Vol 4, No 3 (2017)

Михаил Иванович Давыдов - блистательный хирург-онколог с мировым именем, известный ученый, профессор, главный внештатный онколог Минздрава России, академик РАМН и РАН, главный онколог медицинского центра Управления делами Президента России, член Европейского и Американского обществ хирургов, Международного общества хирургов и Нью-Йоркской академии наук. По оценкам международных экспертов, он входит в пятерку лучших хирургов мира.

There is a large number of healthcare workers who may be exposed to anticancer drugs in different healthcare settings in Russia. Contamination of working environment, throughout the hospital medication system from hospital pharmacy to medical waste facilities, is found in a number of studies. Monitoring of the environmental contamination with these drugs was performed by different methods in various countries. Daily uptake of the anticancer drugs by the personnel exposed for many years may be realized in reproductive impairments and increased cancer risk. The female healthcare workers who handle antineoplastic drugs showed a greater risk of birth defects in offspring, spontaneous abortions, breast cancer and a number of other cancer site revealed by epidemiological methods. Data on the cancer incidence of pharmacists and laboratory workers potentially exposed to the cytostatic drugs are provided. In Russia, the monitoring of occupational cytostatic exposure is required as it would not be correct to apply data obtained in other countries to the Russian conditions. The data for biological and epidemiological monitoring are considered as the background for effective prevention of adverse health effects in healthcare personnel exposed to antineoplastic drugs.

Background. The transforming growth factor beta 1 (TGF-β1) is one of the most important tissue factors secreted by the development of epithelial tumors. Increased expression of TGF-β1 in lung tumors promotes cancer cells survival enhancing their growth, migration, invasion, angiogenesis, immune system suppression.

Objective: to study molecular mechanisms of TGF-β1 action on A549 human lung adenocarcinoma cells by means of proteomic high-resolution mass spectrometry. Results. Intracellular signaling pathways responsible for the involvement of TGF-β1 in the oncogenesis of non-small cell lung cancer have been found, which include the differential expressed proteins of the families of cullin, ETS oncogenes, histone diacelases, cyclin-dependent kinases, and the signaling pathway phosphatidylinositol 3-kinase (PI3K).

Conclusions. Important patterns are determined that could be used for the development of new approaches for detection of lung cancer metastasis candidate markers and potential therapy targets of this decease.

Introduction. Hepatocellular carcinoma (HCC) is characterized by aggressive course, high lethality rate and resistance to current systemic treatment. Analysis of molecular aberrations associated with HCC pathogenesis that control biological properties of HCC allows to evaluate potential efficacy of inhibiting certain oncogenic cascades. The present study is focused on investigation of the impact of reduced expression of the key hepatocyte differentiation regulator, HNF4α, often downregulated in HCC, that influences sensitivity of HCC cells to inhibitors  of the major oncogenic pathways mTOR, CDK4/6-pRb and ROCK.

Materials and methods. Changes in cells proliferation and migration caused by HNF4А gene stable knockdown were tested in human HCC cell cultures HepG2 and Huh7 followed by examination of these cellular properties under mTOR (rapamycin), CDK4/6 (PD0332991, palbociclib) and ROCK 1/2 (Y27632) inhibitors treatment. Gene expression levels were estimated by the real-time polymerase chain reaction method (Real-Time PCR).

Results. HNF4А gene knockdown alters HepG2 and Huh7 cell migration associated with E-cadherin and N-cadherin expression changes. The HNF4α repression weakens Y27632-induced blockade of HCC cells migration potential. HNF4А gene knockdown causes resistance  of Huh7 cells and increase of HepG2 cells sensitivity to rapamycin and PD0332991 that block cells migration ability.

Conclusions. Expression level of HNF4α renders influence on migration of HCC cells and contributes to their sensitivity to mTOR, CDK4/6 and ROCK1/2 inhibitors’ impact on cell migration activity.