Inhibition of TGFβ signaling and its implications in anticancer treatments

The transforming growth factor-β (TGFβ) is a potent regulator of tumorigenesis. In cancer, two distinctive behaviors of TGFβ have been reported as a tumor suppressor at early stage of the disease, and as a tumor promoter at later stages. The past decades, the dualistic role of TGFβ has garnered a lot of attention. As a result, cancer researchers’ has been tasked to elucidate how TGFβ signaling may lead to metastatic dissemination, how to tackle carcinogenesis and which therapeutic strategies should be adopted. Consequently, TGFβ signaling pathways have been considered as appropriate targets for cancer therapy. The TGFβ therapeutic strategies have emerged at three levels: ligand, ligand-receptor interaction and intracellular signaling level. Promising inhibitors of TGFβ signaling have entered clinical trials and shown encouraging results. Here we review the three strategies of TGFβ signa­ling inhibition and theirs applications in treatment of cancer

Proteomic approaches in biological and medical sciences: principles and applications

After the first introduction of the concept of “proteome” more than 10 years ago, large-scale studies of protein expression, localization, activities and interactions have gained an exponential increase of interest, leading to extensive research and technology development. Proteomics is expansively applied in many areas, ranging from basic research, various disease and malignant tumors diagnostic and biomarker discovery to therapeutic applications. Several proteomics approaches have been developed for protein separation and identification, and for the characterization of protein function and structure. Two-dimensional gel electrophoresis, chromatography, capillary electrophoresis and mass spectrometry have become the most used proteomics methods. These techniques are also under constant development. This review provides an overview of the main techniques and their combinations, used in proteomics. The emphasis is made on description of advantages and disadvantages of each technique, to navigate in selection of the best application for solving a specific problem.Развитие протеомики за последние 10 лет стимулировало возрастающий интерес к ее применению для решения важных проблем современной биологии и медицины. Сегодня протеомика активно используется в фундаментальных исследованиях, поиске биомаркеров, диагностике опухолей. Широкомасштабное изучение экспрессии, локализации, активности и взаимодействий белков привело к специализации протеомных технологий и методов. Поэтому вопрос подбора наиболее подходящих методов для решения специфических проблем является особо актуальным. Двухмерный электрофорез, жидкостная хроматография, капиллярный электрофорез и масс-спектрометрия являются наиболее развитыми технологиями протеомики. В этом обзоре проанализированы сильные и слабые стороны этих технологий. Авторы надеются, что этот анализ поможет читателям выбрать наиболее эффективную методику для решения соответствующих научных задач

Kinase suppressor of Ras 2 is involved in regulation of cell proliferation and is up-regulated in human invasive ductal carcinomas of breast

Aim: To study the expression of Kinase Suppressor of Ras 2 (KSR2) in human breast tumors and its effect on proliferation of breast epithelial cells. We reported previously that KSR2 was up-regulated in immortalized human breast epithelial cells. Methods: Proteomics technologies, systems biology tool for a KSR2 network analysis, immunoblotting, siRNA technology, overexpression of KSR2, cell proliferation assays and immunohistochemistry of tissue microarray of human breast tumors and normal breast tissue were used. Results: In conditionally immortalized primary epithelial cells KSR2 expression was shown to be up-regulated. The involvement of KSR2 in regulation of cell proliferation was predicted by a KSR2-centered network analysis. We observed that KSR2 down-regulation with specific siRNA inhibited cell proliferation. By immunohistochemistry of tissue microarray it was demon strated that KSR2 expression was enhanced in human invasive breast carcinomas. Conclusion: Our findings propose KSR2 as a new marker of immortalization, which has an impact on cell proliferation

Intersection between genes controlling vascularization and angiogenesis in renal cell carcinomas

Aim: To show that application of the systemic analysis may significantly improve comparison of different datasets. Different genes and proteins may converge on the same functional outputs. A comparison of 2 datasets by only identification names of affected molecules may miss that, leading to a conclusion that there is nothing in common for these datasets. Systemic analysis may overcome this limitation, by focusing on functions represented by the identification names. Materials and Methods: Datasets were retrieved from open sources. Systemic analysis of vascularization features and angiogenesis signature was performed by using Cytoscape and its plugs-in. Results: In contrary to the initial statement of the lack of overlap between the vascularization features and the angiogenesis genes-signature in renal carcinomas, we observed an intersection on the functional level. Analysis of the networks built with identification names of vascularization and angiogenesis datasets showed an intersection, which included potent regulators of vessel formation and growth. Conclusion: Analysis of networks may expose functional links, which may be missed by a direct identification names comparison. Key Words: cancer, vascularization, angiogenesis, systemic analysis

Acquisition of invasiveness by breast adenocarcinoma cells engages established hallmarks and novel regulatory mechanisms

Background/Aim: Proteomics of invasiveness opens a window on the complexity of the metastasis-engaged mechanisms. The extend and types of this complexity require elucidation. Materials and Methods: Proteomics, immuno -histochemistry, immunoblotting, network analysis and systems cancer biology were used to analyse acquisition of invasiveness by human breast adenocarcinoma cells. Results: We report here that invasiveness network highlighted the involvement of hallmarks such as cell proliferation, migration, cell death, genome stability, immune system regulation and metabolism. Identified involvement of cell-virus interaction and gene silencing are potentially novel cancer mechanisms. Identified 6,113 nodes with 11,055 edges affecting 1,085 biological processes show extensive re-arrangements in cell physiology. These high numbers are in line with a similar broadness of networks built with diagnostic signatures approved for clinical use. Conclusion: Our data emphasize a broad systemic regulation of invasiveness, and describe the network of this regulation. - 2019 International Institute of Anticancer Research. All rights reserved.Scopu