Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that has been linked to breast cancer development. Estrogen metabolic pathway is also involved in breast carcinogenesis and DNA adducts formation. In this study we investigated the effect of TNF-α on the estrogen metabolic pathway in MCF-7, a breast cancer cell line. Capillary liquid chromatography/mass spectrometry (LC/MS) and High performance liquid chromatography (HPLC) were used for analysis of estrogen metabolites and estrogen-DNA adducts levels respectively. Reporter gene assay, Real time reverse transcription polymerase chain reaction (real time RT-PCR) and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes. TNF-α significantly increased the total EM and decreased the estrone (E1) / 17-β estradiol (E2) ratio. Moreover, it altered the expression of genes and enzymes involved in E2 activation and deactivation pathways e.g. Cytochrome P-450 1A1 (CYP1A1), Cytochrome P-450 1B1 (CYP1B1), Catechol-O-methyl transferase (COMT) and Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1 (NQO1). In addition, there were increased levels of some catechol estrogens e.g. 4-hydroxy-estrone (4-OHE1) and 2-hydroxyestradiol (2-OHE2) with decreased levels of methylated catechols e.g. 2-methoxy estradiol (2-MeOE2). DNA adducts especially 4-OHE1-[2]-1-N3 Adenine was significantly increased. TNF-α directs the estrogen metabolism into more hormonally active and carcinogenic products in MCF-7. This may implicate a new possible explanation for inflammation associated breast cancer.

The role of the extracellular matrix (ECM) in uterine fibroids (UF) has recently been appreciated. Overhydroxylation of lysine residues and the subsequent formation of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) cross-links underlie the ECM stiffness and profoundly affect tumor progression. The aim of the current study was to investigate the relationship between ECM of UF, collagen and collagen cross-linking enzymes [lysyl hydroxylases (LH) and lysyl oxidases (LOX)], and the development and progression of UF. Our results indicated that hydroxyl lysine (Hyl) and HP cross-links are significantly higher in UF compared to the normal myometrial tissues accompanied by increased expression of LH (LH2b) and LOX. Also, increased resistance to matrix metalloproteinases (MMP) proteolytic degradation activity was observed. Furthermore, the extent of collagen cross-links was positively correlated with the expression of myofibroblast marker (α-SMA), growth-promoting markers (PCNA; pERK1/2; FAKpY397; Ki-67; and Cyclin D1), and the size of UF. In conclusion, our study defines the role of overhydroxylation of collagen and collagen cross-linking enzymes in modulating UF cell proliferation, differentiation, and resistance to MMP. These effects can establish microenvironment conducive for UF progression and thus represent potential target treatment options of UF.

Background: Tramadol is a commonly abused erotic drug that recently has gained popularity among young men. It is a centrally acting analgesic used to treat moderate to severe pain. This study aimed to evaluate the chronic toxic effects of tramadol on the reproductive system of male albino rats. It was carried out on 60 rats weighing 130-150 g divided into two groups. The first group (control group) included 30 rats and received normal saline 0.9% 1 ml/day orally for 45 days. The second group (tramadol group) included 30 rats and received tramadol 60 mg/kg subcutaneously three times per week for 45 days. Blood samples were obtained from the animals and analysed for serum testosterone, FSH, LH and prolactin levels. Also, the testes were excised and examined for histopathological changes. Results: The results revealed that there was a decrease in the serum levels of testosterone (P = 0.009), FSH (P = 0.057) and LH (P = 0.002) and an increase in the serum prolactin level (P = 0.166) in animals treated with tramadol. In addition, histopathological examination revealed distinct abnormal changes compared with the corresponding control group. Conclusion: The present study affirms the deleterious chronic toxic effects of tramadol on the reproductive system of male albino rats. It is thus advisable that tramadol should be used with caution with appropriate dose monitoring to avoid its undesirable side effects on male fertility.

Objective: The elevated incidence of obesity has been paralleled with higher risks of breast cancer. High adiposity increases leptin secretion from adipose tissue, which in turn increases cancer cell proliferation. The interplay between leptin and estrogen is one of the mechanisms through which leptin influences breast carcinogenesis. An unbalanced estrogen metabolism increases the formations of catechol estrogen quinones, DNA adducts, and cancer mutations. This study aims to investigate the effect of leptin on some estrogen metabolic enzymes and DNA adduction in breast cancer cells. Furthermore, leptin significantly upregulated CYP1B1 promoter activity and protein expression. The luciferase promoter activities of NQO1 and mRNA levels were significantly reduced. Moreover, leptin greatly reduced the reporter activities of the COMT-P1 and COMT-P2 promoters and diminished the protein expression of COMT. Conclusions: Leptin increases DNA adduct levels in breast cancer cells partly by affecting key genes and enzymes involved in estrogen metabolism. Thus, increased focus should be directed toward leptin and its effects on the estrogen metabolic pathway as an effective approach against breast cancer.

Background: The roles of androgen and androgen receptor (AR) signaling in the oncogenesis of prostate cancer are very well established. What is more poorly understood is the role of AR in other human malignancies including bladder cancer. The incidence of bladder cancer is much higher in males than females, but the exact etiology has not been fully elucidated. This gender disparity has raised the possibility of the AR pathway being involved in the genesis of this disease. Thereby, the aim of this work was to evaluate the expression of AR in a group of Egyptian patients with urothelial bladder carcinoma and to assess whether its expression was correlated with other pathological tumor features. Urothelial bladder carcinoma tissue samples from 50 patients were studied by immunostaining for AR expression in tumor cells.Results: AR was positively expressed in 29 (58%) patients, while negative expression was observed in 21 (42%) patients. No statistically significant difference in AR expression with respect to tumor grade (P = 0.07) and pT stage (P = 0.09) was observed. Conclusions:The results obtained in this study indicates a clinical value of the AR expression in Egyptian patients with urothelial bladder carcinoma, providing the basis for further studies to evaluate its role and the possibility of new target-based therapies for urothelial bladder carcinoma.