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Pineda M.,Translational Research Laboratory and Cancer Genetic Counseling Program | Gonzalez S.,Translational Research Laboratory and Cancer Genetic Counseling Program | Lazaro C.,Translational Research Laboratory and Cancer Genetic Counseling Program | Blanco I.,Institute Catala dOncologia IDIBELL | Capella G.,Translational Research Laboratory and Cancer Genetic Counseling Program
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis | Year: 2010

There are two major hereditary colorectal cancer syndromes: Adenomatous Polyposis, secondary to APC germline alterations (FAP, Familial Adenomatous Polyposis) or secondary to MUTYH germline alterations (MAP, MUTYH associated Polyposis), and Lynch syndrome, associated with germline mutations in mismatch repair genes (MLH1, MSH2, MSH6 and PMS2). The elucidation of their genetic basis has depicted an increasingly complex picture that has lead to the implementation of complex diagnostic algorithms that include both tumor profiling and germline analyses. A variety of techniques at the DNA, RNA and protein level are used to screen for molecular alterations both in tumor biopsies (microsatellite instability analysis, mismatch repair protein immunohistochemistry, BRAF-Val600Glu detection and MLH1 promoter hypermethylation analysis) and in the germline (point mutation screening, copy number assessment). Also functional tests are more often used to characterize variants of unknown significance. Methodological issues associated with the techniques analyzed, as well as the algorithms used, are discussed. © 2009 Elsevier B.V.

Alemany R.,Institute Catala dOncologia IDIBELL
Advances in Cancer Research | Year: 2012

During the last decade adenovirus has lost its appeal in gene therapy due to a high immunogenicity that leads to a transient gene expression. However, adenovirus has gained attention as replication-competent vector to treat cancer. Designed for virotherapy, adenovirus has been successfully modified to replicate selectively in tumor cells. After the initial clinical trials with tumor-selective adenoviruses, it has become clear that further improvements on tumor targeting, intratumoral dissemination, and modulation of antiviral and antitumor immune responses are needed to effectively treat cancer. The non-viral delivery of infectious DNA encoding an oncolytic adenovirus armed with extracellular matrix-degrading genes and with genes that regulate the immune system to favor antitumor instead of antiviral immunity are key in the design oncolytic adenovirus. © 2012 Elsevier Inc.

Gallus S.,Istituto di Ricerche Farmacologiche Mario Negri | Muttarak R.,Istituto di Ricerche Farmacologiche Mario Negri | Muttarak R.,University of Florence | Martinez-Sanchez J.M.,Institute Catala dOncologia IDIBELL | And 4 more authors.
Preventive Medicine | Year: 2011

Objective: To provide updated information on smoking prevalence and attributable mortality in Italy. Method: A representative survey on smoking was conducted in 2010 on a sample of 3020 Italian adults (1453 men and 1567 women). We used SAMMEC software to update smoking attributable mortality in Italy. Results: In 2010, 21.7% of Italians (23.9% of men and 19.7% of women) described themselves as current smokers. Smoking prevalence was higher in men than in women in all age groups, except for the middle-aged population (45-64. years; 25.6% in men and 25.9% in women). Age-standardized smoking prevalence was higher in men than in women among less educated subjects and in southern Italy. No substantial difference was observed either in educated subjects or in northern and central Italy. Overall, 71,445 deaths in Italy (52,707 men and 18,738 women, 12.5% of total mortality) are attributable to smoking. Conclusion: The overall smoking prevalence of 21.7% in 2010 is the lowest registered over the last 50. years. Since 1998, smoking related deaths declined by almost 15%. Given that Italy has now reached the final stage of the tobacco epidemic, anti-smoking strategies should focus on support for smoking cessation. © 2011 Elsevier Inc.

Garcia-Carbonero R.,Hospital Universitario Virgen Del Rocio | Salazar R.,Institute Catala dOncologia IDIBELL | Sevilla I.,Hospital Virgen de la Victoria | Isla D.,Hospital Lozano Blesa
Clinical and Translational Oncology | Year: 2011

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) represent a heterogenous family of tumours with growing incidence and challenging clinical management. Unlike other solid tumours, they have the ability to secrete different peptides and neuramines that cause distinct clinical syndromes. However, many are clinically silent until advanced disease. This guideline aims to provide practical recommendations for the diagnosis and treatment of GEP NETs. Most recent histological and staging classifications, as well as available therapeutic approaches, such as surgery, locoregional therapy, peptide receptor radionuclide therapy (PRRT) and hormonal or systemic therapy, are discussed in this manuscript, including some recent relevant achievements with novel targeted agents. Clinical presentation (with or without hormonal syndrome), histological tumour features (including proliferation index (Ki-67) and the presence or not of somatostatin receptors), tumour stage, and location of primary tumour and distant metastasis are all key issues that shall be taken into consideration to properly design and integrate the most adequate therapeutic strategy.

Coleman R.,University of Sheffield | Cameron D.,University of Edinburgh | Dodwell D.,University of Leeds | Bell R.,Andrew Love Cancer Center | And 12 more authors.
The Lancet Oncology | Year: 2014

Background: The role of adjuvant bisphosphonates in early breast cancer is uncertain. We therefore did a large randomised trial to investigate the effect of the adjuvant use of zoledronic acid on disease-free survival (DFS) in high-risk patients with early breast cancer. Methods: In the AZURE trial, an open-label, international, multicentre, randomised, controlled, parallel-group phase 3 trial, women (age ≥18 years) with stage II or III breast cancer were randomly assigned (1:1) by a central automated 24-h computer-generated telephone minimisation system (balanced for number of involved axillary lymph nodes, tumour stage, oestrogen receptor status, type and timing of systemic therapy, menopausal status, statin use, and treatment centre) to receive standard adjuvant systemic treatment alone (control group) or with 4 mg intravenous zoledronic acid every 3-4 weeks for six doses, then every 3 months for eight doses, followed by every 6 months for five doses, for a total of 5 years of treatment. The primary endpoint was disease-free survival (DFS). Secondary endpoints were invasive DFS (IDFS), overall survival, time to bone metastases, time to distant recurrence, and subgroup analyses of variables included in the randomisation. All patients have completed study treatment. Results from the intention-to-treat final analysis of this fully recruited study are presented after a median follow-up of 84 months (IQR 66-93). This final efficacy analysis was planned to take place after 940 DFS events. This trial is registered with ClinicalTrials.gov, NCT00072020. Findings: 3360 women were recruited from 174 centres in seven countries between Sept 4, 2003, and Feb 16, 2006. The number of DFS events did not differ between groups: 493 in the control group and 473 in the zoledronic acid group (adjusted hazard ratio [HR] 0·94, 95% CI 0·82-1·06; p=0·30). IDFS (HR 0·93, 95% CI 0·82-1·05; p=0·22), overall survival (0·93, 0·81-1·08; p=0·37), and distant recurrences (0·93, 0·81-1·07; p=0·29) were much the same in both groups. Zoledronic acid reduced the development of bone metastases, both as a first event (HR 0·78, 95% CI 0·63-0·96; p=0·020) and at any time during follow-up (0·81, 0·68-0·97; p=0·022). The effects of zoledronic acid on DFS were not affected by oestrogen-receptor status. However, zoledronic acid improved IDFS in those who were over 5 years since menopause at trial entry (n=1041; HR 0·77, 95% CI 0·63-0·96) but not in all other (premenopause, perimenopause, and unknown status) menopausal groups (n=2318; HR 1·03, 95% CI 0·89-1·20). 33 cases of suspected osteonecrosis of the jaw have been reported, with 26 confirmed on central review, all in the zoledronic acid group (1·7%, 95% CI 1·0-2·4). Interpretation: These results suggest no overall benefit from the addition of zoledronic acid to standard adjuvant treatments for early breast cancer. However, zoledronic acid does reduce the development of bone metastases and, for women with established menopause, improved disease outcomes. © 2014 Elsevier Ltd.

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