease-associated mutations and rare-sequence variants of putative importance. The large size of the breast cancer 1 gene (BRCA1) and the many mutations found throughout its entire coding sequence make screening for mutations in this gene particularly challenging. We have developed a method for screening exon 11 of the BRCA1 gene based on restriction enzyme digestion of fluorescence-labeled polymerase chain reaction (PCR) products followed by single-strand conformation polymorphism (SSCP) using an automated capillary electrophoresis system, denoted capillary restriction endonuclease fingerprinting (REF)-SSCP electrophoresis. Using this strategy on a control set of samples, we were able to detect 17 of 18 known sequence alterations. The method was then applied to screen 73 Norwegian females with family histories of breast and/or ovarian cancer. A total of 172 sequence alterations were detected, including substitutions, insertions, and deletions. One novel substitution of unknown function was identified. Sequencing of all samples negative in the capillary REF-SSCP system gave no additional mutations confirming the high sensitivity of the described methodology. Capillary REF-SSCP electrophoresis appeared as a technically convenient technique, requiring amplification of fewer PCR fragments than traditional SSCP. The novel strategy allows high-throughput mutation scanning without radioactive labeling and polyacrylamide gel electrophoresis (PAGE).     

Expression and Characterization of Catalytic Domain of T Cell Protein Tyrosine Phosphatase（△TC-PTP） —— Immunohistochemical Study of △TC-PTP Expression in Non-small Cell Lung Carcinomas

This study objective was to express and characterize the catalytic domain of the human T cell protein tyrosine phosphatase（△TC-PTP） and to study immunohistochemically the expression of △TC-PTP in human non-small cell lung cancers. △TC-PTP gene was PCR amplified with the cDNA of human TC-PTP as template, and cloned into the pT7 expression vector. The recombinant pT7-△TC-PTP was expressed in E. coli Rosetta （ DE3 ） host cells and puri- fied. The enzymatic characteristics of △TC-PTP including enzyme activity and kinetics assay were measured. The antiserum was prepared by immunizing rabbit with the purified recombinant △TC-PTP. Rabbit polyclonal antibody against △TC-PTP was purified by PVDF immobilized antigen affinity chromatography. Immunohistochemical staining of lung cancer tissues was performed with antibody against △TC-PTP protein. △TC-PTP gene was correctly cloned, expressed, and purified. The recombinant △TC-PTP had a highly catalytic activity of PTPase. Squamous cell lung carcinoma showed a significantly higher expression rate of △TC-PTP （76. 92%, 10/13 ） than adenocarcinoma （57.14%, 4/7） and normal lung tissue（20%, 1/5 ）. This study represents the first demonstration that △TC-PTP is highly expressed in human squamous cell lung carcinomas. In addition, this study provides an important basis for further studying the biological function of TC-PTP and its relationship with lung carcinomas and other diseases.     

Photokilling Squamous Carcinoma Cells SCCVII with Ultrafine Particles of Selected Metal Oxides

The ability of ultrafine particles of TiO₂, WO₃ and iron-doped TiO₂ to kill cancer cells in the presence of UV irradiation was investigated. The best photokilling effect on carcinoma cells SCVII cultured in vitro showed iron-doped TiO₂ ultrafine particles synthesized by the sol-gel procedure with starting chemicals Ti(IV)-isopropoxide and anhydrous Fe(II)-acetate. It was found that a small particle size and high dispersity influenced citotoxicity and photocatalytic efficiency. The remarkable photokiling effect of highly iron-doped TiO₂ ultrafine particles (the molar ratio Fe/Ti = 0.136) in the presence of UV irradiation was observed. The influence of ultrafine metal oxide particles on the inhibition of cancer cell proliferation was measured using a ³H-thymidine incorporation test. The possible mechanism involved in the photokilling of carcinoma cells with ultrafine particles of selected metal oxides was discussed.     

MTT法测定稀土离子对BEL-7402及K562细胞的毒性及增殖毒性

用MTT法测定稀土离子在不同浓度、不同培养液中,与BEL 7402和K562细胞作用不同时间,对细胞的毒性和增殖毒性。结果表明,在含10%小牛血清培养液中,仅个别稀土离子在较高浓度时对BEL 7402细胞增殖有较弱的抑制作用;对于K562细胞,稀土离子在低浓度时对细胞增殖即表现出较强的抑制作用(P<0.05)。当培养液不含小牛血清时,较低浓度的稀土离子即可抑制BEL 7402细胞的增殖(P<0 05)。     

2型糖尿病患者血清钙镁与甲状腺激素含量变化及临床意义

为了监测 2型糖尿病人血清钙、镁和甲状腺激素含量 ,分析其临床意义及相关性 ,应用放射免疫分析法测定了 1 1 5例 2型糖尿病及 1 5 0例健康人血清甲状腺激素含量。同时用美国杜邦RXL自动生化仪测定了其血清钙、镁含量。结果表明 ,在 2型糖尿病伴有明显并发症者血镁、FT3水平明显降低 (P <0 0 5 ) ,钙镁两种元素与甲状腺激素水平无明显相关性。 2型糖尿病患者适当补镁对预防其并发症是有益的 ,测定FT3 等可作为判断 2型糖尿病严重程度和估计预后的参考指标。