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Tayfun Ozçelik

Publications and source records attributed to Tayfun Ozçelik.

14 recordsLinked to original sources
PubMed2006

Endothelial progenitor cells display clonal restriction in multiple myeloma.

BACKGROUND: In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. METHODS: A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (VH). RESULTS: In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (> or = 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (> or = 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with VH primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI. CONCLUSION: Our results suggest that EPCs in at least a substantial subpopulation of MM patients are related to the neoplastic clone and that this is an important mechanism for upregulation of tumor neovascularization in MM.

Age Factors↗
PubMed2005

Skewed X chromosome inactivation in blood cells of women with scleroderma.

OBJECTIVE: Scleroderma (SSc) is an autoimmune disease of unknown etiology. The disease is 3-8 times more frequent in women than in men. The role of X chromosome inactivation (XCI) in the predisposition of women to autoimmunity has been questioned. Until now this has not been illustrated experimentally. This study was undertaken to test the hypothesis that disturbances in XCI mosaicism may be involved in the pathogenesis of the disease in female patients with SSc. METHODS: Seventy female SSc patients and 160 female controls were analyzed for the androgen receptor locus by the Hpa II/polymerase chain reaction assay to assess XCI patterns in DNA extracted from peripheral blood cells. Furthermore, skin biopsy samples were obtained from 5 patients whose blood revealed an extremely skewed pattern of XCI, and the analysis repeated. Since microchimerism in SSc was reported, Y chromosome sequences were investigated in all samples. RESULTS: Skewed XCI was observed in DNA from peripheral blood cells in 35 of 55 informative patients (64%), as compared with 10 of 124 informative controls (8%) (P < 0.0001). Extreme skewing was present in 27 of the patient group (49%), as compared with only 3 of the controls (2.4%) (P < 0.0001). However, XCI was random in all skin biopsy samples. The potential contribution of microchimerism to the random XCI pattern is highly unlikely based on the medical histories of the patients. CONCLUSION: Skewed XCI mosaicism may play a significant role in the pathogenesis of SSc.

Adult↗
PubMed2005

Expression of IFITM1 in chronic myeloid leukemia patients.

We investigated the peripheral blood gene expression profile of interferon induced transmembrane protein 1 (IFITM1) in sixty chronic myeloid leukemia (CML) patients classified according to new prognostic score (NPS). IFITM1 is a component of a multimeric complex involved in the trunsduction of antiproliferative and cell adhesion signals. Expression level of IFITM1 was found significantly different between the high- and low-risk groups (P = 9.7976 x 10(-11)) by real-time reverse transcription polymerase chain reaction (RT-PCR). Higher IFITM1 expression correlated with improved survival (P = 0.01). These results indicate that IFITM1 expression profiling could be used for molecular classification of CML, which may also predict survival.

Adult↗
PubMed2004

Circulating endothelial progenitor cells in multiple myeloma: implications and significance.

Angiogenesis governs the progression of multiple myeloma (MM). Circulating endothelial cells (CECs) contribute to angiogenesis and comprise mature ECs and endothelial progenitor cells (EPCs). The present study sought to characterize CECs and their relation to disease activity and therapeutic response in 31 consecutive patients with MM. CECs, identified as CD34(+)/CD146(+)/CD105(+)/CD11b(-) cells, were 6-fold higher in patients compared to controls and correlated positively with serum M protein and beta(2)-microglobulin. Circulating EPCs displayed late colony formation/outgrowth and capillary-like network formation on matrigel; these processes were inhibited after effective thalidomide treatment. Co-expression of vascular endothelial growth factor receptor-2 (KDR) and CD133 characterized EPCs in MM, and KDR mRNA elevations correlated with M protein levels. In vitro exposure of ECs to thalidomide or its derivative CC-5013 inhibited gene expression of the receptors for transforming growth factor-beta and thrombin. Thus, elevated levels of CECs and EPCs covary with disease activity and response to thalidomide, underscoring the angiogenic aspect of MM and suggesting that angioblastlike EPCs are a pathogenic biomarker and a rational treatment target in MM. The results also highlight the anti-angiogenic properties of thalidomide and CC-5013 and further elucidate possible mechanisms of their effectiveness against MM. (Blood. 2005;105:3286-3294).

Adult↗
PubMed2003

Germline mutations in the BRCA1 and BRCA2 genes in Turkish breast/ovarian cancer patients.

In this study we genotyped Turkish breast/ovarian cancer patients for BRCA1/BRCA2 mutations: protein truncation test (PTT) for exon 11 BRCA1 of and, multiplex PCR and denaturing gradient gel electrophoresis (DGGE) for BRCA2, complemented by DNA sequencing. In addition, a modified restriction assay was used for analysis of the predominant Jewish mutations: 185delAG, 5382InsC, Tyr978X (BRCA1) and 6174delT (BRCA2). Eighty three breast/ovarian cancer patients were screened: twenty three had a positive family history of breast/ovarian cancer, ten were males with breast cancer at any age, in eighteen the disease was diagnosed under 40 years of age, one patient had ovarian cancer in addition to breast cancer and one patient had ovarian cancer. All the rest (n=30) were considered sporadic breast cancer cases. Overall, 3 pathogenic mutations (3/53-5.7%) were detected, all in high risk individuals (3/23-13%): a novel (2990insA) and a previously described mutation (R1203X) in BRCA1, and a novel mutation (9255delT) in BRCA2. In addition, three missense mutations [two novel (T42S, N2742S) and a previously published one (S384F)] and two neutral polymorphisms (P9P, P2532P) were detected in BRCA2. Notably none of the male breast cancer patients harbored any mutation, and none of the tested individuals carried any of the Jewish mutations. Our findings suggest that there are no predominant mutations within exon 11 of the BRCA1 and in BRCA2 gene in Turkish high risk families.

Adult↗
PubMed2002

Somatic mosaicism for a MECP2 mutation associated with classic Rett syndrome in a boy.

Rett syndrome is a severe neurodevelopmental disorder that arises from mutations in the X-linked MECP2 gene. It is almost exclusively seen in girls due to the predominant occurrence of the mutations on the paternal X-chromosome, and also the early postnatal lethal effect of the disease causing mutations in hemizygous boys. We identified a boy with features of classic Rett syndrome who is mosaic for the truncating MECP2 mutation R270X. Chromosome analysis showed normal karyotype. These results indicate that a MECP2 mutation associated with Rett syndrome in females could lead to a similar phenotype in males as a result of somatic mosaicism.

Child↗
PubMedDate not supplied

Lack of association between RNASEL Arg462Gln variant and the risk of breast cancer.

BACKGROUND: The RNASEL G1385A variant was recently found to be implicated in the development of prostate cancer. Considering the function of RNase L and the pleiotropic effects of mutations associated with cancer, we sought to investigate whether the RNASEL G1385A variant is a risk factor for breast cancer. PATIENTS AND METHODS: A total of 453 breast cancer patients and 382 age- and sex-matched controls from Greece and Turkey were analyzed. Genotyping for the RNASEL G1385A variant was performed using an Amplification Refractory Mutation System (ARMS). RESULTS: Statistical evaluation of the RNASEL G1385A genotype distribution among breast cancer patients and controls revealed no significant association between the presence of the risk genotype and the occurrence of breast cancer. CONCLUSION: Although an increasing number of studies report an association between the RNASEL G1385A variant and prostate cancer risk; this variant does not appear to be implicated in the development of breast cancer.

Adult↗
PubMedDate not supplied

MDM2 T309G polymorphism is associated with bladder cancer.

Recently, a functional T to G polymorphism at nucleotide 309 in the promoter region of the MDM2 gene (rs: 2279744, SNP 309) has been identified. This polymorphism has an impact on the expression of the MDM2 gene, which is a key negative regulator of the tumor suppressor molecule p53. The effect of T309G polymorphism of the MDM2 gene on bladder cancer susceptibility was investigated in a case-control study of 75 bladder cancer patients and 103 controls from Turkey. The G/G genotype exhibited an increased risk of 2.68 (95% CI, 1.34-5.40) for bladder cancer compared with the combination of low-risk genotypes T/T and T/G at this locus. These results show an association between MDM2 T309G polymorphism and bladder cancer in our study group. To the best of our knowledge, this is the first study reporting that MDM2 T309G polymorphism may be a potential genetic susceptibility factor for bladder cancer.

Adult↗
PubMedDate not supplied

DNA repair gene polymorphisms and bladder cancer susceptibility in a Turkish population.

BACKGROUND: Occupational exposure and life style preferences, such as smoking are the main known environmental susceptibility factors for bladder cancer. A growing list of chemicals has been shown to induce oxidative DNA damage. Base excision repair (BER) genes (X-ray repair cross complementing 1, XRCC1 and human 8-oxoguanine DNA glycosylase 1, OGG1) may play a key role in maintaining genome integrity and preventing cancer development. MATERIALS AND METHODS: We tested whether polymorphisms in XRCC1 and OGG1 are associated with bladder cancer risk by using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay. In addition, the possible modifying affect of cigarette smoking was evaluated. RESULTS: No studies, to date, have examined the association between genetic polymorphisms in DNA repair genes and bladder cancer susceptibility, in the Turkish population. We found the OGG1 Cys326Cys genotype to be more frequent among bladder cancer patients (odds ratio (OR): 2.41 (95% CI, 1.36-4.25)). However, in the case of XRCC1, there was no significant difference in susceptibility to bladder cancer development between patients with the Arg399 and these with the Gln399 allele (OR. 0.72 (95% CI, 0.41-1.26)). CONCLUSION: Our data showed that OGG1 genetic polymorphisms might be useful as prognostic genetic markers for bladder cancer in the clinical setting.

Adult↗