Outcomes of feeding activity of the sea cucumber Holothuria tubulosa on quantity, biochemical composition, and nutritional quality of sedimentary organic matter

Introduction: Holothuria tubulosa is one of the most common sea cucumbers in the Mediterranean Sea, generally associated with organically enriched coastal sediments and seagrass beds. As a deposit-feeder, it is responsible for strong bioturbation processes and plays a putative key role in sedimentary carbon cycling and benthic trophodynamics. With the aim of exploring the potential use of holothuroids as a tool for remediating eutrophicated sediments, we investigated the effects of H. tubulosa on sedimentary organic matter quantity, biochemical composition, and nutritional quality. Methods: Holothuroids and associated samples of ambient sediments were collected in two sites located in the Central-Western Mediterranean Sea (Sardinia, Italy) and characterized by different trophic status backgrounds: the site of Oristano characterized by sandy-muddy sediments and the presence of mariculture plants (ranked as meso-eutrophic) and the site of Teulada characterized by sandy sediments and Posidonia oceanica meadows (ranked as oligo-mesotrophic). We compared the biochemical composition (proteins, carbohydrates, lipids) of ambient sediment vs sea cucumbers feces and the sedimentary protein content vs protein content in the sediments retrieved in different gut sections (esophagus, mid gut, end gut) of the holothuroid. Results: Our results reveal that holothuroids feeding on meso-eutrophic sediments can increase protein (1.5 times) and lipid (1.3 times) content through their defecation, thus making these substrates a more labile food source for other benthic organisms. We report here that H. tubulosa feeding on meso-eutrophic sediment is most likely able to actively select particles rich in labile organic matter with buccal tentacles, as revealed by the protein content in the esophagus that is up to 2-folds higher than that in the source sediment. According to the inverse relationship between assimilation rates and availability of organic substrates and the optimal foraging theory, H. tubulosa feeding on oligo-mesotrophic sediments showed potential assimilation of proteins ca. 25% higher than that of specimens feeding on meso-eutrophic sediments. Discussion: Our results reveal that H. tubulosa feeding on meso-eutrophic sediments can profoundly influence the benthic trophic status, specifically modifying the biochemical composition and nutritional quality of organic matter, thus paving the way to its possible use in bioremediation actions of eutrophicated sediments and in Integrated Multi-Trophic Aquaculture systems

Regional climate models' performance in representing precipitation and temperature over selected Mediterranean areas

This paper discusses the relative performance of several climate models in providing reliable forcing for hydrological modeling in six representative catchments in the Mediterranean region. We consider 14 Regional Climate Models (RCMs), from the EU-FP6 ENSEMBLES project, run for the A1B emission scenario on a common 0.22° (about 24 km) rotated grid over Europe and the Mediterranean region. In the validation period (1951 to 2010) we consider daily precipitation and surface temperatures from the observed data fields (E-OBS) data set, available from the ENSEMBLES project and the data providers in the ECA&D project. Our primary objective is to rank the 14 RCMs for each catchment and select the four best-performing ones to use as common forcing for hydrological models in the six Mediterranean basins considered in the EU-FP7 CLIMB project. Using a common suite of four RCMs for all studied catchments reduces the (epistemic) uncertainty when evaluating trends and climate change impacts in the 21st century. We present and discuss the validation setting, as well as the obtained results and, in some detail, the difficulties we experienced when processing the data. In doing so we also provide useful information and advice for researchers not directly involved in climate modeling, but interested in the use of climate model outputs for hydrological modeling and, more generally, climate change impact studies in the Mediterranean region

post hoc analysis of clarinet phase iii study to investigate the influence of diabetic status on progression free survival pfs of patients with neuroendocrine tumours nets treated with lanreotide lan or placebo pbo

n/

Nestin expression associates with poor prognosis and triple negative phenotype in locally advanced (T4) breast cancer

Nestin, an intermediate filament protein, has traditionally been noted for its importance as a neural stem cell marker. However, in recent years, expression of nestin has shown to be associated with general proliferation of progenitor cell populations within neoplasms. There is no reported study addressing nestin expression in T4 breast cancer patients. Thus, the aim of the present study was to investigate, through immunohistochemistry, the expression and distribution of nestin in T4 breast cancer, in order to determine its association with clinical and pathological parameters as well as with patients' outcome. Nestin was detectable in tumoral cells and in endothelial cells of blood microvessels, and it is significantly expressed in triple-negative and in inflammatory breast cancer (IBC) subgroups of T4 breast tumours. The Kaplan-Meier analysis showed that the presence of nestin in tumoral cells significantly predicted poor prognosis at 5-years survival (P=0.02) and with borderline significance at 10-years of survival (P=0.05) in T4 breast cancer patients. On the basis of these observations, we speculate that nestin expression may characterize tumours with an aggressive clinical behavior, suggesting that the presence of nestin in tumoral cells and vessels may be considered an important factor that leads to a poor prognosis. Further studies are awaited to define the biological role of nestin in the etiology of these subgroups of breast cancers

Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.

BACKGROUND: Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy. PATIENTS AND METHODS: This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP). RESULTS: Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. CONCLUSION: Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94

Delta-Radiomics Predicts Response to First-Line Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients with Liver Metastases

SIMPLE SUMMARY: Oxaliplatin-based chemotherapy remains the mainstay of first-line therapy in patients with metastatic colorectal cancer (mCRC). Unfortunately, only approximately 60% of treated patients achieve response, and half of responders will experience an early onset of disease progression. Furthermore, some individuals will develop a mixed response due to the emergence of resistant tumor subclones. The ability to predicting which patients will acquire resistance could help them avoid the unnecessary toxicity of oxaliplatin therapies. Furthermore, sorting out lesions that do not respond, in the context of an overall good response, could trigger further investigation into their mutational landscape, providing mechanistic insight towards the planning of a more comprehensive treatment. In this study, we validated a delta-radiomics signature capable of predicting response to oxaliplatin-based first-line treatment of individual liver colorectal cancer metastases. Findings could pave the way to a more personalized treatment of patients with mCRC. ABSTRACT: The purpose of this paper is to develop and validate a delta-radiomics score to predict the response of individual colorectal cancer liver metastases (lmCRC) to first-line FOLFOX chemotherapy. Three hundred one lmCRC were manually segmented on both CT performed at baseline and after the first cycle of first-line FOLFOX, and 107 radiomics features were computed by subtracting textural features of CT at baseline from those at timepoint 1 (TP1). LmCRC were classified as nonresponders (R−) if they showed progression of disease (PD), according to RECIST1.1, before 8 months, and as responders (R+), otherwise. After feature selection, we developed a decision tree statistical model trained using all lmCRC coming from one hospital. The final output was a delta-radiomics signature subsequently validated on an external dataset. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values in correctly classifying individual lesions were assessed on both datasets. Per-lesion sensitivity, specificity, PPV, and NPV were 99%, 94%, 95%, 99%, 85%, 92%, 90%, and 87%, respectively, in the training and validation datasets. The delta-radiomics signature was able to reliably predict R− lmCRC, which were wrongly classified by lesion RECIST as R+ at TP1, (93%, averaging training and validation set, versus 67% of RECIST). The delta-radiomics signature developed in this study can reliably predict the response of individual lmCRC to oxaliplatin-based chemotherapy. Lesions forecasted as poor or nonresponders by the signature could be further investigated, potentially paving the way to lesion-specific therapies

Delta-Radiomics Predicts Response to First-Line Oxaliplatin-Based Chemotherapy in Colorectal Cancer Patients with Liver Metastases

The purpose of this paper is to develop and validate a delta-radiomics score to predict the response of individual colorectal cancer liver metastases (lmCRC) to first-line FOLFOX chemotherapy. Three hundred one lmCRC were manually segmented on both CT performed at baseline and after the first cycle of first-line FOLFOX, and 107 radiomics features were computed by subtracting textural features of CT at baseline from those at timepoint 1 (TP1). LmCRC were classified as nonresponders (R−) if they showed progression of disease (PD), according to RECIST1.1, before 8 months, and as responders (R+), otherwise. After feature selection, we developed a decision tree statistical model trained using all lmCRC coming from one hospital. The final output was a delta-radiomics signature subsequently validated on an external dataset. Sensitivity, specificity, positive (PPV), and negative (NPV) predictive values in correctly classifying individual lesions were assessed on both datasets. Per-lesion sensitivity, specificity, PPV, and NPV were 99%, 94%, 95%, 99%, 85%, 92%, 90%, and 87%, respectively, in the training and validation datasets. The delta-radiomics signature was able to reliably predict R− lmCRC, which were wrongly classified by lesion RECIST as R+ at TP1, (93%, averaging training and validation set, versus 67% of RECIST). The delta-radiomics signature developed in this study can reliably predict the response of individual lmCRC to oxaliplatin-based chemotherapy. Lesions forecasted as poor or nonresponders by the signature could be further investigated, potentially paving the way to lesion-specific therapies

Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis

Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusion