Холангиоцеллюлярная карцинома сегодня. Литературный аналитический обзор

Cholangiocarcinoma is a group of malignant tumors with signs of differentiation to bile ducts epithelium direction. There are three anatomical types of cholangiocarcinoma: intrahepatic, portal and distal. These types of tumors are different not only anatomically but have different epidemiology, etiology, pathogenesis and treatment.Morbidity and mortality of cholangiocarcinoma have dramatically increased last few decades whereas survival remains low. Variations of cholangiocarcinoma are caused by different factors of risks in different geographic locations. There is information obtained in last few years about genetic transformations of cells of cholangiocarcinoma; moreover, there are carcinoma-dependent fibroblasts revealed in the stroma of cholangiocarcinoma that are stimulating growth of the tumor. There is substantial progress obtained in the understanding of oncogenesis of intrahepatic and portal cholangiocarcinoma. Patients with intrahepatic cholangiocarcinoma usually undergo resectional surgeryand neoadjuvant treatment with liver transplantation serve as a treatment of choice in cases of portal cholangiocarcinoma. This article is a review of the current understanding of the epidemiology, pathogenesis, classification, points of views on the diagnostics andtreatment of cholangiocarcinoma.Холангиокарцинома (ХГК) представляет собой группу злокачественных опухолей с признаками дифференцировки в направлении эпителия желчных путей. Анатомически ХГК подразделяют на внутрипеченочные, воротные и дистальные. Данные подтипы различаются не только по локализации, но и по эпидемиологии, этиологии, патогенезу и лечению. Частота встречаемости и смертность от ХГК за последние десятилетия существенно выросли, в то время как выживаемость остается низкой. В разных географических областях вариации ХГК обусловлены различными факторами риска. В последние годы накоплены данные по генетическим изменениям клеток ХГК, кроме того обнаружено что строма этой опухоли содержит множество карциномазависимых фибробластов (КЗФ), стимулирующих развитие и рост опухоли. В характеристике и понимании онкогенезавнутрипеченочной ХГК и воротной ХГК отмечается существенный прогресс. Пациентов с внутрипеченочной ХГК обычно лечат хирургически. Для воротной ХГК основным методом лечения является трансплантация печени с неоадъювантной химиотерапией. Предлагаем обзор современного понимания эпидемиологии, патогенеза, классификации, взглядов на диагностику и лечение ХГ

Ubiquitination screen using protein microarrays for comprehensive identification of Rsp5 substrates in yeast

Ubiquitin-protein ligases (E3s) are responsible for target recognition and regulate stability, localization or function of their substrates. However, the substrates of most E3 enzymes remain unknown. Here, we describe the development of a novel proteomic in vitro ubiquitination screen using a protein microarray platform that can be utilized for the discovery of substrates for E3 ligases on a global scale. Using the yeast E3 Rsp5 as a test system to identify its substrates on a yeast protein microarray that covers most of the yeast (Saccharomyces cerevisiae) proteome, we identified numerous known and novel ubiquitinated substrates of this E3 ligase. Our enzymatic approach was complemented by a parallel protein microarray protein interaction study. Examination of the substrates identified in the analysis combined with phage display screening allowed exploration of binding mechanisms and substrate specificity of Rsp5. The development of a platform for global discovery of E3 substrates is invaluable for understanding the cellular pathways in which they participate, and could be utilized for the identification of drug targets

An Analysis of the Chemical Composition of the Atmosphere of Venus on an AMS of the Venera-12 Using a Gas Chromatograph

Eight analyses of the atmosphere of Venus were made beginning at an altitude of 42 km right down to the surface of the planet. The following were detected in the atmosphere of Venus: nitrogen in concentrations of 2.5 plus or minus 0.5 volumetric %, argon ir concentrations (4 plus or minus 2) x 10 to the minus 3 power volumetric %, CO--(2.8 plus or minus 1.4) x 10 to the minus 3 power volumetric % and SO2 in concentrations (1.3 plus or minus 0.6) x 10 to the minus 2 power volumetric %. The upper limits were estimated for the content of oxygen and water equal to 2 x 10 to the minus 3 power and 10 to the minus 2 power volumetric %, respectively

Chemical analysis of aerosol in the Venusian cloud layer by reaction gas chromatography on board the Vega landers

The experiment on sulfuric acid aerosol determination in the Venusian cloud layer on board the Vega landers is described. An average content of sulfuric acid of approximately 1 mg/cu m was found for the samples taken from the atmosphere at heights from 63 to 48 km and analyzed with the SIGMA-3 chromatograph. Sulfur dioxide (SO2) was revealed in the gaseous sample at the height of 48 km. From the experimental results and blank run measurements, a suggestion is made that the Venusian cloud layer aerosol consists of more complicated particles than the sulfuric acid water solution does

Проблема современных классификаций гепатоцеллюлярного рака. Аналитический

Hepatocellular carcinoma (HCC) in vast majority of cases develops on the background of the chronic liver diseases, more often – viral hepatitis B and C, and is diagnosed at the advanced stages [1, 3]. Despite the advantages of the modern oncology (some patients live till appearance of brain metastases [1]), prognosis in HCC is still poor. In general, prognosis depends on not only biological characteristics of the tumor itself, but also on the background of the liver condition, often – at the stage of the cirrhosis. As distinct from the other malignant tumor of liver – cholangiocellular carcinoma, there are no universal prognostic classifications for HCC [2]. International classification TNM used for majority of solid tumors is not appropriate to be ‘reference’ for HCC [4]. There are several prognostic scales and classifications created recently in West and Asian countries. For the creation of such systems they use more often the regression model on the basis of prognostic variables of the investigated population. Currently, there is no universal prognostic classification or scale for HCC ГЦР. Almost all these classifications included the features; liver function, tumor characteristics, clinical behavior, undercurrent diseases, presence of the cirrhosis [3]. Гепатоцеллюлярный рак (ГЦР) в подавляющем большинстве случаев развивается на фоне хронических заболеваний печени, чаще – вирусных гепатитов В и С, и часто диагностируется на поздних стадиях [1, 3]. Несмотря на некоторые успехи современной онкологии (некоторые пациенты «доживают» даже до метастазов ГЦР в головной мозг [1]), прогноз при ГЦР остается плохим. В целом прогноз зависит не только от биологических характеристик самой опухоли, но и от фонового заболевания печени, часто – на стадии цирроза. В отличие от другой злокачественной опухоли печени – холангиоцеллюлярной карциномы, для ГЦР нет универсальных прогностических классификаций [2]. Так, международная классификация TNM, используемая для большинства солидных опухолей, не может применяться в качестве «референсной» для ГЦР [4]. Для определения прогноза c последующей тактикой ведения в западных и азиатских странах в последние годы разработаны различные шкалы оценки и классификации ГЦР. Для создания таких систем чаще используют регрессионную модель на основании прогностических переменных изучаемой популяции. На сегодняшний день не существует универсальной и признанной всеми прогностической шкалы или классификации ГЦР. Почти все эти классификации включают в себя такие признаки, как: функция печени, характеристики опухоли, клинические проявления, сопутствующие заболевания, наличие цирроза [3].

Экстратестикулярная шваннома мошонки. Клинический случай и обзор литературы

Schwannoma is a benign tumor that grows from the Schwann cells forming the myelin sheath of peripheral nerves. The clinical manifestations are nonspecific and generally due to compression of the adjacent structures of a growing tumor. The location of the tumor in the scrotum is rare; its primary diagnosis is difficult and only immunohistochemical examination allows the final diagnosis to be established. The authors present a clinical case of a patient operated on at the Urology Department, Moscow Clinical Research Center, for intrascrotal schwannoma causing impaired microcirculation in the scrotal skin to form purulent scrotal ulcers. In terms of the benign pattern and extratesticular localization of the tumor, its removal without orchifuniculectomy can yield a good clinical result.Шваннома – доброкачественная опухоль, растущая из шванновских клеток, формирующих миелиновую оболочку периферических нервов. Клинические проявления неспецифичны и, как правило, обусловлены компрессией прилежащих структур растущей опухолью. Локализация опухоли в мошонке редка, первичная диагностика трудна, и лишь имунногистохимическое исследование позволяет установить окончательный диагноз. Мы представляем клиническое наблюдение пациента, оперированного в урологическом отделение МКНЦ по поводу шванномы мошонки, вызвавшей нарушение микроциркуляции кожи мошонки с формированием гнойной язвы мошонки. С учетом доброкачественного характера опухоли и экстратестикулярной локализации удаление опухоли без выполнения орхфуникулэктомии позволяет достичь хорошего клинического результата

ВТОРИЧНЫЕ ОПУХОЛИ ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ: ОПИСАНИЕ СЛУЧАЕВ И ОБЗОР ЛИТЕРАТУРЫ

Introduction: Metastases in the pancreas are very rare and amount 4.5% of all tumors of the pancreas. As a rule such tumors don’t have any specific symptoms and are diagnosed spontaneously. The most frequent metastasizing to the pancreas tumor is renal cell carcinoma, then in descending order – colorectal cancer, melanoma, sarcoma and lung cancer. Prognosis is based on the histology of the primary tumor and the stage of the disease.Case reports: This article describes cases of metastases of renal cell carcinoma, colorectal cancer, lung cancer and locally advanced cases of gastric cancer and lymphoma.Conclusion: In this article 10 cases of secondary tumors of the pancreas are presented which amounts 5,4% (10 of 184)of all tumors of the pancreas during this period. In 6 cases metastases are found and in 4 cases – local invasion. It is very important to provide differential diagnosis with primary tumors of the pancreas because treatment strategy may differ significantly. It is difficult to choose right treatment strategy in patients with such diagnosis due to its rarity.Введение: метастазы в поджелудочную железу крайне редки и составляют 4,5% всех опухолей поджелудочной железы. Как правило протекают бессимптомно  и выявляются случайно. Наиболее частым раком, метастазирующим в поджелудочную железу, является почечно-клеточный рак, после него в убывающем порядке следуют колоректальный рак, меланома, саркома и рак легких. Прогноз жизни больных определяется гистогенезом первичной опухоли и распространенностью онкологического процесса. Описание случаев: в данной статье представлены случаи метастазов почечно-клеточного рака, рака толстой кишки, рака легкого и местнораспространенных поражений при раке желудка и лимфомы. Вывод: приведено 10 наблюдений вторичных опухолей поджелудочной железы, что составило 5,4% (10 из184) от всех исследованных опухолей железы за этот период. По типу распространения:  в 6-и случаях отмечено метастатическое поражение железы и 4-х случаях — локальная инвазия.  Важным в обследовании  подобных больных является проведение  дифференциального диагноза с первичной  опухолью поджелудочной железы,  поскольку лечебная  тактика может существенно отличаться. Трудно решить вопрос о выборе правильной тактики лечения больных с данными нозологическими формами, за счет их чрезвычайной редкости

The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in mice

Skeletal muscle atrophy is a consequence of muscle inactivity resulting from denervation, unloading and immobility. It accompanies many chronic disease states and also occurs as a pathophysiologic consequence of normal aging. In all these conditions, ubiquitin-dependent proteolysis is a key regulator of the loss of muscle mass, and ubiquitin ligases confer specificity to this process by interacting with, and linking ubiquitin moieties to target substrates through protein:protein interaction domains. Our previous work suggested that the ubiquitin-protein ligase Nedd4-1 is a potential mediator of skeletal muscle atrophy associated with inactivity (denervation, unloading and immobility). Here we generated a novel tool, the Nedd4-1 skeletal muscle-specific knockout mouse (myo(Cre);Nedd4-1(flox/flox)) and subjected it to a well validated model of denervation induced skeletal muscle atrophy. The absence of Nedd4-1 resulted in increased weights and cross-sectional area of type II fast twitch fibres of denervated gastrocnemius muscle compared with wild type littermates controls, at seven and fourteen days following tibial nerve transection. These effects are not mediated by the Nedd4-1 substrates MTMR4, FGFR1 and Notch-1. These results demonstrate that Nedd4-1 plays an important role in mediating denervation-induced skeletal muscle atrophy in vivo

The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms

© 2008 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0).The small guanosine triphosphate (GTP)-binding proteins of the Rho family are implicated in various cell functions, including establishment and maintenance of cell polarity. Activity of Rho guanosine triphosphatases (GTPases) is not only regulated by guanine nucleotide exchange factors and GTPase-activating proteins but also by guanine nucleotide dissociation inhibitors (GDIs). These proteins have the ability to extract Rho proteins from membranes and keep them in an inactive cytosolic complex. Here, we show that Rdi1, the sole Rho GDI of the yeast Saccharomyces cerevisiae, contributes to pseudohyphal growth and mitotic exit. Rdi1 interacts only with Cdc42, Rho1, and Rho4, and it regulates these Rho GTPases by distinct mechanisms. Binding between Rdi1 and Cdc42 as well as Rho1 is modulated by the Cdc42 effector and p21-activated kinase Cla4. After membrane extraction mediated by Rdi1, Rho4 is degraded by a novel mechanism, which includes the glycogen synthase kinase 3β homologue Ygk3, vacuolar proteases, and the proteasome. Together, these results indicate that Rdi1 uses distinct modes of regulation for different Rho GTPases.Deutsche Forschungsgemeinschaf

System Approach to the Development of Intelligent Complexes of Oncological Diagnostics

The system approach to the development of intellectual complexes in cancer diagnosis are discussed in the article. Distinctive features of this approach: the participation of pathologist at the stage of description of recognizable images (the description is based on traditional assessments of quality informative features of tumors); the set of the most similar probabilistic diagnoses is forming on the classification stage of recognition; final histological diagnosis is made by pathologist. The proposed approach has been successfully tested in clinical practice. Keywords: image processing, image description, image classification, pattern recognition, qualitative attributes of tumor images, interactive recognition, cancer diagnosis, decision support syste