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Gandellini P.,Fondazione Istituto Nazionale Tumori
Discovery medicine | Year: 2010

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression. Recent findings indicate that miRNAs are dysregulated in human tumors, suggesting a potential role for these molecules in the pathogenesis of cancer. Thus far, only a limited number of studies have investigated miRNA expression in prostate cancer. Results from these studies indicate that miRNA expression profiles may distinguish carcinoma from non-neoplastic specimens and further classify tumors according to androgen dependence. In addition, a prognostic significance was attributed to specific miRNAs as predictors of clinical recurrence following radical prostatectomy. For a handful of miRNAs, for which a widespread dysregulation in prostate cancer was consistently found, functional investigation has been pursued in prostate cancer experimental models to establish the rationale for the development of miRNA-based therapies. A better understanding of the role exerted by specific miRNAs in the development and progression of prostate cancer is needed, as is a precise definition of their targets relevant to the disease. However, based on available findings, a possible role for miRNAs in the management of prostate cancer as novel biomarkers and new therapeutic targets or intervention tools can be envisioned.

Dallavalle S.,University of Milan | Pisano C.,Oncology Area RandD Sigma Tau S.p.A. | Zunino F.,Fondazione Istituto Nazionale Tumori
Biochemical Pharmacology | Year: 2012

Histone deacetylases (HDAC) play a key role in regulating gene expression by deacetylating histones. Some HDAC isoforms can also modulate the function of nonhistone proteins implicated in regulatory processes, and therefore HDACs are recognized as useful targets for therapeutic purposes. HDAC inhibitors have generated substantial interest as antitumor agents, because they induce various cellular effects, including apoptosis, cell cycle arrest and inhibition of angiogenesis. The nature of cellular response likely depends on the biological context and on the pattern of HDAC isoform inhibition. Various HDAC inhibitors belonging to different structural classes have been developed. Many inhibitors are characterized by a pan-HDAC inhibitory profile. The potential advantages of isoform-selective inhibitors over pan-HDAC inhibitors in terms of efficacy or toxicity remain to be defined. The emerging interest for HDAC6-selective inhibitors is related to the modulation of acetylation of nonhistone regulatory proteins implicated in cancer-relevant processes, including cell migration, metastasis, angiogenesis and stress-response pathways. This review is focused on the recent development of HDAC inhibitors, with particular reference to HDAC6-selective inhibitors, and the efforts and perspectives in optimization of their therapeutic applications. © 2012 Elsevier Inc. All rights reserved.

Dragani T.A.,Fondazione Istituto Nazionale Tumori
Journal of Hepatology | Year: 2010

Hepatocellular carcinoma (HCC) is a common form of cancer that arises from hepatocytes and whose risk may be affected by several known environmental factors, including hepatitis viruses, alcohol, cigarette smoking, and others. Rare monogenic syndromes, such as alpha1-antitrypsin deficiency, glycogen storage disease type I, hemochromatosis, acute intermittent and cutanea tarda porphyria, as well as hereditary tyrosinemia type I are associated with a high risk of HCC. Several common conditions or diseases inherited as polygenic traits e.g. autoimmune hepatitis, type 2 diabetes, a family history of HCC, hypothyroidism, and non-alcoholic steatohepatitis also show an increased risk of HCC compared to the general population. Overall, the genetic susceptibility to HCC is characterized by a genetic heterogeneity; a high individual risk of HCC may thus be caused by several unlinked single gene defects, whose carriers are rare in the general population, or by more common conditions inherited by complex genetics. © 2009 European Association for the Study of the Liver.

Procopio G.,Fondazione Istituto Nazionale Tumori
Expert review of anticancer therapy | Year: 2011

Mounting evidence suggests that, in order to optimize therapeutic benefits, it is important to consider the range of parameters and characteristics relevant to each individual patient. Of note, the six targeted therapies currently approved for the treatment of advanced/metastatic renal cell carcinoma have not been evaluated in all relevant settings and in all prognostic groups. Among different agents currently licensed for the treatment of renal cell carcinoma, sorafenib was the first therapy to show improvements in progression-free survival and overal survival in Phase III trials. This article will discuss the current role of sorafenib in the treatment of elderly patients with renal cell carcinoma.

Demicheli R.,Fondazione Istituto Nazionale Tumori | Coradini D.,University of Milan
Annals of Oncology | Year: 2011

The study of complex systems has clearly evidenced that a few overall behavioural properties cannot be inferred from the properties of their single parts and are rather determined by their architecture. Such an approach has been recently proposed in biology to understand genome functioning and in oncology to endeavour a more consistent explanation of the variegated cancer behaviours. In the present perspective, we summarise the basic concepts of the proposed global approach and then we reconsider, in this new context, tumour dormancy and primary tumour removal effects, which recently emerged as critical points for breast cancer understanding. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

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