Association of genetic variants in the 3'-untranslated region of the mesothelin (MSLN) gene with ovarian carcinoma.

Limited information has been offered regarding the association of mesothelin (MSLN) gene variants at the 3'-untranslated region with the risk of ovarian carcinoma. The primary objective of this work is to assess the impact of the MSLN (rs1057147 and rs57272256) variants on the progression of ovarian carcinoma among Egyptian women. The study was conceived based on 127 women diagnosed with ovarian carcinoma and 106 unrelated cancer-free controls. Genomic DNA of these MSLN variants was genotyped utilizing the PCR technique. The frequencies of the MSLN (rs1057147) variant revealed a significant association with increased risk of ovarian carcinoma under allelic and dominant models (P < .05). Nonetheless, ovarian cancer patients with the MSLN (rs57272256) variant did not attain considerable significance under all genetic models (P > .05). Together, our findings suggested that the MSLN (rs1057147) variant was associated with an increased risk of ovarian carcinoma, but not the MSLN (rs57272256) variant.

Dietary baker's yeast sensitizes Ehrlich mammary adenocarcinoma to paclitaxel in mice bearing tumor.

Baker's yeast, Saccharomyces cerevisiae, has been shown to sensitize a variety of breast cancer cell (BCC) lines to paclitaxel chemotherapy in vitro. The present study evaluated the ability of S. cerevisiae to sensitize BCCs to paclitaxel in animals bearing Ehrlich ascites carcinoma (EAC). Mice bearing EAC were intratumorally injected with dead S. cerevisiae (1x107 cells/ml) in the presence or absence of low- and high-dose paclitaxel [paclitaxel-L, 2 mg/kg body weight (BW) and paclitaxel-H, 10 mg/kg BW, respectively]. At 30 days post tumor inoculation, co-treatment with yeast plus paclitaxel-L showed improvements over paclitaxel-H alone, as measured by tumor weight (-64 vs. -53%), DNA damage (+79 vs. +62%), tumor cell apoptosis (+217 vs. +177%), cell proliferation (-56 vs. -42%) and Ki-67 marker (+95 vs. +40%). Histopathology and ultra-structural examinations showed that yeast plus paclitaxel-L enhanced apoptosis in EAC more than paclitaxel-H alone and caused comparable tumor necrosis. We conclude that baker's yeast may be used with low-dose chemotherapy to achieve the same potency as high-dose chemotherapy in mice bearing EAC. This suggests that baker's yeast may be an anticancer adjuvant and may have clinical implications for the treatment of breast cancer.

Baker's Yeast Sensitizes Metastatic Breast Cancer Cells to Paclitaxel In Vitro.

Our earlier studies have demonstrated that phagocytosis of baker's yeast ( Saccharomyces cerevisiae) induces apoptosis in different cancer cell lines in vitro and in vivo. This study aimed to examine how baker's yeast sensitizes murine and human breast cancer cells (BCC) to paclitaxel in vitro. This sensitizing effect makes lower concentrations of chemotherapy more effective at killing cancer cells, thereby enhancing the capacity of treatment. Three BCC lines were used: the metastatic murine 4T1 line, the murine Ehrlich ascites carcinoma (EAC) line, and the human breast cancer MCF-7 line. Cells were cultured with different concentrations of paclitaxel in the presence or absence of baker's yeast. Cell survival and the IC50 values were determined by MTT assay and trypan blue exclusion method. Percent of DNA damage, apoptosis, and cell proliferation were examined by flow cytometry. Yeast alone and paclitaxel alone significantly decreased 4T1 cell viability postculture (24 and 48 hours), caused DNA damage, increased apoptosis, and suppressed cell proliferation. Baker's yeast in the presence of paclitaxel increased the sensitivity of 4T1 cells to chemotherapy and caused effects that were greater than either treatment alone. The chemosensitizing effect of yeast was also observed with murine EAC cells and human MCF-7 cells, but to a lesser extent. These data suggest that dietary baker's yeast is an effective chemosensitizer and can enhance the apoptotic capacity of paclitaxel against breast cancer cells in vitro. Baker's yeast may represent a novel adjuvant for chemotherapy treatment.

HCV nonstructural protein 4 is associated with aggressiveness features of breast cancer.

BACKGROUND: Hepatitis C virus (HCV) has the lymphotropic feature that is supposed to be the reason of related extrahepatic manifestation. HCV viral oncoproteins may participate in the regulation of some gene expression that has been implicated in tumorigenesis. Our aim is to evaluate the HCV-NS4 circulating levels in breast cancer (BC) and to investigate its relation with BC tumor aggressiveness. METHODS: This study was performed among 158 Egyptian women (120 with BC and 38 with benign breast diseases). ELISA was used for detection of anti-HCV antibodies, HCV-NS4, fibronectin, and CA 15-3. RESULTS: No association between HCV detection in this group of BC patients (27.5% in BC vs. 23.7% in breast benign diseases, P = 0.687). Among HCV-infected patients, the mean HCV-NS4 serum level in BC was significantly higher than benign group (61.7 µg/mL vs. 33.9 µg/mL, P = 0.0005). Fibronectin levels were higher (P = 0.014) in patients infected with HCV than noninfected BC patients. Elevated HCV-NS4 levels were associated with tumor severity features like large size, late stages, high grades, and infiltrated lymph nodes. The elevated levels of HCV-NS4 (> 40 µg/mL) yielded an estimated odds ratio (95% confidence intervals) of 2.5 (0.98-6.36), 1.2 (0.44-3.33), 1.9 (0.53-7.00), and 2.5 (0.87-7.33) for developing large size, late stages, high grades, and infiltrated lymph nodes, respectively. Interestingly, HCV-NS4 levels significantly correlated with other BC tumor marker like CA15-3 (r = 0.535; P = 0.0009) and fibronectin (r = 0.432; P < 0.0001). CONCLUSIONS: HCV-NS4 appears to be associated with BC progression features. Oncologists treating such BC patients should consider HCV screening to enable the early identification and to prevent progression of the disease.

Fenugreek potent activity against nitrate-induced diabetes in young and adult male rats.

Nitrate has described as an endocrine disruptor that promotes onset of diabetes. This study was undertaken to evaluate diabetic effect of high nitrate intake in young and adult male rats and its amelioration by fenugreek administration. The study revealed significant increase in serum glucose and blood glycosylated hemoglobin (HbA1c%), while serum insulin and liver glycogen were decreased among nitrate exposed animals, in particular the young group. A significant reduction in the body weight gain and serum thyroid hormones (T4 & T3) was also recorded. Further reduction in serum levels of urea and creatinine, as well as total protein in serum, liver and pancreas was demonstrated, with elevation in their levels in the urine of all nitrate exposed groups. Meanwhile, the activity of serum transaminases (ALT and AST) was increased, with decline in their activity in the liver tissue. In addition, an elevation in serum total bilirubin, tissues (liver and pancreas) nitric oxide and lipid profile, as well as liver activity of glucose-6-phosphatase was recorded. Fenugreek administration to nitrate exposed rats was found to be effective in alleviating hyperglycemia and other biochemical changes characterizing nitrate-induced diabetes. So, fenugreek can be considered to possess potent activity against onset of nitrate induced-diabetes.