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Sabbatini R.,University Hospital | Ortega C.,Institute for Cancer Research and Treatment IRCC | Procopio G.,Italian National Cancer Institute | Masini C.,University Hospital | And 2 more authors.
Future Oncology | Year: 2013

With seven agents approved for metastatic renal cell carcinoma (RCC) within the past few years, there has undoubtedly been progress in treating this disease. The treatment safety of these new agents, however, now represents a crucial concern, which requires a search for the best possible balance between the minimization of the treatment burden and the need for maintaining appropriate drug dosages able to induce the best clinical benefit. In this review we have analyzed safety data of all approved targeted agents for metastatic RCC available as first-or second-line therapy to provide suggestions aimed at establishing the most appropriate second-line or later treatment on the basis of toxicities that have arisen in therapy. Based on the characteristics and comorbidities of the patients and on the toxicity profile of each treatment, it is possible to plan different therapeutic options. We, therefore, have compiled a list of points that are important to keep in mind when considering the use of the targeted drugs for the treatment of advanced RCC. © 2013 Future Medicine Ltd. Source


Ferrai C.,San Raffaele Scientific Institute | Ferrai C.,Imperial College London | Xie S.Q.,Imperial College London | Luraghi P.,San Raffaele Scientific Institute | And 7 more authors.
PLoS Biology | Year: 2010

The position of genes in the interphase nucleus and their association with functional landmarks correlate with active and/or silent states of expression. Gene activation can induce chromatin looping from chromosome territories (CTs) and is thought to require de novo association with transcription factories. We identify two types of factory: "poised transcription factories," containing RNA polymerase II phosphorylated on Ser5, but not Ser2, residues, which differ from "active factories" associated with phosphorylation on both residues. Using the urokinase-type plasminogen activator (uPA) gene as a model system, we find that this inducible gene is predominantly associated with poised (S5p+S2p-) factories prior to activation and localized at the CT interior. Shortly after induction, the uPA locus is found associated with active (S5p+S2p+) factories and loops out from its CT. However, the levels of gene association with poised or active transcription factories, before and after activation, are independent of locus positioning relative to its CT. RNA-FISH analyses show that, after activation, the uPA gene is transcribed with the same frequency at each CT position. Unexpectedly, prior to activation, the uPA loci internal to the CT are seldom transcriptionally active, while the smaller number of uPA loci found outside their CT are transcribed as frequently as after induction. The association of inducible genes with poised transcription factories prior to activation is likely to contribute to the rapid and robust induction of gene expression in response to external stimuli, whereas gene positioning at the CT interior may be important to reinforce silencing mechanisms prior to induction. © 2009 Ferrai et al. Source


Risio M.,Institute for Cancer Research and Treatment IRCC
Best Practice and Research: Clinical Gastroenterology | Year: 2010

It is well known that adenomas represent the morphologically categorised precursor of the vast majority of colorectal cancers. Only few adenomas actually develop invasive cancer (progressive adenomas), although every adenoma has the capacity of malignant evolution. Most adenomas stabilise their progression or even regress. Easily identifiable but widely ranged pathological features (size, architectural growth, type, grade and gross organisation of dysplasia) are predictive of their natural history in terms of potential of cancerisation and duration of the adenoma-carcinoma sequence. Knowledge of the biological machineries sustaining the progression rates and times could be crucial to refine the natural history assumptions in screening modelling. © 2010 Elsevier Ltd. All rights reserved. Source


Risio M.,Institute for Cancer Research and Treatment IRCC
Best Practice and Research: Clinical Gastroenterology | Year: 2010

It is well known that adenomas represent the morphologically categorised precursor of the vast majority of colorectal cancers. Only few adenomas actually develop invasive cancer (progressive adenomas), although every adenoma has the capacity of malignant evolution. Most adenomas stabilise their progression or even regress. Easily identifiable but widely ranged pathological features (size, architectural growth, type, grade and gross organisation of dysplasia) are predictive of their natural history in terms of potential of cancerisation and duration of the adenoma-carcinoma sequence. Knowledge of the biological machineries sustaining the progression rates and times could be crucial to refine the natural history assumptions in screening modelling. © 2010 Elsevier Ltd. All rights reserved. Source


Biglia N.,University of Turin | Maggiorotto F.,Institute for Cancer Research and Treatment IRCC | Liberale V.,University of Turin | Bounous V.E.,University of Turin | And 4 more authors.
European Journal of Surgical Oncology | Year: 2013

Purpose of the study: A retrospective analysis on 1407 patients with invasive ductal carcinoma (IDC) and 243 invasive lobular carcinoma (ILC) was performed in order to compare the histological features, the immunohistochemical characteristics, the surgical treatment and the clinical outcome in the two groups. Results: ILC seems to be more likely multifocal, estrogen receptor positive, HER-2 negative and to have a lower proliferative index compared to IDC. ILC, when treated with conservative surgery, required more frequently re-excision and/or mastectomy because of positive resection margins. No difference was observed in terms of 5-year disease free survival and local relapse free survival between the two groups, in the whole series and in the subgroup of patients treated with breast-conserving treatment. Conclusion: ILC can be safely treated with conservative surgery but a more accurate preoperative evaluation of tumor size and multifocality could be advocated, in order to reduce the re-excision rate. © 2013 Elsevier Ltd. All rights reserved. Source

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