Scientific and medical team
Learn more about the DOKAR VITA CELLS scientific and medical team and their work.
The main responsibilities of the scientific and medical team include consulting with patients and doctors, creating personalized treatment plans, discussing complex cases, developing new treatment programs, creating new cellular pathways and technologies, conducting trainings, participating in conferences, and conducting scientific research.
Meet each specialist on the DOKAR VITA CELLS scientific and medical team. Click on a card to learn more about each one.
  • Биология.
    Professor. Federal Scientific and Clinical Center of the Federal Medical and Biological Agency. Russia
    Mikhail Konoplyannikov
    Director of the Institute of Cell Technologies, Federal Research and Clinical Center of the Russian Federal Agency for Medical and Biological Sciences.
    Member of the American Heart Association and the International Society for Stem Cell Research (since 2005).
    26 publications, 3 books
  • Biology.
    Professor. Tokyo Medical University, Japan
    Takahiro Ochiya
    A researcher in biochemistry, genetics, molecular biology, and medicine. He works at Tokyo Medical University (Japan). research.comscispace.com
    Some of Ochiya's research areas include:
    extracellular vesicles and their role in disease;
    microRNAs and their regulation in disease;
    circular RNAs and their role in disease;
    molecular mechanisms associated with cancer;
    RNA interference and gene delivery;
    liver physiology and pathology;
    cell adhesion molecule research.

    As of 2025, Ochiya received the "Leader in Biology and Biochemistry in Japan" award from Research.com. research.com
    He has authored over 190 publications. His awards include the 2019 Special Prize from the International Society of Extracellular Vesicles (ISEV), among others.
  • Orthopelia.
    Professor. Central Institute of Traumatology and Orthopedics. Russia.
    Anatoly Orletsky
    Head of the Department of Sports and Ballet Injuries, Doctor of Medical Sciences, Professor, Honored Doctor of the Russian Federation, Laureate of the Russian Government Prize in Science.
  • Biology.
    Professor. Institute of Molecular Biology, Russia
    Anastasia Lipatova
    • Biologist
    • Researcher and creator of oncolytic viruses
    • 90 publications, 10 patents
  • Orthopedics. Therapy. Sports medicine.
    CEO DOKAR VITA CELLS. Bangkok, Thailand.
    Aleksandr Proshkin
    Practicing doctor, experience working with stem cells since 2016. For 20 years he was the chief doctor of the Russian Kyokushinkai karate team. Founder of DOKAR Taping Academy. 2 government awards of the Russian Federation. 5 publication, 2 books.
  • Anti-aging therapy.
    Vice President, DOKAR VITA CELLS. Bangkok, Thailand.
    Veronica Dor
    Practicing doctor, experience working with stem cells since 2018.
  • Urologist, endocrinologist
    Candidate of Medical Sciences. Chief Physician of the Clinic Doctor Prof. Russia
    Olga Malinina
    • Practicing doctor. Experience with stem cells since 2017.
    • Specializes in the treatment of the following conditions:
    • Pyelonephritis;
    • Cystitis;
    • Prostatitis;
    • Urinary incontinence;
    • Chronic pelvic pain;
    • Aesthetic urogynecology;
    • Urethral transposition in women using minimally invasive techniques;
    • Male infertility;
    • Erectile dysfunction
    • Techniques:
    • Urethral transposition in women using minimally invasive techniques;
    • Botulinum toxin therapy in urology;
    • Iotulin therapy for pelvic floor muscles;
    • Intimate plastic surgery;
    • Treatment of premature ejaculation/enlargement of the glans penis;
    • Treatment of vulvodynia using injection methods
  • Regenerative medicine doctor
    Candidate of Medical Sciences. Chief Physician of the Institute of Regenerative Medicine. Russia
    Sergey Vinogradov
    Practicing physician. Experience with stem cells since 2017.
    Specializes in the treatment of the following diseases:
    • Anti-aging therapy
    • Treatment of internal diseases
    • Orthopedics
    • Cosmetology
  • Regenerative Medicine Physician
    Chief Physician, Samitivej Sriracha Hospital, Thailand
    PROMPONG YOTHARASADORN, MD.
    Practicing doctor. Experience with stem cells since 2017.
    Expertise in the following fields:
    • Medical Business Planning and Development
    • Basic and Advanced Cardiopulmonary Life Support (BLS and ACLS)
    • Advanced Trauma Life Support (ATLS)
    • Ground and Air Ambulance Transportation
    • Anti-aging Medicine and Cell Therapy

    History:
    • Head of the Emergency Department at Praram2 Hospital
    • Deputy Director of the Medical Department at Praram2 Hospital
    • Medical Director at Praram2 Hospital
    • Medical Director at MALI Multidisciplinary Hospital
    • Chief Information Officer (CIO) at Praram2 Medical Group
    • Director of the Medical Department at Kasemrad Rattanathibet Hospital
    • Co-founder and Medical Consultant at PD Wellness Clinic
    • Chief Physician at Samitivej Sriracha Hospital
    Other:
    • Diploma of the Thai Council of Emergency Physicians (2012)
    • Medical staff at the Emergency Department of Bhumibol Adulyadej Hospital, Royal Thai Air Force (2012-2013)
    • Development of the constitution and work plan for the National Legislative Assembly's Emergency Services (2017)
    • Consultation on emergency services business development and emergency department standards at Phitsanuwei Hospital, Phitsanulok (2015)
    • Basic Life Support Instructor (2019)
    Specialization in the treatment of the following diseases:
    • Anti-aging therapy
    • Internal Medicine
  • Regenerative medicine physician
    Honored Doctor of the Russian Federation
    Recipient of the Order of Courage
    Valery Tychinin
    In 1986 and 1987, as part of the USSR Ministry of Health's task force, he participated in the cleanup efforts following the accident at Unit 4 of the Chernobyl Nuclear Power Plant. For these efforts, he was awarded the Order of Courage (1996).
    Honored Doctor of the Russian Federation.
    Full Member of the Russian Academy of Natural Sciences (Biomedicine Section).
    He was the CEO of two companies producing biomedical cell products based on mesenchymal stem cells: Innovative Cell Technologies LLC and T-Helper Cell Technologies LLC. He was also the Deputy CEO of Stolichny Doctor Clinic LLC for the development of regenerative medicine and cell therapy.
    Since 2019, he has been a member of the Russian Society of Regenerative Medicine.
    He actively participates in conferences, symposia, and seminars on these topics. She works to educate physicians and the public in the field of regenerative biomedicine and the safety and efficacy of MSC cell therapy for various diseases.
    Since 2021, she has been an adjunct faculty member in the Department of Cellular Biomedicine, Faculty of Continuing Professional Education, N.I. Pirogov Russian National Research Medical University.
  • Regenerative Medicine Physician
    Medivo HZV Clinic (Berlin, Germany)
    Bilal Abbas, M.D.
    01/03/2025 – present
    Assistant Physician (Internal Medicine) / mevido HZV GmbH, Berlin
    09/2023 – 09/2024
    Assistant Physician (Internal Medicine, Geriatrics) / Caritas-Klinik St. Marien, Brandenburg an der Havel
    12/2022 – 01/2023
    Assistant Physician (Oncology and Hematology) / Klinikum Barnim GmbH, Eberswalde
    12/2020 – 05/2021
    Assistant Physician (Internal Medicine) / 5th City Clinical Hospital, Minsk
    11/2019 – 11/2020
    Medical Practice (Internal Medicine) / Praxis Dr. Ezzat Loubani, Teltow
    05.2018 – 10.2019
    Researcher (Neurosurgery) / Praxis Dr. Safwan el Mohammad, Wittenberg
    03.2016 – 03.2017
    Assistant Physician (Pulmonology) / 5th City Clinical Hospital, Minsk
    09.2015 – 05.2017
    Researcher (Internal Medicine, Hematology, Oncology) / Praxis ClinicCon Dr. Jordan, Berlin
    09.2014 – 09.2015
    Assistant Physician (Spinal Diseases) / Klinik Helle Mitte, Berlin
    07.2013 – 07.2014
    Assistant Physician (Cardiology) / Republican Scientific and Practical Center "Cardiology", Minsk
    12.2011 – 06.2013
    Assistant Physician (Internal Medicine) / "5th City Clinical Hospital", Minsk
    10.2010 – 11.2011
    Assistant Physician (Neurosurgery) / Republican Scientific and Practical Center of Traumatology and Orthopedics, Minsk
    11.2009 – 10.2010
    Assistant Physician (General Surgery) / Minsk Regional Clinical Hospital, Minsk District
    10.2009
    Medical Practice (Emergency Care) / Städtisches Krankenhaus, Colmar
    06.2008
    Assistant Physician (General Surgery) / 9th Clinical Hospital, Minsk
    06.2007 – 08.2007
    Assistant Physician / 9th City Polyclinic, Minsk
Mission and areas of work
Scientific innovations for health
Our team brings together medical and scientific professionals to develop innovative healthcare solutions. We focus on research and development aimed at improving people's quality of life. Our core areas of work include scientific research, the development of new medical technologies, and the implementation of best practices in healthcare.
Our services
Explore the services provided by the DOKAR VITA CELLS scientific and medical team, including treatment and diagnostic methods.
  • Remote consultation
    Conducting remote consultations for patients, partners, clinics, and doctors on treatment and the use of cellular products.
  • Development of new treatment programs
    Creation of programs for effective treatment of diseases, revitalization, prevention and anti-aging therapy.
  • Creation of personalized treatment programs
    Development of individual programs for the treatment of diseases, health maintenance and disease prevention.
  • Conducting webinars and trainings
    Conducting webinars, trainings and conferences on cell therapy topics.
  • Creation and improvement of cellular products
    Development of new cellular products.
News and Events
Stay up to date with the latest news and events related to the scientific and medical team of DOKAR VITA CELLS.
Practical training: Dokar Knee treatment program
On August 25, 2026, an informational and practical training was held in Bangkok at the Healthy Life Longevity Center. Ten doctors from Thai clinics participated. The training covered the causes and mechanisms of knee joint diseases, the Dokar Knee Treatment program, treatment results, and other topics. During the practical portion, the doctors learned how to administer knee injections and mastered joint taping. The training was led by Dr. Aleksandr.
Webinar (RU-JP) - Using MSCs to restore reproductive function
On August 2, 2026, a webinar on "Using Cell Technologies to Restore Reproductive Function" was held. 23 doctors from Japan participated in the training. The training program covered the causes and mechanisms of male and female infertility, presented the Dokar treatment program, and discussed international clinical studies on this topic. The webinar was led by Dr. Aleksandr and Professor Mikhail Konoplyannikov.
Webinar (RU-ENG) - Exosomes
On August 9, 2026, a webinar on "Exosomes" was held. This webinar was held in collaboration with DOKAR's partner, AMS ASIA. Eight doctors from Southeast Asia participated. The webinar covered the classification of exosomes, the differences between different types of exosomes, and the main therapeutic effects of exosomal therapy. The Dokar treatment and revitalization program was presented, and international clinical studies on this topic were discussed. The webinar was led by Dr. Aleksandr.
Useful materials
Explore helpful articles, brochures, and infographics on medical topics. Learn more about the latest trends and research in medicine.
Articles and research
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Anatoly Orletsky, professor
Main areas of treatment and diagnostic activities:
  • Surgical treatment of post-traumatic pathology of any complexity in all major joints (knee, ankle, hip, shoulder, elbow, and wrist) – arthroscopic and minimally invasive/open techniques.
  • Surgical treatment of muscle and tendon ruptures and tears (including various Achilles tendon pathologies, ARS syndrome, and Hamstring syndrome).
  • Surgical treatment of bone fractures.
Education:
  • 1976-1982 – Higher education: II Moscow Medical Institute named after N.I. Pirogov, specializing in "Pediatrics".
  • 1982-1984 – Clinical residency: Federal State Budgetary Institution "N.N. Priorov National Medical Research Center of Traumatology and Orthopedics" of the Ministry of Health of the Russian Federation.
  • 1984-1987 – Postgraduate study at the Sports and Ballet Injury Clinic of the Federal State Budgetary Institution "N.N. Priorov National Medical Research Center of Traumatology and Orthopedics" of the Ministry of Health of the Russian Federation.
  • 1987 – Defense of a PhD thesis on the topic: "Surgical methods for the treatment of anteroposterior instability of the knee joint in athletes."
  • 1998 – Defense of a dissertation for the degree of Doctor of Medical Sciences. Topic: "Surgical methods for the treatment of post-traumatic chronic instability of the knee joint in athletes."
Experience:
  • 1987-1991 – Physician at the Sports and Ballet Injury Clinic of the N.N. Priorov National Medical Research Center of Traumatology and Orthopedics of the Russian Ministry of Health.
  • 1991-1998 – Senior Researcher.
  • Since 1998 – Leading Researcher of the Department and Head of the Sports Injury Department.

Scientific activity, professional achievements:
  • Anatoly Korneevich is a highly qualified specialist in sports and ballet trauma and a renowned scientist both in Russia and abroad. He has 36 years of medical experience.
  • He has headed the Sports Trauma Department since 1998.
  • He has developed and widely implemented surgical treatment methods for knee injuries, habitual shoulder dislocations, Achilles tendon injuries, and arthroscopic surgery for intra-articular pathology of large joints into domestic and international medical practice.
  • He is the author of over 173 scientific papers, including:
  • 2 monographs on sports traumatology;
  • 3 patents for inventions;
  • 5 chapters of national guidelines on traumatology and orthopedics;
  • 5 methodological recommendations, many of which are widely used in clinical work and daily practice by national team physicians for the diagnosis and treatment of injuries.
  • He supervised the defense of 10 PhD theses. Anatoly Korneevich annually actively participates in international congresses and conferences dedicated to traumatology, orthopedics, and sports medicine.
  • He served as the chief surgeon of the Russian Olympic team at six Olympic Games: 1996 (Atlanta, USA), 2002 (Salt Lake City, USA), 2004 (Athens, Greece), 2006 (Turin, Italy), 2008 (Beijing, China), and 2010 (Vancouver, Canada). He enjoys great respect among coaches, athletes, and international sports medicine organizations.
Anastasia Lipatova, professor
Main areas of activity:

  • Professor of Molecular Biology
  • Head of the Cell Proliferation Laboratory at the Institute of Molecular Biology
  • Author of ten patents in molecular biology
  • Author of over 90 articles in scientific journals
  • Creator of oncolytic viruses

Patents:
  1. Recombinant Oncolytic Poliovirus Type 3 Strain for Therapy of Solid Tumors of Various Histological Diagnoses. Inventors: Lipatova Anastasia Valerievna, Chumakov Petr Mikhailovich. Status: Application filed
  2. Chimeric Oncolytic Poliovirus Strain for Glioblastoma Therapy. Inventors: Lipatova Anastasia Valerievna, Chumakov Petr Mikhailovich. Status: Application filed
  3. WO2018064134 - Optimized Oncolytic Viruses and Uses Thereof. Authors/Inventors: Chumakov, Peter M.; Lipatova, Anastasia V.; Chumakov, Stepan P.; Tararova, Natalia D.; Charles, Stephen A.; Komar, Anton A.
  4. WO2020227503A1 - Delivery of Oncolytic Viruses Using Dendritic Cells. Authors/Inventors: Chumakov, Peter M.; Berzhytskaya, Darya; Lipatova, Anastasia V.; Chumakov, Stepan P.; Tararova, Natalia D.; Charles, Stephen A.; Komar, Anton A.
  5. Method of Stimulating Mitophagy and Autophagy in Cells, Method for Stimulating Autophagy or Mitophagy to Treat Conditions Associated with Mitochondrial Dysfunction. Patent No.: RU 2765414 C1. Inventors: Maganova Faniya Irshatovna, Lipatova Anastasia Valerievna
  6. Method of Culturing Cells of Malignant Lymphoid Tumor. Patent No.: RU 2728266 C1. Inventors: Babaeva Fatima Elshanovna, Lipatova Anastasia Valerievna, Kochetkov Dmitriy Vladimirovich, Kravchenko Sergey Kirillovich, Chumakov Petr Mikhailovich, Dzhulakyan Unan Levonovich
  7. Express PCR-Based Test Predicting Brain Tumor Sensitivity to Oncolytic Viruses for a Specific Patient. Patent No.: RU 2697412 C2. Inventors: Lipatova Anastasia Valerievna, Kudryavtseva Anna Viktorovna, Kochetkov Dmitriy Vladimirovich, Zheltukhin Andrey Olegovich, Sosnovtseva Anastasiya Olegovna, Chumakov Petr Mikhailovich
  8. Analytical Test System for Determining a Specific Patient’s Malignant Tumor Sensitivity to Oncolytic Biotherapy. Patent No.: RU 2667648 C1. Inventors: Lipatova Anastasia Valerievna, Kudryavtseva Anna Viktorovna, Kochetkov Dmitriy Vladimirovich, Chumakov Petr Mikhailovich
  9. Software Suite for Analyzing Transcriptome Sequencing Data of Malignant Tumors of Various Histogeneses with Consideration of Normal Fibroblast Impurities. Certificate of State Registration for Computer Program: RU 2015662052 (16.11.2015). Application No.: 2015618919 (28.09.2015). Authors: Poteryakhina A.V., Kochetkov D.V., Chumakov P.M.
  10. Software Suite for Identifying and Validating Molecular Genetic Markers of Tumor Cell Sensitivity to Oncolytic Viruses Based on Transcriptome Sequencing Data. Certificate of State Registration for Computer Program: RU 2017611537 (06.02.2017). Application No.: 2016663885 (16.12.2016). Authors: Lipatova A.V., Kochetkov D.V., Chumakov P.M.

Articles:

  • Receptors and Host Factors for Enterovirus Infection: Implications for Cancer Therapy. Authors: Alekseeva, O. N., Hoa, L. T., Vorobyev, P. O., Kochetkov, D. V., Gumennaya, Y. D., Naberezhnaya, E. R., ... & Lipatova, A. V. (2024). Cancers, 16(18), 3139. Desc: This review explores the roles of individual receptors, the impact of host RNA-sensing mechanisms that activate interferon signaling, and other host cell factors influencing the effectiveness of enteroviruses in oncolytic therapy. Link: https://www.mdpi.com/2072-6694/16/18/3139
  • Polyamine Catabolism Revisited: Acetylpolyamine Oxidase Plays a Minor Role Due to Low Expression. Authors: Ivanova, O. N., Gavlina, A. V., Karpenko, I. L., Zenov, M. A., Antseva, S. S., Zakirova, N. F., Lipatova, A. V., & Ivanov, A. V. (2024). Cells, 13(13), 1134. Desc: Biogenic polyamines play a crucial role in cell metabolism, and their dysregulation is linked to diseases like cancer and hyperproliferative disorders. This study shows that acetylpolyamine oxidase (PAOX) activity is minimal in most cell lines, with polyamine catabolism primarily driven by secretion rather than enzymatic back-conversion. Additionally, PAOX overexpression correlates with cancer cell resistance to genotoxic drugs, suggesting its potential as a therapeutic target. Link: https://www.mdpi.com/2073-4409/13/13/1134
  • Non-secreting IL12 expressing oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade glioma: a phase I trial. Authors: Weihai Ning, Xiao Qian, Louisa Chard Dunmall, Funan Liu, Yuduo Guo, Shenglun Li, Dixiang Song, Deshan Liu, Lixin Ma, Yanming Qu, Haoran Wang, Chunyu Gu, Mingshan Zhang, Yaohe Wang, Shengdian Wang & Hongwei Zhang. Desc: This phase I trial evaluated the safety and efficacy of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in eight patients with recurrent high-grade glioma. Link: https://www.nature.com/articles/s41467-024-53041-7
  • Oncolytic virotherapy: basic principles, recent advances and future directions. Authors: Danni Lin, Yinan Shen & Tingbo Liang. Desc: This review highlights recent progress in OV classification and modification, aiming to improve target specificity, safety, and therapeutic effects through innovative "weaponization" strategies, including cytocidal effects, cancer immunotherapy activation, anti-angiogenesis, and metabolic reprogramming. Encouraging clinical trial results emphasize the potential of OVs as powerful tools in cancer treatment, while also outlining the challenges and future directions for their application.. Link: https://www.nature.com/articles/s41392-023-01407-6?fromPaywallRec=false#Bib1
  • Neoadjuvant oncolytic virus orienx010 and toripalimab in resectable acral melanoma: a phase Ib trial. Authors: Jiayong Liu, Xuan Wang, Zhongwu Li, Shunyu Gao, Lili Mao, Jie Dai, Caili Li, Chuanliang Cui, Zhihong Chi, Xinan Sheng, Yumei Lai, Zhichao Tan, Bin Lian, Bixia Tang, Xieqiao Yan, Siming Li, Li Zhou, Xiaoting Wei, Juan Li, Jun Guo & Lu Si. Desc: A phase Ib trial (NCT04197882) assessed the combination of neoadjuvant oncolytic virus orienX010 (ori) and anti-PD-1 toripalimab (tori) for resectable acral melanoma (AM). Among 30 patients treated, the radiographic and pathological response rates were 36.7% and 77.8%, with 1- and 2-year recurrence-free survival (RFS) rates of 85.2% and 81.5%. Pathological responders exhibited high tumor-infiltrating lymphocytes and tertiary lymphoid structures, while the therapy increased proinflammatory cytokines and chemokines in all patients. Adverse events were mainly grade 1–2, and the combination therapy showed promising efficacy and tolerability, with high 2-year RFS and event-free survival (EFS) rates. Link: https://www.nature.com/articles/s41392-024-02029-2
  • Carcinoembryonic antigen-expressing oncolytic measles virus derivative in recurrent glioblastoma: a phase 1 trial. Authors: Evanthia Galanis, Katharine E. Dooley, S. Keith Anderson, Cheyne B. Kurokawa, Xiomara W. Carrero, Joon H. Uhm, Mark J. Federspiel, Alexey A. Leontovich, Ileana Aderca, Kimberly B. Viker, Julie E. Hammack, Randolph S. Marks, Steven I. Robinson, Derek R. Johnson, Timothy J. Kaufmann, Jan C. Buckner, Daniel H. Lachance, Terry C. Burns, Caterina Giannini, Aditya Raghunathan, Ianko D. Iankov & Ian F. Parney. Desc: A first-in-human trial (NCT00390299) evaluated a carcinoembryonic antigen-expressing oncolytic measles virus derivative (MV-CEA) in recurrent glioblastoma (GBM) patients. The treatment, delivered either at the resection cavity or both intratumorally and at the resection cavity, was well tolerated with no dose-limiting toxicities at the maximum feasible dose (2×10⁷ TCID50). The median overall survival was 11.6 months, with a one-year survival rate of 45.5%, exceeding contemporary controls. Secondary endpoints revealed correlations between viral replication, tumor microenvironment remodeling, and immune response, with an ISG-based DLDA algorithm emerging as a potential tool for treatment personalization. This study highlights the promise of MV derivatives for further clinical investigation in GBM therapy. Link: https://www.nature.com/articles/s41467-023-43076-7
  • Development of a recombinant oncolytic poliovirus type 3 strain with altered cell tropism. Authors: Hamad A1,2,3, Soboleva AV1, Vorobyev PO1, Mahmoud M1,2, Vasilenko KV4, Chumakov PM1, Lipatova AV1. Desc: Diffuse gliomas are highly aggressive and incurable, necessitating innovative treatments like selective oncolytic viruses. Researchers developed RVP3, an engineered poliovirus type 3 strain, by replacing its internal ribosome entry site (IRES) with that of human rhinovirus 30. RVP3 selectively replicates in tumor cells while sparing normal cell lines, showing promise as a targeted therapy for gliomas. Link: https://vestnik.rsmu.press/archive/2022/2/13/content?lang=en
  • Recent Developments in Glioblastoma Therapy: Oncolytic Viruses and Emerging Future Strategies. Authors: Azzam Hamad, Gaukhar M Yusubalieva, Vladimir P Baklaushev, Peter M Chumakov, Anastasiya V Lipatova. Desc: Glioblastoma is the most aggressive brain tumor, with standard treatments and traditional immunotherapy offering limited long-term survival benefits. Oncolytic viruses (OVs) present a promising alternative, especially when combined with modern therapies. This review highlights virotherapy for glioblastomas, emphasizing the potential of personalized OV-based treatments and combination therapies to improve patient outcomes. Links: https://pmc.ncbi.nlm.nih.gov/articles/PMC9958853/ https://www.mdpi.com/1999-4915/15/2/547
  • Immunostimulatory Profile of Cancer Cell Death by the AdV-Lumc007-Derived Oncolytic Virus ‘GoraVir’ in Cultured Pancreatic Cancer Cells. Authors: Selas T. F. BotsORCID,Sanne L. Landman,Martijn J. W. E. RabelinkORCID,Diana J. M. van den WollenbergORCID andRob C. Hoeben. Desc: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with strong resistance to treatment. Oncolytic viruses, such as GoraVir, offer a novel therapeutic approach by inducing immunogenic cell death (ICD) and stimulating antitumor immune responses. GoraVir, derived from a gorilla adenovirus, has shown superior lytic activity in PDAC models compared to human adenovirus type 5, inducing ICD independently of STING expression and despite antiviral responses. These findings suggest that GoraVir is a promising candidate for oncolytic virotherapy in PDAC. Link: https://www.mdpi.com/1999-4915/15/2/283
  • Oncolytic Measles Virus Encoding MicroRNA for Targeted RNA Interference. Authors: Sophie C. Anker 1,2,Marie G. Szczeponik 1,3,Jan Dessila 1,Katia Dittus 1,4,5,Christine E. Engeland 1,5,6ORCID,Dirk Jäger 5,Guy Ungerechts 1,5,7 andMathias F. Leber 1,5,*ORCID. Desc: This research highlights the potential of using oncolytic measles viruses to deliver functional microRNAs, enabling targeted knockdown of antiviral factors in tumor cells for improved therapeutic outcomes. Link: https://www.mdpi.com/1999-4915/15/2/308
  • A Renaissance for Oncolytic Adenoviruses?. Authors: Paola Blanchette and Jose G. Teodoro. Desc: This review highlights current clinical strategies and emphasizes the need for further research to optimize adenovirus-based oncolytic and immunotherapy approaches. Link: https://www.mdpi.com/1999-4915/15/2/358
  • Establishing a New Platform to Investigate the Efficacy of Oncolytic Virotherapy in a Human Ex Vivo Peritoneal Carcinomatosis Model. Authors: Jana Koch, Julia Beil, Susanne Berchtold, Dina Mönch, Annika Maaß, Irina Smirnow, Andrea Schenk, Mary E. Carter, Linus D. Kloker, Tobias Leibold, Philipp Renner, Marc-H. Dahlke and Ulrich M. Lauer.. Desc: Oncolytic virotherapy shows promise as a treatment for peritoneal carcinomatosis (PC), a terminal stage of many cancers. Traditional 2D tumor models have limitations in evaluating the efficacy of oncolytic viruses. This study utilized an advanced human ex vivo peritoneum co-culture model with HT-29 cancer cells to test the effectiveness of two oncolytic viruses, GLV-0b347 and MeV-DsRed. Both viruses demonstrated high tumor specificity, successfully infecting and lysing cancer cells while reducing tumor markers over time. The model offers a clinically relevant platform for evaluating virotherapeutic efficacy and exploring immunostimulatory potential in a realistic, patient-derived environment. Link: https://www.mdpi.com/1999-4915/15/2/363
  • Inactivation of the UL37 Deamidase Enhances Virus Replication and Spread of the HSV-1(VC2) Oncolytic Vaccine Strain and Secretion of GM-CSF. Authors: Carolyn M. Clark, Nithya Jambunathan, Therese M. A. Collantes and Konstantin G. Kousoulas. Desc: The HSV-1 (VC2) live-attenuated vaccine strain, engineered to prevent neuronal entry and latency, shows promise as both a vaccine and an oncolytic virus against melanoma and breast cancer. While VC2 replicates efficiently in epithelial cells, its replication and plaque size are smaller than the wild-type HSV-1(F). Modifying the UL37 protein's deamidase function (via the C819S mutation) enhanced replication and plaque size in VC2C819S, approaching wild-type levels. VC2 and FC819S infections stimulate GM-CSF secretion, a key immune response factor, in multiple cell types, though VC2C819S did not further enhance this secretion. These findings highlight the role of UL37 and gK/UL20 in virus replication and immunotherapeutic effects. Link: https://www.mdpi.com/1999-4915/15/2/367
  • Oncolytic Avian Reovirus σA-Modulated Upregulation of the HIF-1α/C-myc/glut1 Pathway to Produce More Energy in Different Cancer Cell Lines Benefiting Virus Replication. Authors: Chao-Yu Hsu, Jing-Wen Huang, Wei-Ru Huang, I-Chun Chen, Ming-Shan Chen, Tsai-Ling Liao, Yu-Kang Chang, Muhammad Munir and Hung-Jen Liu. Desc: The avian reovirus (ARV) protein σA acts as an energy activator by upregulating the HIF-1α/myc/glut1 pathway, altering host cell metabolism to enhance virus replication. In cancer cell lines (A549, B16-F10, HeLa), σA increases the expression of HIF-1α, c-myc, and glut1, boosting ATP production through glycolysis and glutaminolysis. This protein also activates the TCA cycle via glutaminase while suppressing lactate dehydrogenase A (LDHA), preventing the Warburg effect. These findings highlight a novel mechanism by which ARV σA modulates cellular energy pathways to support viral replication.Link: https://www.mdpi.com/1999-4915/15/2/523
  • Synergistic Effect of a Combination of Proteasome and Ribonucleotide Reductase Inhibitors in a Biochemical Model of the Yeast Saccharomyces cerevisiae and a Glioblastoma Cell Line. Authors: Kulagin, K. A., Starodubova, E. S., Osipova, P. J., Lipatova, A. V., Cherdantsev, I. A., Poddubko, S. V., ... & Karpov, D. S. (2024). International Journal of Molecular Sciences, 25(7), 3977. Desc: This study evaluated the combined use of proteasome and RNR inhibitors in yeast and GBM cell models. Results showed that proteasome inhibition increases RNR activity in yeast, and combining proteasome inhibitor bortezomib with RNR inhibitors hydroxyurea or gemcitabine significantly reduced cell growth and survival in yeast and GBM models. Yeast serves as a simple model for testing the efficacy of these drug combinations in cancer therapy. Link: https://pubmed.ncbi.nlm.nih.gov/38612788/
  • Oncolytic therapy with recombinant vaccinia viruses targeting the interleukin-15 pathway elicits a synergistic response. Authors: Y. Shakiba, P Vorobyev, D Kochetkov, K Zajtseva, M Valikhov, G Yusubalieva, V Kalsin, F Zabozlaev, A.Semkina, A Troitskiy, P Chumakov, V Baklaushev, A Lipatova, Molecular Therapy – Oncolytics (2023), 29, pp.158–168. (IF = 7.2). Desc: Researchers developed recombinant oncolytic vaccinia viruses expressing interleukin-15 (IL-15) and its receptor subunit alpha (IL-15Rα) to stimulate immune responses and tested their efficacy against colon and breast cancer models. In vitro, 4T1 breast cancer cells were particularly susceptible to the viruses, and in vivo, a combination of the variants led to significant tumor regression and improved survival in breast cancer-bearing mice. The treatment activated cytotoxic T cells and macrophages without causing damage to the liver or spleen. These findings highlight the potential of combining these recombinant viruses as an effective immunotherapy for breast cancer. Link: https://pubmed.ncbi.nlm.nih.gov/37387795/
  • Oncolytic Efficacy of a Recombinant Vaccinia Virus Strain Expressing Bacterial Flagellin in Solid Tumor Models.. Authors: Shakiba, Y., Vorobyev, P. O., Naumenko, V. A., Kochetkov, D. V., Zajtseva, K. V., Valikhov, M. P., A Lipatova ... & Semkina, A. S. (2023). Viruses, 15, 828.. Desc: This study explored the enhanced antitumor efficacy of thymidine kinase-deficient vaccinia virus (VV, Lister strain) variants engineered to express bacterial flagellin (LIVP-FlaB-RFP), luciferase (LIVP-Fluc-RFP), or fluorescent protein (LIVP-RFP). The LIVP-FlaB-RFP variant showed superior oncolytic activity, particularly in B16 melanoma models, promoting tumor regression and prolonged survival in comparison to controls. Analysis revealed immune activation through tumor-infiltrated lymphocytes and cytokines. These findings suggest that expressing bacterial flagellin in VV can enhance its therapeutic potential against immunosuppressive solid tumors. Link: https://pubmed.ncbi.nlm.nih.gov/37112810/
  • SARS-CoV-2 establishes a productive infection in hepatoma and glioblastoma multiforme cell lines. Authors: Smirnova, O. A., Ivanova, O. N., Fedyakina, I. T., Yusubalieva, G. M., Baklaushev, V. P., Yanvarev, D. V., Kechko, O. I., Mitkevich, V. A., Valuev-Elliston, V. T., Vorobiev, P. O., Fedorov, V. S., Bartosch, B., Lipatova, A. L., Ivanov, A. V., Cancers (accepted for publication) (IF = 6.5). Desc: This study investigates the ability of SARS-CoV-2 to infect liver and central nervous system (CNS) cell lines, finding that certain liver cancer (Huh7.5, HepG2) and glioblastoma cell lines are susceptible to infection due to moderate ACE2 expression and defects in interferon production. However, primary astrocytes, neuroblastoma cells, and non-transformed liver cells were resistant. The findings suggest that liver dysfunction during COVID-19 is more likely caused by systemic inflammation rather than direct viral infection, while tumors might act as reservoirs for the virus. Relation to Oncolytic Virus Treatments: This study is not directly related to oncolytic virus treatments. However, it highlights the interaction between viruses and tumor cells, particularly in glioblastoma, which could provide insights into viral dynamics in tumor environments—a relevant consideration in the context of developing oncolytic virotherapy. Link: https://pubmed.ncbi.nlm.nih.gov/36765590/
  • Recombinant strains of oncolytic vaccinia virus for cancer immunotherapy. Authors: Shakiba, Y., Vorobyev, P.O., Mahmoud, M., Hamad, A., Kochetkov, D.V., A.V. Lipatova - Biochemistry (accepted) (IF = 2.82). Desc: Cancer virotherapy leverages viruses like the vaccinia virus (VV) to selectively infect and destroy tumor cells. VV, with its large genome and proven safety, is an ideal platform for engineering recombinant oncolytic viruses. Genetic modifications can enhance VV's tumor selectivity and therapeutic efficacy by incorporating immune-modulatory genes or proapoptotic molecules, thereby boosting the host immune response and improving tumor cell recognition by T-cells or NK cells. This review highlights bioengineering strategies to develop advanced VV strains for effective cancer immunotherapy. Link: https://link.springer.com/article/10.1134/S000629792306010X
  • 2-Deoxyglucose, an Inhibitor of Glycolysis, Enhances the Oncolytic Effect of Coxsackievirus.. Authors: Vorobyev, P.O., Kochetkov, D.V., Chumakov, P.M., Zakirova, N.F., Zotova-Nefedorova, S.I., Vasilenko, K.V., Alekseeva, O.N., Kochetkov, S.N., Bartosch, B., Lipatova, A.V., Ivanov, A.V. (2022). Cancers, 14(22), 5611. DOI: 10.3390/cancers14225611 (IF = 6.5). Desc: Glioblastoma multiforme (GBM) is a common and aggressive brain tumor with a poor prognosis and a median survival of 14.6 months. Oncolytic viruses, such as Coxsackievirus B5 (CVB5), show significant potential for GBM treatment, demonstrating high oncolytic activity against primary GBM cells and cell lines. Additionally, the glycolysis inhibitor 2-deoxyglucose (2DG) enhances the cytopathic effects of CVB5, particularly in cancer cells with high mitochondrial activity and glycolytic capacity. This suggests that 2DG and similar compounds could serve as effective adjuvants in oncolytic virotherapy for GBM. Link: https://pubmed.ncbi.nlm.nih.gov/36428704/
  • Oncolytic Viruses in the Therapy of Lymphoproliferative Diseases. Authors: Vorobyev, P.O., Babaeva, F.E., Panova, A.V., Shakiba, J., Kravchenko, S.K., Soboleva, A.V., Lipatova, A.V. (2022) Molecular Biology, 56(5), 684-695. DOI: 10.1134/S0026893322050144 (IF = 1.54). Desc: Cancer remains a leading cause of death, with challenges such as relapse, drug resistance, and limited therapy effectiveness persisting, particularly in lymphatic system tumors. Oncolytic viruses offer a promising solution by selectively replicating in and destroying tumor cells while sparing healthy tissues. These viruses also activate antitumor immunity, proving effective against drug-resistant lymphoproliferative diseases and inducing remissions in many cases. Advances in viral biology and host cell interaction mechanisms have enabled the development of highly oncoselective viral strains, now widely utilized in clinical practice. Link: https://link.springer.com/article/10.1134/S0026893322050144
  • Multiomic Profiling Identified EGF Receptor Signaling as a Potential Inhibitor of Type I Interferon Response in Models of Oncolytic Therapy by Vesicular Stomatitis Virus. Authors: Nikitina, A.S., Lipatova, A.V., Goncharov, A.O., Kliuchnikova, A.A., Pyatnitskiy, M.A., Kuznetsova, K.G., Hamad, A., Vorobyev, P.O., Alekseeva, O.N., Mahmoud, M., Shakiba, Y., Anufrieva, K.S., Arapidi, G.P., Ivanov, M.V., Tarasova, I.A., Gorshkov, M.V., Chumakov, P.M., Moshkovskii, S.A. (2022) International Journal of Molecular Sciences, 23(9), 5244. (*Shared first authorship). Desc: This study investigates the differential responses of cancer cell lines to type I interferon treatment in the context of oncolytic therapy using vesicular stomatitis virus (VSV). Glioblastoma (DBTRG-05MG) and osteosarcoma (HOS) cell lines were analyzed, with HOS showing sensitivity and DBTRG-05MG demonstrating resistance to VSV post-treatment. Transcriptome and proteome analysis revealed a higher number of inflammatory-related genes in DBTRG-05MG, while HOS cells exhibited overexpression of EGFR and HER2, which are implicated in attenuating interferon responses. Combined treatment with EGF receptor inhibitors and interferon increased resistance in sensitive cells. HER2 protein levels may serve as predictive biomarkers for tumor resistance to oncolytic viral therapy. Link: https://doi.org/10.3390/ijms23095244 (IF = 6.2)
  • Development of a Recombinant Oncolytic Poliovirus Type 3 Strain with Altered Cell Tropism. Authors: Hamad, A., Soboleva, A.V., Vorobyev, P.O., Mahmoud, M., Vasilenko, K.V., Chumakov, P.M., Lipatova, A.V. (2022). Bulletin of Russian State Medical University, (2), 5-10. DOI: 10.24075/BRSMU.2022.023. Desc: This study developed an oncolytic virus, RVP3, derived from poliovirus type 3, modified with the internal ribosome entry site (IRES) of human rhinovirus 30. RVP3 retained its poliovirus serotype and demonstrated oncolytic efficacy in vitro, selectively replicating in tumor cells while losing the ability to replicate in normal embryonic astrocytes and fibroblasts. This specificity suggests RVP3’s potential as a targeted therapeutic agent for malignant gliomas. Link: https://vestnik.rsmu.press/archive/2022/2/13/abstract?lang=en
  • Infection of non-cancer cells: A barrier or support for oncolytic virotherapy? Authors: Naumenko, V.A., Stepanenko, A.A., Lipatova, A.V., Vishnevskiy, D.A., Chekhonin, V.P. (2022). Molecular Therapy - Oncolytics, 24, 663-682. DOI: 10.1016/j.omto.2022.02.004 (IF = 7.2). Desc: This review explores the ability of oncolytic viruses to infect non-cancerous cells, focusing on their interaction with the tumor microenvironment and secondary lymphoid tissues. It addresses two key questions: how attenuated viruses infect normal cells and the implications of this phenomenon for cancer virotherapy. The study highlights the need for understanding these interactions to optimize oncolytic virus-based therapies. Link: https://pubmed.ncbi.nlm.nih.gov/35284629/
  • Superior infectivity of the fiber chimeric oncolytic adenoviruses Ad5/35 and Ad5/3 over Ad5-delta-24-RGD in primary glioma cultures. Authors: Stepanenko, A.A., Sosnovtseva, A.O., Valikhov, M.P., Chernysheva, A.A., Cherepanov, S.A., Yusubalieva, G.M., Ruzsics, Z., Lipatova, A.V., Chekhonin, V.P. (2022). DOI: 10.1016/j.omto.2021.12.013 (IF = 7.2). Desc: The study compares the efficacy of fiber-modified recombinant adenoviruses (rAds) for glioma therapy, focusing on Ad5-delta-24-RGD and its variants. Ad5/35-delta-24 and Ad5/3-delta-24 showed superior infectivity and cytolytic efficacy in human glioma cells compared to Ad5-delta-24-RGD, though tumor cell selectivity was not observed. Mouse models demonstrated that Ad5/35-delta-24 armed with the immune costimulator OX40L led to long-term survival and tumor rejection upon rechallenge. The findings highlight the potential of Ad5/35-delta-24-based immunovirotherapy for glioblastoma treatment. Link: https://pubmed.ncbi.nlm.nih.gov/35071746/
  • Cultivation of cells in a physiological plasmax medium increases mitochondrial respiratory capacity and reduces replication levels of RNA viruses. Authors: Golikov, M.V., Karpenko, I.L., Lipatova, A.V., Ivanova, O.N., Fedyakina, I.T., Larichev, V.F., Zakirova, N.F., Leonova, O.G., Popenko, V.I., Bartosch, B., Kochetkov, S.N., Smirnova, O.A., Ivanov, A.V. (2022). DOI: 10.3390/antiox11010097 (IF = 7.76). Desc: The study highlights the advantages of using Plasmax, a medium designed to mimic human plasma, for cellular and metabolic research. Plasmax enhances mitochondrial respiration, promotes mitochondrial network formation, increases reactive oxygen species (ROS) production, and reduces lysosome abundance in cultured cells compared to standard media. It also supports replication of various RNA viruses, including HCV, IAV, and SARS-CoV-2, though with delayed kinetics and lower levels. These findings suggest Plasmax is a more physiologically relevant medium for studying metabolism and viral infections, particularly in the context of mitochondria, lysosomes, and redox systems. Link: https://pubmed.ncbi.nlm.nih.gov/35052601/
  • Multi-omics analysis of glioblastoma cells’ sensitivity to oncolytic viruses. Authors: Lipatova, A.V., Soboleva, A.V., Gorshkov, V.A., Bubis, J.A., Solovyeva, E.M., Krasnov, G.S., Kochetkov, D.V., Vorobyev, P.O., Ilina, I.Y., Moshkovskii, S.A., Kjeldsen, F., Gorshkov, M.V., Chumakov, P.M., Tarasova, I.A. (2021). Cancers, 13(21), 5268. DOI: 10.3390/cancers13215268 (IF = 6.5). Desc: This study investigates the role of interferon-dependent antiviral mechanisms in the effectiveness of oncolytic virus (OV) therapy for glioblastoma multiforme (GBM). It analyzes how GBM cells respond to type I interferons by examining gene and protein expression patterns. Results show that GBM cells overexpress interferon-stimulated genes (ISGs), similar to normal cells, with specific molecular patterns influencing their antiviral resistance. Importantly, the study highlights that suppressing individual ISGs does not necessarily enhance sensitivity to OVs, and in some cases, silencing certain genes like IFIT3 and PLSCR1 can reduce viral internalization. These findings underline the complex interplay of interferon responses and other factors in determining tumor cell sensitivity to oncolytic viruses. Link: https://pubmed.ncbi.nlm.nih.gov/34771433/
  • The State of The Jak/Stat Pathway Affects the Sensitivity of Tumor Cells to Oncolytic Enteroviruses. Authors: Le, T.H., Lipatova, A.V., Volskaya, M.A., Tikhonova, O.A., Chumakov, P.M. (2020). Molecular Biology, 54(4), 570-577. DOI: 10.1134/S002689332004010X. Desc: This study investigated the sensitivity of seven colon cancer cell lines to 12 nonpathogenic human enteroviruses and found significant differences in how well the viruses could infect and replicate within the cells. The variability in sensitivity was linked to the state of antiviral mechanisms, particularly the type I interferon response via the Jak/STAT signaling pathway. Using engineered HEK293T cell lines with IFNAR1 and STAT2 gene knockouts, researchers observed increased sensitivity to infection by several enterovirus strains and vesicular stomatitis virus. Knockout cells showed higher viral replication compared to control cells. These findings highlight that deficiencies in the Jak/STAT signaling pathway in tumor cells enhance their sensitivity to oncolytic viruses, making them more susceptible to virotherapy. Link: https://pubmed.ncbi.nlm.nih.gov/32799226/
  • NLRX1 regulates TNF-α-induced mitochondria-lysosomal crosstalk to maintain the invasive and metastatic potential of breast cancer cells. Authors: Singh, K., Roy, M., Prajapati, P., Lipatova, A., Sripada, L., Gohel, D., Singh, A., Mane, M., Godbole, M.M., Chumakov, P.M., Singh, R. (2019). Biochimica et Biophysica Acta - Molecular Basis of Disease, 1865(6), 1460-1476. DOI: 10.1016/j.bbadis.2019.02.018 (Cited 16 times). Desc: This study examines the role of NLRX1, a mitochondrial receptor protein, in breast cancer cell metabolism, autophagy, and metastasis under inflammatory conditions induced by TNF-α. NLRX1 was found to be highly expressed in basal-like and metastatic breast cancer. Depleting NLRX1 in triple-negative breast cancer cells disrupted oxidative phosphorylation (OxPhos) and lysosomal function, impairing mitochondrial turnover via mitophagy. This led to reduced proliferation and migration of cancer cells reliant on OxPhos. The findings highlight NLRX1's critical role in coordinating mitochondrial and lysosomal functions, which supports the invasive and metastatic capabilities of breast cancer cells. Link: https://pubmed.ncbi.nlm.nih.gov/30802640/ Oncolytic Activity of the Vaccine Strain of Type 3 Poliovirus on the Model of Rat Glioma C6 Cells. Authors: Sosnovtseva, A.O., Zheltukhin, A.O., Lipatova, A.V., Chumakov, P.M., Chekhonin, V.P. (2019). Bulletin of Experimental Biology and Medicine, 167(1), 111-115. DOI: 10.1007/s10517-019-04472-6. Desc: This study used a rat glioma cell line (C6-PVR-BFP) expressing the human poliovirus receptor (PVR) to examine the effects of type 1 interferon (IFN) signaling on sensitivity to a poliovirus type 3 (PV3) vaccine strain. Knocking out the IFNα/β receptor subunit 1 gene (Ifnar1) increased the cells' susceptibility to PV3. In a subcutaneous tumor xenograft model, PV3 demonstrated oncolytic activity against C6-PVR-BFP cells, which was enhanced by disruptions in the IFN response pathways. These findings highlight the role of IFN signaling and PVR expression in modulating the effectiveness of oncolytic virotherapy using poliovirus. Link: https://pubmed.ncbi.nlm.nih.gov/31177454/
  • Relationship between Cell Receptors and Tumor Cell Sensitivity to Oncolytic Enteroviruses. Authors: Lipatova, A.V., Le, T.H., Sosnovtseva, A.O., Babaeva, F.E., Kochetkov, D.V., Chumakov, P.M. (2018). Bulletin of Experimental Biology and Medicine, 166(1), 58-62. DOI: 10.1007/s10517-018-4289-1. Desc: This study assessed the replication capabilities of five oncolytic enterovirus strains across 18 human normal and tumor cell lines. The ability of cells to support viral replication varied widely, with some cell lines being highly sensitive to certain viral strains while resistant to others. The expression of the CXADR receptor did not correlate with sensitivity to Coxsackie B virus, but complete inactivation of the CXADR or PVR gene eliminated sensitivity to Coxsackie B5 and poliovirus, respectively. Identifying additional expression markers could help explain the differing sensitivity of tumor cells to oncolytic viruses. Link: https://pubmed.ncbi.nlm.nih.gov/30450519/
  • Persistence of oncolytic coxsackie virus A7 in subcutaneous human glioblastoma xenografts in mice in the context of experimental therapy. Authors: Sidorenko, A.S., Zheltukhin, A.O., Le, T.H., Soboleva, A.V., Lipatova, A.V., Golbin, D.A., Chumakov, P.M. (2018). Bulletin of Russian State Medical University, 7(3), 41-46. DOI: 10.24075/brsmu.2018.032. Desc: This study explores the use of natural and vaccine strains of enteroviruses, such as Coxsackie A7, as potential treatments for glioblastoma multiforme, the most aggressive brain tumor. Enteroviruses can selectively replicate in cancer cells, causing tumor lysis, but their ability to persist and spread in tumor tissue remains unclear. Using human glioblastoma-derived neurospheres in immunodeficient mice, the researchers demonstrated that human peripheral blood leukocytes infected with Coxsackie A7 can effectively deliver the virus to tumor cells. A single intravenous injection of virus-carrying leukocytes caused gradual tumor regression, with the virus persisting in the blood until complete tumor destruction. This suggests that leukocytes can serve as efficient carriers for delivering oncolytic viruses, leading to effective tumor eradication. Link: https://www.researchgate.net/publication/327256781_Persistence_of_oncolytic_Coxsackie_virus_A7_in_subcutaneous_human_glioblastoma_xenografts_in_mice_in_the_context_of_experimental_therapy
  • Glioblastoma multiforme stem cells are highly sensitive to some human non-pathogenic enteroviruses. Authors: Soboleva, A.V., Seryak, D.A., Gabdrakhmanova, A.F., Sosnovtseva, A.O., Tkhe, L.H., Kochetkov, D.V., Ilyinskaya, G.V., Golbin, D.A., Lipatova, A.V., Chumakov, P.M. (2018). Journal of Pharmaceutical Sciences and Research, 10(4), 936-939. Desc: This study investigates the use of oncolytic enteroviruses as a potential treatment for glioblastoma multiforme (GBM), a highly aggressive and incurable brain tumor known for inevitable relapse after conventional treatments. Tumor stem cells, which resist chemotherapy and radiotherapy, are the primary cause of relapse. The researchers tested four nonpathogenic human enteroviruses on GBM cells from five patients, comparing the sensitivity of differentiated GBM cells (grown as monolayers) and stem cell-enriched neurospheres. Both cell types showed high sensitivity to the enteroviruses, with effective virus replication and tumor cell destruction, including stem cells. These findings suggest that oncolytic enteroviruses have significant potential as a therapy for GBM, targeting both differentiated tumor cells and the resistant stem cell population. Link: https://www.jpsr.pharmainfo.in/Documents/Volumes/vol10Issue04/jpsr10041857.pdf. Human enteroviruses exhibit selective oncolytic activity in the model of human glioblastoma multiforme xenografts in immunodeficient mice. Authors: Zheltukhin, A.O., Soboleva, A.V., Le, T.H., Ilyinskaya, G.V., Kochetkov, D.V., Lipatova, A.V., Chumakov, P.M. (2018). Bulletin of Russian State Medical University, (2), 42-48. DOI: 10.24075/BRSMU.2018.026/TRANSLATION. Desc: This study addresses the challenge of glioblastoma multiforme (GBM) relapses caused by stem cells deeply embedded in brain tissue. Researchers tested the sensitivity of GBM cells to non-pathogenic enteroviruses, including type 1 poliovirus (Sabin vaccine strain), Coxsackievirus A7, A9, and B5, both in vitro and in vivo using a mouse xenograft model. Coxsackievirus A7 and type 1 poliovirus demonstrated the strongest oncolytic and replicative properties, effectively preventing tumor development when pre-incubated with glioblastoma neurosphere cultures. Coxsackievirus B5 reduced tumor numbers, while Coxsackievirus A9 had no impact. These findings highlight the potential of certain non-pathogenic enteroviruses as promising therapeutic agents for relapse-free treatment of GBM by targeting its stem cells. Link: https://vestnik.rsmu.press/archive/2018/2/7/abstract?lang=en
  • Changes in the sensitivity of human glioblastoma cells to oncolytic enteroviruses induced by passaging. Authors: Soboleva, A.V., Lipatova, A.V., Kochetkov, D.V., Chumakov, P.M. (2018). Bulletin of Russian State Medical University, 7(2), 37-41. DOI: 10.24075/brsmu.2018.025. Desc: Existing therapies for glioblastoma multiforme fail to ensure patient recovery due to the persistence of glioblastoma-initiating stem cells, which drive relapses. Oncolytic viruses (OVs) offer a promising alternative, but their effectiveness varies among patients, necessitating sensitivity testing on live tumor cells. This study evaluated how tumor cell sensitivity to four non-pathogenic enteroviruses changes with cell culture passaging. Primary glioblastoma cultures from three patients showed varying virus sensitivity, with significant differences in the virus dose required for infection. Passaging induced shifts in sensitivity, correlating with changes in virus production. The findings highlight the importance of testing virus sensitivity in primary cultures early in the cell passaging process. Link: https://vestnik.rsmu.press/archive/2018/2/6/content?lang=en
  • Biomarkers of prostate cancer sensitivity to the Sendai virus. Authors: Belova, A.A., Sosnovtseva, A.O., Lipatova, A.V., Njushko, K.M., Volchenko, N.N., Belyakov, M.M., Sudalenko, O.V., Krasheninnikov, A.A., Shegai, P.V., Sadritdinova, A.F., Fedorova, M.S., Vorobjov, N.V., Alekseev, B.Y., Kaprin, A.D., Kudryavtseva, A.V. (2017). Molekuliarnaia biologiia, 51(1), 94-103. DOI: 10.7868/S0026898417010049 (Cited 2 times). Desc: Metastatic prostate cancer, particularly castration-resistant prostate cancer (CRPC), requires innovative treatment approaches. Oncolytic viruses, such as the murine Sendai virus (SeVM), can selectively kill tumor cells while sparing normal cells. This study found that the sensitivity of prostate adenocarcinoma cell lines to SeVM varies significantly. Quantitative PCR revealed that lower expression levels of TLR3 and TLR7 genes, which encode specific Toll-like receptors, are associated with greater cell sensitivity to the virus. These findings suggest that TLR3 and TLR7 expression levels could serve as biomarkers to predict the effectiveness of Sendai virus-based therapies. Link: https://pubmed.ncbi.nlm.nih.gov/28251971/
  • Sensitivity of C6 glioma cells carrying the human poliovirus receptor to oncolytic polioviruses. Authors: Sosnovtseva, A.O., Lipatova, A.V., Grinenko, N.F., Baklaushev, V.P., Chumakov, P.M., Chekhonin, V.P. (2016). Bulletin of Experimental Biology and Medicine, 161(6), 821-825. DOI: 10.1007/s10517-016-3520-1 (Cited 2 times). Desc: A humanized rat C6 glioma cell line expressing the human poliovirus receptor was developed to evaluate its sensitivity to the oncolytic effects of poliovirus vaccine strains (types 1, 2, and 3). While the presence of the poliovirus receptor on the glioma cell surface was essential for interaction with the viruses, it was not sufficient to achieve complete oncolysis by the polioviruses. Link: https://pubmed.ncbi.nlm.nih.gov/27783287/
  • Oncolytic viruses for therapy of malignant glioma. Authors: Sosnovtceva, A.O., Grinenko, N.F., Lipatova, A.V., Chumakov, P.M., Chekhonin, V.P. (2016). Biomeditsinskaya Khimiya, 62(4), 376-390. DOI: 10.18097/PBMC20166204376 (Cited 5 times). Desc: Malignant glioma, the most common primary brain tumor, has a poor prognosis with a median survival of just over 14 months. Oncolytic virotherapy, which selectively targets and replicates in tumor cells while sparing normal brain tissue, has shown promise in early-phase clinical trials but has not yet advanced to phase III trials. Despite 25 years of research since the introduction of genetically engineered oncolytic viruses, key challenges remain, including understanding their mechanisms, optimizing treatment strategies, and integrating them with other therapies. Oncolytic viral therapy holds significant potential to improve glioma treatment in the future. Link: https://pubmed.ncbi.nlm.nih.gov/28265902/
Konoplyannikov Mikhail, professor
  • Laboratory of Cell Technologies, Federal Research Clinical Center, Federal Medical and Biological Agency of Russia - Director. Moscow, Russia
Education:
  • PhD in Biophysics, 2000, Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia
  • Dissertation: "Lymphoid Cell Death under the Influence of Oxidative Stress and Genotoxic Agents"
  • MSc in Chemical Engineering (Biotechnology), 1996, Moscow State Academy of Fine Chemical Technology / Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
  • Dissertation: "Study of the 5q31.1 Region of the Human Chromosome Using the Method of cDNA Selection on Cosmid Clones"
Awards and memberships in professional associations:
  • Soros International Graduate Fellowship in Science, 1998
  • American Heart Association (since 2007)
  • International Society for Stem Cell Research (since 2005)
Professional experience:
  • May 2012 – present. Head of the Cell Technologies Laboratory at the Federal Research Clinical Center of the Federal Medical and Biological Agency of Russia. Our laboratory provides services for the development, production, clinical evaluation, and implementation of cell therapies and nanocontainerized drugs for the Center's clinical departments. We translate research results into clinical practice through reliable protocols for the production, storage, and use of cells and pharmacotherapy that meet internationally recognized requirements. Our goals include the development, production, clinical evaluation, and implementation of new treatments for various socially significant diseases, as well as the education and training of clinical and scientific personnel. Our laboratory provides patients with access to new treatments, often in cases where alternative therapeutic options are practically unavailable. Our integrated laboratory services allow us to obtain, store, culture, and distribute investigational therapeutic agents for treatment. In addition to conducting our own clinical trials, we also support pharmaceutical and other research by providing specialized storage for drugs intended for specific patients. Our laboratory operations comply with international, national, local, and institutional guidelines and regulations, ensuring world-class cell and pharmaceutical processing and the high quality of cellular and pharmaceutical products. Key laboratory projects include the use of adipose tissue-derived stromal vascular fraction (VSD), platelet-rich plasma (PRP), bone marrow-derived mononuclear cells (BMDCs), mesenchymal stem cells (MSCs), and nanocontainer preparations for the treatment of musculoskeletal diseases, trauma, COPD, critical lower limb ischemia, diabetes, and inflammatory bowel disease; and adoptive cancer immunotherapy.
  • September 2010 – May 2012: Senior Researcher, Department of Medical Nanobiotechnology, Russian State Medical University. Participated in projects investigating the therapeutic effects of systemic MSC transplantation in patients with various diseases. We also studied the cellular and genetic mechanisms controlling brain cancer stem cells to identify new therapeutic strategies for brain tumor treatment.
  • January 2010 – August 2010: Postdoctoral Research Fellow, Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD. Participated in projects investigating the mechanisms of vascular calcification and the role of transglutaminases in this process. My primary experimental work involves animal studies using rat and zebrafish models.
  • April 2007 – December 2009: Postdoctoral Research Fellow, Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH. Participated in projects investigating the therapeutic potential of adult stem cells (mesenchymal stem cells and skeletal myoblasts) for cardiovascular regeneration after myocardial infarction. We used a novel approach combining stem cell transplantation with therapeutic gene therapy through genetic modulation of donor cells prior to transplantation. This involved the delivery of therapeutic genes such as IGF-1, VEGF, SDF-1, and HGF. We manipulated stem cells ex vivo using viral and non-viral vector gene delivery systems and used these genetically modified cells for transplantation into infarcted hearts via direct intramyocardial injection.
  • November 2004 – March 2007: Postdoctoral Research Fellow, NHLBI-NIH, Bethesda, MD. Participated in projects investigating the cellular and molecular mechanisms of cardiovascular regeneration during wound healing and the use of stem cells in this process. We investigated the role of stem cell-mediated vascular regeneration and studied the lineage of cells involved in this process using genetic lineage tracing. Subsequent studies are aimed at identifying the molecular pathways of stem cell differentiation and their interactions with the local microenvironment during vascular remodeling. Additionally, I participated in a project studying the regenerative capacity of bone marrow-derived pluripotent stem cells (BMSCs) after their transplantation into ischemic tissue. We demonstrated that bone marrow-derived mesenchymal stem cells (BMSCs) recruit blood mononuclear cells to ischemic tissue via the VEGF/SDF1 pathway. These recruited cells initiate wound healing via paracrine mechanisms, and cell therapy can modulate this process. I also participated in a project to identify vascular progenitor cells in a mouse model using the label-retaining cell (LRC) assay. Young animals were injected subcutaneously with BrdU, and cells that retained the label after 2 months were identified as LRCs. It is possible that non-proliferating cells, LRCs within blood vessels, may represent vascular stem cells. We analyzed their role in vascular regeneration and repair.
  • October 2003 – October 2004. Researcher, Bioscreening Department, ASINEX LLC, Moscow, Russia. Research Associate, Bioscreening Department, ASINEX Ltd., Moscow, Russia. Worked on drug discovery projects. Tested a number of compounds for the development of new kinase inhibitors using high-throughput protein kinase screening assays.
  • September 2002 – September 2003: Product Manager, Bio-Rad Laboratories, Moscow, Russia
  • September 2001 – August 2002: Research Associate, Department of Food Science, Food Technology, and Nutrition, University College Cork, Cork, Ireland. My work focused on the safety assessment of phytosterols (cytotoxicity, genotoxicity, and effects on cellular antioxidant status) and their oxidized derivatives using established mammalian cell culture models in vitro. This work was funded by a grant from the Institutional Research in Food Science Program (FIRM project 561/800/1208). The results were published in a journal article and presented at the 2002 meeting of the Irish Section of the Society of Nutrition.
  • January 2000 – August 2001. Research Fellow, Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia. Participated in a joint project between the Institute of Chemical Physics and the Medical Radiological Research Center (MRC) of the Russian Academy of Medical Sciences. The project focused on developing a method for obtaining cardiomyoblasts from mesenchymal stem cells of autologous human and rat bone marrow, as well as methods for their transplantation into the body under conditions of stimulation of the microenvironment of the transplanted cells. Participated in all experimental studies for this project. The project was supported by the International Scientific and Technical Center (project ISTC 799B). Participated in all experimental studies for this project. The project was supported by the International Scientific and Technical Center (project ISTC 799B).
  • December 1996 – December 1999. Graduate student, Institute of Chemical Physics, Russian Academy of Sciences, Moscow, Russia. During my graduate studies, I participated in research supported by a grant from the Russian Foundation for Basic Research (RFBR, project 95-04-1225a). My work focused on the mechanisms of lymphoid cell death and associated cellular damage induced by irradiation, treatment with anticancer chemotherapeutic agents, and oxidative stress (photodynamic therapy, the effects of menadione, nitric oxide donors, etc.), studied in culture models and in clinical trials. During this same period, I participated in a study of the inhibitory effect of phenytoin on nitric oxide production in the tissues of gamma-irradiated mice. I also assisted in the supervision of two graduate students enrolled in the Master of Science (MSc) program in biophysics.
Experimental methods:
  • Cell culture methods;
  • FACS;
  • Confocal microscopy;
  • Immunohistochemistry;
  • DNA isolation, cloning, and sequencing;
  • Real-time PCR;
  • Western blotting;
  • Animal surgery, tissue and blood collection;
  • Comet assay;
  • Cytotoxicity assays;
  • Apoptosis detection methods;
  • Antioxidant activity assays;
  • HPLC and GC/MS;
  • ELISA.
Main publications:
Books
  • Konoplyannikov, M., Knyazev, O., Timashev, P., Baklaushev, V. (2022). Mesenchymal stem cell therapy for inflammatory bowel diseases. In: Haider, K.H. (ed.) Handbook of stem cell therapy. Springer, Singapore. ISBN: 978-981-19-2654-9. doi: 10.1007/978-981-19-2655-6_8.
  • Pavel Orekhov, Mikhail Konoplyannikov, Vladimir Baklaushev, Petr Timashev, and Anatoly Konoplyannikov (2020). Cell therapy for critical limb ischemia: current progress and future prospects. In: Haider, K.H. (ed.) Stem cells: from hype to hope, World Scientific. pp. 85-115.
  • Konoplyannikov A.G., Proskuryakov S.Ya., Konoplyannikov M.A. Survival of adult stem cells (Series "Stem cells - laboratory and clinical studies"). Nova Science Publishers, New York, 2010.
Magazine articles
  • Masalova O.V., Lesnova E.I., Kalsin V.A., Klimova R.R., Fedorova N.E., Kozlov V.V., Demidova N.A., Yurlov K.I., Konoplyannikov M.A., Nikolaeva T.N., Pronin A.V., Baklaushev V.P., Kushch A.A. Human mesenchymal stem cells modified with the hepatitis C virus NS5A gene induce a cellular immune response that exceeds the response to DNA immunization with this gene. Biology (Basel). 2023 May 30;12(6):792.
  • Sitnikov D., Revkova V., Ilyina I., Shatalova R., Komarov P., Struleva E., Konoplyannikov M., Kalsin V., Baklaushev V. Sensitivity of neuroblastoma and induced neuronal progenitor cells to high-intensity THz radiation. Int J Mol Sci. 31 Mar 2023;24(7):6558.
  • Sitnikov D.S., Revkova V.A., Ilina I.V., Gurova S.A., Komarov P.S., Struleva E.V., Konoplyannikov M.A., Kalsin V.A., Baklaushev V.P. Study of the genotoxic effect of high-intensity terahertz radiation on fibroblasts and tumor cells of the central nervous system. Journal of Biophotonics. Jan 2023;16(1):e202200212.
  • Konoplyannikov M.A., Eremina A.S., Kargina Yu.V., Le-Daigen I.M., Kharin A.Yu., Bazilenko T.Yu., Yusubalieva G.M., Revkova V.A., Matchuk O.N., Zamulaeva I.A., Abramova M.R., Kotova S.L., Timashev P.S., Baklaushev V.P., Timoshenko V.Yu. Mesoporous silica nanoparticles loaded with salinomycin for cancer treatment. Microporous and mesoporous materials. 2021; 328, 111473.
  • Sitnikov D.S., Pronkin A.A., Ilyina I.V., Revkova V.A., Konoplyannikov M.A., Kalsin V.A., Baklaushev V.P. Numerical modeling and experimental verification of thermal effects in living cells exposed to powerful pulses of THz radiation. Sci Rep. September 9, 2021; 11(1):17916.
  • Baklaushev V.P., Durov O.V., Kalsin V.A., Gulaev E.V., Kim S.V., Gubsky I.L., Revkova V.A., Samoilova E.M., Melnikov P.A., Karal-ogly D.D., Orlov S.V., Troitsky A.V., Chekhonin V.P., Averyanov A.V., Alfors J.E. Disease-modifying treatment of spinal cord injury using directly reprogrammed neural progenitor cells in non-human primates. World J Stem Cells 2021; 13(5): 452-469
  • Namestnikova D.D., Gubsky I.L., Revkova V.A., Sukhinich K.K., Melnikov P.A., Gabashvili A.N., Cherkashova E.A., Vishnevsky D.A., Kurilo V.V., Burunova V.V., Semkina A.S., Abakumov M.A., Gubsky L.V., Chekhonin V.P., Alfors J-E, Baklaushev V.P., Yarygin K.N. Intra-arterial stem cells Transplantation for experimental stroke in rats: real-time MR imaging of transplanted cells from their first passage through the brain, taking into account therapeutic effect. Front Neurosci March 2, 2021; 15: 641970.
  • Revkova V.A., Sidoruk K.V., Kalsin V.A., Melnikov P.A., Konoplyannikov M.A., Kotova S., Frolova A.A., Rodionov S.A., Smorchkov M.M., Kovalev A.V., Troitsky A.V., Timashev P.S., Chekhonin V.P., Bogush V.G., Baklaushev V.P. Spidroin silk fibers with bioactive extracellular protein motifs for neural tissue engineering. ASU Omega. May 30, 2021;6(23):15264-15273. PMID: 34151105; PMCID: PMC8210451.
  • Revkova V.A., Grebenik E.A., Kalsin V.A., Demina T.S., Bardakova K.N., Shavkuta B.S., Melnikov P.A., Samoilova E.M., Konoplyannikov M.A., Efremov Yu.M., Zhang S., Akopova T.A., Troitsky A.V., Timashev P.S., Baklaushev V.P. Potential of chitosan-g-oligo(L,L-lactide) hydrogel copolymer for neural stem cell differentiation. Tissue Eng Part A April 21, 2020
  • Samoylova EM, Baklaushev VP. Cell reprogramming preserving epigenetic age: advantages and limitations. Biochemistry (Moscow). 2020 Sep;85(9):1035-1047. PMID: 33050850.
  • Baklaushev VP, Bogush VG, Kal'sin VA, Sovetnikov NN, Samoylova EM, Revkova VA, Sidoryuk KV, Konoplyannikov MA, Timashev PS, Kotova SL, Yushkov KB, Averyanov AV, Troitsky AV, Alfors YuE. Tissue-engineered neural constructs consisting of neural progenitor cells, recombinant spidroin, and PRP for nerve tissue regeneration. Scientific Rep., 2019 Feb 28; 9 (1): 3161
  • Averjanov A, Koroleva I, Konoplyannikov M, Revkova V, Lesnyak V, Kalsin V, Danilevskaya O, Nikitin A, Sotnikova A, Kotova S, Baklaushev V. First human high-cumulative-dose stem cell therapy for idiopathic pulmonary fibrosis with rapid decline in lung function. STEM CELLS Translational Medicine, 2019
  • Baklaushev VP, Durov OV, Kim SV, Gulaev EV, Gubskiy IL, Konoplyannikov MA, Zabozlaev FG, Zhang S, Agrba VZ, Orlov SV, Lapin BA, Troitskiy AV, Averyanov AV, Alfors JE. Development of a spinal cord injury model in non-human primates using motor and somatosensory evoked potentials. J Neurobiology and Methods. 2019, Jan 01; 311:200–214.
  • Konoplyannikov M, Nurminskaya M. Novel therapeutic approaches to arterial calcification through transglutaminase and β-catenin inhibition. Curr Pharm Des. 2014; 20(37): 5811–20.
  • Beasley KE, Bagnard D, Lima F, Deasy SK, Nurminsky DI, Konoplyannikov M, Nurminskaya MV. Transglutaminase inhibitors attenuate vascular calcification in a preclinical model. Arterioscler Thromb Vasc Biol. 2013, Jan; 33 (1): 43–51.
  • Konoplyannikov M., Haider K.H., Lai W.K., Ahmed R.P., Jiang S., Ashraf M. Activation of diverse signaling pathways by ex vivo delivery of multiple cytokines for myocardial repair. Stem Cells Dev. 2013 Jan 15; 22 (2): 204-15.
  • Konoplyannikov A.G., Agrba V.Z., Kalsina S.Sh., Agaeva E.V., Konoplyannikov M.A., Kursova L.V. Mesenchymal stem cells as a key element of physiological regeneration and "emergency" restoration of the whole organism. Fundamental and Applied Aspects of Medical Primatology, 2011, Vol. 2: 200-206.
  • Durrani S., Konoplyannikov M., Haider H.H., Ashraf M. Skeletal myoblasts for cardiac regeneration (mini-review). Regenerative Medicine, November 2010; 5 (6): 919-32. Ma M, Ding S, Lundquist A, Sun H, Fang F, Konoplyannikov M, Berry S, Beltran LE, Chen G, Kovacic JC, Boehm M. MHC-I expression on ESC-derived vascular progenitor cells is critical for survival of syngeneic transplantation. Stem Cells. 2010 Sep; 28 (9): 1465-75.
  • Konoplyannikov M; Haider HH; Jiang S; Ahmed RPH, Ashraf M. Reversibility of ischemic cardiomyopathy using reprogrammed skeletal myoblasts expressing multiple therapeutic growth factor genes. Circulation (supplement). 2009; Vol. 120; Issue 18: S773-S774.
  • Wragg A, Mellad JA, Beltran LE, Konoplyannikov M, Sun H, Boozer S, Deans RJ, Mathur A, Lederman RJ, Kovacic JK, Boehm M. VEGFR1/CXCR4-positive progenitor cells modulate local inflammation and enhance tissue perfusion via an SDF-1-dependent mechanism. J Mol Med. 2008; 86 (11): 1221-32.
  • Tsyb AF, Konoplyannikov AG, Kolesnikova AI, Pavlov VV, Kaplan MA, Klyutch VE, Lepechina LA, Kal'sina S.Sh., Konoplyannikov MA, Proskuryakov S.Ya. The use of autologous bone marrow mesenchymal stem cells to obtain cell cultures used for transplantation in the treatment of various diseases. Cytokines and Inflammation, 2005, Vol. 4, No. 2, pp. 113-114.
  • Tsyb A.F., Konoplyannikov A.G., Kolesnikova A.I., Pavlov V.V., Konoplyannikov M.A. Production and medical use of cell cultures from autologous human bone marrow mesenchymal stem cells (MSCs). Cellular Technologies in Biology and Medicine. 2004; 1(2): 35-41
  • Maguire L*, Konoplyannikov M, Ford A, Maguire A, O'Brien N. Comparison of the cytotoxic effects of β-sitosterol oxide and cholesterol oxide, 7β-hydroxycholesterol, in cultured mammalian cells. British J Nutrition. 2003; 90: 1-10. This work was performed by L. Maguire under my supervision.
  • Konoplyannikov A.G., Proskuryakov S.I., Shtein L.V., Kucherenko N.G., Skvortsov V.G., Ivannikov A.I., Konoplyannikov M.A., Verkhovsky Yu.G. Inhibitory effect of phenytoin on nitric oxide production in tissues of gamma-irradiated mice. Biull Eksp Biol Med. 1999 Jun; 127(6): 648-50
  • Tronov V.A., Nikolskaya T.A., Konoplyannikov M.A., Lisitsyna T.A., Durnev A.D. Spontaneous death of mononuclear cells obtained from healthy donors and patients with systemic lupus erythematosus. Cytology. 1999; 41(5): 400-4
  • Tronov V.A., Nikolskaya T.A., Konoplyannikov M.A. DNA comets as markers of cell death. Biophysics. 1999 Mar-Apr; 44(2): 288-95
  • Tronov V.A., Konoplyannikov M.A., Nikolskaya T.A., Konstantinov E.M. Apoptosis of unstimulated human lymphocytes and DNA strand breaks induced by the topoisomerase II inhibitor etoposide (VP-16). Biochemistry (Moscow). 1999 Mar; 64(3): 345-52
  • Tronov V.A., Tereshchenko D.G., Konoplyannikov M.A. The mechanism of radiation death of human peripheral blood lymphocytes assessed by the DNA comet assay. Biophysics. 1998 Jan-Feb; 43(1): 115-24
  • Lisitsyna T.A., Tronov V.A., Konoplyannikov M.A., Durnev A.D., Ivanova M.M. Study of DNA damage in blood mononuclear cells in patients with systemic lupus erythematosus using the DNA comet assay. Biophysics. Experimental Biology. 1998 Jan; 125(1): 75-8
Takahiro Ochiya, professor
A researcher in the fields of biochemistry, genetics, molecular biology, and medicine. He works at Tokyo Medical University (Japan).
Some of Ochiya's research interests include:
  • Extracellular vesicles and their role in disease;
  • microRNAs and their regulation in disease;
  • Circular RNAs and their role in disease;
  • Molecular mechanisms associated with cancer;
  • RNA interference and gene delivery;
  • Liver physiology and pathology;
  • Research on cell adhesion molecules.

As of 2025, Ochiya received the "Leader in Biology and Biochemistry in Japan" award. He is the author of over 190 publications. His awards include the 2019 Special Prize from the International Society of Extracellular Vesicles (ISEV), among others.

Takahiro Ochiya works at Tokyo Medical University in Japan. His research focuses primarily on biochemistry, genetics, molecular biology, and medicine, with significant contributions in areas such as molecular biology, cancer research, surgery, pulmonology and respiratory medicine, and oncology.
Their research covers several key topics, including extracellular vesicles in disease, microRNAs in disease regulation, circular RNAs in disease, molecular mechanisms associated with cancer, RNA interference and gene delivery, liver physiology and pathology, and cell adhesion molecule research.
Ochiya has made significant contributions to the literature, including:
  • Minimum Information for Extracellular Vesicle Studies (MISEV2023): From Basic to Advanced Approaches, 2024, Journal of Extracellular Vesicles
  • MISEV Update: Evolving Minimum Requirements for Extracellular Vesicle Studies, 2021, Journal of Extracellular Vesicles
  • Key Aspects in the Development of Efficacy Tests for Therapeutic Use of Small Extracellular Vesicles Derived from Mesenchymal Stromal Cells, 2021, Cytotherapy
  • Pulmonary Fibrosis Therapy Using Human Bronchial Epithelial Cell-Derived Extracellular Vesicles via Inhibition of TGF-β-WNT Interaction, 2021, Journal of Extracellular Vesicles
  • Quantitative Proteomics Identifies Proteins Enriched in Large and Small Extracellular Vesicles, 2022, Molecular and Cellular Proteomics
Top publications:
  • Minimum Information Requirements for Extracellular Vesicle Research 2018 (MISEV2018): A Statement of the International Society on Extracellular Vesicles and an Update to the MISEV2014 Guidelines. Clotilde Teri, Kenneth W. Witwer, Elena Aikawa, Maria José Alcaraz. 12011 citations
  • Secretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells. Nobuyoshi Kosaka; Haruhisa Iguchi; Yusuke Yoshioka; Fumitaka Takeshita. Citations 1959 citations
  • Systemically Administered EGFR-Targeted Exosomes Deliver Antitumor MicroRNAs to Breast Cancer Cells. Shin Ichiro Ohno; Masakatsu Takanashi; Katsuko Sudo; Shinobu Ueda. 1,752 citations
  • Circulating microRNAs in Biological Fluids: A Novel Potential Biomarker for Cancer Diagnosis and Prognosis. Nobuyoshi Kosaka; Haruhisa Iguchi; Takahiro Ochiya. 1,567 citations
  • Use of Extracellular Vesicle-Based Therapies in Clinical Trials - ISEV Position Paper. Thomas Lehner; Mario Himona; Ludwig Aigner; Verena Börger. 1,451 citations
  • Neutral Sphingomyelinase 2 (nSMase2)-Dependent Exosomal Transfer of Angiogenic MicroRNAs Regulates Cancer Cell Metastasis. Nobuyoshi Kosaka; Haruhisa Iguchi; Keitaro Hagiwara; Yusuke Yoshioka. 800 citations
  • Metastatic brain cancer cells release extracellular vesicles containing microRNA-181c, which can disrupt the blood-brain barrier. Naumi Tominaga, Nobuyoshi Kosaka, Makiko Ono, Takeshi Katsuda. 748 citations
  • Adipose-derived mesenchymal stem cells as a source of human hepatocytes. Agnieszka Banas; Takumi Teratani; Yusuke Yamamoto; Makoto Tokuhara. 712 citations
  • Exosomes derived from bone marrow mesenchymal stem cells contain microRNA that promotes dormancy in metastatic breast cancer cells. Makiko Ono; Nobuyoshi Kosaka; Naumi Tominaga; Yusuke Yoshioka. 699 citations
  • microRNA as a novel immunoregulatory agent in breast milk. Nobuyoshi Kosaka; Hirohisa Izumi; Kazunori Sekine; Takahiro Ochiya. 611 citations
  • Ultrasensitive liquid biopsy of circulating extracellular vesicles using ExoScreen. Yusuke Yoshioka; Nobuyoshi Kosaka; Yuki Konishi; Hideki Ota. 565 citations
  • Human adipose-derived mesenchymal stem cells secrete functional neprilysin-associated exosomes. Takeshi Katsuda; Reiko Tsuchiya; Nobuyoshi Kosaka; Yusuke Yoshioka. 547 citations
  • Drug resistance is mediated by cancer stem cells and their niche. Marta Prieto-Vila; Ryo Y. Takahashi; Wataru Usuba; Isaku Kohama. 530 citations
  • New roles for long non-coding RNAs in cancer development. Anna Sanchez Calle, Yumi Kawamura, Yusuke Yamamoto, Fumitaka Takeshita. 527 citations
  • Systemic delivery of synthetic microRNA-16 suppresses the growth of metastatic prostate tumors by reducing the expression of multiple cell cycle genes. Fumitaka Takeshita; Lubna Patravala; Mitsuhiko Osaki; Ryo Y. Takahashi. 510 citations
  • Exosomal microRNAs in serum are a novel biomarker for colorectal cancer recurrence in humans. T. Matsumura; K. Sugimachi; H. Iinuma; Y. Takahashi. 483 citations
  • Efficient delivery of small interfering RNAs to metastatic bone tumors using atelocollagen in vivo. Fumitaka Takeshita, Yoshiko Minakuchi, Shunji Nagahara, Kimi Honma. 442 citations
  • Therapeutic Potential of Extracellular Vesicles Derived from Mesenchymal Stem Cells. Takeshi Katsuda; Nobuyoshi Kosaka; Fumitaka Takeshita; Takahiro Ochiya. 426 citations
  • Comparative Analysis of Extracellular Vesicle Markers in Different Types of Human Cancer. Yusuke Yoshioka, Yuki Konishi, Nobuyoshi Kosaka, Takeshi Katsuda. 416 citations
  • Use of Extracellular Vesicle-Based Therapies in Clinical Trials. Thomas Lehner; Mario Himona; Ludwig Aigner; Verena Börger. 5 citations
Olga Malinina, PhD, urologist, endocrinologist
  • Head and Chief Physician of the Doctor PROF Medical Center
Education
  • Diploma in General Medicine, Nizhny Novgorod State Medical Academy (2005)
  • Residency in Urology, Nizhny Novgorod State Medical Academy (2007)
  • Diploma in Andrology, Moscow State University of Medicine and Dentistry (2007)
  • Professional Retraining Diploma, Military Medical Institute of the Federal Security Service of Russia (2007)
  • Postgraduate Study, Nizhny Novgorod State Medical Academy (2011)
  • Candidate of Medical Sciences (2011)
Refresher courses:
  • Certificate in "Healthcare Organization and Public Health," Military Medical Institute of the Federal Security Service of Russia (2007)
  • "Endourology," Nizhny Novgorod State Medical Academy (2008)
  • "Thermal Treatment of Urological Patients," Fiuggi, Italy (2009)
  • "Ultrasound Diagnostics in Urology," Russian Medical Academy of Postgraduate Education of the Russian Ministry of Health (2010)
  • "Endocrine Aspects of Andrological Diseases," Peoples' Friendship University of Russia (2010)
  • "Chronic Pelvic Pain," France (2012)
  • "Healthcare Organization and Public Health," Institute for Advanced Studies of the Federal Medical and Biological Agency (2014)
  • "Aesthetic and Reconstructive Surgery of the Urogenital Region," I.M. Sechenov First Moscow State Medical University (2016)
  • Certificate Specialist in Ugology, I.M. Sechenov Moscow State Medical University (2017)
  • Certificate in Ugology, I.M. Sechenov Moscow State Medical University (2017)
  • Specialist Certificate in Clinical Electroneuromyography in the Diagnosis of Nervous System Diseases, Sesil Educational Center, Private Institution of Continuing Professional Education (2017)
  • Certificate in Clinical Electroneuromyography in the Diagnosis of Nervous System Diseases, Sesil Educational Center, Private Institution of Continuing Professional Education (2017)
  • Specialist Certificate in Healthcare Organization and Public Health, N.A. Semashko Federal State Budgetary Scientific University (2020)
  • Certificate in Healthcare Organization and Public Health, N.A. Semashko Federal State Budgetary Scientific University (2020)
  • Training Center Academy of Professional Development, Moscow, professional retraining in Endocrinology, endocrinologist, diploma of professional retraining and specialist certificate in Endocrinology, 2020
Work experience:
  • Urologist, private clinics, Moscow
  • Resident Physician, Urology Department, Zheleznodorozhnaya Hospital, Nizhny Novgorod (2005-2008)
  • Polyclinic of the Research Institute of Physicochemical Medicine and City Clinical Hospital No. 29 named after N.E. Bauman (2008-2019)
  • Private Medical Center "Doctor PROF" (2018-present)
Specialization in the treatment of the following diseases:
  • Pyelonephritis;
  • Cystitis;
  • Prostatitis;
  • Urinary incontinence;
  • Chronic pelvic pain;
  • Aesthetic urogynecology;
  • Transposition of the urethra in women using minimally invasive methods;
  • Male infertility;
  • Erectile dysfunction

Methods:
  • Urethral transposition in women using minimally invasive techniques;
  • Botulinum toxin therapy in urology;
  • Iotunica toxin therapy for pelvic floor muscles;
  • Intimate plastic surgery;
  • Treatment of premature ejaculation/penis enlargement;
  • Treatment of vulvodynia using injection methods
Contacts
If you have any questions, please write to us.
dokartest@gmail.com
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