The combination of gene therapy and radiation is a promising new treatment for cancer. This study aimed to clarify the synergistic effect of targeted oncolytic adenovirus (radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand) and radiotherapy on colorectal cancer cells and elucidate the mechanisms of the underlying antitumor activity. Viability, cell cycle status, and apoptosis of treated colorectal cancer cells were determined via MTT and flow cytometric assays. The molecular mechanism underlying apoptotic pathway activation was elucidated through Western blot analysis of caspase-8, caspase-3, and PARP proteins. Combination treatment with radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand and radiotherapy displayed significantly greater antitumor activity than either of the monotherapies. The primary mechanism behind the antitumor activity in the SW480 and Lovo colorectal cancer cell lines was apoptosis induction through the caspase pathway and G1 phase arrest. In an SW480 xenograft model of colorectal cancer, the combination therapy achieved a significantly greater reduction in tumor volume than the monotherapies. Overall, in this study, we demonstrate that the oncolytic radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand construct can sensitize human colorectal cancer cells to radiation-induced apoptosis both in vitro and in vivo. Therefore, our findings point toward a novel synergistic approach to colorectal cancer treatment.
Abstract:The purpose of this study is to improve the cementing quality of shale gas well by mud cake solidification, as well as to provide the better annular isolation for its hydraulic fracturing development. Based on the self-established experimental method and API RP 10, the effects of mud cake solidifiers on the shear strength at cement-interlayer interface (SSCFI) were evaluated. After curing for 3, 7, 15 and 30 days, SSCFI was remarkably improved by 629.03%, 222.37%, 241.43% and 273.33%, respectively, compared with the original technology. Moreover, the compatibility among the mud cake solidifier, cement slurry, drilling fluid and prepad fluid meets the safety requirements for cementing operation. An application example in a shale gas well (Yuanye HF-1) was also presented. The high quality ratio of cementing quality is 93.49% of the whole well section, while the unqualified ratio of adjacent well (Yuanba 9) is 84.46%. Moreover, the cementing quality of six gas-bearing reservoirs is high. This paper also discussed the mechanism of mud cake solidification. The reactions among H 3 AlO 4 2-and H 3 SiO 4 -from alkali-dissolved reaction, Na + and H 3 SiO 4 -in the mud cake solidifiers, and Ca 2+ and OH -from cement slurry form the natrolite and calcium silicate hydrate (C-S-H) with different silicate-calcium ratio. Based on these, SSCFI and cementing quality were improved.
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