Investigation of P53 Gene Codon72 Polymorphism in Colon Cancer

22nd Biennial Congress of the European-Association-for-Cancer-Research -- JUL 07-10, 2012 -- Barcelona, SPAINWOS: 000313036501038…European Assoc Canc Re

The Relationship Between Colon Cancer and Methylenetetrahydrofolate Reductase (MTHFR) C677T Polymorphism

22nd Biennial Congress of the European-Association-for-Cancer-Research -- JUL 07-10, 2012 -- Barcelona, SPAINWOS: 000313036501039…European Assoc Canc Re

Plasminogen Activator Inhibitor Type-1 (PAI-1) Gene 4G/5G Polymorphism and Genetic Tendency to Colon Cancer

22nd Biennial Congress of the European-Association-for-Cancer-Research -- JUL 07-10, 2012 -- Barcelona, SPAINWOS: 000313036501043…European Assoc Canc Re

Effect of leptin on renal ischemia-reperfusion damage in rats

Tumor necrosis factor-alfa (TNF-a) has been established as an important mediator in of renal ischemia-reperfusion (I/R) injury. Leptin, a product of the ob gene, has been known to exhibit cytoprotective effects on renal tissue, but its effect on renal tissue TNF-a level after renal I/R injury in rats remains unknown. The purpose of the study was to evaluate the effects of leptin on renal tissue TNF-a, malondialdehyde (MDA), protein carbonyls (PCs) and total sulfydryl group (SH) levels, and plasma nitrite levels after renal I/R injury in rats. The animals were divided into three groups: control, I/R and I/R+leptin. Rats were subjected to renal ischemia by clamping the left pedicle for 45 min, and then reperfused for 1 h. The I/R+leptin group was pretreated intraperitoneally with leptin (10 mg/kg) 30 min before the induction of ischemia. Our results indicate that MDA, TNF-a levels, and PCs were significantly higher in the I/R group than those in the control group (p<0.05). The administration of leptin decreased these parameters (p<0.05) significantly. The SH level was observed to significantly decrease after I/R injury when compared to the control group (p<0.05). Leptin treatment significantly increased tissue SH and plasma nitrite levels when compared to the I/R group (p<0.05). Plasma nitrite levels did not change significantly in I/R when compared to the control. These results suggest that leptin could exert a protective effect on I/R induced renal damage by through decreasing TNF-a levels and increasing nitrite levelEl factor de necrosis tumoral alfa (TNF-a) es un mediador importante en la lesión renal tras isquemia y reperfusión (I/R). Dado que se ha observado que la leptina presenta un efecto citoprotector sobre el tejido renal, se estudia en este trabajo el efecto de la hormona sobre el contenido en el tejido renal de TNF-a, malondialdehido (MDA), niveles de grupos carbonilo protéicos (PC) y de los grupos de sulfhidrilo total (SH), y el nivel plasmático de nitrito tras lesión renal por isquemia/reperfusión en rata. Los animales se repartían en tres grupos de 8 ejemplares: control, I/R, e I/R+leptina. Las ratas se sometían a una isquemia renal durante 45 minutos con ulterior reperfusión de una hora. A los del grupo I/R+leptina se les había administrado por vía intraperitoneal leptina (10 mg/kg) 30 minutos antes de la inducción de la isquemia. Los resultados indican que el contenido en MDA, TNF-a y PC está significativamente elevado en el grupo I/R respecto del grupo de control (p<0,05), mientras que el de SH se reduce tras la lesión I/R y el nivel de nitrito en el plasma no varía. El tratamiento con leptina anula los incrementos de los niveles renales de TNF-a, MDA y PC y de la disminución de grupos SH en tejido renal y de nitritos plasmáticos por isquemia/reperfusión renal. Estos resultados sugieren que la leptina ejerce un efecto protector sobre la lesión renal inducida por isquemia y reperfusión por la disminución de TNF-a y el aumento plasmático de nitrit

The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats

The aim of the present study was to evaluate the effects of phosphodiesterase type 5 (PDE5) inhibitory drugs, Tadalafil and Sildenafil, on inducible NOS (iNOS), endothelial NOS (eNOS) and p53 genes expressions and apoptosis in ischemia/reperfusion (I/R) induced oxidative injury in rat renal tissue. Eighty Sprague-Dawley rats (300-350 g) were divided into four groups. In ischemia/reperfusion group, rats were subjected to renal ischemia by clamping the left pedicle for 60 min, and then reperfused for 90 min. On the other hand, in other two groups the rats were individually pretreated with Tadalafil and Sildenafil 1 h before the induction of ischemia. Malondialdehyde (MDA) is determined in renal tissue homogenates by high-performance liquid chromatography, the number of apoptotic cell were calculated by TUNEL method and p53 and eNOS expression were detected with immunohistochemistry. On the other hand, myeloperoxidase (MPO) levels were measured by spectrophotometric method and the mRNA level of iNOS in renal tissue was determined by Real-time PCR (RT-PCR). Our results indicate that MDA and MPO levels were increased in the I/R group than those in the control group. Both Tadalafil and Sildenafil treatment decreased the MDA levels in ischemia/reperfusion group, whereas this effect was more potent with Sildenafil. RT-PCR results showed that, iNOS gen expression increased in the I/R group, but decreased in the PDE5 inhibitory drugs treated group. Apoptotic cells, eNOS levels and p53 positive cells were also decreased in PDE5 inhibitory drugs treated group. We suggest that Tadalafil and Sildenafil have beneficial effects against I/R related renal tissue injury and this protective effect is clearer for Sildenafil than Tadalafil

Leptin receptor (Ob-R) mRNA expression and serum leptin concentration in patients with colorectal and metastatic colorectal cancer

The objective of the present study was to investigate the effect of leptin on the progression of colorectal carcinoma to metastatic disease by analyzing the serum leptin concentration and Ob-R gene expression in colon cancer tissues. Tissue samples were obtained from 31 patients who underwent surgical resection for colon (18 cases) and metastatic colon (13 cases) cancer. Serum leptin concentration was determined by an enzyme-linked immunosorbent assay (ELISA) and Ob-R mRNA expression by real-time polymerase chain reaction (RT-PCR) for both groups. ELISA data were analyzed by the Student t-test and RT-PCR data were analyzed by the Mann-Whitney U-test. RT-PCR results demonstrated that mRNA expression of Ob-R in human metastatic colorectal cancer was higher than in local colorectal cancer tissues. On the other hand, mean serum leptin concentration was significantly higher in local colorectal cancer patients compared to patients with metastatic colorectal cancer. The results of the present study suggest a role for leptin in the progression of colon cancer to metastatic disease without weight loss. In other words, significantly increased Ob-R mRNA expression and decreased serum leptin concentration in patients with metastatic colon cancer indicate that sensitization to leptin activity may be a major indicator of metastasis to the colon tissue and the determination of leptin concentration and leptin gene expression may be used to aid the diagnosis