BRCA1 polymorphism in breast cancer patients from Argentina.

Breast cancer is the most common type of cancer in females in Argentina, with an incidence rate similar to that in the USA. However, the contribution of the BRCA1 or BRCA2 mutation in breast cancer incidence has not yet been investigated in Argentina. In order to evaluate which BRCA1 polymorphisms or mutations characterize female breast cancer in Argentina, the current study enrolled 206 females with breast cancer from several hospitals from the southeast of Argentina. A buccal smear sample was obtained in duplicate from each patient and the DNA samples were processed for polymorphism analysis using the single-strand conformational polymorphism technique. The polymorphisms in BRCA1 were investigated using a combination of 15 primers to analyze exons 2, 3, 5, 20 and 11 (including the 11.1 to 11.12 regions). The BRCA1 mutations were confirmed by direct sequencing. Samples were successfully examined from 154 females and, among these, 16 mutations were identified in the BRCA1 gene representing 13.9% of the samples analyzed. One patient was identified with a polymorphism in exon 2 (0.86%), four in exon 20 (3.48%), four in exon 11.3 (3.48%), one in exon 11.7 (0.86%), two in exon 11.8 (1.74%), one in exon 11.10 (0.86%) and one in exon 11.11 (0.86%). The most prevalent alteration in BRCA1 was located in exon 11 (11 out of 16 patients; 68.75%). The objective of our next study is to evaluate the prevalence of mutations in the BRCA2 gene and analyze the BRCA1 gene in the healthy relatives of BRCA1 mutation carriers.

Heme oxygenase-1 has antitumoral effects in colorectal cancer: involvement of p53.

The expression of heme oxygenase-1 (HO-1) has been shown to be up-regulated in colorectal cancer (CRC), but the role it plays in this cancer type has not yet been addressed. The aims of this study have been to analyze HO-1 expression in human invasive CRC, evaluate its correlation with clinical and histo-pathological parameters and to investigate the mechanisms through which the enzyme influences tumor progression. We confirmed that HO-1 was over-expressed in human invasive CRC and found that the expression of the enzyme was associated with a longer overall survival time. In addition, we observed in a chemically-induced CRC animal model that total and nuclear HO-1 expression increases with tumor progression. Our investigation of the mechanisms involved in HO-1 action in CRC demonstrates that the protein reduces cell viability through induction of cell cycle arrest and apoptosis and, importantly, that a functional p53 tumor suppressor protein is required for these effects. This reduction in cell viability is accompanied by modulation of the levels of p21, p27, and cyclin D1 and by modulation of Akt and PKC pathways. Altogether, our results demonstrate an antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity.

Low activity of 13-cis-retinoic acid plus interferon alpha 2a in advanced renal cell carcinoma.

Retinoids and interferon alpha have shown synergistic activity against metastatic renal cell carcinoma in previous preclinical and clinical studies. Based on these results, we conducted a phase II trial of 13-cis-retinoic acid (cRA) at 1 mg/kg/dose interferon alpha2a (IFN) at initial dose of 9 MU three times a week. Thirty-one patients were entered, all evaluable for toxicity and 30 evaluable for response. One patient achieved a partial response and 10 patients achieved stable disease. Toxicity was mild and primarily related to interferon. No toxic deaths were reported. Median survival time was 10 months. At the dose and schedule used, cRA and interferon-alpha2a showed low activity against metastatic renal cell carcinoma. Further studies with this combination are not recommended.