Apurinic/apyrimidinic endonuclease (APE1), a bifunctional AP endonuclease/redox factor, is important in DNA repair and redox signaling, may be associated with radioresistance. Here we investigate whether targeted inhibition of APE1 can sensitize tumor cells to irradiation in vitro and in vivo. We first constructed chimeric adenoviral vector Ad5/F35 carrying human APE1 siRNA (Ad5/ F35-APE1 siRNA). The infectivity of chimeric Ad5/F35 to LOVO colon cancer cells was greater than that of Ad5. APE1 was strongly expressed and nuclear factor kB (NF-kB), a downstream molecule of APE1, known as a radioresistance factor, was constitutively active in LOVO cells. Infection of LOVO cells with Ad5/F35-APE1 siRNA resulted in a dose-dependent decrease of APE1 protein and AP endonuclease activity in vitro. Ad5/F35-APE1 siRNA significantly enhanced sensitivity of LOVO cells to irradiation in clonogenic survival assays, associated with increased cell apoptosis. The APE1 expression in LOVO cells was induced by irradiation in a dose-dependent manner, accompanied with the enhancement of DNA-binding activity of NF-kB and Ad5/F35-APE1 siRNA effectively inhibited constitutive and irradiation-induced APE1 expression and NF-kB activation. In a subcutaneous nude mouse colon cancer model, Ad5/F35-APE1 siRNA (5 Â 10 8 IU, intratumoral injection) inhibited the expression of APE1 protein in LOVO xenografts, and significantly enhanced inhibition of tumor growth by irradiation. In conclusion, APE1 may be involved as one of the radioresistance factors, and targeted inhibition of APE1 shows an effective means of enhancing tumor sensitivity to radiotherapy.
The objective of this prospective, randomized, controlled trial, conducted from May 2002 to December 2007, was to compare post-operative anastomotic leakage and stricture formation following layered manual versus stapler oesophagogastric anastomosis in patients who underwent resection of oesophageal or gastric cardia carcinoma. Patients (n = 516) were randomized to receive either layered manual or circular stapled oesophagogastric anastomosis. Mean follow-up time was > 12 months. Anastomotic leakage occurred in one (0.4%) patient in the layered group and six (2.2%) in the stapler group; no statistically significant between-group difference. After operation, two (0.8%) patients in the layered group and 13 (5.0%) in the stapler group developed a benign oesophageal stricture; the difference between the groups was statistically significant. Compared with stapler anastomosis, layered manual anastomosis may significantly reduce the incidence of anastomotic strictures. This method is easy to apply and could be used as an alternative procedure for oesophagogastric anastomosis after resection for oesophageal or cardia carcinoma.
In this study, PCR-SSCP analysis was used to identify genetic variation in IGFBP-3 gene in Chinese Merino and Kazakh sheep. A PCR product of 178 bp corresponding to partial intron1 illustrated three unique binding patterns by SSCP analysis. Frequencies of the genotype AA, AB, BB and allele A, B in Chinese Merino sheep were 0.70, 0.24, 0.06, and 0.82, 0.18 respectively , and they were 0.87, 0.13, 0.00, and 0.93, 0.07 respectively in Kazaka sheep. Sequence analysis revealed a G/T transversion at position 122 of the fragment. This polymorphic locus of IGFBP-3 gene was at Hardy-Weinberg dis-equilibrium (P<0.01) in the two breeds. Different genotypes slightly affected several wool traits of Chinese Merino sheep. The individuals of genotype AA, AB, and BB had no significant difference in post-shearing weight and clean wool rate. Sta-ple length (SL) was decreased with the genotype of AA, AB, and BB, and the difference between AA and AB was significant (P<0.01). Greasy fleece weight (GFW) and follicle density in individuals of genotype AA was significantly lower than that in individuals of genotype AB (P<0.01) and BB (P<0.05); Average fiber diameter (AFD) in individuals of genotype AA was significantly higher than that in individuals of genotype AB (P<0.01) and BB (P<0.05).
Abstract. The 14 April 2010 M s = 7.1 Yushu Earthquake (YE) had caused severe damage in the Jiegu township, the residential centre of Yushu Tibetan Autonomous Prefecture, Qinghai Province, China. In view of the fragile geological conditions after YE, risk assessment of secondary geohazards becomes an important concern for the reconstruction. A quantitative methodology was developed to assess the risk of debris flow by taking into account important intensity information. Debris flow scenarios were simulated with respect to rainfall events with 10, 50 and 100 yr returning period, respectively. The possible economic loss and fatalities caused by damage to buildings were assessed both in the settlement area and in the low hazard settlement area regarding the simulated debris flow events. Three modelled building types were adopted, i.e. hollow brick wood (HBW), hollow brick concrete (HBC) and reinforced concrete (RC) buildings. The results suggest that HBC structure achieves a good balance for the cost-benefit relationship compared with HBW and RC structures and thus could be an optimal choice for most of the new residential buildings in the Jiegu township. The low hazard boundary presents significant risk reduction efficiency in the 100 yr returning debris flow event. In addition, the societal risk for the settlement area is unacceptable when the 100 yr returning event occurs but reduces to ALARP (as low as reasonably practicable) level as the low hazard area is considered. Therefore, the low hazard area was highly recommended to be taken into account in the reconstruction. Yet, the societal risk might indeed approach an unacceptable level if one considers that YE has inevitably increased the occurrence frequency of debris flow. The quantitative results should be treated as a perspective for the reconstruction rather than precise numbers of future losses, owing to the complexity of the problem and the deficiency of data.
We performed thymectomy on the immature and mature male mice and made a quantitative assay of various germ cells of the seminiferous epithelium in the testis with Image Analyser System 35 days following thymectomy. The results indicated that as compared with the control group, all germ cells of the spermatogenesis lineage decreased in the immature group and in the mature group after thymectomy. The present study showed that thymus and its hormone stimulated not only the mitotic division, but also the meiotic division of germ cells during spermatogenesis, suggesting that thymus-sexual axis may play an important role in the process of spermatogenesis in the testis.
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