[Predictors of asthenia in breast and prostate cancer patients undergoing curative radiotherapy]. / Facteurs de risque d'asthénie en cours de la radiothérapie des cancers du sein et de la prostate.

PURPOSE: Patients frequently report asthenia during radiation. The present study aimed at identifying the correlation between numerous clinical and tumoral factors and asthenia in breast and prostate cancer patients treated by curative radiotherapy. MATERIALS AND METHODS: A retrospective study was conducted at the Lucien Neuwirth Cancer Institute (France). All breast and prostate cancer patients undergoing curative radiotherapy during 2015 were screened (n=806). Patient's self-evaluation of asthenia and radiotherapy tolerance was assessed through verbal analogic scale (0/10 to 10/10). Data about toxicities, travel distance and travel time, tumor's characteristics, radiotherapy treatment planning, previous cancer therapies, were collected from medical records. RESULTS: 500 patients were included (350 in the breast cancer group and 150 in the prostate cancer group). In all, 86% of patients in the breast cancer group reported asthenia, with a 5/10 median score. In all, 54% of patients in the prostate cancer group reported asthenia, with a 2/10 median score. Univariate analysis showed correlation between asthenia and radiotherapy tolerance as well as tumor staging, in the prostate cancer group. No other correlation was evidenced. CONCLUSION: Radiotherapy-related fatigue is a common side effect. This study showed that most of the factors related to patients or disease that are commonly used to explain fatigue during curative treatments, seem finally to be not correlated with asthenia.

Squamous cell carcinoma of the larynx with subglottic extension: is larynx preservation possible?

PURPOSE: Squamous cell carcinoma of larynx with subglottic extension (sSCC) is a rare location described to carry a poor prognosis. The aim of this study was to analyze outcomes and feasibility of larynx preservation in sSCC patients. PATIENTS AND METHODS: Between 1996 and 2012, 197 patients with sSCC were treated at our institution and included in the analysis. Stage III-IV tumors accounted for 76%. Patients received surgery (62%), radiotherapy (RT) (18%), or induction chemotherapy (CT) (20%) as front-line therapy. RESULTS: The 5-year actuarial overall survival (OS), locoregional control (LRC), and distant control rate were 59% (95% CI 51-68), 83% (95% CI 77-89), and 88% (95% CI 83-93), respectively, with a median follow-up of 54.4 months. There was no difference in OS and LRC according to front-line treatments or between primary subglottic cancer and glottosupraglottic cancers with subglottic extension. In the multivariate analysis, age > 60 years and positive N stage were the only predictors for OS (HR 2, 95% CI 1.2-3.6; HR1.9, 95% CI 1-3.5, respectively). A lower LRC was observed for T3 patients receiving a larynx preservation protocol as compared with those receiving a front-line surgery (HR 14.1, 95% CI 2.5-136.7; p = 0.02); however, no difference of ultimate LRC was observed according to the first therapy when including T3 patients who underwent salvage laryngectomy (p = 0.6). In patients receiving a larynx preservation protocol, the 5-year larynx-preservation rate was 55% (95% CI 43-68), with 36% in T3 patients. The 5-year larynx preservation rate was 81% (95% CI 65-96) and 35% (95% CI 20-51) for patients who received RT or induction CT as a front-line treatment, respectively. CONCLUSION: Outcomes of sSCC are comparable with other laryngeal cancers when managed with modern therapeutic options. Larynx-preservation protocols could be a suitable option in T1-T2 (RT or chemo-RT) and selected T3 sSCC patients (induction CT).

Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response.

Rhomboid domain containing 2 (RHBDD2) was previously observed overexpressed and amplified in breast cancer samples. In order to identify biological pathways modulated by RHBDD2, gene expression profiles of RHBDD2 silenced breast cancer cells were analyzed using whole genome human microarray. Among the statistically significant overrepresented biological processes, we found protein metabolism­with the associated ontological terms folding , ubiquitination, and proteosomal degradation­cell death, cell cycle, and oxidative phosphorylation. In addition, we performed an in silico analysis searching for RHBDD2 co-expressed genes in several human tissues. Interestingly, the functional analysis of these genes showed similar results to those obtained with the microarray data, with negative regulation of protein metabolism and oxidative phosphorylation as the most enriched gene ontology terms. These data led us to hypothesize that RHBDD2 might be involved in endoplasmic reticulum (ER) stress response. Thus, we specifically analyzed the unfolding protein response (UPR) of the ER stress process. We used a lentivirus-based approach for stable silencing of RHBDD2 mRNA in the T47D breast cancer cell line, and we examined the transcriptional consequences on UPR genes as well as the phenotypic effects on migration and proliferation processes. By employing dithiothreitol as an UPR inducer, we observed that cells with silenced RHBDD2 showed increased expression of ATF6, IRE1, PERK, CRT, BiP, ATF4, and CHOP (p <0.01). We also observed that RHBDD2 silencing inhibited colony formation and decreased cell migration. Based on these studies, we hypothesize that RHBDD2 overexpression in breast cancer could represent an adaptive phenotype to the stressful tumor microenvironment by modulating the ER stress response.

Macrobrachium borellii hepatopancreas contains a mitochondrial glycerol-3-phosphate acyltransferase which initiates triacylglycerol biosynthesis.

Mammals express four isoforms of glycerol-3-phosphate acyltransferase (GPAT). The mitochondrial isoform GPAT1 may have been the acyltransferase that appeared first in evolution. The hepatopancreas of the crustacean Macrobrachium borellii has a high capacity for triacylglycerol (TAG) biosynthesis and storage. In order to understand the mechanism of glycerolipid biosynthesis in M. borellii, we investigated its hepatopancreas GPAT activity. In hepatopancreas mitochondria, we identified a GPAT activity with characteristics similar to those of mammalian GPAT1. The activity was resistant to inactivation by SH-reactive N-ethylmaleimide, it was activated by polymyxin-B, and its preferred substrate was palmitoyl-CoA. The reaction products were similar to those of mammalian GPAT1. A 70-kDa protein band immunoreacted with an anti-rat liver GPAT1 antibody. Surprisingly, we did not detect high GPAT specific activity in hepatopancreas microsomes. GPAT activity in microsomes was consistent with mitochondrial contamination, and its properties were similar to those of the mitochondrial activity. In microsomes, TAG synthesis was not dependent on the presence of glycerol-3 phosphate as a substrate, and the addition of monoacylglycerol as a substrate increased TAG synthesis 2-fold. We conclude that in M. borellii the de novo triacylglycerol biosynthetic pathway can be completed in the mitochondria. In contrast, TAG synthesis in the ER may function via the monoacylglycerol pathway.