• At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence. Zoya N Demidenko

     

    At concentrations that inhibit mTOR, resveratrol suppresses cellular senescence

    Abstract
    Here we demonstrated that, at cytostatic, near-toxic concentrations, resveratrol inhibited S6 phosphorylation and prevented the senescence morphology in human cells. Using a sensitive functional assay, we found that resveratrol partially prevented loss of the proliferative potential associated with cellular senescence. Resveratrol was less effective than rapamycin, because aging-suppression by resveratrol was limited by its toxicity at high concentrations. We discuss whether concentrations of resveratrol that inhibit mTOR (target of rapamycin) and suppress cellular senescence are clinically achievable and whether partial inhibition of mTOR by resveratrol might be sufficient to affect organismal aging. https://www.researchgate.net/scientific-contributions/39445053_Zoya_N_Demidenko
     

    oncotarget research Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .
     
    When general population mention modern medicine, precision plays one of the most significant roles and human lives are directly dependent on it. Hereby, any researches pertaining to medicine are necessary to comply with the top standards. The issue nowadays is that any results of researches can be posted online and used as a reference without being precisely verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this challenge and decided to create an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been established back in 2010. The major principle of this journal is related to Altmetric scores that are used as a quality indicator. That assists both readers and authors to validate publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website provides a complete publications list with respective scores higher than 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the necessary assistance to anyone, who has interest in oncology.
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This study was published back in 2018 by Oncotarget and completed by different experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and provides an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The paper has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are aiming to comprehend the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Likewise, the paper about melanoma, was utilized for citations in various news articles 69 times. In addition, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their news on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
    Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This research has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get useful scientific facts. Oncotarget is proud to have the ability to share with online viewers this highly appreciated and high-quality information, that is trustworthy and reliable.
     

     


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  • Cellular quiescence caused by the Mdm2 inhibitor Nutlin-3A. Zoya N Demidenko

     

    Cellular quiescence caused by the Mdm2 inhibitor Nutlin-3A

    Abstract
    Cellular senescence is characterized by irreversible loss of proliferative potential and a large, flat cell morphology. Ectopic p21 and doxorubicin induced cellular senescence in HT1080 and WI-38-tert cell lines. In the same cell lines, the Mdm2 inhibitor nutlin-3a induced p53 but, unexpectedly, caused quiescence (reversible arrest) with a small cell morphology. We discuss that Mdm antagonists could be used in combination with chemotherapy to reversibly arrest normal cells, thus protecting them during chemotherapy of cancer (cyclotherapy). https://www.researchgate.net/scientific-contributions/39445053_Zoya_N_Demidenko

    oncotarget impact Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .
     
     
    When people mention today’s medicine, accuracy plays one of the most important roles and people’s lives are literally dependent on it. Likewise, any researches related to medicine are required to meet the highest standards. The problem today is that any conclusions of researches can be published online and used as a reference without being adequately verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this issue and attempted to come up with an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been founded back in 2010. The major principle of this journal is based on Altmetric scores that are used as a quality measure. That assists both readers and authors to validate publications with Altmetric Article Reports that provide “real-time feedback containing data summary related to a particular publication.” Oncotarget website provides a full publications list with respective scores above 100 as well as reports mentioned above. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it provides the necessary assistance to anyone, who has interest in oncology.
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was released back in 2018 by Oncotarget and written by various experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The publication has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that most of readers are aiming to understand the very meaning of it. Based on the Altmetric website, the score relates to “how many people have been exposed to and engaged with a scholarly output.” Hence, the paper about melanoma, was used for citations in various news articles 69 times. In addition, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
    Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This research has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a short overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is proud to have the ability to share with online customers this highly appreciated and high-quality information, that is trustworthy and reliable.

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  • Pseudo-DNA damage response in senescent cells. Zoya N Demidenko

     

    Pseudo-DNA damage response in senescent cells

    Abstract
    Cellular senescence is currently viewed as a response to DNA damage. In this report, we showed that non-damaging agents such as sodium butyrate-induced p21 and ectopic expression of either p21 or p16 cause cellular senescence without detectable DNA breaks. Nevertheless, senescent cells displayed components of DNA damage response (DDR) such as gammaH2AX foci and uniform nuclear staining for p-ATM. Importantly, there was no accumulation of 53BP1 in gammaH2AX foci of senescent cells. Consistently, comet assay failed to detect DNA damage. Rapamycin, an inhibitor of mTO R, which was shown to suppress cellular senescence, decreased gammaH2AX foci formation. Thus, cellular senescence leads to activation of atypical DDR without detectable DNA damage. Pseudo-DDR may be a marker of general over-activation of senescent cells.

    oncotarget impact Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .
     
    Mikhail (Misha) V. Blagosklonny graduated with an MD and PhD from First Pavlov State Medical University of St. Petersburg, Russia. Dr. Mikhail V. Blagosklonny has then immigrated to the United States, where he received the prestigious Fogarty Fellowship from the National Institutes of Health. During his fellowship in Leonard Neckers’ lab at the National Cancer Institute (NCI), he was a co-author of 18 publications on various biomedical themes, including targeting HSP90, p53, Bcl2, Erb2, and Raf-1. He also was the last author for a clinical phase I/II trial article. 
    After authoring seven papers during a brief yet productive senior research fellowship in the El-Deiry Cancer Research Lab at the University of Pennsylvania, Dr. Blagosklonny returned to NCI to work with Tito Fojo. Together, they published 26 papers. Moreover, Dr. Blagosklonny published many of experimental research papers and theoretical papers as sole author. The abovementioned sole-author articles discussed two crucial topics. The first of these discussed selectively killing cancer cells with deregulated cell cycle or drug resistance via verifying their resistance. The outcomes and underlying notion were so revolutionary that they were incorrectly cited by other scientists as “reversal of resistance,” even though the publication was titled, “Exploiting of drug resistance instead of its reversal.” One big supporter of this concept was the world-famous scientist Arthur Pardee, with whom Dr. Blagosklonny co-authored a joint publication in 2001.
    The second theme throughout Dr. Blagosklonny’s sole-author articles is a research method to develop knowledge by bringing several facts together from seemingly irrelevant areas. This results in new notions with testable forecasts, which in turn can be “tested” via analyzing the literature further. Likewise, the concept was co-authored by Arthur Pardee in a 2002 article in Nature. The first success of the new research methodology was the description of the feedback regulation of p53, as confirmed by the discovery of mdm2/p53 loop; and the explanation why mutant p53 is always overexpressed, published in 1997. The most important result revealed by Dr. Blagosklonny’s research methodology is the hyperfunction (or quasi-programmed) theory of aging and the revelation of rapamycin as an exclusively well-tolerated anti-aging drug, published in 2006. As mentioned in Scientific American, Michael Hall, who discovered mTOR in 1991, gives Dr. Blagosklonny credit for “connecting dots that others can’t even see.”
    In 2002, Dr. Blagosklonny became associate professor of medicine at New York Medical College. He agreed to accept responsibilities as a senior scientist at Ordway Research Institute in Albany, New York, in 2005, before receiving another position at Roswell Park Cancer Institute as professor of oncology in 2009.
    Since coming to Roswell Park Comprehensive Cancer Center in 2009, Dr. Blagosklonny has studied the prevention of cancer (an age-related disease) via stopping organism aging - in other words, “preventing cancer via staying young.” His laboratory closely worked together with Andrei Gudkov’s and conducted research on the suppression of cellular senescence, namely suppression of cellular conversion from healthy quiescence to permanent senescence. This led to the discovery of additional anti-aging medicines beyond rapamycin. The cell culture studies were complemented by studies in mice, including several models like normal and aging mice, p53-deficient mice, and mice on a high-fat diet.
    Dr. Blagosklonny has also published extensively on the stoppage of cellular senescence via rapamycin and other mTOR inhibitors, life extension and cancer stoppage in mice, and combinations of anti-aging medicines to be taken by humans. A rapamycin-based combination of seven clinically available medications has been named the “Koschei Formula” and is now used for the treatment of aging in patients at the Alan Green Clinic in Little Neck, New York. 

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  • Antidepressants synergize with chemotherapy against cancerstem cells

     
    Antidepressants synergize with chemotherapy against cancerstem cells 


    In a recent report [1], the antidepressant drug desmethylclomipramine has shown an interesting synergistic effect with cisplatin, gemcitabine or placlitax on lung cancer stem cells. The fact that antidepressant drugs potentiate chemotherapy in poorly responding cancer is of major relevance, and opens up potential innovative therapeutic effects. But what are the underlying molecular mechanisms for this therapy? Can this be transferred to other poorly responding cancers? We originally identified the HECT containing ITCH as the ubiquitin E3 ligase responsible for the degradation of p63 and p73, and, based on that, we performed an high throughput (HTS) screening using an ELISA-based HTS with purified recombinant proteins and GST-autoubiquitylation as readout for ITCH activity [2]. The automated HTS on a 22,000 compound library was robust, according to an average recorded Z’ of 0.7 (range 0.5-0.7), and resulted in the identification of 46 compounds showing <50% residual activity, 20 of which were confirmed at single point, and 6 of these showed a dose-dependent inhibition of ITCH. The most active validated inhibitors were the antidepressant drugs clomipramine, norclomipramine and their active metabolite desmethylclomipramine [2]. Interestingly, the validation and analysis of the results revealed clomipramine as a regulator of autophagy [2-3]. This was an intriguing observation as clomipramine has been used for over 40 years for the treatment of patients with psychiatric disorders, with a long-standing record of tolerance and safety. Antidepressants are known to act on the serotonin uptake, so the inhibition of an E3 ligase would suggest that either there is an alternative mode of action, or that an ITCH-related E3 ligase is involved in the process, for example as a regulator of the receptor or of the intracellular recycling pathway. Still, the regulation of autophagy opens interesting opportunities for cancer therapy based on the evidence that autophagy inhibitors potentiate the effect of chemotherapy. Indeed several clinical trials are under way in phase I-II using chloroquine to potentiate chemotherapy (e.g. ClinicalTrials.gov Identifier: NCT01510119, NCT01480154, NCT01023477, NCT02421575, NCT01649947). In vitro, clomipramine does potentiate the effect of chemotherapeutic agents on differen bladder, breast, prostate cancer cell lines [2]. However, to be more effective, this effect should be tested on cancer stem cells. And indeed, the work of BongiornoBorbone et al. [1] revealed that clomipramide compounds have a significant effect on the growth properties of lung cancer stem cells isolated from nonsmall-cell lung cancers’ surgical specimens. Desmethylclomipramine, by interfering with the autophagic flux and blocking the degradation of the autophagic cargo, decreases the stemness potential of cancer stem cells and increases the cytotoxic effect of conventional chemotherapeutic agents on lung cancer [1]. To check whether this effect is due to a selective inhibition of ITCH itself and not to another off target effect, including the inhibition of other HECTcontaining E3 ubiquitin ligases, the authors have silenced ITCH. The results indicate that the silencing of ITCH is sufficient to phenocopy the effect of clomipramide. Moreover, the analysis of the expression of ITCH in two distinct data sets of lung adenocarcinoma (GSE31210 and GSE11969) demonstrates that the expression of ITCH is a significant negative prognostic marker, affecting long term Kaplan-Maier survival. https://www.aging-us.com/issue/v7i12


    When general population refer to contemporary medicine, precision plays one of the most crucial roles and people’s lives are directly dependent on it. Hence, any researches pertaining to medicine are required to comply with the top standards. The problem today is that any recommendations of researches can be published online and used as a reference without being adequately verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this issue and tried to come up with an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been founded back in 2010. The key principle of this journal is based on Altmetric scores that are used as a quality indicator. That helps both readers and authors to verify publications with Altmetric Article Reports that create “real-time feedback containing data summary related to a particular publication.” Oncotarget website provides a complete publications list with respective scores higher than 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it provides the necessary assistance to anybody, who has interest in oncology.
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This paper was released back in 2018 by Oncotarget and completed by several experts from Hollywood Private Hospital, Edith Cowan University, Dermatology Specialist Group, St. John of God Hospital and The University of Western Australia. The introduction of the study discusses “recent data shows that Australians are four times more likely to develop a cancer of the skin than any other type of cancer”, and shares an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The paper has got an Altmetric score of 594. Mikhail (Misha) Blagosklonny realizes that majority of readers are aiming to comprehend the very meaning of it. Based on the Altmetric website, the score indicates “how many people have been exposed to and engaged with a scholarly output.” Hereby, the paper about melanoma, was used for citations in different news articles 69 times. Besides that, it was quoted in 2 online blogs, as well as 25 Tweets on Twitter and 1 Facebook post. FOX23 of Tulsa, Oklahoma has headlined their report on July 20, 2018 as “New blood test could detect skin cancer early”, using the main content of Australia study 
    Another Oncotarget’s study with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This research has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is glad to have the chance to share with online viewers this highly appreciated and top-quality information, that is trustworthy and reliable.
     
    oncotarget removed from pubmed Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .

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  • Hormesis does not make sense except in the light of TOR-driven aging

     

    Hormesis does not make sense except in the light of TOR-driven aging



    Abstract

    Weak stresses (including weak oxidative stress, cytostatic agents, heat shock, hypoxia, calorie restriction) may extend lifespan. Known as hormesis, this is the most controversial notion in gerontology. For one, it is believed that aging is caused by accumulation of molecular damage. If so, hormetic stresses (by causing damage) must shorten lifespan. To solve the paradox, it was suggested that, by activating repair, hormetic stresses eventually decrease damage. Similarly, Baron Munchausen escaped from a swamp by pulling himself up by his own hair. Instead, I discuss that aging is not caused by accumulation of molecular damage. Although molecular damage accumulates, organisms do not live long enough to age from this accumulation. Instead, aging is driven by overactivated signal-transduction pathways including the TOR (Target of Rapamycin) pathway. A diverse group of hormetic conditions can be divided into two groups. “Hormesis A” inhibits the TOR pathway. “Hormesis B” increases aging-tolerance, defined as the ability to survive catastrophic complications of aging. Hormesis A includes calorie restriction, resveratrol, rapamycin, p53-inducing agents and, in part, physical exercise, heat shock and hypoxia. Hormesis B includes ischemic preconditioning and, in part, physical exercise, heat shock, hypoxia and medical interventions.

     

    Paraphrasing the famous quote “Nothing in Biology Makes Sense Except in the Light of Evolution”, one can say that nothing in aging makes sense except in the light of TOR-driven quasi-programmed aging, a continuation of developmental growth driven by growth-promoting pathways. And life span extension by mild damage makes no sense, if aging is a decline caused by accumulation of damage.

    Conventional view on aging

    It is believed that aging is a decline, deterioration due to accumulation of random molecular and cellular damage caused by free radicals, radiation, stresses, pathogens, toxins, carcinogens, mistakes in replication/translation, protein misfolding and even mechanical forces. If aging is caused by damage, then damaging stresses would accelerate aging (Figure 1A). However, mild stresses (including oxidative stress) can extend life span in different species [1-30].

    Paradoxical links between damage and aging

    Figure 1. Paradoxical links between damage and aging. (A) If agings is caused by damage, then hormetic damage should accelerate aging. Also food by providing resources should becelerate aging. Both prediction contradict observations, making the model incorrect. (B) Paradoxical model assumes that (a) damage decrease damage and (b) the less resources (food), the more resources can be used for anti-aging repair. These assumptions are paradoxical but nevertheless are needed to fit predictions and observations. Paradoxical links are shown in red.

    How this can be reconciled with the conventional theory of aging. There are 3 options:

    First, hormesis is an artefact. Certainly there are many artefacts in this field. Yet, there are also solid data especially on the life-extension by calorie restriction, ROS, heat shock and phytochemicals.

    Second, the phenomenon of hormesis rules out the conventional theory of aging. Furthermore, as it was already reviewed, “damage-induced aging” theory was ruled out by other evidence too [31-38]. It was discussed that aging is not the life-long accumulation of molecular damage, is not decline and is not caused by reactive oxygen species (ROS) [35].

    Third, instead of rejecting the damage-induced theory, paradoxical assumptions were suggested to reconcile it with hormesis (Figure 1B). To explain extension of lifespan by mild and repeated stresses, it was suggested that (a) mild stresses stimulate maintenance and repair pathways and (b) cause adaptation of cells and the ability to tolerate stronger stresses. Let us briefly review the attempt to reconcile hormesis and molecular damage-driven aging. https://www.aging-us.com/article/100411/text

     

    oncotarget acceptance rate Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .
     
    Mikhail (Misha) V. Blagosklonny graduated with an MD and PhD from First Pavlov State Medical University of St. Petersburg, Russia. Dr. Mikhail V. Blagosklonny has then immigrated to the United States, where he received the prestigious Fogarty Fellowship from the National Institutes of Health. During his fellowship in Leonard Neckers’ lab at the National Cancer Institute (NCI), he was a co-author of 18 publications on various biomedical themes, including targeting HSP90, p53, Bcl2, Erb2, and Raf-1. He also was the last author for a clinical phase I/II trial article. 
    After authoring seven papers during a brief yet productive senior research fellowship in the El-Deiry Cancer Research Lab at the University of Pennsylvania, Dr. Blagosklonny returned to NCI to work with Tito Fojo. Together, they published 26 papers. Moreover, Dr. Blagosklonny published many of experimental research papers and theoretical papers as sole author. The abovementioned sole-author articles discussed two crucial topics. The first of these discussed selectively killing cancer cells with deregulated cell cycle or drug resistance via verifying their resistance. The outcomes and underlying notion were so revolutionary that they were incorrectly cited by other scientists as “reversal of resistance,” even though the publication was titled, “Exploiting of drug resistance instead of its reversal.” One big supporter of this concept was the world-famous scientist Arthur Pardee, with whom Dr. Blagosklonny co-authored a joint publication in 2001.
    The second theme throughout Dr. Blagosklonny’s sole-author articles is a research method to develop knowledge by bringing several facts together from seemingly irrelevant areas. This results in new notions with testable forecasts, which in turn can be “tested” via analyzing the literature further. Likewise, the concept was co-authored by Arthur Pardee in a 2002 article in Nature. The first success of the new research methodology was the description of the feedback regulation of p53, as confirmed by the discovery of mdm2/p53 loop; and the explanation why mutant p53 is always overexpressed, published in 1997. The most important result revealed by Dr. Blagosklonny’s research methodology is the hyperfunction (or quasi-programmed) theory of aging and the revelation of rapamycin as an exclusively well-tolerated anti-aging drug, published in 2006. As mentioned in Scientific American, Michael Hall, who discovered mTOR in 1991, gives Dr. Blagosklonny credit for “connecting dots that others can’t even see.”
    In 2002, Dr. Blagosklonny became associate professor of medicine at New York Medical College. He agreed to accept responsibilities as a senior scientist at Ordway Research Institute in Albany, New York, in 2005, before receiving another position at Roswell Park Cancer Institute as professor of oncology in 2009.
    Since coming to Roswell Park Comprehensive Cancer Center in 2009, Dr. Blagosklonny has studied the prevention of cancer (an age-related disease) via stopping organism aging - in other words, “preventing cancer via staying young.” His laboratory closely worked together with Andrei Gudkov’s and conducted research on the suppression of cellular senescence, namely suppression of cellular conversion from healthy quiescence to permanent senescence. This led to the discovery of additional anti-aging medicines beyond rapamycin. The cell culture studies were complemented by studies in mice, including several models like normal and aging mice, p53-deficient mice, and mice on a high-fat diet.
    Dr. Blagosklonny has also published extensively on the stoppage of cellular senescence via rapamycin and other mTOR inhibitors, life extension and cancer stoppage in mice, and combinations of anti-aging medicines to be taken by humans. A rapamycin-based combination of seven clinically available medications has been named the “Koschei Formula” and is now used for the treatment of aging in patients at the Alan Green Clinic in Little Neck, New York. 

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