Cancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia‐responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR‐124 and miR‐144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3′UTR of PIM1. Functional study showed that miR‐124 or miR‐144 overexpression can inhibit hypoxia‐induced autophagy and enhance radiosensitivity at least via downregulating PIM1. Therefore, hypoxia induced miR‐124 and miR‐144 downregulation may contribute to a prosurvival mechanism of prostate cancer cells to hypoxia and irradiation at least through attenuated suppressing of PIM1. This finding presents a potential therapeutic target for prostate cancer.
The tumor-suppressive let-7 family of microRNAs (miRNAs) has been previously identified to induce cell apoptosis, proliferation‑inhibition and suppression of the self‑renewal capacities of cancer stem cells (CSCs). However, let‑7‑mediated sensitization of tumors to radiation treatment remains to be investigated fully in triple negative breast cancer (TNBC), of which the clinical treatment is challenging. The inhibitory effect of let‑7 miRNAs on the self‑renewal ability of CSCs from TNBC was investigated. It was identified that radiation inhibited the self‑renewal ability of TNBC stem cells by inhibiting cyclin D1 and protein kinase B (Akt1) phosphorylation. Let‑7d stimulates radiation‑induced tumor repression, exerting synergistic effects with radiotherapy on stem cell renewal. Through western blotting, immunofluorescence and a luciferase assay, it was identified that reduced cyclin D1/Akt1/wingless type MMTV integration site family member 1 (Wnt1) signaling activity accounts for the let‑7‑induced radiation sensitization. Let‑7 directly inhibits cyclin D1 expression, resulting in low phosphorylation of Akt1, which is critical for the let‑7‑induced inhibition of mammosphere numbers. The let‑7d‑induced Akt1 inhibition contributed to tumor repression, with similar results to those obtained with Akt inhibitors. Furthermore, it was identified that the inhibition of Wnt1 is critical for the functioning of let‑7d, and that addition of recombinant Wnt1 abolished the effects of let‑7d on sensitization to radiotherapy. Let‑7d is suggested to be a promising therapeutic agent in the treatment of TNBC by targeting CSCs and sensitizing tumors to radiotherapy via inhibition of cyclin D1/Akt1/Wnt1 signaling.
Background As a rare benign lung tumour, pulmonary sclerosing pneumocytoma (PSP) is often misdiagnosed as atypical peripheral lung cancer (APLC) on routine imaging examinations. This study explored the value of enhanced CT combined with texture analysis to differentiate between PSP and APLC. Methods Forty-eight patients with PSP and fifty patients with APLC were retrospectively enrolled. The CT image features of the two groups of lesions were analysed, and MaZda software was used to evaluate the texture of CT venous phase thin-layer images. Independent sample t-test, Mann–Whitney U tests or χ2 tests were used to compare between groups. The intra-class correlation coefficient (ICC) was used to analyse the consistency of the selected texture parameters. Spearman correlation analysis was used to evaluate the differences in texture parameters between the two groups. Based on the statistically significant CT image features and CT texture parameters, the independent influencing factors between PSP and APLC were analysed by multivariate logistic regression. Extremely randomized trees (ERT) was used as the classifier to build models, and the models were evaluated by the five-fold cross-validation method. Results Logistic regression analysis based on CT image features showed that calcification and arterial phase CT values were independent factors for distinguishing PSP from APLC. The results of logistic regression analysis based on CT texture parameters showed that WavEnHL_s-1 and Perc.01% were independent influencing factors to distinguish the two. Compared with the single-factor model (models A and B), the classification accuracy of the model based on image features combined with texture parameters was 0.84 ± 0.04, the AUC was 0.84 ± 0.03, and the sensitivity and specificity were 0.82 ± 0.13 and 0.87 ± 0.12, respectively. Conclusion Enhanced CT combined with texture analysis showed good diagnostic value for distinguishing PSP and APLC, which may contribute to clinical decision-making and prognosis evaluation.
The aim of the current study was to investigate the role of polymorphisms in DNA repair pathways on the clinical outcome of gastric cancer patients treated with platinum-based chemotherapy. A total of 380 gastric cancer patients treated with platinum-based chemotherapy were included in the present study. The genotypes of ERCC1 rs11615 (Asn118Asn) and rs3212986 (*197G>T), ERCC2 rs1799793 (Asn312Asp) and rs13181 (Lys751Gln), NBN rs1805794 (Gln185Gln) and rs1063054 (*1209A>C), RAD51 rs1801321 (−61G>T) and rs12593359 (*502T>G), and XRCC3 rs861539 (Thr241Met) were determined by polymerase chain reaction-restriction fragment length polymorphism, according to the manufacturer's instructions. The TC+CC genotypes of ERCC1 rs11615 and GA+AA genotypes of ERCC2 rs1799793 were found to be associated with improved response to chemotherapy, with an adjusted odds ratio of 1.66 (95% CI, 1.07–2.56) and 1.61 (95% CI, 1.05–2.49), respectively. Based on the results of Cox analysis, patients with TC+CC genotypes of ERCC1 rs11615 and GA+AA genotypes of ERCC2 rs1799793 exhibited a significantly decreased risk of mortality, with hazard ratios of 1.71 (95% CI, 1.06–2.72) and 1.97 (95% CI, 1.28–3.03), respectively. In conclusion, these results suggest that ERCC1 rs11615 and ERCC2 rs1799793 in the DNA repair pathways may be used as predictive factors of the clinical outcome in gastric cancer patients.
The observer performances for detection of small solitary non-calcified pulmonary nodules by radiologists with varying degrees of experience were comparable between the 2, 3 and 5 megapixel monochrome LCDs.
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