Oncotarget
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Despite progress in the treatment of head and neck squamous cell carcinoma (HNSCC) in recent decades, including new surgical techniques, radiotherapy advances and chemotherapy schedules, the prognosis for the affected patients has not improved at the same pace, and still, most HNSCC patients are diagnosed in advanced stages. To increase their survival, the development of better screening methods for early detection is required and appropriate tailored therapeutic interventions are desired. The aim of the present study was to evaluate miRNAs as prognostic biomarkers in patients undergoing organ preservation protocol for locally advanced HNSCC. ⋯ Furthermore, considering the entire cohort, patients with high expression of miR-21 had worse survival. A multivariate Cox regression analysis also showed miR-21 (HR=2.05; 95%CI 1.05-4.02; p=0.036) and clinical stage IV (HR=3.17; 95%CI 1.49-6.77; p=0.003) as independent prognostic factors (model adjusted for age, tumor site, tumor resectability, and sets 'screening' or 'validation'). In conclusion, the results of this study suggest that the evaluation of miR-21 expression could be an important tool for treatment planning and a prognosis predictior for HNSCC patients undergoing organ preservation protocols.
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Progression of prostate cancer (PC) to castration-recurrent growth (CRPC) remains dependent on sustained expression and transcriptional activity of the androgen receptor (AR). A major mechanism contributing to CRPC progression is through the direct phosphorylation and activation of AR by Src-family (SFK) and ACK1 tyrosine kinases. However, the AR-dependent transcriptional networks activated by Src during CRPC progression have not been elucidated. ⋯ The differential expression of a subset (DPP4, BCAT1, CNTNAP4, CDH3) correlates with earlier PC metastasis onset and poorer survival, with the expression of BCAT1 required for Src-induced androgen-independent proliferation. Lastly, Src enhances AR binding to non-canonical ARBS enriched for FOXO1, TOP2B and ZNF217 binding motifs; cooperative AR/TOP2B binding to a non-canonical ARBS was both Src- and DHT-sensitive and correlated with increased levels of Src-induced phosphotyrosyl-TOP2B. These data suggest that CRPC progression is facilitated via Src-induced sensitization of AR to intracrine androgen levels, resulting in the engagement of canonical and non-canonical ARBS-dependent gene signatures.
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Review Meta Analysis
Toxicity profile of approved anti-PD-1 monoclonal antibodies in solid tumors: a systematic review and meta-analysis of randomized clinical trials.
Nivolumab and pembrolizumab are antibodies against the programmed-death-receptor- 1 (PD-1) which are associated with distinct immune related adverse effects (AEs). This meta-analysis of randomized clinical trials aims to summarize current knowledge regarding the toxicity profile of these agents. ⋯ Approved PD-1 inhibitors are well tolerated, associated with significant low risk of severe treatment-related AEs and increased risk of thyroid dysfunction, pruritus, and vitiligo.
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Immune Checkpoint Inhibitors (ICIs) are improving the survival of cancer patients, however only the 20-30% of treated patients present clinical benefits. Toxicity represents the major cause of reduced dosage, delayed drug administration and therapy discontinuation. ⋯ The loss of the protective function of intestinal barriers that interacts with the environment measured as increased intestinal permeability and the changes occurring in the microbiota composition have been proposed as a mechanism potentially explaining the pathogenesis of immune related toxicity. In this review we discuss the new perspectives on the involvement of PD-1 and PDL-1 in the cross talk between gut microbiota and immune fitness and how gut microbiota impacts on the efficacy of anti-PD-1 and anti-PDL-1 treatments in cancer.
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Comparative Study
A novel nomogram based on LODDS to predict the prognosis of epithelial ovarian cancer.
To develop and validate a nomogram based on log of odds between the number of positive lymph node and the number of negative lymph node (LODDS) in predicting the overall survival (OS) and cancer specific survival (CSS) for epithelial ovarian cancer (EOC) patients. ⋯ LODDS works as an independent prognostic factor for predicting survival in patients with EOC regardless of the tumor stage. By incorporating LODDS, our nomogram may be superior to the currently utilized FIGO staging system in predicting OS and CSS among post-operative EOC patients.