ß-catenin expression increased. These data presume that the cytoskeleton is loose. Further, previous studies show that the mitogen-activated protein kinase (MAPK) pathway can induce cardiac hypertrophy. Our data showed that p-p38 expression increased with the overexpression of GSN in H9c2, and the transcription factor p-GATA4 expression also increased, suggesting that the overexpression of GSN in H9c2-induced cardiac hypertrophy seemed to be regulated by the p38/GATA4 pathway. Moreover, we used both the p38 inhibitor (SB203580) and GSN siRNA to confirm our conjecture. We found that both of these factors significantly suppressed gelsolin-induced cardiac hypertrophy which through p38/GATA4 signaling pathway.Conclusions: Therefore, we predict that the gene silencing of GSN and/or the downstream blocking of GSN along the p38 pathway could be applied to ameliorate pathological cardiac hypertrophy in the future.
PP.42.15 ANGIOTENSIN II-DEPENDENT DIFFERENTIAL MIRNA EXPRESSION IN RAT RENAL EPITHELIAL TUBULAR CELLS
In the study 140 patients with II-III stage were included. After long course of chemoradiation and further surgery the pathology examination showed pCR in 38 (27.1%) of the patients. From every patients' CTsimulation image, the tumor volumes extracted 850 features (119,000 in total number). KS test showed statistically difference between pCR-groups and non-pCR. Logistic regression showed high value of wavelet contribution to model. Multilayer perceptron model showed high predictive importance of wavelet in the model. Applying TwoStep cluster analysis for classifying the texture and wavelet parameters three cluster were defined with predominant wavelet features importance. Conclusion: Current study reports, for the first time, the feasibility of using non-diagnostic CT images as data source for texture analysis in combination with wavelets features analysis for predicting pCR in locally advanced rectal cancer patients. The model performance shows the importance of including wavelets features in radiomics analysis.
To explore a surrogate endpoint for long-term outcomes in locally advanced gastric cancer after pre-operative chemoradiotherapy (CRT). Materials/Methods: From April 2012 to April 2019, 95 patients enrolled in 4 prospective studies (ClinicalTrial.gov NCT01291407, NCT02296658, NCT03427684 and NCT04062058) with locally advanced gastric cancer who received preoperative concurrent radio-chemotherapy were included. All patients were stage T3 / 4, N +. The local control (LC), distant metastasis-free (DMFS), disease-free (DFS) and overall survival (OS) were evaluated. The clinicopathological factors related with the long-term prognosis were analyzed by uni-and multi-variant analysis. Down-staging depth score (DDS), a novel method of evaluating CRT response, was used for predicting long-term outcomes. Results: The median follow-up for survivors was 30 months. The AUC value of ROC curve predicted by DDS was 0.728, which was better than that of pCR, histological response and ypN0 (AUC Z 0.634, 0.640 and 0.643). DDS cutoff value was 4. DDS and surgery were correlated with DMFS, DFS and OS (p Z 0.009, 0.013, 0.032 and 0.001, 0.000, 0.000). pCR and ypN0 were associated with OS (p Z 0.026, 0.049). Multivariate analysis showed that DDS was an independent DFS prognostic factor (p Z 0.021). Conclusion: Preoperative CRT was effective for local advanced gastric cancer. DDS, a simple, short-term indicator, seemed to be a better surrogate endpoint for DFS in gastric cancer patients with preoperative CRT
thorough characterization of white matter microstructure through quantitative diffusivity metrics. The most commonly used diffusivity metric, fractional anisotropy (FA), provides insight into the overall white matter microstructural properties, whereas radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) suggest changes in myelination, axonal integrity & underlying neuro-inflammation and edema respectively. Study purpose is to find whether trigeminal nerve diffusivity metrics at a single, early time point after frameless SRS is predictive of long-term pain relief in patients with TN. Materials/Methods: Study cohort comprised of 44 pts with inclusion criteria were: 1) diagnosis of classic, type 1 TN 2) SRS treatment with no prior surgical procedures for TN; 3) 3 tesla MRI scans at 6 months posttreatment (range 5−7 months); and 4) at least 12 months of clinical follow-up. Patients with TN secondary to multiple sclerosis, cranial tumors, or vertebrobasilar dolichoectasia compressing the brainstem were excluded from the study. For each patient, diffusivity metrics (FA, MD, RD, and AD) were extracted from both the affected and unaffected trigeminal nerves at 6 months posttreatment 6 months diffusivity metrics were compared with long-term clinical outcome. Patients were identified as long-term responders if they achieved at least 75% reduction in preoperative pain for 12 months or longer following SRS. Average microstructural diffusivity differences (within group -pre and post treatment; across group -responder & non-responders) were analyzed using paired / Independent T test. Results: Trigeminal nerve diffusivity at 6 months post-SRS was predictive of long-term clinical effectiveness, where long-term responders (n = 36) showed significantly lower fractional anisotropy at the radiosurgical target of their affected nerve compared to their contralateral, unaffected nerve and to nonresponders. Radial diffusivity and mean diffusivity, correlates of myelin alterations and inflammation, were also significantly higher in the affected nerve of long-term responders compared to their unaffected nerve. Nonresponders (n = 8) did not exhibit any characteristic diffusivity changes after SRS. Conclusion: DTI, FA specifically, appears to be a strong, objective measure to assess the effects of radiation on a nerve. Incorporating early DTI assessment can provide prognostic information that supplements clinical measures.
Research assessing health-related quality of life (HRQoL) (or health state utility) which can be applied for economic evaluation in patients with Barretts esophagus (BE)and esophageal cancer is limited. This study derived health state utilities for patients with various 'stages' of BE and Cancer. Methods: A crosssectional survey was conducted with potential participants sought from South Australia, including patients with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or esophageal adenocarcinoma. HRQoL was assessed using two generic instruments, the EQ-5D-5L and the SF-36, and a cancerspecific instrument -the EORTC QLQ-C30. Health state utilities were derived by applying the general population preference-based scoring algorithms pertaining to all three instruments. Outcomes were compared for health states and following different treatments. Results: Ninety-seven respondents (80% male, mean age: 68 years) returned questionnaires. The mean (standard deviation) health state utilities for the total sample were 0.79 (0.24) for the EQ-5D-5L, 0.57 (0.29) for the SF-6D (derived from SF-36) and 0.73 (0.20) for the QLU-C10D (derived from EORTC QLQ-C30). No statistically significant differences were observed when different stages of BE or type of intervention received (surveillance, endoscopic treatment, surgery). However, patients who had undergone surgery for cancer reported better psychological wellbeing than those under surveillance or following endoscopic treatments. Conclusions: HRQoL for patients under surveillance for BE and following treatment of cancer was similar. Oesophagectomy was associated with better post-treatment psychological functioning, compared to endoscopic interventions, which can be attributed to a reduction in the perceived risk of cancer.
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