Methylation of the MGMT gene promoter is associated with a favorable prognosis in adult patients with GBM treated with TMZ. We determined the incidence of pseudoprogression according to the MGMT ...methylation status and the potential value of DSC perfusion MR images for predicting pseudoprogression.
New or enlarged enhancing lesions after CCRT in adult patients with newly diagnosed GBMs were prospectively assessed by measuring their rCBV by using DSC perfusion MR images. Tumor tissue was assayed to determine MGMT promoter methylation status. All patients were regularly followed up at an interval of 2 months by MR images, including DSC perfusion MR images.
Ninety eligible patients were enrolled in this study. After CCRT, new or enlarged enhanced lesions were found in 59 of 90 patients, which were subsequently classified as pseudoprogression (26 patients, 28.9%) and real progression (33 patients, 36.7%). Overall, there was a significant difference in the mean rCBV between pseudoprogression and real tumor progression (P = .003). The ROC curve revealed that an rCBV ratio >1.47 had an 81.5% sensitivity and a 77.8% specificity. The unmethylated MGMT promoter group had a significant difference of mean rCBV between pseudoprogression and real progression (P = .009), though the methylated MGMT promoter group had no significant difference (P = .258).
The current study suggests that rCBV measured by DSC perfusion MR images has a differential impact on the predictability of pseudoprogression in patients with GBM.
The multiparametric imaging can show us different aspects of tumor behavior and may help differentiation of tumor recurrence from treatment related change. Our aim was to differentiate tumor ...progression from pseudoprogression in patients with glioblastoma by using multiparametric histogram analysis of 2 consecutive MR imaging studies with relative cerebral blood volume and ADC values.
Thirty-five consecutive patients with glioblastoma with new or increased size of enhancing lesions after concomitant chemoradiation therapy following surgical resection were included. Combined histograms were made by using the relative cerebral blood volume and ADC values of enhancing areas for initial and follow-up MR imaging, and subtracted histograms were also prepared. The histogram parameters between groups were compared. The diagnostic accuracy of tumor progression based on the histogram parameters of initial and follow-up MR imaging and subtracted histograms was compared and correlated with overall survival.
Twenty-four pseudoprogressions and 11 tumor progressions were determined. Diagnosis based on the subtracted histogram mode with a multiparametric approach was more accurate than the diagnosis based on the uniparametric approach (area under the receiver operating characteristic curve of 0.877 versus 0.801), with 81.8% sensitivity and 100% specificity. A high mode of relative cerebral blood volume on the subtracted histogram by using a multiparametric approach (relative cerebral blood volume ×ADC) was the best predictor of true tumor progression (P < .001) and worse survival (P = .003).
Multiparametric histogram analysis of posttreatment glioblastoma was useful to predict true tumor progression and worse survival.
The purpose of our study is to summarise the current scientific findings regarding the impact of obesity on total hip arthroplasty (THA); specifically the influence of obesity on the timing of THA, ...incidence of complications, and effect on clinical and functional outcomes.
We performed a systematic review that was compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify prospective studies from the PubMed/Medline, Embase, and Cochrane Library databases that evaluated primary THA in obese (body mass index (BMI) ≥ 30 kg/m
) patients.
There were 17 articles included in the review, which encompassed 13 722 THA patients. Analysis of the included studies showed that, when compared with non-obese patients, obesity was associated with younger age at time of primary THA, and an increased incidence of complications (up to four-fold). Results were mixed on the influence of obesity on the outcomes of primary THA, with three studies showing a detrimental effect on outcomes of a BMI ≥ 30 kg/m
, while eight studies showed no effect.
Obesity is associated with significantly younger age at time of primary THA and obese patients are likely to experience a higher rate of peri-operative complications. More investigation is needed into the effect of obesity on clinical outcomes, as the current literature is mixed. Cite this article: Bone Joint J 2017;99-B(1 Supple A):31-6.
Despite the emerging importance of fibroblast growth factor 21 (FGF21) as a metabolic hormone regulating energy balance, its direct effects on renal function remain unexplored. FGF21 was injected ip ...daily for 12 weeks into db/db mice. Compared with control vehicle injection, FGF21 treatment significantly improved lipid profiles and insulin resistance and resulted in significantly higher serum adiponectin levels. In contrast, serum insulin and 8-isoprostane levels were significantly decreased. Interestingly, FGF21 and its receptor components in the kidneys were found to be significantly up-regulated in db/db mice, which suggests an FGF21-resistant state. FGF21 treatment significantly down-regulated FGF21 receptor components and activated ERK phosphorylation. FGF21 administration also markedly decreased urinary albumin excretion and mesangial expansion and suppressed profibrotic molecule synthesis. Furthermore, FGF21 improved renal lipid metabolism and oxidative stress injury. In cultured renal cells, FGF21 was mainly expressed in mesangial cells, and knockdown of FGF21 expression by stealth small interfering RNA further aggravated high-glucose-induced profibrotic cytokine synthesis in mesangial cells. Our results suggest that FGF21 improves insulin resistance and protects against renal injury through both improvement of systemic metabolic alterations and antifibrotic effects in type 2 diabetic nephropathy. Targeting FGF21 could therefore provide a potential candidate approach for a therapeutic strategy in type 2 diabetic nephropathy.
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► Photocrosslinking provides insight into context-dependent interactions. ► Interactome dynamics can be determined by photocrosslinking. ► Use of photocrosslinkers defines specific ...interaction interfaces within large complexes. ► Crosslinking captures transient interaction complexes containing IDPs and glycoproteins.
Photocrosslinking approaches can be used to map interactome networks within the context of living cells. Photocrosslinking methods rely on use of metabolic engineering or genetic code expansion to incorporate photocrosslinking analogs of amino acids or sugars into cellular biomolecules. Immunological and mass spectrometry techniques are used to analyze crosslinked complexes, thereby defining specific interactomes. Because photocrosslinking can be conducted in native, cellular settings, it can be used to define context-dependent interactions. Photocrosslinking methods are also ideally suited for determining interactome dynamics, mapping interaction interfaces, and identifying transient interactions in which intrinsically disordered proteins and glycoproteins engage. Here we discuss the application of cell-based photocrosslinking to the study of specific problems in immune cell signaling, transcription, membrane protein dynamics, nucleocytoplasmic transport, and chaperone-assisted protein folding.
Chronic inflammation caused by high glucose and high free fatty acid (FFA) concentrations is a major contributor to the pathogenesis of type 2 diabetes. Recent evidence suggests that activation of ...Toll-like receptor (TLR) signaling induces peripheral insulin resistance and mediates central insulin and leptin resistance. In this study, we investigated the renal effects of TLR4 signaling blockade in type 2 diabetic mice. Eight-week-old db/db mice were treated for 12 weeks with (S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid (GIT27), which targets macrophages through the inhibition of TLR4- and TLR2/6-mediated signaling pathways. Although GIT27 treatment improved glycemic control and insulin tolerance, which is associated with a lower lipid profile, it did not impact body weight or food consumption. GIT27 treatment also markedly decreased urinary albumin excretion, decreased proinflammatory cytokine synthesis, improved tissue lipid metabolism, induced oxidative stress, and improved glomerulosclerosis compared with the control db/db group. In cultured podocytes and adipocytes, high glucose levels with FFA stimulation increased TLR4 expression and proinflammatory cytokine synthesis, but the effects were abolished by GIT27 treatment. In addition, knockdown of TLR4 expression by stealth small interfering RNA abolished FFA-induced proinflammatory cytokine synthesis in cultured podocytes. In conclusion, our results suggest that GIT27 treatment improves insulin resistance and protects against the renal injury that occurs in type 2 diabetic nephropathy through both metabolic and antiglomerulosclerotic mechanisms. These results suggest that TLR pathway inhibition might play a direct protective role in diabetic kidney disease.
The previous recommendation system applied the matrix factorization collaborative filtering (MFCF) technique to only single domains. Due to data sparsity, this approach has a limitation in overcoming ...the cold-start problem. Thus, in this study, we focus on discovering latent features from domains to understand the relationships between domains (called domain coherence). This approach uses potential knowledge of the source domain to improve the quality of the target domain recommendation. In this paper, we consider applying MFCF to multiple domains. Mainly, by adopting the implicit stochastic gradient descent algorithm to optimize the objective function for prediction, multiple matrices from different domains are consolidated inside the cross-domain recommendation system (CDRS). Additionally, we design a conceptual framework for CDRS, which applies to different industrial scenarios for recommenders across domains. Moreover, an experiment is devised to validate the proposed method. By using a real-world dataset gathered from Amazon Food and MovieLens, experimental results show that the proposed method improves 15.2% and 19.7% in terms of computation time and MSE over other methods on a utility matrix. Notably, a much lower convergence value of the loss function has been obtained from the experiment. Furthermore, a critical analysis of the obtained results shows that there is a dynamic balance between prediction accuracy and computational complexity.
The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation of the in vivo tumor biology and low clinical translatability. ...Here, we report on longitudinal epigenetic and transcriptional profiling of seven glioblastoma spheroid cell line models cultured over an extended period. Molecular profiles were associated with drug response data obtained for 231 clinically used drugs. We show that the glioblastoma spheroid models remained molecularly stable and displayed reproducible drug responses over prolonged culture times of 30 in vitro passages. Integration of gene expression and drug response data identified predictive gene signatures linked to sensitivity to specific drugs, indicating the potential of gene expression-based prediction of glioblastoma therapy response. Our data thus empowers glioblastoma spheroid disease modeling as a useful preclinical assay that may uncover novel therapeutic vulnerabilities and associated molecular alterations.
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•Glioma spheroid cell lines are molecularly stable in vitro models over time.•Tumor spheroid cell lines allow for reproducible drug testing.•Gene expression profiles may predict in vitro drug response of glioma cells.
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