Santa Maria Nuova, Italy
Santa Maria Nuova, Italy

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Bonanno L.,Instituto Oncologico Veneto Irccs | Costa C.,Laboratory of translational Oncology | Majem M.,Claret Medical | Sanchez J.-J.,Autonomous University of Madrid | And 11 more authors.
BMC Cancer | Year: 2016

Background: BRCA1 is a main component of homologous recombination and induces resistance to platinum in preclinical models. It has been studied as a potential predictive marker in lung cancer. Several proteins modulate the function of BRCA1. The E3 ubiquitin ligase HERC2 facilitates the assembly of the RNF8-UBC13 complex to recruit BRCA1 to DNA damage sites. The combined analysis of multiple components of the pathway leading to the recruitment of BRCA1 at DNA damage sites has the potentiality to improve the BRCA1 predictive model. Methods: We retrospectively analyzed 71 paraffin-embedded tumor samples from advanced non-small-cell lung cancer patients treated with first-line platinum based chemotherapy and measured the mRNA expression levels of BRCA1, RNF8, UBC13 and HERC2 using real-time PCR. The mRNA expression was categorized using median value as cut-off point. Results: The median progression-free survival of all 71 patients was 7.2 months whereas the median overall survival of the study population was 10.7 months. Among patients with low BRCA1 expression, the median PFS was 7.4 months in the presence of low HERC2 levels and 5.9 months for patients expressing high HERC2 levels (p = 0.01). The median OS was 15.3 months for patients expressing low levels of both genes and 7.4 months for those with low BRCA1 but high HERC2 (p = 0.008). The multivariate analysis showed that among patients with Eastern Cooperative Oncology Group performance status 0-1, the combined low expression of both BRCA1 and HERC2 clearly reduced the risk of progression (p = 0.03) and of death (p = 0.004). Conclusions: These findings confirm the potentiality of integrated DNA repair components analysis in predicting the sensitivity to platinum in lung cancer. The study indicates a predictive role for HERC2 mRNA expression and paves the way for further refinement of the BRCA1 predictive model. © 2016 Bonanno et al.


PubMed | Claret Medical, University of Padua, Hospital du Cluzeau, General Hospital of Alicante and 5 more.
Type: | Journal: BMC cancer | Year: 2016

BRCA1 is a main component of homologous recombination and induces resistance to platinum in preclinical models. It has been studied as a potential predictive marker in lung cancer. Several proteins modulate the function of BRCA1. The E3 ubiquitin ligase HERC2 facilitates the assembly of the RNF8-UBC13 complex to recruit BRCA1 to DNA damage sites. The combined analysis of multiple components of the pathway leading to the recruitment of BRCA1 at DNA damage sites has the potentiality to improve the BRCA1 predictive model.We retrospectively analyzed 71 paraffin-embedded tumor samples from advanced non-small-cell lung cancer patients treated with first-line platinum based chemotherapy and measured the mRNA expression levels of BRCA1, RNF8, UBC13 and HERC2 using real-time PCR. The mRNA expression was categorized using median value as cut-off point.The median progression-free survival of all 71 patients was 7.2months whereas the median overall survival of the study population was 10.7months. Among patients with low BRCA1 expression, the median PFS was 7.4months in the presence of low HERC2 levels and 5.9months for patients expressing high HERC2 levels (p=0.01). The median OS was 15.3months for patients expressing low levels of both genes and 7.4months for those with low BRCA1 but high HERC2 (p=0.008). The multivariate analysis showed that among patients with Eastern Cooperative Oncology Group performance status 0-1, the combined low expression of both BRCA1 and HERC2 clearly reduced the risk of progression (p=0.03) and of death (p=0.004).These findings confirm the potentiality of integrated DNA repair components analysis in predicting the sensitivity to platinum in lung cancer. The study indicates a predictive role for HERC2 mRNA expression and paves the way for further refinement of the BRCA1 predictive model.


Marin-Aguilera M.,Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Reig O.,Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS | Reig O.,Hospital Clinic | Lozano J.J.,CIBER ISCIII | And 12 more authors.
Oncotarget | Year: 2015

The enumeration of circulating tumor cells (CTCs) in peripheral blood correlates with clinical outcome in castration-resistant prostate cancer (CRPC). We analyzed the molecular profiling of peripheral blood from 43 metastatic CRPC patients with known CTC content in order to identify genes that may be related to prostate cancer progression. Global gene expression analysis identified the differential expression of 282 genes between samples with ≥5 CTCs vs <5 CTCs, 58.6% of which were previously described as over-expressed in prostate cancer (18.9% in primary tumors and 56.1% in metastasis). Those genes were involved in survival functions such as metabolism, signal transduction, gene expression, cell growth, death, and movement. The expression of selected genes was evaluated by quantitative RT-PCR. This analysis revealed a two-gene model (SELENBP1 and MMP9) with a high significant prognostic ability (HR 6; 95% CI 2.61-13.79; P<0.0001). The combination of the two-gene signature plus the CTCs count showed a higher prognostic ability than CTCs enumeration or gene expression alone (P<0.05). This study shows a gene expression profile in PBMNC associated with CTCs count and clinical outcome in metastatic CRPC, describing genes and pathways potentially associated with CRPC progression.


Albini A.,Laboratory of Translational Oncology | Bertolini F.,Italian National Cancer Institute | Bassani B.,Scientific and Technology Park | Bruno A.,Scientific and Technology Park | And 5 more authors.
ecancermedicalscience | Year: 2015

With the great advances made in the treatment and prevention of infectious diseases over the last century, chronic degenerative Diseases-cardiovascular, cerebrovascular, and cancer-represent the major causes of death in the developed world. Although massive efforts and investments have been made in cancer therapy, the progress made towards reducing mortality has been more successful for cardiovascular disease than for tumours. This can be attributable largely to an active prevention approach implemented for cardiovascular disease. Cardiologists treat their patients before the overt disease becomes life threatening, performing early interventions in phenotypically healthy patients, by using several markers that predict risk. If the concept of prevention could be applied to cancer in a more extensive way, a significant number of tumours could be avoided through preventive measures. Prevention approaches range from avoiding tobacco exposure to dietary strategies to active pharmacological approaches in higher risk groups. Host targets rather than the tumour cells themselves are attractive for chemoprevention, in particular endothelial and immune cells. Angioprevention i.e. preventing cancer angiogenesis is a key concept that we introduced; yet one of the major current challenges for anti-angiogenesis in therapy and prevention is finding the right biomarkers. Here we discuss the importance of angioprevention and the potential use of VEGF, PlGF, CD31, Ang and Tie, circulating vascular cell precursors, and microRNA as potential biomarkers. © the authors.


PubMed | University of Insubria, Scientific and Technology Park, Italian National Cancer Institute and Laboratory of Translational Oncology
Type: | Journal: Ecancermedicalscience | Year: 2015

With the great advances made in the treatment and prevention of infectious diseases over the last century, chronic degenerative diseases-cardiovascular, cerebrovascular, and cancer-represent the major causes of death in the developed world. Although massive efforts and investments have been made in cancer therapy, the progress made towards reducing mortality has been more successful for cardiovascular disease than for tumours. This can be attributable largely to an active prevention approach implemented for cardiovascular disease. Cardiologists treat their patients before the overt disease becomes life threatening, performing early interventions in phenotypically healthy patients, by using several markers that predict risk. If the concept of prevention could be applied to cancer in a more extensive way, a significant number of tumours could be avoided through preventive measures. Prevention approaches range from avoiding tobacco exposure to dietary strategies to active pharmacological approaches in higher risk groups. Host targets rather than the tumour cells themselves are attractive for chemoprevention, in particular endothelial and immune cells. Angioprevention i.e. preventing cancer angiogenesis is a key concept that we introduced; yet one of the major current challenges for anti-angiogenesis in therapy and prevention is finding the right biomarkers. Here we discuss the importance of angioprevention and the potential use of VEGF, PlGF, CD31, Ang and Tie, circulating vascular cell precursors, and microRNA as potential biomarkers.


PubMed | Hospital Clinic, Hospital Plato, Laboratory of Translational Oncology, Institute dInvestigacions Biomediques August Pi i Sunyer IDIBAPS and Althia Inc.
Type: Journal Article | Journal: Oncotarget | Year: 2015

The enumeration of circulating tumor cells (CTCs) in peripheral blood correlates with clinical outcome in castration-resistant prostate cancer (CRPC). We analyzed the molecular profiling of peripheral blood from 43 metastatic CRPC patients with known CTC content in order to identify genes that may be related to prostate cancer progression. Global gene expression analysis identified the differential expression of 282 genes between samples with 5 CTCs vs <5 CTCs, 58.6% of which were previously described as over-expressed in prostate cancer (18.9% in primary tumors and 56.1% in metastasis). Those genes were involved in survival functions such as metabolism, signal transduction, gene expression, cell growth, death, and movement. The expression of selected genes was evaluated by quantitative RT-PCR. This analysis revealed a two-gene model (SELENBP1 and MMP9) with a high significant prognostic ability (HR 6; 95% CI 2.61 - 13.79; P<0.0001). The combination of the two-gene signature plus the CTCs count showed a higher prognostic ability than CTCs enumeration or gene expression alone (P<0.05). This study shows a gene expression profile in PBMNC associated with CTCs count and clinical outcome in metastatic CRPC, describing genes and pathways potentially associated with CRPC progression.

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