Up-regulation of expression and lack of 5' CpG island hypermethylation of p16 INK4a in HPV-positive cervical carcinomas

BACKGROUND: High risk type human papilloma viruses (HR-HPV) induce carcinomas of the uterine cervix by expressing viral oncogenes E6 and E7. Oncogene E7 of HR-HPV disrupts the pRb/E2F interaction, which negatively regulates the S phase entry. Expression of tumor suppressor p16(ink4a )drastically increases in majority of HR-HPV associated carcinomas due to removal of pRb repression. The p16(ink4a )overexpression is an indicator of an aberrant expression of viral oncogenes and may serve as a marker for early diagnostic of cervical cancer. On the other hand, in 25–57% of cervical carcinomas hypermethylation of the p16 INK4a promoter has been demonstrated using a methylation-specific PCR, MSP. To evaluate a potential usage of the p16 INK4a 5' CpG island hypermethylation as an indicator of tumor cell along with p16(ink4a )overexpression, we analyzed the methylation status of p16 INK4a in cervical carcinomas METHODS: Methylation status of p16 INK4a was analyzed by MSP and by bisulfite-modified DNA sequencing. The expression of p16(ink4a )was analyzed by RT-PCR and by immunohistochemical technique. RESULTS: The extensive methylation within p16 INK4a 5' CpG island was not detected either in 13 primary cervical carcinomas or in 5 cancer cell lines by bisulfite-modified DNA sequencing (including those that were positive by MSP in our hands). The number and distribution of rare partially methylated CpG sites did not differ considerably in tumors and adjacent normal tissues. The levels of the p16 INK4a mRNA were increased in carcinomas compared to the normal tissues independently of the number of partially methylated CpGs within 5'CpG island. The transcriptional activation of p16 INK4a was accompanied by p16(ink4a )cytoplasmic immunoreactivity in the majority of tumor cells and presence of a varied number of the p16 positive nuclei in different tumors. CONCLUSION: Hypermethylaion of the p16INK4a 5' CpG island is not a frequent event in HR-HPV-positive cervical carcinomas and cannot be an effective marker of cancer cells with up-regulated expression of p16(ink4a). Our data confirm other previous studies claiming specific p16INK4a up-regulation in the majority of cervical carcinomas at both the protein and mRNA levels. Cytoplasmic accumulation of p16(ink4a )is a feature of cervical carcinomas

Influence of metabolic therapy on the adaptive potential of the cardiovascular system of children with attention deficit hyperactivity disorder

During the last decade, scientific interest in researching the problem of attention deficit hyperactivity disorder (ADHD) in children has not faded. Despite the large number of published proceedings, this topic does not cease to interest specialists - not only doctors, but also pedagogical workers. This is explained by the fact that the problem of ADHD leads to social maladaptation and causes not only medical, but also pedagogical difficulties, which worsen the quality of life of the child and the family. The purpose of this study is to evaluate the adaptive mechanisms of the autonomic nervous system of children with ADHD and the possibility of metabolic correction by using omega-3-polyunsaturated fatty acid (omega-3-PUFA) and zinc agents

A TYPICAL PATIENT WITH HIV TODAY: COMPREHENSIVE CHARACTERIZATION AND ANTIRETROVIRAL TREATMENT OPTIONS (BASED ON DATA OF THE ST. PETERSBURG AIDS CENTER)

The objective of the study was to describe patients with HIV infection, who were diagnosed in 2016 in St Petersburg AIDS Center, including provided antiretroviral therapy (ART).A retrospective review of 521 patients’ case histories was performed. The case history selection was done by random sampling, in which the only criterion was the year of HIVinfection registration.The majority of patient were young people (middle age -), socially adapted, with higher or secondary special education (%),acquired HIV by sexual rout (%). 44% of patients had a CD4-lymphocyte count less than 350 cells / mm3, indicating a late detection of HIV and advanced stage of the disease at the moment of HIV registration. 25% of patients with a CD4 counts more than 350 cells / mm3 also had clinical symptoms of HIV-infection and needed ART.41% of patients with HIV had different concomitant noncommunicable diseases, of which one third (29%) received therapy for these diseases. This situation dictates the need for careful choice of ART regimens taking into account the clinical features of patients, concomitant therapy and drugdrug interactions

Short course of the essentials pediatrics (lectures for 4th year)

This publication offers lecture materials on pediatrics created in accordance with the standard program for students of the 4th course of the international faculty of higher medical educational institutions of the IV level of accreditation. The materials cover modern classifications, leading mechanisms of pathogenesis, diagnostic criteria, and the basics of therapy

СОВРЕМЕННЫЙ ПАЦИЕНТ С ВИЧ-ИНФЕКЦИЕЙ: КОМПЛЕКСНАЯ ХАР И ВЫБОР АНТИРЕТРОВИРУСНОЙ ТЕРАПИИ (ПО МАТЕРИАЛАМ САНКТ-ПЕТЕРБУРГСКОГО ЦЕНТРА СПИД)

The objective of the study was to describe patients with HIV infection, who were diagnosed in 2016 in St Petersburg AIDS Center, including provided antiretroviral therapy (ART).A retrospective review of 521 patients’ case histories was performed. The case history selection was done by random sampling, in which the only criterion was the year of HIVinfection registration.The majority of patient were young people (middle age -), socially adapted, with higher or secondary special education (%),acquired HIV by sexual rout (%). 44% of patients had a CD4-lymphocyte count less than 350 cells / mm3, indicating a late detection of HIV and advanced stage of the disease at the moment of HIV registration. 25% of patients with a CD4 counts more than 350 cells / mm3 also had clinical symptoms of HIV-infection and needed ART.41% of patients with HIV had different concomitant noncommunicable diseases, of which one third (29%) received therapy for these diseases. This situation dictates the need for careful choice of ART regimens taking into account the clinical features of patients, concomitant therapy and drugdrug interactions. Целью настоящего исследования послужила комплексная характеристика больных ВИЧ-инфекцией, вставших на учет в Центр по профилактике и борьбе со СПИД и инфекционными заболеваниями в 2016 г., включая выбор антиретровирусной терапии (АРТ).Проведен ретроспективный анализ 521 медицинской карты пациентов. Отбор проводился методом случайной выборки, при которой единственным критерием был год постановки на учет.Преобладали молодые люди (средний возраст 38±0,5 лет), социально адаптированные, с высшим или средним специальным образованием (70%), заразившиеся преимущественно половым путем (68%). 44% пациентов имели уровень CD4-лимфоцитов менее 350 кл/мкл, что свидетельствует о позднем выявлении ВИЧ и продвинутой стадии болезни при постановке на диспансерный учет. В группе пациентов с уровнем CD4-лимфоцитов более 350 кл/мкл у 25% больных выявлялись клинические симптомы заболевания, и они также нуждались в назначении АРТ.41% пациентов с ВИЧ-инфекцией имели различные сопутствующие неинфекционные заболевания, из них треть (29%) получали терапию по поводу этих заболеваний. Данная ситуация диктует необходимость тщательного подбора схем АРТ с учетом клинических особенностей пациентов, сопутствующей терапии и межлекарственных взаимодействий.