Khadiga M. Gaafar

Leptin is overexpressed in the tumor microenvironment of obese patients with estrogen receptor positive breast cancer

The present study aimed to investigate the potential role of leptin in the progression of breast cancer and the associated cell proliferation signalling pathway(s). A total of 44 female patients diagnosed with breast cancer and 24 healthy donors from Ain Shams University Hospitals (Cairo, Egypt) were enrolled in the present study. The present study assessed leptin expression in breast cancer tissues at the gene and protein level using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The results demonstrate that the expression of leptin was significantly higher in tissue of breast cancer samples from obese patients than overweight and control samples (P<0.001). ELISA results indicated a significant increase (P<0.001) of leptin expression in obese patients. To investigate whether there is any difference in leptin expression between the peripheral and tumor microenvironment blood of patients with breast cancer, the concentration of leptin was assessed in plasma from both using ELISA assays. The results demonstrated a statistically significant increase in the level of leptin in plasma samples from the tumor microenvironment of obese patients with estrogen receptor positive (ER+) breast cancer, compared with peripheral plasma samples. Furthermore, the leptin gene was overexpressed in obese ER+ breast cancer tissue. RT-qPCR was also performed to assess the expression of genes involved in proliferation pathways including leptin receptor (LEPR), aromatase, mitogen activated protein kinase (MAPK) and signal transducer and activator of transcription-3 (STAT3). A positive association between leptin expression, LEPR, aromatase, MAPK and STAT3 was detected in tissue samples of patients with breast cancer. The current study concluded that leptin may enhance breast cancer progression by inducing the expression of JAK/STAT3, ERK1/2 and estrogen pathways in obese patients breast cancer.

Establishing the first institutional animal care and use committee in Egypt

BackgroundAlthough animal research ethics committees (AREC) are well established in Western countries, this field is weakly developed and its concept is poorly understood in the Middle East and North Africa region.ObjectiveOur main objective was to introduce the concept and requirements of ethical approaches in dealing with experimental animal in research and teaching in Egypt.MethodsDue to its very recent inception, Cairo University, Faculty of Science IACUC decided to operate in accordance with Guide for the Care and Use of Laboratory Animals 8th Edition 2011 (the Guide) since Egypt has not yet compiled its own guide.ResultsFifty protocols were reviewed in 2013–2014. Only ten protocols were reviewed in 2013, but in 2014, forty protocols were reviewed. In 2013 all protocols were approved and in 2014, number of approvals were 35, the number of deferrals were 4, and one refused protocol. Master’s theses (MSc) research protocols constituted the majority of the total reviewed protocols. This is attributed to the decision of the Board of the Faculty of Science, Cairo University in September, 2013 that the approval of the IACUC is mandatory before conducting any research involving animals or theses registration.ConclusionThe first IACUC was established in the Cairo University, Faculty of Science, since 2012. The challenges encountered by the committee were diverse, such as the absence of laws that control the use of animal models in scientific research, lack of guidelines (protocols for experimental animals in research) and, mandatory ethical approval for any experimental animal research.

THE PROTECTIVE POTENCY OF VITAMINS E AND C IN METHANOL-INDUCED OXIDATIVE STRESS AND RETINOTOXICITY

The protective effects of vitamins E and C against methanol-induced free radical production with its subsequent tissue injury in liver and retina of male albino rats were assessed. The rats were divided into four groups: (1) control, (2) antioxidant (Ao) control group receiving 5 mg of each vitamin, E and C, (3) daily ip-injected methanol (2 mL/kg b.wt.) group, killed after three and six doses, and (4) Ao/methanol group administered the vitamins 3 weeks prior to and along with methanol injection and killed as the latter group [Sharpe et al. Methanol Optic Neuropathy: A Histopathological Study. Neurology 1982, 32 (10), 1093–1100]. Methyl alcohol drastically altered the Ao defense system and energy status of rat liver, where highly significant depletion of glutathione levels and inhibition of superoxide dismutase activity, concurrent with significant increase in thiobarbituric acid reactive substances indicating marked elevation in lipid peroxidation. These effects were reversed when the vitamins were administered denoting their role in promoting the Ao defense system. Furthermore, they also increased the methanol-induced depletion in adenylate energy charge, phosphate potential, and ATP values. The amelioration in the energy status as a result of vitamins E and C supplementation suggests that their role as Aos is effective in relieving the impaired oxidative phosphorylation in order to increase the energy demand under physiologically stressful conditions. Histopathological and ultrastructural results of rat retina confirmed the protective effect of Ao vitamins. As compared to the methanol-intoxicated group, the protected group showed preservation of the membranous structures of the retinal cells, especially mitochondria that assumed their normal shape. This may be attributed to the inhibition of free radical production and lipid peroxidation and subsequently minimum degree of tissue damage. Amelioration of mitochondrial structure reflected the improvement of impaired oxidative phosphorylation of intoxicated animals with an approximately normal level of energy demand. This suggests that Ao vitamins may alter the retinotoxic effects of methanol by promoting the internal Ao defense system and preserving the energy status of the animal.

Lipidemic effect of methanol

The effect of methanol on some of the lipid components in serum was studied in rats. Methanol was administered by stomach tube in doses of 2 and 6 ml/kg b.wt daily for 21 and 6 days, respectively. Methanol was found to accumulate lipids; thus, cholesterol, phospholipids and triglycerides increased significantly. Concurrently, modification of the lipoid content of organs has been considered. It was concluded that methanol and not only formate, is toxic to rats, inspite of the alleged difference in routes of its metabolism in primates and rodents.