[ occurrence and contribution of germline BRCA1/2 sequence alterations in Iranian patients with breast cancer]

Breast cancer is the most common form of hereditary cancer worldwide and is an important cause of morbidity and mortality. Approximately 5-10% of breast and ovarian cancers are due to the highly penetrating germline mutations in cancer predisposing genes. Two genes, BRCA1 and BRCA2, account for at least half of these cases. The demand for BRCA1 and BRCA2 mutation screening is rapidly increasing as their identification will affect the medical management of people at increased risk for the disease. Therefore, the aim of this study was to investigate BRCA1/2 mutations in 100 high risk Iranian families. One hundred families who met the minimal risk factors for breast/ovarian cancer were screened among the families referred to Kawsar Human Genetics Research Center for the diseases in 2009-2011. The entire coding sequences and each intron/exon boundaries of BRCA1/2 genes were screened for by direct sequencing and MLPA in both patients and the controls. In the present study, we could detect the following novel mutations: p.Gly1140Ser, p.Ile26Val, p.Leu1418X, p.Glu23Gln, p.Leu3X, p.Asn1403His, p.Asn1403Asp, p.Lys581X, p.Pro938Arg, p.Thr77Arg, p.Leu6Val, p.Arg7Cys, p.Leu15Ile, p.Ser177Thr, IVS7+83[-TT], IVS8-70[-CATT], IVS2+9[G>C], IVS1-20[G>A], IVS1-8[A>G], p.Met1Ile, IVS2+24[A>G], IVS5-8 [A>G], IVS2[35-39]TTcctatGAT, IVS13+9 G>C in BRCA1 and p.Glu1391Gly, p. Val1852Ile, IVS6-70[T>G], 1994-1995 [InsA] in BRCA2. Ten mutations seemed to be pathogenic and the disease-causing mutations were seen in 16% of the families. In addition, from the total number of substitutions and reassortments [42], 80% related to BRCA1 and 20% to mutations in BRCA2 genes

[Evaluation of immunization of BALB/c mice by plasmid encoding complete ROP2 gene of Toxoplasma gondii]

Toxoplasma gondii is an obligate intracellular protozoan that causes Toxoplasmosis in human and animal. In recent years, significant progress has been made in the identification of vaccine candidates which can induce protective responses. In this study we used complete Rhoptry protein 2 gene of Toxoplasma gondii as a single DNA vaccine and evaluated its immune responses in comparison with control groups. BALB/c mice were immunized intramuscularly with three weaks time interval with pcROP2 [as case group] and pc-DNA3 and PBS [as control groups]. After immunization, we evaluated the immune response using cytokine and antibody measurements. The results of cytokine [IFN-gamma, IL-4] assays showed that mice immunized with pcROP2, elicited stronger Th1-type cellular immune responses than those immunized with empty plasmid, or PBS [high level of IFN-gamma and low-level of IL-4]. Also Anti-T. gondii IgG titres [OD] increased markedly in the pcROP2 group, which was significantly higher than those of control groups [P<0.05]. When challenged with the highly virulent Toxoplasma gondii RH strain, mice immunized with pcROP2 had siginificantly higher survival rates compared to control groups [P<0.05]. This study showed that pc-ROP2 as a single DNA vaccine is effective to prime enhanced and balanced cellular and humeral immunity responses, and relatively improved mice survival time against toxoplasmosis