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71.
Poly (ADP-ribose) polymerase (PARP) is a key molecule in the DNA damage response (DDR), which is a major target of both chemotherapies and radiotherapies. PARP inhibitors therefore comprise a promising class of anticancer therapeutics. In this study, we evaluated the efficacy of the PARP inhibitor olaparib, and also sought to identify the mechanism and predictive marker associated with olaparib sensitivity in head and neck cancer (HNC) cells. A total of 15 HNC cell lines, including AMC HNC cells, were tested. AMC-HN3 and HN4 exhibited stronger responses to olaparib. Among cisplatin-resistant cell lines, only AMC HN9-cisR cells were significantly suppressed by olaparib. We found that basal poly (ADP-ribose) (PAR) levels, but not PARP-1 levels, correlated with olaparib sensitivity. AMC-HN3 and HN4 cells exhibited higher basal levels of NF-κB that decreased significantly after olaparib treatment. In contrast, apoptotic proteins were intrinsically expressed in AMC-HN9-cisR cells. As interference with p53 expression led to NF-κB reactivation, we concluded that elevated basal PAR and NF-κB levels are predictive of olaparib responsiveness in HNC cells; in addition, olaparib inhibits HNC cells via PAR–p53–NF-κB interactions. 相似文献
72.
Yunji Hwang Kyu Eun Lee Elisabete Weiderpass Young Joo Park Young Jun Chai Hyungju Kwon Do Joon Park BeLong Cho Ho-Chun Choi Daehee Kang Sue K. Park 《PloS one》2016,11(3)
Background
This study evaluated the effects of acute high-dose and chronic lifetime exposure to alcohol and exposure patterns on the development of differentiated thyroid cancer (DTC).Methods
The Thyroid Cancer Longitudinal Study (T-CALOS) included 2,258 DTC patients (449 men and 1,809 women) and 22,580 healthy participants (4,490 men and 18,090 women) who were individually matched by age, gender, and enrollment year. In-person interviews were conducted with a structured questionnaire to obtain epidemiologic data. Clinicopathologic features of the patients were obtained by chart reviews. Odds ratios (ORs) and 95% confidence intervals (95%CI) were estimated using conditional regression models.Results
While light or moderate drinking behavior was related to a reduced risk of DTC, acute heavy alcohol consumption (151 g or more per event or on a single occasion) was associated with increased risks in men (OR = 2.22, 95%CI = 1.27–3.87) and women (OR = 3.61, 95%CI = 1.52–8.58) compared with never-drinkers. The consumption of alcohol for 31 or more years was a significant risk factor for DTC for both men (31–40 years: OR = 1.58, 95%CI = 1.10–2.28; 41+ years: OR = 3.46, 95%CI = 2.06–5.80) and women (31–40 years: OR = 2.18, 95%CI = 1.62–2.92; 41+ years: OR = 2.71, 95%CI = 1.36–5.05) compared with never-drinkers. The consumption of a large amount of alcohol on a single occasion was also a significant risk factor, even after restricting DTC outcomes to tumor size, lymph node metastasis, extrathyroidal extension and TNM stage.Conclusion
The findings of this study suggest that the threshold effects of acute high-dose alcohol consumption and long-term alcohol consumption are linked to an increased risk of DTC. 相似文献73.
Induction of MiR-21 by Stereotactic Body Radiotherapy Contributes to the Pulmonary Fibrotic Response
Ok-Seon Kwon Keun-Tae Kim Eunioo Lee Myoungjae Kim Seo-Hyun Choi Henghong Li Albert J. Fornace Jr. Jae-Ho Cho Yun-Sil Lee Ji-Seon Lee Yoon-Jin Lee Hyuk-Jin Cha 《PloS one》2016,11(5)
Radiation-induced lung fibrosis, the most serious effect of lung cancer radiotherapy on normal tissue, remains a major technical obstacle to the broader application of radiotherapy to patients with lung cancer. This study describes the use of an image-guided irradiation system in mice mimicking stereotactic body radiotherapy (SBRT) to examine the molecular features of chronic fibrotic response after radiation injury. MicroRNA (miR) array analysis of injured pulmonary tissue identified a set of miRs whose expression was significantly increased in damaged lung tissue. In particular, miR-21 expression was increased at the radiation injury site, concurrent with collagen deposition. Although the inhibition of miR-21 by its specific inhibitor anti-miR-21 only marginally affected endothelial-mesenchymal transition (EndMT) in lung endothelial cells, this inhibition significantly reduced collagen synthesis in lung fibroblasts. Furthermore, ectopic expression of miR-21 was sufficient to promote a fibrotic response in lung fibroblasts, enhancing Smad2 phosphorylation concurrent with Smad7 downregulation. These findings indicate that the induction of miR-21 expression is responsible for fibrotic responses observed in mesenchymal cells at the injury site through the potentiation of TGF-β signaling. Local targeting of miR-21 at the injured area could have potential therapeutic utility in mitigating radiation-induced lung fibrosis. 相似文献
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Ying-Hua Li Yong-Nan Xu Zi-Li Lin JeongWoo Kwon Xiang-Shun Cui 《Animal cells and systems.》2016,20(5):253-259
The Arp2/3 complex, which nucleates actin filaments, comprises a stable assembly of seven-protein subunits including two actin-related proteins (Arp2 and Arp3). Previous work showed that Arp2/3 binds to the sides of actin filaments and is concentrated at the leading edges of motile cells. In the present study, we show that the Arp2/3 complex is critical for cytokinesis during early embryonic development in porcine parthenotes. The Arp2/3 complex is concentrated at the cortex of each cell at the 1-, 2-, and 4-cell stages, and at the periphery at the morula stage. The amount of Arp2/3 significantly decreased at the blastocyst stage in parthenogenetically activated porcine embryos. Inhibition of the Arp2/3 complex in the pig embryos by the Arp2/3-specific inhibitor CK666 resulted in abnormal cell division, a decrease in developmental rate and total cell numbers, and an increase in the ratio of trophectoderm cell number to inner cell mass number in blastocyst-stage embryos. In addition, 4-cell stage embryos subjected to CK666 treatment exhibited significantly decreased expression of ZGA genes (Pou5f1, Sox2, and Nanog), suggesting that the Arp2/3 complex plays an important role in early porcine embryo development. Thus, our data demonstrate that the Arp2/3 complex is required for early embryonic development in pigs and appears to regulate the expression of pluripotency genes. 相似文献
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Md Ruhul Amin Nabanita Paul Nancy Md Ramiz Uddin Miah Md Giashuddin Miah Ohseok Kwon Sang Jae Suh 《Entomological Research》2019,49(5):223-228
The study was conducted with the aim of furthering our understanding of seasonality in the population dynamics and infestation rates of the fruit fly Bactrocera spp. in sweet gourd (Cucurbita moschata) during winter and summer in 2017. We also investigated the effects of using methyl eugenol traps on fly abundance and infestation. Two fruit fly species, namely, B. cucurbitae and B. dorsalis, were present in the sweet gourd field, and we observed fluctuations in their abundance. Compared to B. dorsalis, B. cucurbitae was significantly more abundant in both winter and summer. Infestation level was found to be the highest in fields lacking methyl eugenol traps in both seasons. Fruit fly larval population per infested fruit was higher in summer than in winter. Fly abundance was significantly and positively correlated with mean temperature and rainfall but significantly and negatively correlated with light intensity. Relative humidity was insignificantly but positively correlated with fly abundance. The temperature, light intensity, relative humidity, and rainfall individually explained 48.9, 24.1, 0.8, and 1.6% of variation in fruit fly abundance, respectively. The combined effect of the weather parameters on fruit fly abundance was 75.4% and was significant predictor of fruit fly abundance. 相似文献
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