Meme kist sıvısı serbest amino asit profili

Amaç: Kistik meme hastalıkları kadınlarda en fazla görülen meme hastalığıdır. Apokrin epitelli (Na/K3) olmak üzere iki tip meme kisti bulunmaktadır. Yapılan çeşitli çalışmalar memesinde kistik bir oluşum bulunan kadınların 1.7-7.5 kat daha fazla meme kanserine yakalanma riski taşıdıklarını ortaya koymuştur. Kanserli hastaların periferal dolaşımına bakıldığında ise genellikle anormal bir amino asit profili saptanmıştır. Ayrıca, amino asit profilindeki değişiklikler organ düzeyindeki kanserler ile ilişkili bulunmuştur. Bu çalışmanın amacı meme kanseri gelişimi yönünden yüksek ve düşük risk grubu kistlerdeki amino asit düzeylerini incelemek ve bu kistlerden meme kanseri gelişimi yönündeki olası mekanizmaları araştırmaktır. Gereç ve Yöntemler: Çalışmada kistik meme hastalığı olan kadınlardan alınan meme kist sıvısı kullanıldı. Meme kist sıvısı amino asit düzeyleri HPLC metodu ile ölçüldü. Bulgular: Apokrin epitelli kist grubunda aspartik asit, glutamik asit, hidroksiprolin, serin, glisin, treonin, alanin, prolin, tirozin, metiyonin, izolösin, fenilalanin ve triptofan düzeyleri anlamlı olarak yüksek, lizin düzeyi ise düşük bulundu. Sonuç: Kanser gelişimi yönünden yüksek riske sahip olan apokrin epitelli kistlerde bulunan daha yüksek amino asit düzeyleri, amino asitlerin meme kanseri gelişim sürecinde potansiyel bir role sahip olabileceğini göstermektedir.Objective: Gross cystic breast disease (GCBD) is the most common benign breast disease. There are two types of breast cyst; lined by apocrine epithelium (Na/K<3) or flattened epithelium (Na/K>3). Several studies have shown that women with palpable breast cysts may have 1.7-7.5 times higher risk of developing breast cancer. Patients with malignant disease usually show abnormal amino acid profiles in the peripheral circulation. Changes in amino acid profile diagnostically correlate with organ sites of malignancy. The aim of this study was to investigate the levels of amino acids in two cyst groups and possible mechanisms involved in the development of breast cancer. Material and Methods: The breast cyst fluid aspirated from women with GCBD were analysed. Breast cyst fluid amino acid levels were determined with HPLC. Results: Aspartic acid, glutamic acid, hydroxyproline, serine, glycine, threonine, alanine, proline, tyrosine, methionine, isoleucine, leucine, phenylalanine and tryptophan levels were significantly higher, and lysine levels were lower in the apocrine epithelial cysts. Conclusion: In this study, higher concentrations of amino acids in apocrine cysts, which are also known to have a higher risk of developing breast cancer, may indicate the possible role(s) of amino acids in the mechanism of breast cancer development

Effects of mutational combinations on philadelphia-negative myeloproliferative neoplasms

WOS: 000399199200015PubMed ID: 28360451Philadelphia-negative myeloproliferative neoplasms (MPNs) were first described 65 years ago. Yet, the molecular features of the disease have become of interest since 2005 following the identification of the JAK2V617F mutation.1 Between 90% and 98% of patients with polycythemia vera and about 50% of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF) harbor the JAK2V617F mutation.2 In recent years, additional genetic factors such as the mutations of IDH1/2, TET2, EZH2, ASXL1, and CALR have been identified in Ph-negative MPNs.3 However, the significance of mutational combinations on Ph-negative MPNs remains unknown

The clinical significance of IDH mutations in essential thrombocythemia and primary myelofibrosis

Background: Limited data exist regarding impact of IDH mutations in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs). Prognostic significance of IDH mutations was asessed in 184 Ph-negative MPN patients - 107 essential thrombocythemia (ET) and 77 primary myelofibrosis (PMF). Methods: High-resolution melting (HRM) analysis was used to detect IDH1 and IDH2 mutations. Results: PMF and ET patients showed no significant difference for prevalence of IDH mutations. Mutant IDH (IDH1 or IDH2) was documented in five of PMF (6.5%) and two of ET patients (1.9%). IDH mutations in ET patients included one IDH1 R132C and one IDH2 R140Q. Of the five IDH-mutated PMF patients, four (80%) displayed IDH1 (three IDH1 R132C and one IDH1 R132S) and one (20%) carried IDH2 (IDH2 R140Q) mutation. Sixty percent (three in five) of IDH-mutated PMF patients carried JAK2V617F with following allele burdens: 31-50%, 5-12.5% and 31-50%, respectively. Three of 77 PMF patients (3.9%) simultaneously harbored IDH and JAK2V617F mutations. IDH mutations in PMF showed a trend towards higher rate in females (100% and 52.8%, respectively). Bleeding complications were significantly higher in IDH-mutated PMF patients compared to IDH wild-type counterparts. Trend towards a lower prevalance of acetylsalicylic acid (ASA) use was present in IDH mutant PMF patients compared to wild-type counterparts (20% and 63.9%, respectively). Death rate was higher in IDH-mutated PMF patients compared to IDH wild-type PMF patients (60% and 15.3%). In univariate analysis, a significantly shorter leukemia-free survival (LFS) was observed in IDH-mutated PMF patients. Conclusions: We conclude that IDH mutations indicate a risk for leukemic transformation in PMF