A comparative approach to understanding tissue-specific expression of uncoupling protein 1 expression in adipose tissue

Peer reviewedPublisher PD

HOX D13 expression across 79 tumor tissue types.

HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Locus D HOX genes play an important role in limb generation and mesenchymal condensation. Dysregulated HOXD13 expression has been detected in breast cancer, melanoma, cervical cancer and astrocytomas. We have investigated the epidemiology of HOXD13 expression in human tissues and its potential deregulation in the carcinogenesis of specific tumors. HOXD13 homeoprotein expression has been detected using microarray technology comprising more than 4,000 normal and neoplastic tissue samples including 79 different tumor categories. Validation of HOXD13 expression has been performed, at mRNA level, for selected tumor types. Significant differences are detectable between specific normal tissues and corresponding tumor types with the majority of cancers showing an increase in HOXD13 expression (16.1% normal vs. 57.7% cancers). In contrast, pancreas and stomach tumor subtypes display the opposite trend. Interestingly, detection of the HOXD13 homeoprotein in pancreas-tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer independent of the T or N stage at the time of diagnosis. Our study provides, for the first time, an overview of a HOX protein expression in a large series of normal and neoplastic tissue types, identifies pancreatic cancer as one of the most affected by the HOXD13 hoemoprotein and underlines the way homeoproteins can be associated to human cancerogenesis

Hepatocellular carcinoma in adult thalassemia patients: an expert opinion based on current evidence

Beta-thalassemia represents a heterogeneous group of haemoglobin inherited disorders, among the most common genetic diseases in the world, frequent in the Mediterranean basin. As beta-thalassemia patients' survival has increased over time, previously unknown complications are observed with increasing frequency. Among them, an increased risk of hepatocellular carcinoma (HCC) has been registered. Our aim is to reduce inequalities in diagnosis and treatment and to offer patients univocal recommendations in any institution. The members of the panel - gastroenterologists, radiologists, surgeons and oncologists -were selected on the basis of their publication records and expertise. Thirteen clinical questions, derived from clinical needs, and an integration of all the committee members' suggestions, were formulated. Modified Delphi approach involving a detailed literature review and the collective judgement of experts, was applied to this work. Thirteen statements were derived from expert opinions' based on the current literature, on recently developed reviews and on technological advancements. Each statement is discussed in a short paragraph reporting the current key evidence. As this is an emerging issue, the number of papers on HCC in beta-thalassemia patients is limited and based on anecdotal cases rather than on randomized controlled studies. Therefore, the panel has discussed, step by step, the possible differences between beta-thalassemia and non beta-thalassemia patients. Despite the paucity of the literature, practical and concise statements were generated. This paper offers a practical guide organized by statements describing how to manage HCC in patients with beta-thalassemia

First record of Ozognathus cornutus (LeConte, 1859) (Coleoptera Ptinidae) from Sardinia, Italy.

Ozognathus cornutus (LeConte, 1859) is recorded on the invasive alien tree Robinia pseudocacia L. (Fabaceae) in an urban area in Italy. The species has already been reported in two other Italian regions, but this is the first record for the Sardinian fauna. Due to the great adaptability of this alien species and the increasingly cosmopolitan trend, we suggest monitoring it with caution for early detection and to plan an appropriate rapid management response

Molecular Refinement of Clinical Staging in Hepatocellular Carcinoma Patients Evaluated for Potentially Curative Therapies

Abstract: Aim: VEGF and AFP mRNA determinations in the blood are promising prognostic factors for patients with HCC. This study explores their potential prognostic synergy in a cohort of HCC patients evaluated for potentially curative therapies. Methods: One hundred twenty-four patients with a diagnosis of HCC were prospectively enrolled in the study. Inclusion criteria were: (a) histological diagnosis of HCC and assessment of tumour grade and (b) determination of AFP mRNA status and VEGF levels in the blood before therapy. Results: At baseline evaluation, 40% of the study group had AFP mRNA in the blood (AFP mRNA positive), and 35% had VEGF > 23 pg ml(-1) (VEGF positive). Surgery was performed in 58 patients (47%), 54 (43%) had tumour ablation, and 12 had chemoembolisation (10%). Median follow-up and survival of the study group were 19 and 26 months (range, 1 to 60), respectively. The association of AFP mRNA and VEGF proved to be prognostically more accurate than their single use in discriminating the risk of death (ROC curve analysis) and survival probability (Cox analysis). In particular, we identified 3 main molecular stages (p < 0,0001): both negative (3-year survival = 63%), one positive (3-year survival = 40%), both positive (3-year survival = 16%). Multivariate analysis identified BCLC staging, surgery, and molecular staging as the most significant survival variables. Conclusions: The preoperative determination of AFP mRNA status and VEGF may potentially refine the prognostic evaluation of HCC patients and improve the selection process for potentially curative therapies

The hemodynamics of aneurysms treated with flow-diverting stents considering both stent and aneurysm/artery geometries

Flow diverting stents are deployed to reduce the blood flow into the aneurysm, which would thereby induce thrombosis in the aneurysm sac; the stents prevent its rupture. The present study aimed to examine and quantify the impacts of different flow stents on idealized configurations of the cerebral artery. In our study, we considered a spherical sidewall aneurysm located on curved and tortuous idealized artery vessels and three stents with different porosities (70, 80 and 90%) for deployment. Using computational fluid dynamics, the local hemodynamics in the presence and absence of the stents were simulated, respectively, under the assumption that the blood flow was unsteady and non-Newtonian. The hemodynamic parameters, such as the intra-aneurysmal flow, velocity field and wall shear stress and its related indices, were examined and compared among the 12 cases simulated. The results illustrated that with the stent deployment, the intra-aneurysmal flow and the wall shear stress and its related indices were considerably modified depending on both stent and aneurysm/artery geometries, and that the intra-aneurysmal relative residence time increased rapidly with decreasing stent porosity in all the vessel configurations. These results also inform the rationale for selecting stents for treating aneurysms of different configurations.This research was funded by the Saskatchewan Health Research Foundation (SHRF grant reference #2784). M. Malvè was supported by grant PRX17/00335 financed by the Spanish Ministry of Education within the National Program 'Salvador de Madariaga'. The support of the Spanish Ministry of Economy, Industry and Competitiveness through research project DPI2017-83259-R (AEI/FEDER, UE) and of the Department of Economic Development of the Navarra Government through research project PC086-087-088 CONDE is highly appreciated. Finally, we gratefully acknowledge the Instituto de Salud Carlos III (ISCIII) through the CIBER-BBN initiative.This research was funded by the Saskatchewan Health Research Foundation (SHRF grant reference #2784). M. Malvé was supported by grant PRX17/00335 financed by the Spanish Ministry of Education within the National Program "Salvador de Madariaga." The support of the Spanish Ministry of Economy, Industry and Competitiveness through research project DPI2017-83259-R (AEI/FEDER, UE) and of the Department of Economic Development of the Navarra Government through research project PC086-087-088 CONDE is highly appreciated. Finally, we gratefully acknowledge the Instituto de Salud Carlos III (ISCIII) through the CIBER-BBN initiative

SerpinB3 as hepatic marker of post-resective shear stress

Post-resective liver failure is a frequent complication of liver surgery and it is due to portal hyperperfusion of the remnant liver and to arterial vasoconstriction, as buffer response of the hepatic artery. In this context, splenectomy allows a reduction of portal flow and increases the survival chance in preclinical models. SerpinB3 is over-expressed in the liver in oxidative stress conditions, as a mechanism of cell defense to provide survival by apoptosis inhibition and cell proliferation. In this study, the expression of SerpinB3 was assessed as predictor of liver damage in in vivo models of major hepatic resection with or without splenectomy. Wistar male rats were divided into 4 groups: group A received 30% hepatic resection, group B > 60% resection, group C > 60% resection with splenectomy and group D sham-operated. Before and after surgery liver function tests, echo Doppler ultrasound and gene expression were assessed. Transaminase values and ammonium were significantly higher in groups that underwent major hepatic resection. Echo Doppler ultrasound showed the highest portal flow and resistance of the hepatic artery in the group with > 60% hepatectomy without splenectomy, while the association of splenectomy determined no increase in portal flow and hepatic artery resistance. Only the group of rats without splenectomy showed higher shear-stress conditions, reflected by higher levels of HO-1, Nox1 and of Serpinb3, the latter associated with an increase of IL-6. In conclusion, splenectomy controls inflammation and oxidative damage, preventing the expression of Serpinb3. Therefore, SerpinB3 can be considered as a marker of post-resective shear stress

Liver transplantation is a preferable alternative to palliative therapy for selected patients with advanced hepatocellular carcinoma

Background: Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT). Materials & Methods: All patients listed in the Toronto liver transplant program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiological images were reviewed by two independent radiologists. The primary endpoint was patient survival. Results: Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p=0.02) and tumor burden (p <0.001). The majority of those listed underwent LT (n=69, 72%). Both tumor progression on waiting list (HR 4.973 [1.599 – 15.464], p=0.006) and peak AFP ≥400ng/ml (HR 4.604 [1.660 – 12.768], p=0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% (n=24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p=0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93%, 71%, and 66%. Conclusion: LT provides significantly better survival rates than palliation for patients with selected advanced HCC