Role of Oxidative Stress in Prognosis of Ovarian Cancer.

Ovarian cancer is one of the most lethal gynecological malignancies. Mitochondria are the predominant source of reactive oxygen species (ROS) in the cell. Besides mitochondria nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) enzymes generate a significant amount of ROS in the cell. The present work establishes an interesting link between NOX4 enzyme (which is an important source of reactive oxygen species "ROS") and PHB1 (as a holdase type chaperone in mitochondrial stress). The current study was conducted on 60 patients with ovarian tumours (benign, borderline and malignant) and 20 healthy volunteers (as a control group). NOX4 expression was assessed by TaqMan® real time gene expression assay, while cellular expression of prohibitin was evaluated by immunohistochemistry. There was a significant increase in prohibitin expression from benign cystadenoma to malignant tumors. In addition, there was an increase in NOX4 expression. In conclusion, over-expression of PHB1 and NOX4 in malignant ovarian tissues suggest that PHB1 is associated with tumorigenesis via activation of NOX4 enzyme with subsequent release of ROS in the cells.

Prohibitin: targeting peptide coupled to ovarian cancer, luteinization and TGF-ß pathways.

BACKGROUND: Ovarian epithelial tumor (OET) is a silent disease of late diagnosis and poor prognosis. Currently treatment options are limited and patient response to treatment is difficult to predict so there is a serious need to delineate the real pathogenesis to predict tumour prognosis. Prohibitin (PHB) is an evolutionarily protein that regulates the cell cycle. TGF-ß has been shown to be a positive and negative regulator of cellular proliferation and differentiation. The present study provides an overview on the role played by PHB1, TGF-ß and LH in ovarian cancer. METHODS: The study was conducted on 60 patients with ovarian tumors (benign, borderline and malignant) and 20 healthy volunteers. LH and TGF-ß serum levels were measured by ELISA. Expression of prohibitin and LHR-mRNA were assessed by IHC and TaqMan® real time gene expression assay, respectively. RESULTS: Serum levels of LH and TGF-ß were significantly decreased among borderline and malignant groups. There was significant over-expression of LHRmRNA in malignant group. Prohibitin expression was significantly increased in malignant ovarian tissue. Strong negative correlations were found between LHR mRNA expression and serum LH levels, and between IHC score of prohibitin and serum levels of LH among patients with borderline ovarian tumors. CONCLUSION: Steady decline of LH and TGF-B serum levels, from benign cystadenoma to borderline tumor to carcinoma, suggests their inhibitory role against OET cell growth. Increased PHB1 expression in OET suggests its proliferative activity that can be regulated by luteinisation and/or TGF-ß. Furthermore increased LHR mRNA tissue expression can provide hope for using LH in treatment of some types of ovarian cancers.

The role and prognostic value of inducible nitric oxide synthase (iNOS) and interleukin-33 (IL-33) in serous and mucinous epithelial ovarian tumours.

Understanding different mechanisms contributing to the aggressive behaviour of epithelial ovarian cancer (EOC) is a large challenge. Interaction between inflammation, immunity and carcinogenesis occurs in different cancers; however, the potential roles of different molecules involved in these processes in relation to ovarian carcinogenesis were not fully investigated. Inducible nitric oxide synthase (iNOS) and interleukin-33 (IL-33) are implicated in carcinogenesis. iNOS is an NOS isoform that generates nitric oxide, which plays important roles in various stages of carcinogenesis. IL-33 is a cytokine implicated in modulation of anti-tumour immunity and tumour growth. This work aimed at studying the immunohistochemical expression of iNOS and IL-33 in serous and mucinous epithelial ovarian tumours to investigate their role and prognostic significance. Immunohistochemical expressions of iNOS and IL-33 were assessed in 90 patients with epithelial ovarian tumours (45 serous and 45 mucinous tumours, categorized as benign, borderline, and malignant tumours). iNOS and IL-33 showed significantly higher expressions in borderline and malignant serous and mucinous tumours compared to benign ones (p=0.0001). The differences between borderline and malignant tumours were statistically insignificant (p=0.2351&0.6321). iNOS showed significantly higher expression with increasing tumour grade in malignant mucinous tumours (p=0.0011). IL-33 showed significantly higher expression with increasing tumour grade in both malignant serous and mucinous tumours (p=0.0074 and 0.0007). Upregulation of iNOS and IL-33 expression in borderline and malignant epithelial ovarian tumours indicates their involvement in the development and progression of EOC, and their increased expression in less differentiated cancers suggests their association with poor prognosis in this category of tumours.

Relevance of HLA-DP/DQ and ICAM-1 SNPs among Ovarian Cancer Patients.

BACKGROUND: Ovarian cancer is one of the most lethal gynecological malignancies and the fifth leading cause of cancer deaths among women. The high mortality rate is largely attributed to its diagnosis in advanced stages. Poor prognosis of ovarian cancer is usually due to the lack of specific or effective screening and diagnostic methods for identifying early-stage disease. AIM: Our study aimed to study the role of HLA-DP, HLA-DQ, and ICAM-1 SNPs in diagnosis and/or prognosis of ovarian tumors. SUBJECTS AND METHODS: The current study was conducted on 60 patients with ovarian tumors (benign, borderline, and malignant) and 20 healthy volunteers. Genotyping of HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs was done using 5' nuclease assay. RESULTS: We found significant association of HLA-DP rs3077 AA, HLA-DQ rs3920 GG, ICAM-1 rs1437 CC, and CT genotypes with increased risk of ovarian cancer (OR = 43.5, 6, 25, and 2.6, respectively). In addition, HLA-DQ rs3920 and ICAM-1 rs1437 alleles vary significantly among different types of ovarian cancer (P = 0.003 and 0.001, respectively). CONCLUSION: HLA-DP rs3077, HLA-DQ rs3920, and ICAM-1 rs1437 SNPs could help in the diagnosis and prognosis of ovarian cancer.