Notes

Socioeconomic reputation and also the building mind : A deliberate overview of neuroimaging findings in children's.
The C-index of the nomogram for LRFS, DMFS and DSS were statistically higher than the C-index values of the AJCC seventh edition (P < 0.001). In the test set, the nomogram discrimination was also superior to the AJCC Staging systems (P < 0.001). The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome.

Prognostic score models were successfully established and validated to predict LRFS, DMFS, and DSS over a 5-year period after IMRT and chemotherapy, which will be useful for individual treatment.
Prognostic score models were successfully established and validated to predict LRFS, DMFS, and DSS over a 5-year period after IMRT and chemotherapy, which will be useful for individual treatment.Copper promotes tumor angiogenesis, nevertheless the mechanisms involved remain to be fully understood. We have recently demonstrated that the G-protein estrogen receptor (GPER) cooperates with hypoxia inducible factor-1α (HIF-1α) toward the regulation of the pro-angiogenic factor VEGF. Here, we show that copper sulfate (CuSO4) induces the expression of HIF-1α as well as GPER and VEGF in breast and hepatic cancer cells through the activation of the EGFR/ERK/c-fos transduction pathway. Worthy, the copper chelating agent TEPA and the ROS scavenger NAC prevented the aforementioned stimulatory effects. We also ascertained that HIF-1α and GPER are required for the transcriptional activation of VEGF induced by CuSO4. In addition, in human endothelial cells, the conditioned medium from breast cancer cells treated with CuSO4 promoted cell migration and tube formation through HIF-1α and GPER. The present results provide novel insights into the molecular mechanisms involved by copper in triggering angiogenesis and tumor progression. Our data broaden the therapeutic potential of copper chelating agents against tumor angiogenesis and progression.RMRP, the RNA component of mitochondrial RNA processing endoribonuclease, is a non-coding RNA (ncRNA) part of the RNase MRP complex functioning in mitochondrial and ribosomal RNA processing. Even though various mutations in the RMRP gene are linked to developmental defects and pathogenesis, its relevance to cancer etiology has not been well established. Here we examined the expression of RMRP and found a significant increase in colorectal and breast cancer patient tissues. So we tested whether the oncogenic signaling pathways, Wnt/β-catenin and Hippo/YAP pathways, are relevant to the enhanced expression of RMRP in cancer cells because of the predicted β-catenin/TCF and YAP/TBX5 elements in the upstream regions of the RMRP gene. As expected, Wnt signal activation significantly induced the RMRP transcription thru β-catenin and YAP transcription factors. More importantly, YAP protein was critical for RMRP transcription by association to the proximal site near the transcription start site of the RMRP gene, a Pol III promoter, along with β-catenin and TBX5 proteins. We propose that the interplay of Wnt and Hippo signaling pathways could regulate target genes, coding or non-coding, by the β-catenin/YAP/TBX5 transcription complex in cancer cells.Autophagy is an intracellular pathway for bulk protein degradation and the removal of damaged organelles by lysosomes. Autophagy was previously thought to be unselective; however, studies have increasingly confirmed that autophagy-mediated protein degradation is highly regulated. Abnormal autophagic protein degradation has been associated with multiple human diseases such as cancer, neurological disability and cardiovascular disease; therefore, further elucidation of protein degradation by autophagy may be beneficial for protein-based clinical therapies. Macroautophagy and chaperone-mediated autophagy (CMA) can both participate in selective protein degradation in mammalian cells, but the process is quite different in each case. Here, we summarize the various types of macroautophagy and CMA involved in determining protein degradation. For this summary, we divide the autophagic protein degradation pathways into four categories the post-translational modification dependent and independent CMA pathways and the ubiquitin dependent and independent macroautophagy pathways, and describe how some non-canonical pathways and modifications such as phosphorylation, acetylation and arginylation can influence protein degradation by the autophagy lysosome system (ALS). Finally, we comment on why autophagy can serve as either diagnostics or therapeutic targets in different human diseases.The effects of many chemotherapeutic drugs on ribosome biogenesis have been underestimated for a long time. Indeed, many drugs currently used for cancer treatment--and which are known to either damage DNA or hinder DNA synthesis--have been shown to exert their toxic action mainly by inhibiting rRNA synthesis or maturation. Moreover, there are new drugs that have been proposed recently for cancer chemotherapy, which only hinder ribosome biogenesis without any genotoxic activity. Even though ribosome biogenesis occurs in both normal and cancer cells, whether resting or proliferating, there is evidence that the selective inhibition of ribosome biogenesis may, in some instances, result in a selective damage to neoplastic cells. The higher sensitivity of cancer cells to inhibitors of rRNA synthesis appears to be the consequence of either the loss of the mechanisms controlling the cell cycle progression or the acquisition of activating oncogene and inactivating tumor suppressor gene mutations that up-regulate the ribosome biogenesis rate. This article reviews those cancer cell characteristics on which the selective cancer cell cytotoxicity induced by the inhibitors of ribosome biogenesis is based.The MUS81 protein belongs to a conserved family of DNA structure-specific nucleases that play important roles in DNA replication and repair. Inactivation of the Mus81 gene in mice has no major deleterious consequences for embryonic development, although cancer susceptibility has been reported. We have investigated the role of MUS81 in human cells by acutely depleting the protein using shRNAs. We found that MUS81 depletion from human fibroblasts leads to accumulation of ssDNA and a constitutive DNA damage response that ultimately activates cellular senescence. Moreover, we show that MUS81 is required for efficient replication fork progression during an unperturbed S-phase, and for recovery of productive replication following replication stalling. These results demonstrate essential roles for the MUS81 nuclease in maintenance of replication fork integrity.Experiments and numerical simulations using a flow phantom for magnetic drug targeting have been undertaken. The flow phantom is a half y-branched tube configuration where the main tube represents an artery from which a tumour-supplying artery, which is simulated by the side branch of the flow phantom, branches off. In the experiments a quantification of the amount of magnetic particles targeted towards the branch by a magnetic field applied via a permanent magnet is achieved by impedance measurement using sensor coils. Measuring the targeting efficiency, i.e. the relative amount of particles targeted to the side branch, for different field configurations one obtains targeting maps which combine the targeting efficiency with the magnetic force densities in characteristic points in the flow phantom. It could be shown that targeting efficiency depends strongly on the magnetic field configuration. A corresponding numerical model has been set up, which allows the simulation of targeting efficiency for variable field configuration. With this simulation good agreement of targeting efficiency with experimental data has been found. Thus, the basis has been laid for future calculations of optimal field configurations in clinical applications of magnetic drug targeting. Moreover, the numerical model allows the variation of additional parameters of the drug targeting process and thus an estimation of the influence, e.g. of the fluid properties on the targeting efficiency. Corresponding calculations have shown that the non-Newtonian behaviour of the fluid will significantly influence the targeting process, an aspect which has to be taken into account, especially recalling the fact that the viscosity of magnetic suspensions depends strongly on the magnetic field strength and the mechanical load.
While the English-speaking world may have reached a consensus about Kees Waaldjik's classification of obstetric fistulas, no unanimity around this classification exists among French-speaking medical workers. The objective of this review is to propose a classification, based on long experience in the care of these women, by setting up a comparison with Waaldjik's. Our classification takes two criteria into account (1) the environment of the fistula, that is (a) fistula with a soft (relatively unscarred) vagina, b) fistula with vaginal sclerosis (bands or adhesions, vaginal stenosis or atresia), (c) vesicovaginal fistula associated with a (high or low) rectovaginal fistula or perineal lacerations (first, second or third degree); (2) the anatomical site of fistula, of which there are five types (a) type I fistula of the vesicovaginal wall, (b) type II vesico-cervico-urethral fistula, with two major subgroups type IIA (without destruction of the urethra) and type IIB (with destruction of the urethra), type IIA being subdivided in three subgroups IIAa, IIAB and cIAI, (c) type III fistulae trigono-Neck utero-vaginal, (d) type IV complex mixed fistula, (e) type V, high fistulas the vesico-cervical-uterine fistula and classical vesicouterine.

Our classification is simple, not simplistic, with some resemblance to that of Waaldjjik.
Our classification is simple, not simplistic, with some resemblance to that of Waaldjjik.Nucleosomes, the basic units of chromatin, are involved in transcription regulation and DNA replication. Intronless genes, which constitute 3 percent of the human genome, differ from intron-containing genes in evolution and function. Our analysis reveals that nucleosome positioning shows a distinct pattern in intronless and intron-containing genes. The nucleosome occupancy upstream of transcription start sites of intronless genes is lower than that of intron-containing genes. In contrast, high occupancy and well positioned nucleosomes are observed along the gene body of intronless genes, which is perfectly consistent with the barrier nucleosome model. Intronless genes have a significantly lower expression level than intron-containing genes and most of them are not expressed in CD4+ T cell lines and GM12878 cell lines, which results from their tissue specificity. However, the highly expressed genes are at the same expression level between the two types of genes. The highly expressed intronless genes require a higher density of RNA Pol II in an elongating state to compensate for the lack of introns. Additionally, 5' and 3' nucleosome depleted regions of highly expressed intronless genes are deeper than those of highly expressed intron-containing genes.Proteins carry out their function in a cell through interactions with other proteins. A large scale protein-protein interaction (PPI) network of an organism provides static yet an essential structure of interactions, which is valuable clue for understanding the functions of proteins and pathways. PPIs are determined primarily by experimental methods; however, computational PPI prediction methods can supplement or verify PPIs identified by experiment. Here, we developed a novel scoring method for predicting PPIs from Gene Ontology (GO) annotations of proteins. Unlike existing methods that consider functional similarity as an indication of interaction between proteins, the new score, named the protein-protein Interaction Association Score (IAS), was computed from GO term associations of known interacting protein pairs in 49 organisms. IAS was evaluated on PPI data of six organisms and found to outperform existing GO term-based scoring methods. Crenolanib cost Moreover, consensus scoring methods that combine different scores further improved performance of PPI prediction.
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