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Effect of pEGFP-survivin on GBC-SD cell growth and chemotherapy sensitivity

Hanbin SHEN MD, Bin ZHANG MBA, Song ZHAO BM, Qichang ZHENG MD, Jianping GONG MD, Xiaotang CAI BM,

《医学前沿（英文）》 2009年第3卷第4期页码 485-490 doi: 10.1007/s11684-009-0089-3

摘要： This paper is aimed to investigate the effect of survivin shRNA on chemotherapy resistance in human gallbladder carcinoma GBC-SD cells. The viability of human gallbladder carcinoma GBC-SD, GBC-SD/enhanced green fluorescent protein (EGFP), and GBC-SD/survivin cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and mRNA and protein of survivin were tested by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. After the cells were treated with cisplatin (DDP) (3.0 μg/mL) for the same time, cell survival rate and IC was detected with MTT, cell apoptosis was detected with fluorescence-activated cell sorting (FACS), and the nuclear alteration was observed by TdT-mediated deoxyuridine triphosphate nick end labeling (TUNEL). In addition, caspase-3 activity was detected by using colorimetric method. Cell viability was decreased significantly in GBC-SD/survivin cells, and survivin expression was decreased significantly (mRNA and protein of survivin were decreased by 74.7% and 71.5%, respectively). After treatment with DDP, cell survival rate and IC was decreased significantly (2.03±0.24 μg/mL) in GBC-SD/survivin cells, while apoptotic rate (84.3%) was elevated significantly as compared with the other two groups. There were brown apoptotic nuclei in all the cells. Caspase-3 activity in all the cells was increased at first and then decreased, but the caspase-3 activity in GBC-SD/survivin cells was significantly higher than the other two groups. The survivin shRNA could down-regulate the expression of survivin in GBC-SD cells significantly and improve the sensibility to chemotherapy.

关键词： survivin shRNA chemotherapy sensibility GBC-SD

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Reproductive toxicity study with a novel deoxyguanosine analogue (Metacavir) in pregnant SD rats

null

《医学前沿（英文）》 2015年第9卷第1期页码 82-89 doi: 10.1007/s11684-015-0376-0

摘要：

Our preliminary studies demonstrated that Metacavir has potential to become a new anti-HBV agent. The main targets of the toxic effects of Metacavir, in rhesus monkeys, were gastrointestinal tracts, liver, blood, and kidneys, which were not related to mitochondrial effects. In this study, the maternal toxicity, embryo-fetal developmental toxicity and teratogenicity were studied in pregnant Sprague-Dawley rats after intragastric administration of Metacavir (200, 100, 50, 0 mg/kg body weight) during the first 6–15 days of pregnancy. Slower weight gain was observed in 5 out of 21 rats subjected to a 200 mg/kg dose, as well as 2 out of 20 subjected to a 100 mg/kg dose. Compared with the solvent control group, the calibration weight gain in the 200 mg/kg and 100 mg/kg dosage groups respectively, during first 6–20 pregnant days were significantly different (P<0.01, P<0.05). Significant dose related adverse effects to other reproductive parameters were not seen in F0 and F1, but the number of stillbirths in high dose group showed notably difference compared with the control group (P<0.05), while the litter incidence showed no difference. No Metacavir-associated pathological changes were observed. The present research indicated that at a dose of 200 mg/(kg·d) (i.e., 40 times the effective dose in rats), Metacavir shows some maternal toxicity to SD rats. The embryotoxicity in the 200 mg/kg group encompass decreased fetal body weight, and higher fetal mortality rates, compared with the control group. However, the litter incidence showed no statistical difference. All the treated rats displayed normal bone development, no teratogenicity and without adverse effects on fetal development, thus indicating that below a dose of 200 mg/(kg·d) there is no teratogenic side effects.

关键词： deoxyguanosine analogue Metacavir pregnancy maternal toxicity embryo toxicity teratogenicity