We evaluated the interaction between Punica granatum (pomegranate) methanolic extract (PGME) and antibiotics against 30 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA). Susceptibility testing of the isolates to PGME and antibiotics was performed by the broth dilution method. Synergic activity was detected between PGME and the 5 antibiotics tested, chloramphenicol, gentamicin, ampicillin, tetracycline, and oxacillin, ranging from 38% to 73%. For some isolates, PGME did not interfere with the action of any of the antibiotics tested. The bactericidal activity of PGME (0.1 x MIC) in combination with ampicillin (0.5 x MIC) was assessed using chosen isolates by time-kill assays, and they confirmed the synergic activity. Using this combination, cell viability was reduced by 99.9% and 72.5% in MSSA and MRSA populations, respectively. PGME increased the post-antibiotic effect (PAE) of ampicillin from 3 to 7 h. In addition, PGME demonstrated the potential to either inhibit the efflux pump NorA or to enhance the influx of the drug. The detection of in vitro variant colonies of S. aureus resistant to PGME was low and they did not survive. In conclusion, PGME dramatically enhanced the activity of all antibiotics tested, and thus, offers an alternative for the extension of the useful lifetime of these antibiotics.

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Abstract. The function of microsatellite instability (MSI) and the optimal panel of markers for epithelial ovarian cancer (EOC) are not well established. This study aimed to use the National Cancer Institute (NCI) markers BAT25, BAT26, D2S123, D5S346 and D17S250 to evaluate MSI in patients with ovarian serous cystadenocarcinoma, compared with ovarian serous cystadenoma and normal ovaries. A total of 37 patients were divided into three groups, as follows: cystadenocarcinoma (n=13), cystadenoma (n=10) and normal ovaries (n=14). DNA was extracted with TRIzol and quantified by spectrophotometry. MSI was evaluated by polymerase chain reaction (PCR), and classified as high (MSI-H), low (MSI-L) or stable (MSS). FIGO staging was I/II in 23.1% and III/IV in 76.9% of the cystadenocarcinoma group. Polymorphisms were found using at least one marker in 32 women, and were observed with D2S123 (83.7%), D17S250 (81.1%), D5S346 (72.9%), BAT25 (21.6%) and BAT26 (16.2%) markers. In the cystadenocarcinoma group, BAT25, BAT26, D2S123, D5S346 and D17S250 markers were positive in 30.8, 76.9, 53.8, 69.2 and 69.2% of patients, respectively. The same markers were positive in 30, 50, 40, 60 and 30% of the cystadenoma group, and 50, 71.4, 71.4, 64.3 and 63.3% in the normal ovary group, respectively. MSI-H was present in 84.6, 60 and 78.6% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. MSI-L was detected in 0, 30 and 7.1%, and MSS was identified in 15.4, 10 and 14.3% of the cystadenocarcinoma, cystadenoma and normal patients, respectively. The frequency of MSI in both benign epithelial ovarian neoplasms and in normal ovaries was high, as well as in EOC, with no statistically significant difference between the groups. This suggests that MSI may arise as a consequence of the ovulatory process, and not solely as a feature of malignant ovarian tumors. IntroductionEpithelial ovarian cancer (EOC) has a high mortality rate (1); it is the leading cause of death among gynecological tumors, and the fourth leading cause of cancer-related mortality among women in the United States (2). Due its nonspecific symptoms and lack of effective screening methods (3), approximately two-thirds of cases are diagnosed in stages III and IV, with a five-year survival rate of 10-20% (4,5). Approximately 90% of ovarian tumors originate from epithelial cells (6,7). The mortality rate has not changed in the last two decades (8).A group of enzymes known as the DNA mismatch repair (MMR) system is responsible for repairing mutations. Hereditary nonpolyposis colorectal cancer (HNPCC) is the third leading cause of hereditary ovarian cancer, and is caused by mutations in genes of the MMR system. One of the consequences of deficient MMR is microsatellite instability (9), which carries somatic mutations in tumor suppressor genes, oncogenes, apoptosis and detoxification genes, and is involved in both the initiation and progression of tumors (10).HNPCC has been studied using a panel of five National Cancer Institute (NCI) markers, which includes two mono...

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, with the presence of chemoresistance contributing to the poor prognosis. Heat Shock Proteins (HSPs) genes are activated in response to pathophysiological stress and serve a role in a variety of stages in carcinogenesis, acting primarily as anti-apoptotic agents and in chemotherapy resistance in a variety of tumor types. The current study evaluated the HSP gene expression profile in women with ovarian cancer (OC) and their correlation with clinical and pathological aspects of patients with OC. A total of 51 patients included in the current study were divided into four groups: Primary Epithelial Ovarian Cancer (EOC; n=14), metastatic EOC (n=11), ovarian serous cystadenoma (n=7) and no evidence of ovarian malignancy or control groups (n=19). RNA extraction and reverse transcription-quantitative (RT-q) PCR was then performed on the samples obtained. RT-qPCR was performed to compare TNF receptor associated protein 1 (TRAP1), heat shock protein family (HSP) HSPB1, HSPD1, HSPA1A and HSPA1L expression in primary and metastatic EOCs. TRAP1, HSPB1, HSPD1, HSPA1A and HSPA1L gene expression did not differ among groups. HSPA1A, HSPA1L and TRAP1 were revealed to be underexpressed in the primary and metastatic EOC groups, with HSPA1L exhibiting the lowest expression. TRAP1 expression was higher in tumors at stages I/II compared with those at stages III/IV. No correlation was exhibited between HSP expression and age, menarche, menopause, parity, period after menopause initiation, cytoreduction, CA-125 or overall and disease-free survival. HSPA1A was negatively correlated with the risk of mortality from OC. The results indicated that the downregulation of HSPA1A, HSPA1L and TRAP1 could be associated with the clinical prognostic features of women with EOC.