Methylation of SFRPs and APC genes in ovarian cancer infected with high risk human papillomavirus.

BACKGROUND: Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. MATERIALS AND METHODS: DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. RESULTS: The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. CONCLUSION: This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.

Increased expression of biological markers as potential therapeutic targets in Saudi women with triple-negative breast cancer.

AIMS AND BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2). Although TNBC represents only 15% of all types of breast cancer, it accounts for a large number of metastatic cases and deaths. Because of the high metastatic rate and both local and systemic recurrence associated with TNBC, extensive research efforts are actively looking for target therapies to effectively treat this aggressive disease. Accordingly, this study has been initiated to investigate the differential expression of biological markers in TNBC and non-TNBC Saudi women that might be utilized as potential targeted therapy and/or predict the sensitivity to currently available therapeutic regimens. METHODS AND STUDY DESIGN: Two hundred formalin-fixed, paraffin-embedded (FFPE) breast cancer tissues were selected and divided into 3 groups: benign breast tissues (20), TNBC tissues (80) and non-TNBC tissues (100). Expression of mRNA in FFPE tissues was analyzed using real-time polymerase chain reaction (RT-PCR) for the following genes: poly (ADP-ribose) polymerase 1 (PARP-1), topoisomerase 2A (TOPO-2A), vascular endothelial growth factor (VEGF), C-MYC, basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMP-2 and MMP-9), human epidermal growth factor 1 (HER1) and multidrug resistance (MDR) genes. RESULTS: In the TNBC group, expression of PARP-1, TOPO-2A, HER1, C-MYC, VEGF, bFGF and MMP-2 showed a highly significant increase compared to the non-TNBC group. CONCLUSIONS: The results of this study suggest that (1) TNBC patients will benefit more from TOPO-2A inhibitors as well as antiangiogenic and antimetastatic therapies; (2) inhibition of these target genes is emerging as one of the most exciting and promising targeted therapeutic strategies to treat TNBC in which the intended targets are DNA repair, tumor angiogenesis and metastasis.

Gene expression profiling of non-hodgkin lymphomas.

BACKGROUND: Chromosomal translocations are genetic aberrations associated with specific non-Hodgkin lymphoma (NHL) subtypes. This study investigated the differential gene expression profile of Egyptian NHL cases based on a microarray approach. MATERIALS AND METHODS: The study included tissue samples from 40 NHL patients and 20 normal lymph nodes used as controls. Total RNA was extracted and used for cDNA microarray assays. The quantitative real time polymerase chain reaction was used to identify the aberrantly expressed genes in cancer. RESULTS: Significant associations of 8 up-regulated and 4 down-regulated genes with NHL were observed. Aberrant expression of a new group of genes not reported previously was apparent, including down-regulated NAG14 protein, 3 beta hydroxy-delta 5-c27 steroid oxi-reductase, oxi-glutarate dehydrogenase (lipo-amide), immunoglobulin lambda like polypeptide 3, protein kinase x linked, Hmt1, and caveolin 2 Tetra protein. The up-regulated genes were Rb binding protein 5, DKFZP586J1624 protein, protein kinase inhibitor gamma, zinc finger protein 3, choline ethanolamine phospho-transferase CEPT1, protein phosphatase, and histone deacetylase-3. CONCLUSIONS: This study revealed that new differentially expressed genes that may be markers for NHL patients and individuals who are at high risk for cancer development.

SEN virus infection in Egyptian patients undergoing maintenance hemodialysis: prevalence and clinical importance.

BACKGROUND AND PURPOSE: SEN virus (SENV) is assumed to be responsible for post-transfusion non-A to -E hepatitis. Phylogenetic analysis of SENV has shown 9 different strains. Two strains, SENV-H and SENV-D, were described as possible candidates for post-transfusion hepatitis. This study examined the prevalence of SENV infection and its clinical importance for patients undergoing hemodialysis. METHODS: Serum samples were obtained from 63 long-term hemodialysis patients, and examined for SENV-H and SENV-D viremia by polymerase chain reaction. Serum samples were also obtained from 20 patients with chronic kidney diseases (CKD) who were not undergoing hemodialysis and from 20 apparently healthy blood donors to act as controls. For SENV screening, a primer pair was used for the conserved ORF1 region among all SENV genotypes from A to I. RESULTS: SENV infection was significantly more frequent among hemodialysis patients (33/63; 52.4%) and those with CKD (10/20; 50.0%) than among the control participants (2/20; 10.0%) [p = 0.003]. Twenty three of 33 hemodialysis patients had SENV-H or -D, 61% of whom were positive for SENV-H only, 4% were positive for SENV-D only, and 36% were positive for both SENV-H and SENV-D. SENV infection was not associated with age, sex, amount or duration of hemodialysis, or liver function test results. Elevated alanine aminotransferase was significantly associated with HCV viremia, but not with SENV infection. CONCLUSIONS: Egyptian hemodialysis patients and those with CKD are at higher risk for SENV transmission. SENV-H is more prevalent than SENV-D.