B hücreli kronik lenfositik lösemide C-Met protoonkogeni ve ligandi hepatosit büyüme faktörünün apopotoz mekanizmaları üzerine etkileri

B hücreli kronik lenfositik lösemi (B-KLL) uzun yaşam süreli ve iyi diferansiye klonal B lenfositlerinin periferal kan, lenfoid doku ve kemikiliğinde ilerleyici birikimi ile karakterizedir. Lenfositozun görüldüğü B-KLL' de B hücre proliferasyonunun artmasından çok lenfosit yaşam sürelerindeki uzunluk dikkati çeker. Bu apoptoz yolundaki defekti gösteren bir durumdur . Bu çalışmada amaç, B-KLL'de apoptotik sinyal yollarının araştırılması ve lenfositozun nedeninin ortaya konulmasıdır. Bu nedenle B-KLL hastaları, hücre soyları ve kontrollerden elde edilen protein lizat örnekleri kullanıldı. Poliakrilamid jel elektroforezi ile proteinler PVDF membranlar üzerine blot edilldi ve apoptotik sinyal moleküllerinin bir kısmı araştırıldı (bad, fosfobad, PI3K, Akt, Bcl-xL). Yaşam yolları ile diğer sinyal yollarını kullandığı bilinen ve bir büyüme faktörü olan HGF' nin apoptotik sinyal proteinlerine etkisi araştırıldı, hücreler HGF ile kültüre edildi ve benzer moleküller benzer metod ile değerlendirildi. Akt, PI3K ve fosfobad gibi yaşam faktörlerinin B-KLL lenfositleri üzerinde ekspresse edildiği, bax, bad gibi apoptotik faktörlerin zayıf ekspresse olduğu bulundu. Ek olarak HGF' nin yaşam molekülleri ekspresyonunu artırdığı gözlemlendi. Apoptoz ve yaşam yolları arasındaki dengenin bozulmasının B-KLL'de lenfositozun sebebi olabileceği söylendi. SUMMARY The effects of c-Met protooncogene and its ligand Hepatocyte Growth Factor on apoptosis mechanisms in B Cell Chronic Lymphocytic Leukemia B cell chronic lymphocytic leukemia ( B-CLL) is characterized by a progressive accumulation of long lived and well differentiated colonial B lymphocytes in peripheral blood, lymphoid tissue and bone marrow. Lymphocytosis seen in B-CLL is the result of extended lymphocyte life rather than increased lymphocyte proliferation of B cells. This is an indication of defect in apoptosis way. In this work, we aimed to investigate the part of apoptotic signaling patways in B-CLL and to relate our results to the causes of lymphocytosis. Therefore, protein lysate samples from B-CLL patients and, cell lines as controls are used. Following polyacrylamide gel electrophoresis, proteins were blotted on PVDF membranes and a part of apoptotic signaling molecules including bad, phosphobad, PI3K, Akt, BclXL, bax were investigated. To investigate the effect of HGF, which was known as a growth factor uses mutual signaling pathways with other surviving pathway, on the apoptotic signaling proteins, cells were cultured with HGF and the same molecules were again evaluated with the same method. We have found that, surviving factors such as Akt, PI3K and phospho-bad were expressed on CLL lymphocytes, while the expression of apoptotic factors such as bax and bad were weakly expressed. Additionally, HGF were increased the expression of surviving related molecules. We suggest that impaired balance between apoptosis and survival pathways might be one of the causes of lymphocytosis seen in B-CLL

B hücreli kronik lenfositik lösemide C-Met protoonkogeni ve ligandi hepatosit büyüme faktörünün apopotoz mekanizmaları üzerine etkileri

ÖZETB hücreli kronik lenfositik lösemi (B-KLL) uzun yaşam süreli ve iyi diferansiye klonal B lenfositlerinin periferal kan, lenfoid doku ve kemikiliğinde ilerleyici birikimi ile karakterizedir. Lenfositozun görüldüğü B-KLL' de B hücre proliferasyonunun artmasından çok lenfosit yaşam sürelerindeki uzunluk dikkati çeker. Bu apoptoz yolundaki defekti gösteren bir durumdur .Bu çalışmada amaç, B-KLL'de apoptotik sinyal yollarının araştırılması ve lenfositozun nedeninin ortaya konulmasıdır. Bu nedenle B-KLL hastaları, hücre soyları ve kontrollerden elde edilen protein lizat örnekleri kullanıldı. Poliakrilamid jel elektroforezi ile proteinler PVDF membranlar üzerine blot edilldi ve apoptotik sinyal moleküllerinin bir kısmı araştırıldı (bad, fosfobad, PI3K, Akt, Bcl-xL).Yaşam yolları ile diğer sinyal yollarını kullandığı bilinen ve bir büyüme faktörü olan HGF' nin apoptotik sinyal proteinlerine etkisi araştırıldı, hücreler HGF ile kültüre edildi ve benzer moleküller benzer metod ile değerlendirildi. Akt, PI3K ve fosfobad gibi yaşam faktörlerinin B-KLL lenfositleri üzerinde ekspresse edildiği, bax, bad gibi apoptotik faktörlerin zayıf ekspresse olduğu bulundu. Ek olarak HGF' nin yaşam molekülleri ekspresyonunu artırdığı gözlemlendi.Apoptoz ve yaşam yolları arasındaki dengenin bozulmasının B-KLL'de lenfositozun sebebi olabileceği söylendi.SUMMARYThe effects of c-Met protooncogene and its ligand Hepatocyte Growth Factor on apoptosis mechanisms in B Cell Chronic Lymphocytic LeukemiaB cell chronic lymphocytic leukemia ( B-CLL) is characterized by a progressive accumulation of long lived and well differentiated colonial B lymphocytes in peripheral blood, lymphoid tissue and bone marrow. Lymphocytosis seen in B-CLL is the result of extended lymphocyte life rather than increased lymphocyte proliferation of B cells. This is an indication of defect in apoptosis way.In this work, we aimed to investigate the part of apoptotic signaling patways in B-CLL and to relate our results to the causes of lymphocytosis. Therefore, protein lysate samples from B-CLL patients and, cell lines as controls are used. Following polyacrylamide gel electrophoresis, proteins were blotted on PVDF membranes and a part of apoptotic signaling molecules including bad, phosphobad, PI3K, Akt, BclXL, bax were investigated. To investigate the effect of HGF, which was known as a growth factor uses mutual signaling pathways with other surviving pathway, on the apoptotic signaling proteins, cells were cultured with HGF and the same molecules were again evaluated with the same method. We have found that, surviving factors such as Akt, PI3K and phospho-bad were expressed on CLL lymphocytes, while the expression of apoptotic factors such as bax and bad were weakly expressed. Additionally, HGF were increased the expression of surviving related molecules. We suggest that impaired balance between apoptosis and survival pathways might be one of the causes of lymphocytosis seen in B-CLL

The role of Kallikrein10 (KLK10) polymorphism in prostate cancer susceptibility

Purpose: The present study aims to investigate the potential role of Kallikrein 10 (KLK10) genotype and allele frequencies in predisposition to prostate cancer. Materials and methods: KLK10 (rs7259451) gene polymorphisms were determined by real-time polymerase chain reaction analysis in patients with prostate cancer (n=69) and controls (n=76). Results: KLK10 gene frequencies were significantly different in the case and control groups (P = .028). GG carriers were significantly higher in the control group (P = .034), whereas TT carriers were higher in the prostate cancer group (P = .033). Furthermore, The patients with GG genotype had the lowest PSA levels while TT carriers had the highest (P = .005). Conclusion: According to the results, we suggested that carrying variant T allele and also carrying homozygote TT genotype could be a potential risk, while ancestral homozygote GG genotype and G allele are risk reducing factors for prostate cancer.No sponso

Investigation of catechol-o-methyltransferase (comt) gene Val158Met polymorphism in ovarian cancer

Objective: Catechol-o-methyltransferase (comt), the product of the COMT gene, detoxifies the carcinogenic catechol estrogens. The aim of the present study was to examine the relationship between comt Val158Met polymorphism and the risk of ovarian cancer. Material and methods: The study groups consist of 94 individuals as a patients group with ovarian cancer (n=47) and control group (n=47). The allele and genotype frequencies were determined according to Hardy-Weinberg equilibrium (HWE). The allele and genotype frequencies. determined according to HWE. Genetic analysis were performed by real-time-polymerase chain reaction instrument, and the statistical analysis were performed by SPSS program. Results: Although no significant relationship was obtained among groups (p=0.413) regarding comt gene Val158Met polymorphism, the genotype frequencies for comt Val158Met (rs4860) polymorphism in groups was homozygote wild type GG genotype 25.5%, heterozygote GA genotype 46.8%, homozygote mutant AA genotype 27.7%. Conclusion: This study is the first to investigate the relationship between ovarian cancer and the Val158Met polymorphism in the comt gene in a Turkish population. No statistically significant relationship was identified among genotypes belonging to the patient and control groups although sample sizes were relatively small and the analysis should be repeated in a larger cohort.No sponso

Investigation of circulating miRNA-133, miRNA-26, and miRNA-378 as candidate biomarkers for left ventricular hypertrophy

Background/aim: Left ventricular hypertrophy (LVH) involves increased muscular mass of the left ventricle due to increased cardiomyocyte size and is caused by cardiomyopathies. Several microRNAs (miRNAs) have been implicated in processes that contribute to heart disease. This study aimed to examine miRNA-133, miRNA-26 and miRNA-378 as candidate biomarkers to define prognosis in patients with LVH. Patients and methods: The study group consisted of 70 patients who were diagnosed with LVH and 16 unaffected individuals who served as the control group. Real-time polymerase chain reaction (RT-PCR) was used to analyze serum miRNA-133, miRNA-26, and miRNA-378 expression levels in LVH patients and the control group. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic capability of miRNA-378. Results: When crossing threshold (CT) values were compared between patient and control samples, we found that there were no statistically significant differences in miRNA-133 and miRNA-26 CT values, while the miRNA-378 expression was significantly increased in LVH patients. ROC analysis demonstrated that the expression levels of miRNA-378 (AUC=0.484, p=0.0013) were significantly different between groups. Conclusion: We observed a statistically significant relationship between miRNA-378 expression levels and LVH, suggesting that circulating miRNA-378 may be used as a novel biomarker to distinguish patients who have LVH from those who do not.No sponso

Dual effects of testosterone in Behcet's disease: Implications for a role in disease pathogenesis

WOS: 000383111500003PubMed ID: 27467286Behcet's disease (BD) exhibits more severe disease course and higher mortality among male patients. However, underlying mechanisms of gender differences in clinical manifestations and disease severity are unclear. The aim of this study was to determine whether testosterone (T) has any role on BD pathogenesis. We studied peripheral blood mononuclear cells (PBMC) and neutrophils of BD patients and controls. Functional assay of neutrophils, cytokine measurements of culture supernatants and gene expressions on both cells were analyzed before and after T incubation. Neutrophils were significantly activated after incubation with T in only BD patients. Incubation with T caused significantly elevated interleukin (IL)-12 and IL-2 in BD. Gene expression of IL-10 was significantly downregulated after incubation with T in BD, especially in male patients. The same difference was observed in IL-10 levels in culture supernatant after T. Baseline TLR4 expression was significantly higher in BD patients compared to healthy donors (HC). Toll-like receptor (TLR) 4 expression on PBMC was significantly elevated in female BD patients. ERAP1 expressions of all patients and controls were decreased under the T effect but it differed significantly between BD vs HC. Baseline IL23R expression was higher in BD males compared with females but the difference disappeared after T. When BD patients were analyzed separately, baseline C-C motif chemokine receptor1 (CCR1), STAT4, TLR4 and KLRC4 expressions were lower in males. Despite immunosuppressive behavior in healthy subjects, T causes neutrophil hyperactivation and TH1 type immune alterations in BD patients. Our results suggest that T may have a role in BD pathogenesis by altering the expression level of IL-10, TLR4, ERAP1, CCR1