AimTo develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment.Materials and MethodsA total of 883 patients with stage II–III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS), local recurrence (LR) and distant metastases (DM). Cox models were performed to develop a predictive model for each endpoint. The performance of model prediction was validated by cross validation and on an independent group of patients.ResultsThe 5-year LR, DM and OS rates were 22.3%, 32.7% and 63.8%, respectively. Two prognostic nomograms were successfully developed to predict 5-year OS and DM-free survival rates, with c-index of 0.70 (95% CI = [0.66, 0.73]) and 0.68 (95% CI = [0.64, 0.72]) on the original dataset, and 0.76 (95% CI = [0.67, 0.86]) and 0.73 (95% CI = [0.63, 0.83]) on the validation dataset, respectively. Factors in our models included age, gender, carcinoembryonic antigen value, tumor location, T stage, N stage, metastatic lymph nodes ratio, adjuvant chemotherapy and chemoradiotherapy. Predicted by our nomogram, substantial variability in terms of 5-year OS and DM-free survival was observed within each TNM stage category.ConclusionsThe prognostic nomograms integrated demographic and clinicopathological factors to account for tumor and patient heterogeneity, and thereby provided a more individualized outcome prognostication. Our individualized prediction nomograms could help patients with preoperatively under-staged rectal cancer about their postoperative treatment strategies and follow-up protocols.
Purpose: To assess the safety and outcomes of radiotherapy (RT) or chemoradiotherapy (CRT) in elderly patients (≥70) with rectal cancer. Methods: Elderly patients aged 70 and older with rectal cancer, who were treated with RT or CRT at a single institution, were retrospectively analyzed. Performance status (KPS and ECOG score) and comorbidity (Charlson comorbidity index) were calculated, and their correlation with treatment toxicity and overall survival were studied. Risk factors for overall survival were investigated using univariate and multivariate survival analysis.Results: A total of 126 patients with locally advanced disease, local recurrence or synchronous metastasis were included, with a 3-year OS rate of 48.1%. Scheduled dosage of radiation was delivered to 69% of patients. Grade 3 toxicities occurred more often in patients treated with CRT versus RT. The occurrence of grade 3 toxicities was not related to KPS score, ECOG score, number of comorbidities, and Charlson score. Multivariate analysis found that only age and Charlson score were independent prognostic factors for predicting patients' 3-year OS. The 3-year OS rate was significantly higher in patients with Charlson score <4 vs Charlson score ≥4 (71.1% vs. 26.4%, P=0.0003).Conclusions: Although toxicities may be significant, elderly patients with rectal cancer of varied stages can be safely treated with RT or CRT with careful monitoring and frequent modification of treatment. Except for patients' age, Charlson comorbidity index may be helpful in assessing patients' outcomes in elderly patients with rectal cancer.
MMP-1 was involved in OA development in rabbit ACLT model and the amount of its expression was related with the degree of cartilage degradation. The increase of MMP-1 expression in synovium lagged behind that in cartilage, suggesting OA pathology was originated from cartilage, but synovitis may also paticipate in cartilage degradation, especially in middle and late stage of OA.
Genistein influences proliferation of HSC, suppresses the expression of alpha-SMA in HSC and t inhibits the intensity of c-fos, c-jun and cyclin D(1) expression of HSCs. Genistein has therapeutic potential against liver fibrosis.
Human dental pulp stem cells (DPSCs) are oral mesenchymal stem cells with potential to differentiate into various cell types. Recent studies of DPSCs have focused on microRNAs (miRNAs), a class of small noncoding RNAs that play crucial roles in regulating DPSC phenotypes. In the current study, the expression of miR-140-5p was significantly decreased during lipopolysaccharide (LPS)-mediated differentiation of DPSCs in vitro. Overexpression of miR-140-5p enhanced proliferation of DPSCs and inhibited DPSC differentiation, whereas suppression of miR-140-5p produced the opposite effect. Moreover, the expression of toll-like receptor 4 (TLR-4), a critical regulator of DPSCs, was negatively correlated with the levels of miR-140-5p. A luciferase reporter analysis confirmed that miR-140-5p could regulate TLR-4 by directly binding to the 3'-untranslated region (3'-UTR) of the TLR4 mRNA. Additionally, we suppressed TLR-4 expression by treating cells with a TLR-4 inhibitor, CLI-095, and demonstrated that the effect of the miR-140-5p inhibitor on DPSC proliferation and differentiation could be partially reversed by blocking TLR-4. Taken together, our data suggest that miR-140-5p is a novel miRNA that regulates DPSC proliferation and differentiation.
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