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// Svetlana O. Zhikrivetskaya 1,* , Anastasiya V. Snezhkina 1,* , Andrew R. Zaretsky 2 , Boris Y. Alekseev 3 , Anatoly V. Pokrovsky 4 , Alexander L. Golovyuk 4 , Nataliya V. Melnikova 1 , Oleg A. Stepanov 1,3 , Dmitry V. Kalinin 4 , Alexey A. Moskalev 1 , George S. Krasnov 1 , Alexey A. Dmitriev 1 and Anna V. Kudryavtseva 1,3 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 2 M.M. Shemyakin - Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia 3 National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia 4 A.V. Vishnevsky Institute of Surgery, Moscow, Russia * These authors have contributed equally to this work Correspondence to: Anna V. Kudryavtseva, email: // Keywords : paragangliomas, pheochromocytomas, molecular markers, germline and somatic mutations, signaling pathways Received : August 02, 2016 Accepted : January 23, 2017 Published : February 08, 2017 Abstract Paragangliomas/pheochromocytomas comprise rare tumors that arise from the extra-adrenal paraganglia, with an incidence of about 2 to 8 per million people each year. Approximately 40% of cases are due to genetic mutations in at least one out of more than 30 causative genes. About 25–30% of pheochromocytomas/paragangliomas develop under the conditions of a hereditary tumor syndrome a third of which are caused by mutations in the VHL gene. Together, the gene mutations in this disorder have implicated multiple processes including signaling pathways, translation initiation, hypoxia regulation, protein synthesis, differentiation, survival, proliferation, and cell growth. The present review contemplates the mutations associated with the development of pheochromocytomas/paragangliomas and their potential to serve as specific markers of these tumors and their progression. These data will improve our understanding of the pathogenesis of these tumors and likely reveal certain features that may be useful for early diagnostics, malignancy prognostics, and the determination of new targets for disease therapeutics.

Colorectal cancer (CRC) ranks third in the incidences of cancer morbidity and mortality worldwide. CRC is rather heterogeneous with regard to molecular genetic characteristics and pathogenic pathways. A wide spectrum of biomarkers is used for molecular subtype determination, prognosis, and estimation of sensitivity to different drugs in practice. These biomarkers can include germline and somatic mutations, chromosomal aberrations, genomic abnormalities, gene expression alterations at mRNA or protein level and changes in DNA methylation status. In the present review we discuss the most important and well-studied CRC biomarkers, and their potential clinical significance and current approaches to molecular classification of colorectal tumors.

// Ksenia Lezhnina 1,2 , Olga Kovalchuk 3,4 , Alexander A. Zhavoronkov, 2,5,6 , Mikhail B. Korzinkin 1 , Anastasia A. Zabolotneva 7 , Peter V. Shegay 8 , Dmitry G. Sokov 9 , Nurshat M. Gaifullin 10,11 , Igor G. Rusakov 8 , Alexander M. Aliper 1,2 , Sergey A. Roumiantsev 2 , Boris Y. Alekseev 8 , Nikolay M. Borisov 12 and Anton A. Buzdin 1,2,7 1 Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR 2 Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia 3 Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4 4 Canada Cancer and Aging Research Laboratories, Lethbridge, AB, Canada 5 Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, MD 6 Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology 7 Group for Genomic Regulation of Cell Signaling Systems, Shemyakn-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia 8 P.A. Herzen Moscow Oncological Research Institute, Moscow, Russia 9 Moscow 1st Oncological Hospital, Moscow, Russia 10 Lomonosov Moscow State University, Faculty of Fundamental Medicine, Moscow, Russia 11 Russian medical postgraduate academy , Moscow, Russia 12 Laboratory of Systems Biology, A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia Correspondence: Anton A. Buzdin, email: // Keywords : Bladder cancer, Intracellular signaling pathway activation, Gene expression, Transcriptome profiling, Molecular markers, AUC Received : August 21, 2014 Accepted : September 15, 2014 Published : September 16, 2014 Abstract We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression in 17 cancer and seven non-cancerous bladder tissue samples. These experiments were done in two independent laboratories located in Russia and Canada. We calculated pathway activation strength values for the investigated transcriptomes and identified signaling pathways that were regulated differently in bladder cancer (BC) tissues compared with normal controls. We found, for both experimental datasets, 44 signaling pathways that serve as excellent new biomarkers of BC, supported by high area under the curve (AUC) values. We conclude that the OncoFinder approach is highly efficient in finding new biomarkers for cancer. These markers are mathematical functions involving multiple gene products, which distinguishes them from “traditional” expression biomarkers that only assess concentrations of single genes.

// Anna Kudryavtseva 1, 2, * , George Krasnov 1, * , Anastasiya Lipatova 1 , Boris Alekseev 2 , Faniya Maganova 3 , Mikhail Shaposhnikov 4 , Maria Fedorova 1 , Anastasiya Snezhkina 1 , Alexey Moskalev 1, 4, 5 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia 2 National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, 125284, Russia 3 Initium-Pharm, LTD, Moscow, 142000, Russia 4 Institute of Biology of Komi Science Center of Ural Branch of RAS, Syktyvkar, 167982, Russia 5 Moscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia * These authors have contributed equally to this work Correspondence to: Alexey Moskalev, email: amoskalev@ib.komisc.ru Keywords: Abies sibirica, plant extract, terpenoids, anti-aging effects, anti-cancer effects Received: August 12, 2016 Accepted: October 19, 2016 Published: November 19, 2016 ABSTRACT A large number of terpenoids exhibit potential geroprotector and anti-cancer properties. Here, we studied whole transcriptomic effects of Abisil, the extract of fir ( Abies sibirica ) terpenes, on normal and cancer cell lines. We used early passaged and senescent none-immortalized fibroblasts as cellular aging models. It was revealed that in normal fibroblasts, terpenes induced genes of stress response, apoptosis regulation and tissue regeneration. The restoration of the expression level of some prolongevity genes after fir extract treatment was shown in old cells. In Caco-2 and AsPC-1 cancer cell lines, Abisil induced expression of both onco-suppressors (members of GADD45, DUSP, and DDIT gene families), and proto-oncogenes ( c-Myc , c-Jun , EGR and others). Thus, the study demonstrates the potential anti-aging and anti-cancer effects of Abisil on senescent and cancer cell lines.

// Anna V. Kudryavtseva 1,2 , George S. Krasnov 1 , Alexey A. Dmitriev 1 , Boris Y. Alekseev 2 , Olga L. Kardymon 1 , Asiya F. Sadritdinova 1,2 , Maria S. Fedorova 1 , Anatoly V. Pokrovsky 3 , Nataliya V. Melnikova 1 , Andrey D. Kaprin 2 , Alexey A. Moskalev 1,4 and Anastasiya V. Snezhkina 1 1 Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia 2 National Medical Research Radiological Center, Ministry of Health of the Russian Federation, Moscow, Russia 3 A.V. Vishnevsky Institute of Surgery, Moscow, Russia 4 Moscow Institute of Physics and Technology, Dolgoprudny, Russia Correspondence to: Anna V. Kudryavtseva, email: // Keywords : oxidative stress, mitochondrial dysfunction, ROS, aging, cancer, Gerotarget Received : November 23, 2015 Accepted : May 28, 2016 Published : June 05, 2016 Abstract Aging and cancer are the most important issues to research. The population in the world is growing older, and the incidence of cancer increases with age. There is no doubt about the linkage between aging and cancer. However, the molecular mechanisms underlying this association are still unknown. Several lines of evidence suggest that the oxidative stress as a cause and/or consequence of the mitochondrial dysfunction is one of the main drivers of these processes. Increasing ROS levels and products of the oxidative stress, which occur in aging and age-related disorders, were also found in cancer. This review focuses on the similarities between ageing-associated and cancer-associated oxidative stress and mitochondrial dysfunction as their common phenotype.