Purpose To 1) describe textural features from diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) maps that can distinguish low-grade bladder cancer from high-grade one, and 2) propose a radiomics-based strategy for cancer grading using texture features. Materials and Methods 61 patients with bladder cancer (29 in high- and 32 in low-grade groups) were enrolled in this retrospective study. Histogram- and gray-level co-occurrence matrix (GLCM)-based radiomics features were extracted from cancerous volumes of interest (VOIs) on DWI and corresponding ADC maps of each patient acquired from 3.0T MR. Mann-Whitney U test was applied to select features with significant difference between low-and high-grade groups (p<0.05). Then support vector machine with recursive feature elimination (SVM-RFE) and classification strategy was adopted to find an optimal feature subset and then to establish a classification model for grading. Results A total 102 features were derived from each VOI and among them, 47 candidate features were selected, which showed significant inter-group difference (p<0.05). By the SVM-RFE method, an optimal feature subset including 22 features was further selected from candidate features. The SVM classifier using the optimal feature subset achieved the best performance in bladder cancer grading, with an area under the receiver operating characteristic curve, accuracy, sensitivity and specificity of 0.861, 82.9%, 78.4% and 87.1%, respectively. Conclusion Textural features from DWI and ADC maps can reflect the difference between low- and high-grade bladder cancer, especially those GLCM features from ADC maps. The proposed radiomics strategy using these features, combined with the SVM classifier, may better facilitate image-based bladder cancer grading preoperatively.

3D radiomic signatures derived from T2WI and its high-order derivative maps could reflect muscular invasiveness of bladder cancer, and the proposed strategy can be used to facilitate the preoperative prediction of muscular invasiveness in patients with bladder cancer.

BackgroundPrevious studies had showed that Apelin 13 could protect against apoptosis induced by ischemic/reperfusion (I/R). However, the mechanisms whereby Apelin 13 protected brain I/R remained to be elucidated. The present study was designed to determine whether Apelin 13 provided protection through AMPK/GSK-3β/Nrf2 pathway.MethodsIn vivo, the I/R model was induced and Apelin 13 was given intracerebroventricularly 15 min before reperfusion. The neurobehavioral scores, infarction volumes, and some cytokines in the brain were measured. For in vitro study, PC12 cells were used. To clarify the mechanisms, proteases inhibitors or siRNA were used. Protein levels were investigated by western blotting.ResultsThe results showed that Apelin 13 treatment significantly reduced infarct size, improved neurological outcomes, decreased brain edema, and inhibited cell apoptosis, oxidative stress, and neuroinflammation after I/R. Apelin 13 significantly increased the expression of Nrf2 and the phosphorylation levels of AMPK and GSK-3β. Furthermore, in cultured PC12 cells, the same protective effects were also observed. Silencing Nrf2 gene with its siRNA abolished the Apelin 13’s prevention of I/R-induced PC12 cell injury, oxidative stress, and inflammation. Inhibition of AMPK by its siRNA decreased the level of Apelin 13-induced Nrf2 expression and diminished the protective effects of Apelin 13. The interplay relationship between GSK-3β and Nrf2 was also verified with relative overexpression. Using selective inhibitors, we further identified the upstream of AMPK/GSK-3β/Nrf2 is AR/Gα/PLC/IP3/CaMKK.ConclusionsIn conclusion, the previous results showed that Apelin 13 protected against I/R-induced ROS-mediated inflammation and oxidative stress through activating the AMPK/GSK-3β pathway by AR/Gα/PLC/IP3/CaMKK signaling, and further upregulated the expression of Nrf2-regulated antioxidant enzymes.

Our results suggest that 3D texture features derived from intensity and high-order derivative maps can better reflect heterogeneous distribution of cancerous tissues. Texture features optimally selected together with sample augmentation could improve the performance on differentiating bladder carcinomas from wall tissues, suggesting a potential way for tumor noninvasive staging of bladder cancer preoperatively.

Genistein (4',5,7-trihydroxyisoflavone), a naturally occurring phenolic compound, possesses well-known preventive activity in breast and prostate cancer, cardiovascular diseases, and postmenopausal problems. The aim of this study is to investigate the distribution and dose-dependent absorption, metabolism, and excretion of genistein in rats. Genistein was orally administered to rats at different doses. At various time intervals, blood, bile, and urine samples were collected and incubated with glucuronidase to hydrolyze the glucuronidated genistein. Genistein was detected by HPLC. High levels of glucuronidated genistein were detected in the plasma, bile, and urine after genistein administration. When genistein was administered to rats at 6.25, 12.5, and 50 mg x kg (-1) doses, the AUC (0- t) values for genistein were 23.5, 80.9, and 177.9 mg x min x L (-1); the oral absolute bioavailabilities were 21.9, 33.5, and 19.0%; the AUC (0- t) values of glucuronidated genistein were 173.8, 470.7, and 1721.2 mg x min x L (-1), respectively. The cumulative biliary excretion of genistein respective to each dose was 42.6 +/- 6.5, 75.2 +/- 18.9, and 126.6 +/- 34.8 microg; the cumulative biliary excretion of glucuronidated genistein was 108.5 +/- 35.2, 423.5 +/- 158.3, and 853.7 +/- 320.8 microg for each dose, respectively. The cumulative urinary excretion of genistein was 34.8 +/- 10.8, 187.3 +/- 67.0 and 213.6 +/- 30.6 microg for each dose, respectively; the cumulative levels of glucuronidated genistein excreted in the urine were 217.8 +/- 52.1, 583.1 +/- 106.9, and 1108.4 +/- 88.1 microg, respectively. These results indicated that at high doses absorption, biotransformation, and excretion of genistein occurred in a nonlinear dose-dependent manner. Therefore, the results of these pharmacokinetic studies raise important questions about the therapeutic significance of consuming large quantities of genistein, genistein analogues, or soy-based neutraceuticals.

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Triptolide, a compound extracted from the traditional Chinese medicine preparation of Tripterygium wilfordii Hook F., has been reported to have anti-inflammatory and anti-cancer activities. However, its effect on ovarian cancer invasion is unknown. We observed that MMP7 and MMP19 expression increased in ovarian cancer tissue. Triptolide treatment inhibited the migration and invasion of ovarian cancer cells SKOV3 and A2780 at the concentration of 15 nM. We also observed that triptolide suppressed MMP7 and MMP19 promoter activity in a dose-dependent manner, down-regulating the expressions of these promoters on mRNA and protein level. Moreover, triptolide enhanced E-cadherin expression in ovarian cancer cells. In vivo, triptolide inhibited tumor formation and metastasis in nude mice, and suppressed MMP7 and MMP19 expression; it also enhanced E-cadherin expression in tumor in a dose-dependent manner. Over expression of MMP7 and MMP19, or suppression of E-cadherin expression partially abolished the inhibitory effect of triptolide on invasion of ovarian cancer cells. To summarize, triptolide significantly inhibited the migration and invasion of ovarian cancer cells by suppression of MMP7 and MMP19 and up-regulation of E-cadherin expression. This study shows that triptolide is a good candidate for the treatment of ovarian cancer and reduction of metastasis.

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