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Garofalo M.,Ohio State University | Condorelli G.L.,IRCCS MultiMedica | Croce C.M.,Ohio State University | Condorelli G.,University of Naples Federico II | Condorelli G.,CNR Institute of Neuroscience
Cell Death and Differentiation | Year: 2010

Death receptors, belonging to the TNF receptor superfamily, induce apoptosis through two different pathways, one involving the effector caspases directly (type I cells or mitochondria-independent death), the other one amplifying the death signal through the mitochondrial pathway (type II cells or mitochondria-dependent death). MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate the stability or translational efficiency of targeted messenger RNAs. MiRNAs are involved in many cellular processes that are altered in cancer, such as differentiation, proliferation and apoptosis. In this review we will discuss recent findings implicating miRNAs as regulators of death receptors and pro-and antiapoptotic genes involved in programmed cell death pathways. © 2010 Macmillan Publishers Limited All rights reserved.

Krankel N.,University of Zurich | Spinetti G.,IRCCS MultiMedica | Amadesi S.,University of Bristol | Madeddu P.,University of Bristol
Pharmacology and Therapeutics | Year: 2011

Regenerative cardiovascular medicine is the frontline of 21st-century health care. Cell therapy trials using bone marrow progenitor cells documented that the approach is feasible, safe and potentially beneficial in patients with ischemic disease. However, cardiovascular prevention and rehabilitation strategies should aim to conserve the pristine healing capacity of a healthy organism as well as reactivate it under disease conditions. This requires an increased understanding of stem cell microenvironment and trafficking mechanisms. Engagement and disengagement of stem cells of the osteoblastic niche is a dynamic process, finely tuned to allow low amounts of cells move out of the bone marrow and into the circulation on a regular basis. The balance is altered under stress situations, like tissue injury or ischemia, leading to remarkably increased cell egression. Individual populations of circulating progenitor cells could give rise to mature tissue cells (e.g. endothelial cells or cardiomyocytes), while the majority may differentiate to leukocytes, affecting the environment of homing sites in a paracrine way, e.g. promoting endothelial survival, proliferation and function, as well as attenuating or enhancing inflammation. This review focuses on the dynamics of the stem cell niche in healthy and disease conditions and on therapeutic means to direct stem cell/progenitor cell mobilization and recruitment into improved tissue repair. © 2010 Elsevier Inc. All rights reserved.

Cetta F.,IRCCS MultiMedica
Pathology Research International | Year: 2015

Familial Nonmedullary Thyroid Carcinoma (FNMTC) makes up to 5-10% of all thyroid cancers, also including those FNMTC occurring as a minor component of familial cancer syndromes, such as Familial Adenomatous Polyposis (FAP). We give evidence that this extracolonic manifestation of FAP is determined by the same germline mutation of the APC gene responsible for colonic polyps and cancer but also shows some unusual features (F: M ratio = 80: 1, absence of LOH for APC in the thyroid tumoral tissue, and indolent biological behaviour, despite frequent multicentricity and lymph nodal involvement), suggesting that the APC gene confers only a generic susceptibility to thyroid cancer, but perhaps other factors, namely, modifier genes, sex-related factors, or environmental factors, are also required for its phenotypic expression. This great variability is against the possibility of classifying all FNMTC as a single entity, not only with a unique or prevalent causative genetic factor, but also with a unique or common biological behavior and a commonly dismal prognosis. A new paradigm is also suggested that could be useful (1) for a proper classification of FAP associated PTC within the larger group of FNMTC and (2) for making inferences to sporadic carcinogenesis, based on the lesson from FAP. © 2015 Francesco Cetta.

Introduction: Type 2 diabetes mellitus (T2DM) is associated not only with high direct healthcare costs, but also with indirect costs, as diabetic complications and the disease itself result in loss of productivity. Vildagliptin is a novel dipeptidyl peptidase-4 inhibitor that is given either alone or in combination with oral hypoglycemic drugs, including metformin. The study was designed to assess the hypothesis that fixed-combination vildagliptin/metformin improves work productivity measured as Work Productivity and Activity Impairment (WPAI) scores. Secondary objectives were the assessment of patient satisfaction by means of the Diabetes Treatment Satisfaction Questionnaire (DTSQs), the change in anthropometric measurements and in glucose control (glycated hemoglobin [HbA1c]), and the evaluation of resource utilization (Resources Utilization Questionnaire). Methods: This study was an addendum to a mandatory, prospective, observational study carried out by the Italian Medicines Agency (Agenzia Italiana del Farmaco [AIFA]) in 49 diabetes centers in Italy. The addendum included 1,046 adult outpatients with a diagnosis of T2DM, who were no longer responding to metformin monotherapy. Patients were observed for up to 1 year. Results: Mean activity impairment improved by 40.6% (15.4 ± 17.4 vs. 26.1 ± 24.4; P < 0.0001), absenteeism by 49.9% (2.0 ± 9.4 vs. 3.8 ± 13.3; P = 0.0076), and total work productivity by 37.6% (14.9 ± 15.9 vs. 21.5 ± 24.6; P < 0.0001). This resulted in a reduction of the annual indirect cost due to impaired productivity of €400 per working patient and €135 per patient in general. The DTSQ score increased by 30.2% (29.6 ± 5.6 vs. 22.8 ± 6.9; P < 0.0001). The satisfaction rate increased from baseline by 44.7%; the hyperglycemia-free or almost hyperglycemia-free perception rate by 37.9%; and the hypoglycemia- free or almost hypoglycemia-free rate by 15.2%. Mean healthcare costs per patients diminished by 19.2% in the second semester of treatment. Conclusion: This observational study suggests that the fixed combination of vildagliptin/ metformin increases work productivity, reducing indirect costs, and improves quality of life, especially in terms of perception of blood glucose variability, in patients with T2DM. © The Author(s) 2013.

Albini A.,IRCCS MultiMedica | Tosetti F.,Azienda Ospedaliera Universitaria San Martino | Li V.W.,Institute for Advanced Studies | Noonan D.M.,University of Insubria | Li W.W.,Institute for Advanced Studies
Nature Reviews Clinical Oncology | Year: 2012

Healthy individuals can harbour microscopic tumours and dysplastic foci in different organs in an undetectable and asymptomatic state for many years. These lesions do not progress in the absence of angiogenesis or inflammation. Targeting both processes before clinical manifestation can prevent tumour growth and progression. Angioprevention is a chemoprevention approach that interrupts the formation of new blood vessels when tumour cell foci are in an indolent state. Many efficacious chemopreventive drugs function by preventing angiogenesis in the tumour microenvironment. Blocking the vascularization of incipient tumours should maintain a dormancy state such that neoplasia or cancer exist without disease. The current limitations of antiangiogenic cancer therapy may well be related to the use of antiangiogenic agents too late in the disease course. In this Review, we suggest mechanisms and strategies for using antiangiogenesis agents in a safe, preventive clinical angioprevention setting, proposing different levels of clinical angioprevention according to risk, and indicate potential drugs to be employed at these levels. Finally, angioprevention may go well beyond cancer in the prevention of a range of chronic disorders where angiogenesis is crucial, including different forms of inflammatory or autoimmune diseases, ocular disorders, and neurodegeneration. © 2012 Macmillan Publishers Limited. All rights reserved.

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