Репозиторий Университета

© 2018 The Author(s). Introduction: Due to the beginning of the use of immunophenotypic and cytogenetic techniques, new nosological forms of lymphoproliferative diseases have appeared over the past few decades. According to the WHO classification (2008), today there are more than 50 known lymphoproliferative diseases. Case Presentation: We present the case of a 51-year-old man with lymphoproliferative syndrome. Our patient underwent morphological and immunohistochemical investigations of biopsy materials from the right inguinal lymph node. The morphological picture was characteristic for small cell lymphoma. Immunophenotypically, tumor proliferate cells expressed CD20, CD76b, CD5, and cyclin D, and the tumor immunophenotype matched mantle cell lymphoma. Discussion: At the present stage of the development of medicine, the diagnosis of lymphoproliferative diseases is based on the clinical picture of the disease with the definition of localization and characteristics of the tumor process, morphological study of tumor tissue and cells, and immunophenotypic and/or cytogenetic analyses are mandatory to determine the final diagnosis.

© 2018 Denisenko et al. Background: Proton pump inhibitors (PPIs) are metabolized by cytochrome P450. CYP2C19 is the main isoenzyme for the majority of PPI, whereas CYP3A family is a secondary enzyme for PPI biotransformation. Purpose: The aim of the study was to find if CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*3, and CYP2C19*17 genotypes are connected with CYP3A and CYP2C19 activities in Russian peptic ulcer patients taking omeprazole. Patients and methods: Forty-eight gastric or duodenal ulcer patients (15 men, 33 women; mean age 55.0±15.3 years, age range 18–91 years) from Moscow region of Russia were enrolled. Peripheral venous blood was collected for DNA extraction, and real-time polymerase chain reaction was performed for CYP3A5*3A6986G (rs776746), CYP3A4*22 C>T in intron 6 (rs35599367), CYP2C19*2G681A (rs4244285), CYP2C19*3G636A (rs4986893), and CYP2C19*17C-806T (rs12248560) polymorphism analyses. Urine samples of patients were collected in the morning between 6 and 9 am before food or drug intake. Urine cortisol and 6β-hydroxycortisol concentrations (for CYP3A activity) and omeprazole and 5-hydroxyomeprazole concentrations (for CYP2C19 activity) were measured using high-performance liquid chromatography/mass spectroscopy. Results: We found a connection between CYP2C19 genotypes and CYP3A activity. Median metabolic ratios 6β-hydroxycortisol/cortisol (25%–75% percentiles) were 2.84 (1.99–4.39) for CYP2C19 extensive metabolizers (EMs), 2.51 (1.86–4.73) for CYP2C19 ultra-rapid metabolizers (UMs), and 1.45 (1.12–2.16) for CYP2C19 intermediate metabolizers (IMs) + poor metabolizers (PMs). A statistically significant difference in CYP3A activity (Mann–Whitney test) was found between CYP2C19 EMs vs CYP2C19 IMs+PMs (p=0.006), between CYP2C19 UMs vs CYP2C19 IMs+PMs (p=0.018), and in multiple comparison Kruskal–Wallis test (p=0.014). Conclusion: In CYP2C19 IMs+PMs, CYP3A activity was significantly lower than in CYP2C19 EMs and UMs.

© 2018 Sychev et al. Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction. In clinical practice, the process of phenotyping of CYP isoenzymes and some endogenous substrates in the ratio of cortisol to 6β-hydroxycortisol in urine for the evaluation of CYP3A4 activity has been deemed to be a quite promising, safe and minimally invasive method for patients nowadays.

© 2018 Ima-Press Publishing House. All Rights Reserved. Up to 15% of patients with secondary brain tumors of unknown primary are admitted to a neurosurgery department. Identification of a primary tumor site on the basis of surgical material immunophenotyping in routine clinical practice has a significant potential; however, this requires systematization. Objective: to detect the primary focus of brain carcinoma. Patients and methods: Surgical specimens from 7 patients with brain tumor of unknown primary were investigated using light optical microscopy and an immunohistochemical (IHC) panel including EMA, CK AE1/3, CK7, CK5/6, GFAP, S-100, Vimentin, p63, TTF-1, Uroplakin III (UPIII), CDX2, and Her2/neu. Results and discussion: A study using the IHC panel made it possible to obtain the following tumor phenotypes in the patients: CK5/6+, p63+, CK7+, UPIII+ (urothelial cancer) (n=3); CK5/6-, CK7+, TTF-1+, CDX2- (lung adenocarcinoma) (n=2); CK5/6+, p63+, CK7-, UPIII, TTF-1- (squamous cell carcinoma) (n=1), and CK5/6-, CK7+, TTF-1-, CDX2-, Her2/neu+ (breast cancer) (n=1). Evidence of the primary focus of the tumors was subsequently confirmed by instrumental techniques in all cases when cancer of the breast, lung and urinary system was directly sought. The findings were used to elaborate an algorithm for the differential diagnostic immunophenotyping of brain metastases. Conclusion: The primary focus of brain carcinoma was detected in all cases on the proposed IHC panel. The systematized algorithm for differential diagnostic immunophenotyping can be used in clinical practice.