Effects of PPARs Agonists on Cardiac Metabolism in Littermate and Cardiomyocyte-Specific PPAR-γ –Knockout (CM-PGKO) Mice

Understanding the molecular regulatory mechanisms controlling for myocardial lipid metabolism is of critical importance for the development of new therapeutic strategies for heart diseases. The role of PPARγ and thiazolidinediones in regulation of myocardial lipid metabolism is controversial. The aim of our study was to assess the role of PPARγ on myocardial lipid metabolism and function and differentiate local/from systemic actions of PPARs agonists using cardiomyocyte-specific PPARγ –knockout (CM-PGKO) mice. To this aim, the effect of PPARγ, PPARγ/PPARα and PPARα agonists on cardiac function, intra-myocyte lipid accumulation and myocardial expression profile of genes and proteins, affecting lipid oxidation, uptake, synthesis, and storage (CD36, CPT1MIIA, AOX, FAS, SREBP1-c and ADPR) was evaluated in cardiomyocyte-specific PPARγ –knockout (CM-PGKO) and littermate control mice undergoing standard and high fat diet (HFD). At baseline, protein levels and mRNA expression of genes involved in lipid uptake, oxidation, synthesis, and accumulation of CM-PGKO mice were not significantly different from those of their littermate controls. At baseline, no difference in myocardial lipid content was found between CM-PGKO and littermate controls. In standard condition, pioglitazone and rosiglitazone do not affect myocardial metabolism while, fenofibrate treatment significantly increased CD36 and CPT1MIIA gene expression. In both CM-PGKO and control mice submitted to HFD, six weeks of treatment with rosiglitazone, fenofibrate and pioglitazone lowered myocardial lipid accumulation shifting myocardial substrate utilization towards greater contribution of glucose. In conclusion, at baseline, PPARγ does not play a crucial role in regulating cardiac metabolism in mice, probably due to its low myocardial expression. PPARs agonists, indirectly protect myocardium from lipotoxic damage likely reducing fatty acids delivery to the heart through the actions on adipose tissue. Nevertheless a direct non- PPARγ mediated mechanism of PPARγ agonist could not be ruled out

Long-term local disease control in a recurrent soft-tissue sarcoma of the thigh treated by radiofrequency ablation

In 2008, we performed radiofrequency ablation (RFA) in an elderly patient with a large recurrent soft-tissue sarcoma of the thigh, previously treated with surgery and radiotherapy. After ablation, a marked shrinkage of tumor was obtained. Further local recurrences occurred during follow-up, all safely treated by RFA, with local control of the disease maintained until 6-year follow-up. RFA was safe, effective, and repeatable for soft-tissue sarcoma recurrences, and allowed long-term local control of the disease. J. Surg. Oncol. 2015 111:708-710. (c) 2015 Wiley Periodicals, Inc

A Nanoplasmonic-Based Biosensing Approach for Wide-Range and Highly Sensitive Detection of Chemicals

In a specific biosensing application, a nanoplasmonic sensor chip has been tested by an experimental setup based on an aluminum holder and two plastic optical fibers used to illuminate and collect the transmitted light. The studied plasmonic probe is based on gold nanograting, realized on the top of a Poly(methyl methacrylate) (PMMA) chip. The PMMA substrate could be considered as a transparent substrate and, in such a way, it has been already used in previous work. Alternatively, here it is regarded as a slab waveguide. In particular, we have deposited upon the slab surface, covered with a nanograting, a synthetic receptor specific for bovine serum albumin (BSA), to test the proposed biosensing approach. Exploiting this different experimental configuration, we have determined how the orientation of the nanostripes forming the grating pattern, with respect to the direction of the input light (longitudinal or orthogonal), influences the biosensing performances. For example, the best limit of detection (LOD) in the BSA detection that has been obtained is equal to 23 pM. Specifically, the longitudinal configuration is characterized by two observable plasmonic phenomena, each sensitive to a different BSA concentration range, ranging from pM to µM. This aspect plays a key role in several biochemical sensing applications, where a wide working range is required

A Nanoplasmonic-Based Biosensing Approach for Wide-Range and Highly Sensitive Detection of Chemicals

In a specific biosensing application, a nanoplasmonic sensor chip has been tested by an experimental setup based on an aluminum holder and two plastic optical fibers used to illuminate and collect the transmitted light. The studied plasmonic probe is based on gold nanograting, realized on the top of a Poly(methyl methacrylate) (PMMA) chip. The PMMA substrate could be considered as a transparent substrate and, in such a way, it has been already used in previous work. Alternatively, here it is regarded as a slab waveguide. In particular, we have deposited upon the slab surface, covered with a nanograting, a synthetic receptor specific for bovine serum albumin (BSA), to test the proposed biosensing approach. Exploiting this different experimental configuration, we have determined how the orientation of the nanostripes forming the grating pattern, with respect to the direction of the input light (longitudinal or orthogonal), influences the biosensing performances. For example, the best limit of detection (LOD) in the BSA detection that has been obtained is equal to 23 pM. Specifically, the longitudinal configuration is characterized by two observable plasmonic phenomena, each sensitive to a different BSA concentration range, ranging from pM to µM. This aspect plays a key role in several biochemical sensing applications, where a wide working range is required

Percutaneous CT-guided irreversible electroporation followed by chemotherapy as a novel neoadjuvant protocol in locally advanced pancreatic cancer: Our preliminary experience

Introduction: Irreversible electroporation (IRE) is a non-thermal ablation technique recently used in pancreatic cancer. In our prospective study we evaluated safety, feasibility and efficacy of a neoadjuvant protocol based on CT-guided percutaneous IRE followed by chemotherapy in patients with locally advanced pancreatic cancer (LAPC).Methods: We performed CT-guided percutaneous IRE in 20 patients with LAPC, followed by a combination of gemcitabine (1000 mg/mq) and oxaliplatin (100 mg/mq) biweekly. Imaging follow-up was performed by a contrast enhanced CT scan at 1, 3, 6 months and then every 3 months.Results: No major complications occurred. Two patients died 3 and 4 months after IRE because of rapidly progressive disease. In the remaining 18 patients 6-month imaging follow-up showed a mean lesions volumetric decrease percentage of 42.89% (95% Confidence Interval: 34.90e54.88%). Thanks to lesions downstaging, three patients underwent R0 resection. At last available follow-up (mean follow-up 91 months; range 6-14), imaging showed no disease progression or post-surgical relapse in all 18 cases. The mean estimated survival was 12,950 months (95% CI: 11,570-14,332).Conclusions: Our preliminary study suggests that IRE followed by chemotherapy is safe, feasible and effective in producing local control of LAPC, with a possible downstaging effect to resectable lesions. (C) 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved

Multiparametric MRI for prostate cancer detection: Performance in patients with prostate-specific antigen values between 2.5 and 10 ng/mL

Purpose To assess the diagnostic performance of multiparametric MRI (mpMRI), in the detection of prostate cancer, including morphologic sequences (mMRI), diffusion-weighted imaging (DWI), and MR spectroscopy (MRS). Combined morphological and functional MRI scoring systems was used for urological–radiological work-up of patients with a prostate-specific antigen (PSA) value ≤ 10 ng/mL. Materials and Methods The study included 136 of 200 consecutive patients with PSA values between 2.5 and 4 ng/mL and an abnormal digital rectal examination (DRE), or patients with PSA values between 4 and 10 ng/mL, independently from DRE. Each patient provided informed consent to undergo at serum free/total PSA ratio (f/t PSA) assay, mMRI, MRS, DWI, and transrectal ultrasonography (TRUS) biopsy. The MRI datasets were scored singularly; then mMRI and DWI, mMRI and MRS data were combined in a coupled score, and finally mMRI, DWI, and MRS data were combined in a single score (cMRI score). Results Scores were correlated to negative biopsies and significant/insignificant Gleason score biopsies. Receiver-operator-characteristic curve and McNemar tests were performed. Cancer was diagnosed in 18% of patients. The cMRI score showed: (i) the highest sensitivity (0.84) and negative predictive value (0.93); (ii) a significant correlation with Gleason score; and (iii) a statistically different median value between significant and insignificant Gleason score. Conclusion The cMRI score could identify patients with a PSA≤10 ng/mL who will have a negative work-up, for its high negative predictive value, and patients at high risk for significant prostate cancer because of its correlation with the Gleason score