No significant difference was noted between single cardiac tumours and multiple tumours regarding the degree of fetal heart damage. Cardiac rhabdomyoma is the most common cardiac tumour in fetus. The correlation between cardiac rhabdomyoma and TSC is high regardless of the presence of single or multiple tumours. This article is protected by copyright. All rights reserved.
Cancer treatments induce cell stress to trigger apoptosis in tumor cells. Many cancers repress these apoptotic signals through alterations in the Bcl2 proteins that regulate this process. Therapeutics that target these specific survival biases are in development, and drugs that inhibit Bcl2 activities have shown clinical activity for some cancers. Mcl1 is a survival factor for which no effective antagonists have been developed, so it remains a principal mediator of therapy resistance, including to Bcl2 inhibitors. We used a synthetic-lethal screening strategy to identify genes that regulate Mcl1 survival activity using the pediatric tumor neuroblastoma (NB) as a model, as a large subset are functionally verified to be Mcl1 dependent and Bcl2 inhibitor resistant. A targeted siRNA screen identified genes whose knockdown restores sensitivity of Mcl1-dependent NBs to ABT-737, a small molecule inhibitor of Bcl2, BclXL and BclW. Three target genes that shifted the ABT-737 IC50 >1 log were identified and validated: PSMD14, UBL5 and PRPF8. The latter two are members of a recently characterized subcomplex of the spliceosome that along with SART1 is responsible for non-canonical 5′-splice sequence recognition in yeast. We showed that SART1 knockdown similarly sensitized Mcl1-dependent NB to ABT-737 and that triple knockdown of UBL5/PRPF8/SART1 phenocopied direct MCL1 knockdown, whereas having no effect on Bcl2-dependent NBs. Both genetic spliceosome knockdown or treatment with SF3b-interacting spliceosome inhibitors like spliceostatin A led to preferential pro-apoptotic Mcl1-S splicing and reduced translation and abundance of Mcl1 protein. In contrast, BN82865, which inhibits the second transesterification step in terminal spliceosome processing, did not have this effect. These findings demonstrate a prominent role for the spliceosome in mediating Mcl1 activity and suggest that drugs that target either the specific UBL5/PRPF8/SART1 subcomplex or SF3b functions may have a role as cancer therapeutics by attenuating the Mcl1 survival bias present in numerous cancers.
ObjectiveTo predict vascular endothelial growth factor (VEGF) expression in patients with diffuse gliomas using radiomic analysis.Materials and methodsPreoperative magnetic resonance images were retrospectively obtained from 239 patients with diffuse gliomas (World Health Organization grades II–IV). The patients were randomly assigned to a training group (n = 160) or a validation group (n = 79) at a 2:1 ratio. For each patient, a total of 431 radiomic features were extracted. The minimum redundancy maximum relevance (mRMR) algorithm was used for feature selection. A machine-learning model for predicting VEGF status was then developed using the selected features and a support vector machine classifier. The predictive performance of the model was evaluated in both groups using receiver operating characteristic curve analysis, and correlations between selected features were assessed.ResultsNine radiomic features were selected to generate a VEGF-associated radiomic signature of diffuse gliomas based on the mRMR algorithm. This radiomic signature consisted of two first-order statistics or related wavelet features (Entropy and Minimum) and seven textural features or related wavelet features (including Cluster Tendency and Long Run Low Gray Level Emphasis). The predictive efficiencies measured by the area under the curve were 74.1% in the training group and 70.2% in the validation group. The overall correlations between the 9 radiomic features were low in both groups.ConclusionsRadiomic analysis facilitated efficient prediction of VEGF status in diffuse gliomas, suggesting that using tumor-derived radiomic features for predicting genomic information is feasible.
BACKGROUND AND PURPOSE:The accuracy of preoperative blood oxygen level-dependent fMRI remains controversial. This study assessed the association between the anatomic location of a tumor and the accuracy of fMRI-based motor function mapping in diffuse lower-grade gliomas.
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