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Öğe Activation of RAF/MEK/ERK and PI3K/AKT/mTOR pathways in pituitary adenomas and their effects on downstream effectors(BIOSCIENTIFICA LTD, 2009) Dworakowska, D.; Wlodek, E.; Leontiou, C. A.; Igreja, S.; Cakir, M.; Teng, M.; Prodromou, N.Raf/MEK/ERK and phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) cascades are key signalling pathways interacting with each other to regulate cell growth and tumourigenesis. We have previously shown B-Raf and Akt overexpression and/or overactivation in pituitary adenomas The aim of this study is to assess the expression of their downstream components (MEK1/2, ERK1/2, mTOR, TSC2, p70S6K) and effectors (c-MYC and CYCLIN D1) We studied tissue from 16 non-functioning pituitary adenomas (NFPAs), six GH-omas, six prolactinomas and six ACTH-omas, all collected at transsphenoidal surgery; 16 normal autopsy pituitaries were used as controls The expression of phospho and total protein was assessed with western immunoblotting, and the mRNA expression with quantitative RT-PCR. The expression of pSer217/221 MEK1/2 and pThr183 ERK1/2 (but not total MEK1/2 or ERK1/2) was significantly higher in all tumour subtypes in comparison to normal pituitaries. There was no difference in the expression of phosphorylated/total mTOR, TSC2 or p70S6K between pituitary adenomas and controls. Neither c-MYC phosphorylation at Ser 62 nor total c-MYC was changed in the tumours However, c-MYC phosphorylation at Thr58/Ser62 (a response target for Akt) was decreased in all tumour types CYCLIN D1 expression was higher only in NFPAs. The mRNA expression of MEK1, MEK2, ERK1, ERK2, c-MYC and CCND1 was similar in all groups. Our data indicate that in pituitary adenomas both the Raf/MEK/ERK and PI3K/Akt/mTOR pathways are upregulated in their initial cascade, implicating a pro-proliferative signal derangement upstream to their point of convergence. However, we speculate that other processes, such as senescence, attenuate the changes downstream in these benign tumours. Endocrine-Related Cancer (2009) 16 1329-1338Öğe Anaphylaxis in pediatric patients: a multi-center, retrospective, case study(WILEY, 2009) Orhan, F.; Boz, Bingol A.; Yilmaz, O.; Reisli, I; Cakir, M.; Karakas, T.; Yuksel, H.[Abstract not Available]Öğe Gallbladder Motor Function in Patients with Different Thyroid Hormone Status(JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH, 2009) Cakir, M.; Kayacetin, E.; Toy, H.; Bozkurt, S.Hypothyroidism and hyperthyroidism are known to affect cholesterol metabolism, bile acid synthesis and bile content. There are previous Studies reporting increased prevalence of gallstone and common bile duct stone formation in hypothyroidism. The aim Of this Study was to compare gallbladder (GB) motor function between euthyroid, hypothyroid and hyperthyroid Subjects by conventional ultrasonography. Eighteen euthyroid, 14 hypothyroid and 20 hyperthyroid, age, sex and body mass index matched subjects were included in the study. Etiology of hypothyroidism comprised of thyroidectomy, Hashimoto's thyroiditis and previous radioactive iodine therapy. Hyperthyroid group included patients with toxic nodular goitre and Graves' disease. Patients who have diseases or are under drug treatment known to affect biliary function were not included in the study. Fasting and post-stimulus GB volumes were measured by real-time conventional ultrasonography and computer unit (Aloka UST-979, 3.5 mHz electronic convex probe, Japan). No significant differences were noted for fasting, post-stimulus GB volumes and GB ejection fraction between euthyroid, hypothyroid and hyperthyroid subjects. Measuring GB motility accurately is not straightforward because besides being not static during fasting, after a meal, intermittent emptying and refilling of GB occurs. Ultrasonography is affected by GB filling and measures "net" GB emptying. Although cumbersome, additional evaluation with cholescintigraphy which detects "absolute" GB emptying and is not affected by GB filling may provide complete assessment of motor function and may be more informative in evaluating subjects with different thyroid hormone status.Öğe Levels of testosterone and gonadotrophins in men with long-standing tetraplegia(NATURE PUBLISHING GROUP, 2009) Cakir, M.[Abstract not Available]Öğe Radiotherapy-induced Hypopituitarism in Nasopharyngeal Carcinoma: the Tip of an Iceberg(JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH, 2015) Ipekci, S. H.; Cakir, M.; Kiyici, A.; Koc, O.; Artac, M.Background: Radiation-induced hypopituitarism is an important late complication of cranial radiotherapy in children and adults. The purpose of this cross-sectional study was to evaluate the effects of radiotherapy on pituitary function in adult nasopharyngeal carcinoma patients. Methods: Pituitary function was evaluated in 30 patients after cranial radiotherapy for nasopharyngeal carcinoma. Somatotroph and corticotroph axes were assessed by insulin tolerance test while gonadotroph and thyroid axes were evaluated by basal pituitary and end organ hormone levels at 10-133 months after radiotherapy. Results: At least one hormonal disorder was observed in 28 (93%) patients after radiotherapy. 26 (87%) patients had one or more anterior pituitary hormone deficiencies. The rates of pituitary hormone deficiencies were 77% for growth hormone, followed by adrenocorticotropic hormone (73%), thyroid-stimulating hormone (27%) and gonadotropins (7%). Hyperprolactinemia was present in 13 (43%) patients. Conclusions: Radiation-induced hypopituitarism is more common than expected in patients with nasopharyngeal carcinoma.