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Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs

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Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs Abstract Metabolomic fingerprint of breast cancer cells treated with the antidiabetic drug metformin revealed a significant accumulation of 5-formimino-tetrahydrofolate, one of the tetrahydrofolate forms carrying activated one-carbon units that are essential for the de novo synthesis of purines and pyrimidines. De novo synthesis of glutathione, a folate-dependent pathway interconnected with one-carbon metabolism was concomitantly depleted in response to metformin. End-product reversal studies demonstrated that thymidine alone leads to a significant but incomplete protection from metformin's cytostatic effects. The addition of the substrate hypoxanthine for the purine salvage pathway produces major rightward shifts in metformin's growth inhibition curves. Metformin treatment failed to activate the DNA repair protein ATM kinase and the met

Cancer Genomics and Biology 2015 – Meeting Report

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Cancer Genomics and Biology 2015 – Meeting Report ABSTRACT The Cancer Genomics and Biology 2015 meeting embodied a three way collaboration among colleagues from the Global Cancer Genomics Consortium (GCGC), the Unifaith Cancer Institute China and Jiujiang University of China. The meeting marks the fifth and the last meeting of GCGC, which was formed in 2010.  Previous four GCGC meetings have been held at the Tata Memorial Center- Mumbai, Institute of Molecular Medicine-Lisbon, and Graduate Medical School Kyoto University-Kyoto. In contrast to the genomic themes of the previous meetings, the 2015 conference theme was at the interface of laboratory and translation research and emerging therapeutics as reflected in the shared interests of all three collaborative entities – Cancer Genomics and Biology 2015. This year’s conference was co-organized by the Jiujiang University at the Run Run Shaw building, Jiujiang University, Jiujiang City, China, on November 13 and 14, 2015. The conference a

Editor-in-Chief Oncotarget

Mikhail Blagosklonny Location  New York ,  New York ,  United States Regions  Greater New York Area ,  East Coast ,  Northeastern US Gender  Male Website  about.me/mikhailblagosklonny Facebook  View on Facebook LinkedIn  View on LinkedIn Twitter  View on Twitter Mikhail (Misha) V. Blagosklonny, MD, Ph.D. Professor of Oncology at Roswell Park Cancer Institute, Buffalo, NY, USA. His research interests range from molecular and cellular biology to clinical investigations and specifically include oncogenes and tumor suppressors, signal transduction, cell cycle, mitosis, apoptosis, anticancer therapeutics with emphasis on translation of basic science into new anticancer strategies such as exploiting cancer cell cycling and drug resistance for selective protection of normal cells. He has extended this approach to other age-related diseases and aging itself, thus revealing anti-aging drugs such as rapamycin to be used today (Cell Cycle, 2006, 5 : 2087 - 2102). He is an author of hyper-function

Rejuvenating immunity: “anti-aging drug today” eight years later

Rejuvenating immunity: “anti-aging drug today” eight years later https://doi.org/10.18632/oncotarget.3740 Mikhail V. Blagosklonny 1 1  Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA Correspondence to: Mikhail V. Blagosklonny, email:  mikhail.blagosklonny@roswellpark.org Keywords : mTOR, TOR, gerosuppression, rapalogs, lifespan, longevity, diseases Received : February 16, 2015  Accepted : March 28, 2015  Published : March 31, 2015 ABSTRACT The 2014 year ended with celebration: Everolimus, a rapamycin analog, was shown to improve immunity in old humans, heralding ‘a turning point’ in research and new era in human quest for immortality. Yet, this turning point was predicted a decade ago. But what will cause human death, when aging will be abolished? https://www.oncotarget.com/article/3740/ When public refer to modern medicine, precision plays one of the most crucial roles and people’s lives are literally dependent on it. Likewise, any researches pertaining to medici

From rapalogs to anti-aging formula

From rapalogs to anti-aging formula   https://doi.org/10.18632/oncotarget.18033 Mikhail V. Blagosklonny 1 1  Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA Correspondence to: Mikhail V. Blagosklonny, email:  mikhail.blagosklonny@roswellpark.org email:  blagosklonny@rapalogs.com   Keywords : lifespan, longevity, rejuvenation, health, diseases Received : February 17, 2017  Accepted : April 30, 2017  Published : May 22, 2017 ABSTRACT Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism. Here, I further suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signa

Professor of Oncology

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Mikhail Blagosklonny Professor of Oncology, RPCI and Editor-in-Chief, Oncotarget Verified email at oncotarget.com https://scholar.google.com/citations?user=REO9YogAAAAJ&hl=en Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009 G Kroemer, L Galluzzi, P Vandenabeele, J Abrams, ES Alnemri, ... Cell death & differentiation 16 (1), 3-11 3039 2009 Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012 L Galluzzi, I Vitale, JM Abrams, ES Alnemri, EH Baehrecke, ... Cell Death & Differentiation 19 (1), 107-120 2316 2012 Stabilization of wild-type p53 by hypoxia-inducible factor 1α WG An, M Kanekal, MC Simon, E Maltepe, MV Blagosklonny, LM Neckers Nature 392 (6674), 405-408 995 1998 Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 L Galluzzi, I Vitale, SA Aaronson, JM Abrams, D Adam, P Agostinis, ... Cell Death & Differentiation