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Purpose Hindlimb ischemia and reperfusion leads to lung injury in various animal models. We investigated the effectiveness of FK506, an immunosuppressive agent, which also modulates neutrophilic infiltration, in preventing lung injury after hindlimb ischemia and reperfusion in a rat model. Methods Twenty-seven male Sprague-Dawley rats were randomized to received FK506 at doses of 0.3?mg/kg, 0.5?mg/kg, or 1?mg/kg body weight per day, or normal saline injections, as pretreatment, and there was also a sham group. On the 4th day, the animals were subjected to 2?h of ischemia induced by a tourniquet, followed by reperfusion of the extremities for 2?h. Lung tissue assays were performed for the lipid peroxidation product malondialdehyde (MDA) and total glutathione (GSH). Lung tissues were also examined histopathologically under light and electron microscopy. Results The MDA levels in the study groups were significantly lower than those in the control group ( P < 0.05), but the total GSH levels did not differ significantly among the groups. Histopathologically, there were no significant differences among the groups given different doses of FK506, but there was a significant difference between the control group and all the treatment groups. Conclusion FK506 ameliorates the lung injury associated with ischemia and reperfusion of the lower limbs, and might have an inhibitory effect on the neutrophils that cause remote organ damage. [ABSTRACT FROM AUTHOR]

It is known that disorders in apoptosis function play an important role in the pathogenesis of many types of cancer, including lung cancer. Tumor necrosis factor related apoptosis inducing ligand (TRAIL), a type II transmembrane protein, is a death ligand capable of inducing apoptosis by activating distinctive death receptor. Our purpose in this study is to investigate the gene polymorphisms in TRAIL molecular pathway and TRAIL gene expression levels in non-small cell lung cancer (NSCLC) patients in terms of pathogenesis and prognosis of the disease. In this study, TRAIL C1595T polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis in 158 patients with NSCLC and 98 healthy individuals. Surgically resected tissues were examined and classified histopathologically. In addition, TRAIL gene expression levels in tumor tissue and tumor surrounding tissue samples of 48 patients with NSCLC were determined using real-time polymerase chain reaction. TRAIL gene expression levels of NSCLC patients were detected significantly 28.8 fold decrease in the tumor tissue group compared to the control group (p=0.026). When patients were compared to tumor stage, expression of TRAIL gene in advanced tumor stage was found to be significantly 7.86 fold higher than early tumor stage [p=0.028]. No significant relationship was found between NSCLC predisposition and prognostic parameters of NSCLC with TRAIL genotypes, but the frequency of TRAIL gene 1595 CT genotype was observed to be lower in the patients compared to the other genotypes, and the difference was found to be very close to statistical significance (p=0.07). It can be suggested that TRAIL may play an important role in the development of NSCLC and may be an effective prognostic factor in tumor progression.: It is known that disorders in apoptosis function play an important role in the pathogenesis of many types of cancer, including lung cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a type II transmembrane protein, is a death ligand capable of inducing apoptosis by activating distinctive death receptor. Our purpose in this study is to investigate the gene polymorphisms in TRAIL molecular pathway and TRAIL gene expression levels in non-small cell lung cancer (NSCLC) patients in terms of pathogenesis and prognosis of the disease.

Background and Objectives: Previous studies have shown alterations in the cell cycle regulatory proteins in breast carcinomas. However, the results of these studies remain controversial. Cyclin D1 (CCND1) and p27(KIP1) (CDKN1B) are two essential regulators of cell cycle progression. This study aimed to investigate the associations of CCND1 A870G and CDKN1B C79T polymorphisms with breast cancer risk., Patients and Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype and allelic frequencies of polymorphisms. Seventy-eight breast cancer patients and 84 age-matched healthy controls were included in the study., Results: Frequencies of CT genotype and T allele of CDKN1B were found to be higher in breast cancer patients than in controls (p=0.013, OR: 1.514 95% CI: 1.086-2.114.15; p=0.007, OR=1.496; 95% CI: 1.111-2.014, respectively). The frequency of AA genotype of CCND1 was decreased in hormone receptor- (estrogen and progesterone receptors) negative patients with breast cancer (p<0.049, OR=0.286; 95% CI: 0.071-1.142), Conclusions: Even though CDKN1B polymorphism appears to be an important predictive factor for breast cancer risk and CCND1 polymorphism may be a prognostic biomarker for breast cancer, further investigations with larger study groups are needed to fully elucidate the role of CCND1 and CDKN1B polymorphisms in the development and prognosis of breast cancer.

Background/aims: Endometriosis is regarded as a complex disese, in which genetic and environmental factors contribute to the disease phenotype. Whether vascular endothelial growth factor (VEGF) -460 C/T and +405 G/C polymorphisms are associated with susceptibility to endometriosis was investigated., Patients and Methods: Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. Sixty out of the 112 women enrolled had no endometriosis, 11 had mild or early-stage endometriosis and 41 had severe endometriosis. Polymerase chain reaction (PCR), restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to determine the -460 C/T and +405 G/C genotypes., Results: The VEGF +405 G/C genotype frequencies among the cases and controls were CC 55.8% and 35%; GC 30.8% and 50.0%; GG 13.5% and 15.0%, respectively. The allelic frequencies were C 71.15% (cases) and 60.0% (controls) and G 28.8% (cases) and 40% (controls). Patients with endometriosis had a higher incidence of the VEGF +405 CC genotype compared with the controls (p=0.027). Women with VEGF +405 CC genotype had 2.3-fold higher risk for endometriosis. VEGF +405 GC genotype and G allele in the control group was higher than the endometriosis group (p=0.039, p=0.027 respectively). The VEGF -460 C/T genotype frequencies among the cases were CC 21.2%, CT 26.9% and TT 51.9%; the C and T allelic frequencies were 34.6% and 65.3%, respectively. The VEGF -460 genotype frequencies among the controls were CC 31.70%, CT 18.3% and TT 50.0%; the C and T allelic frequencies were 40.8% and 59.1%, respectively (p>0.05). There was linkage disequilibrium between VEGF -460 C/T and +405 G/C polymorphisms (D': 0.197, r(2)=0.013). We observed that the VEGF 460T/405C haplotype frequency was significantly higher in patients compared to controls (p=0.011)., Conclusion: Our data suggest that the CC genotype of VEGF +405 and 460T/405C haplotypes of VEGF may be associated with the risk of endometriosis, but the G allele of VEGF +405 appears to be protective against endometriosis.

Background: Multiple genetic and epigenetic alterations in several genes are implicated in the multistep process of human gastric carcinogenesis. In this study, we examined the polymorphisms of six DNA repair genes: APE1, HOGG1, XRCC1, XRCC3, XPD, and XPG in patients with gastric cancer (GC)., Patients and Methods: Forty patients with GC and 247 controls were included in this study. DNA polymorphisms were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) method., Results: The frequency of the Asp/Glu genotype and Glu allele of APE1 in patients with GC was significantly higher than in the control group (p=0.05). We also observed a higher frequency of the Ser/Ser genotype of HOGG1 in grade III tumors, and in tumors with metastasis to adjacent tissue and solid organs (p<0.05)., Conclusion: Our results suggest that (i) APE1 gene polymorphism may be associated with GC risk and (ii) HOGG1 gene polymorphism may be informative in the prognosis of GC.