There is some evidence to indicate an association between ABCB1 rs1045642T and colorectal cancer risk in Asians. Compared with the ABCB1 gene SNPs rs1045642, rs2032582 or rs3789243 alone, combined haplotypes of several SNPs might be a better marker to determine the genetic influence on the susceptibility to colorectal cancer among Caucasians.
Radiotherapy is commonly used to treat thoracic malignancies, but often causes severe lung injury. Currently there are no effective protective strategies against radiation-induced lung injury (RILI). This study aimed to evaluate the ability of an angiogenesis antagonist, Endostar, against RILI, and the underlying mechanism in a mouse model. A total of 108 C57BL/6 female mice were randomized into 4 groups (n=27): i) control group; ii) Endostar group, animals were administered 7.75 ml/kg Endostar through intraperitoneal injection; iii) irradiation group, RILI was induced by exposing the animals to a single external irradiation on the thoraces (6 MV X-ray, 12 Gy); and iv) irradiation plus Endostar group, animals were subjected to Endostar treatment and irradiation as in groups 2 and 3. A total of 3 animals from each of the 4 groups were sacrificed at 1, 6, 12, 24 and 72 h and at 2, 4, 8 and 24 weeks following treatment. Clinical signs and pathology of RILI were examined. The expression of transforming growth factor-β 1 (TGF-β1) in lungs was analyzed by real-time quantitative polymerase chain reaction (RT-QPCR) and immunohistochemistry. Compared with the control group, irradiation induced evident interstitial edema and a significant increase in inflammatory cells in the lungs (P<0.05). Correlated with these changes, a notable increase in TGF-β1 mRNA level and a robust increase in TGF-β1 immunoreactivity were observed in lung tissues in a time-dependent manner following irradiation (P<0.05). Endostar administration effectively attenuated the magnitude of the increase in inflammatory cells as well as the elevation of TGF-β1 expression in lung tissues after RILI (P<0.05). In conclusion, radiation induced an increased expression of the inflammatory mediator TGF-β1 and the associated pathogenesis in the lung, while Endostar was able to at least partially attenuate RILI through downregulating the expression of TGF-β1 in mice. Our findings suggest that Endostar may be a novel protective agent against RILI.
SummaryPublished data on the association between the transforming growth factor B1 (TGF-B1) gene 509C/T polymorphism and gastric cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis of the TGFB1-509C/T polymorphism (with 2130 cases and 2374 controls) from seven published case-control studies was performed. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the codominant model, the dominant model, and the recessive model. In the overall analysis, the T allele was significantly associated with susceptibility to gastric cancer in the recessive model (TT vs. CC+CT) (TT vs. CC+CT: OR = 1.35, 95% CI: 1.10-1.66, P = 0.10 for heterogeneity) when all the included studies were pooled into the meta-analysis. In the stratified analysis by country, the T allele was also found to be significantly associated with increased gastric cancer risk in the recessive model (TT vs. CC+CT) in Chinese studies and in T versus C in the Indian study. In conclusion, this meta-analysis supports the TGFB1-509T polymorphism as a susceptibility factor for gastric cancer.
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