• Par oncojornal02 dans Accueil le 11 Juin 2020 à 10:17

    Put on your thinking cap: G‐quadruplexes, helicases, and telomeres

     
    June 11, 2020
    Put on your thinking cap:  G‐quadruplexes, helicases, and telomeres

    Understanding how G-quadruplex (G4) DNA structures that form in G-rich tracts of the genome affect chromosomal stability and processes such as copying the genetic information (DNA replication) or decoding the information (RNA transcription) has posed a significant challenge to researchers in the field. Although historically there has been some controversy over the existence of G4 DNA structures in vivo, emerging evidence suggests that they are indeed likely to form and have cellular consequences. In a recent study, Smith et al. investigated a role of G4 DNA in telomere capping [1], i.e., the adaptation of a nucleoprotein structure that prevents the chromosomal DNA ends from being recognized as DNA breaks and protects them from becoming degraded or fused. Telomere capping is a fairly complex process since a number of proteins have been shown to bind telomeric single-stranded or double-stranded DNA at the chromosome end. Moreover, the ability of telomeric DNA to form a variety of conformations including tloops and G-quadruplexes adds to the complexity of how competing proteins and DNA structures influence the structural topology and metabolism of chromosome ends [2]. Using genetic and pharmacological approaches, Smith et al. showed that under conditions that stabilize G4 DNA structures, which form from a guanine-rich telomeric ssDNA exposed in a yeast temperature sensitive cdc13-1 mutant, telomere capping is in turn enhanced and phenotypes associated with capping defects are suppressed [1]. Conversely, telomere uncapping occurs under conditions that dissuade the formation of telomeric G4 DNA in the cdc13-1 mutant. The authors proposed a model in which G4 DNA structure enables G4 DNA binding proteins to further stabilize the telomere end by binding  to G-quadruplex DNA, thereby preventing 5’ to 3’ exonucleolytic resection when the normal protein that blocks telomeric end processing is defective. Rad53- mediated checkpoint activation is also dampened, permitting suppression of the growth defects characteristic of the cdc13-1 mutant at the nonpermissive temperature. https://www.aging-us.com/issue/v3i4

    impact factor oncotarget 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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  • Par oncojornal02 dans Accueil le 11 Juin 2020 à 09:39

    Spontaneous inactivating p53 mutations and the “selfish cell”

     
    June 11, 2020
    Spontaneous inactivating p53 mutations and the “selfish cell”


    Odell et al. reported in Aging that murine embryo fibroblasts (MEFs) undergo p53 mutations and subsequent immortalizations in culture. This “release from cell cycle arrest” occurs in murine fibroblasts with a humanized or murine WT p53 [1]. The authors also noted that the cultured cells had frequently sustained a mutation matching a human tumor p53 mutation. Jang, et al. also reported spontaneous “immortalization and tumorigenic transformation” of human keratinocytes associated with p53 inactivating mutations [2]. Odell’s remarkable findings are of great interest to us and support a recently proposed hypothesis for tumorigenesis. We and others have proposed that cells seek to survive, in a Darwinian sense [3,4,5]. Specifically we have presented evidence to suggest that while WT p53 might primarily function as the “guardian of the genome” (inducing cells to undergo apoptosis or cell cycle arrest under stress), the WT p53 gene sequence is evolutionarily maintained such that it is susceptible to inactivating mutations and consequent cell survival (with the untoward result of tumorigenesis). The facts that these mutations occur spontaneously and frequently are the exact mutations seen in human cancers lends key support to this notion. Taken together, spontaneous mutations allowing cell survival and tumorigenesis might be referred to as the “Selfish Cell Theory” in recognition of Dawkin’s The Selfish Gene published in 1976. 

    oncoscience impact factor Misha Blagosklonny
    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. 
     
     
    When people refer to contemporary medicine, precision plays one of the most crucial roles and people’s lives are directly dependent on it. Hence, any researches related to medicine are necessary to comply with the top standards. The problem today is that any outcomes of researches can be published online and used as a reference without being properly checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this problem and attempted to develop an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been established back in 2010. The key principle of this journal is related to Altmetric scores that are used as a quality indicator. That assists both readers and authors to quality-check publications with Altmetric Article Reports that provide “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a complete publications list with corresponding scores above 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it provides the necessary help to anyone, who has interest in oncology.
    “A diagnostic autoantibody signature for primary cutaneous melanoma” has the Altmetric score of 594. This article was released back in 2018 by Oncotarget and written 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 mentions that “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 article 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 indicates “how many people have been exposed to and engaged with a scholarly output.” Hereby, the article about melanoma, was used for citations in various 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 article has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a short overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is proud to have the chance to share with online viewers this highly appreciated and top-quality information, that is trustworthy and reliable.
    https://endnote.com/style_download/oncotarget/

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  • Par oncojornal02 dans Accueil le 11 Juin 2020 à 09:38

    Linking Nutrition, Maturation and Aging: From Thrifty Genes to the Spendthrift Phenotype

     
    June 11, 2020

    Linking Nutrition, Maturation and Aging: From Thrifty Genes to the Spendthrift Phenotype



    Introduction

    Nearly 50 years ago geneticist James Neel famously proposed that “thrifty genes” were important contributors to the rising prevalence of diabetes [1]. Such genes promote efficient use and conservation of food energy, he theorized, and thus were favored by natural selection to help our ancient ancestors cope with famines. Now widespread in various populations, they predispose to obesity and diabetes, abetting a tendency to prepare for famines that never come.

    Though intuitively appealing, the theory has often been challenged. Perhaps the strongest objection has been that there's little evidence our ancestors faced frequent, high-mortality famines that would have selected for thrifty genotypes [2]. Recently, the theory's proponents have countered that thrifty genes' selective advantage probably had more to do with fertility than survival—women who rapidly deposited fat during periods of adequate nutrition would have been able to sustain relatively high reproductive rates during lean times and make larger contributions to the gene pool [3,4]. Here I propose an extension of this reproduction-centered version of Neel's theory that bears on aging. One of my key premises is that many windows of opportunity for reproductive booms occurred during the Holocene as agricultural innovations spread, periodically increasing food availability between times of nutritional stress. The periods of plenty selected for genotypes capable of rapidly ramping up fecundity as food intake increased. Sexually mature females would have quickly added fat—a certain level of maternal body fat is critical for reproduction [5]. Prepubertal females would have similarly added fat in conjunction with the acceleration of development and earlier onset of sexual maturity.

    I believe the boom times' selection of genotypes prone to nutrition-cued accelerated development is having an especially problematic effect today because of widespread childhood overnutrition. Accelerated development, which enhanced reproductive success in the past, now has a pro-aging effect with rapidly growing costs. Indeed, when viewed through the lens of the antagonistic pleiotropy theory of aging [6], this effect seems anything but thrifty: It predisposes toward what might be called the spendthrift phenotype, characterized by chronic activation of pro-growth pathways—notably those involving mTOR, insulin, and insulin-like growth factor-1—that support rapid development and sexual maturation but that also underlie later senescence [7]. The modern fallout encompasses a much broader array of age-associated ills than the diabetes that prompted Neel's original hypothesis. Indeed, the spendthrift phenotype may well increase the age-associated risks of most if not all diseases of aging, like the ruinous adult legacy of flush, fast-living youth.

     
    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. 
     
     
    When people speak of today’s medicine, precision plays one of the most significant roles and human lives are literally dependent on it. Likewise, any researches related to medicine are necessary to meet the highest standards. The challenge nowadays is that any recommendations of researches can be shared online and used as a reference without being precisely verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this problem and decided 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 indicator. That assists both readers and authors to validate publications with Altmetric Article Reports that create “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a complete publications list with corresponding scores above 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the required help 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 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 provides an insight on melanoma that “is curable by surgical excision in the majority of cases, if detected at an early stage.”
    The article 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 indicates “how many people have been exposed to and engaged with a scholarly output.” Hence, the paper about melanoma, was used for citations in different 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 article has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have come across a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive useful scientific facts. Oncotarget is happy to have the chance to share with online customers this highly appreciated and high-quality information, that is trustworthy and reliable.

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  • Par oncojornal02 dans Accueil le 11 Juin 2020 à 09:38

    Cellular proteome, coregulators, endocrine system and the human brain: the Regulatory biology of humanism

     
    June 11, 2020

    Cellular proteome, coregulators, endocrine system and the human brain: the Regulatory biology of humanism



    The Regulatory Biology of Humanism

    There is little doubt that humans are the masters of their known universe. A lively debate could center on why this is so. Although humans have many specialized physical features, such as the marvelous human hand and fingers, other species also have distinguishing features that outclass similar physical features of humans – features such as more acute hearing, smell, or sight. There is little debate, however, that our crowning evolutionary achievement is the human brain. There appears to be no species or other mammal capable of competing with our ability to reason, plan, calculate, and emote. How did this impressive jump in evolution occur? Although not a question that can be answered by hard data, it remains a lively topic for discussion. In my opinion, the two most advanced biologic ‘systems’ that we humans have are (1) the central and peripheral endocrine system and (2) the cellular proteome. It is these two points I would like to further develop in this Perspective.

    Our endocrine system and our cellular proteome form an intimate connection with the human brain to construct a powerful troika responsible for our unique capacities as a species. This partnership likely co-evolved to cope with the diversity of our environment and with the intense metabolic demands required to nurture, operate and preserve the human brain. Hormones comprise the endocrine system. The word itself emanates from the Latin word ‘hormo’ which means to ‘set in motion’. Hormones do that in great fashion, as they move all cells and organs of our body into action. Our cells and tissues would be relatively inert without them. These chemical regulators control our genesis, development, maturation, and then function in adulthood to support the growth and metabolic functions of all organs, including the brain and its peripheral links. Hormones are not unique to humans, however. They exist even in plants, worms and flies. Mammals, however, have a more highly developed endocrine system that contains many specialized hormones. It is uncertain as to how many hormones actually exist in mammals. We often list ~50 of the more common hormones, but the actual numbers likely are in the hundreds, and perhaps will reach closer to a thousand when finally all are identified. At an earlier period in the field of Endocrinology, we defined hormones as ‘chemical signals released from an organ into the blood stream to act on distant target tissues. Clearly, this definition has been outdated for some years, and a compete list of hormones probably should include a variety of paracrine and autocrine chemical signals, including growth factors, immune cell secretions, cytokines, chemokines, and perhaps even neurotransmitters. There is no greater diversity of environmental signals and physical and emotional stresses for a mammal to bear than those to which a human being has been subjected over the course of evolution.


    When people discuss modern medicine, precision plays one of the most important roles and human lives are directly dependent on it. Hereby, any researches pertaining to medicine are necessary to comply with the highest standards. The issue nowadays is that any conclusions of researches can be published online and used as a reference without being thoroughly verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this problem 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 major principle of this journal is based on Altmetric scores that are used as a quality indicator. That helps both readers and authors to quality-check publications with Altmetric Article Reports that provide “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a full publications list with corresponding scores above 100 as well as reports discussed above. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the required help to anybody, 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 diversified 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 majority of readers are willing to understand 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.” Hence, the paper about melanoma, was utilized 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 publication has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a short overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive useful scientific facts. Oncotarget is proud to have the chance to share with online readers this highly appreciated and top-quality information, that is trustworthy and reliable.
    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. 
    https://triberr.com/mishablagosklonny

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  • Par oncojornal02 dans Accueil le 11 Juin 2020 à 09:27

    Quantifying pharmacologic suppression of cellular senescence: prevention of cellular hypertrophy versus preservation of proliferative potential. Zoya N Demidenko

     
    June 11, 2020

    Quantifying pharmacologic suppression of cellular senescence: prevention of cellular hypertrophy versus preservation of proliferative potential

    Abstract
    Development of agents that suppress aging (aging suppressants) requires quantification of cellular senescence. Cellular senescence in vitro is characterized by a large cell morphology and permanent loss of proliferative potential. When HT-1080 cells were arrested by p21, they continued to grow exponentially in size and became hypertrophic with a 15-fold increase in the protein content per cell. These changes were mirrored by accumulation of GFP (driven by CMV promoter) per cell, which also served as a marker of cellular hypertrophy. Preservation of proliferative potential (competence) was measured by an increase in live cell number, when p21 was switched off. While modestly decreasing hypertrophy in p21-arresrted cells, rapamycin considerably preserved competence, converting senescence into quiescence. Preservation of proliferative potential (competence) correlated with inhibition of S6 phosphorylation by rapamycin. When p21 was switched off, competent cells, by resuming proliferation, became progressively less hypertrophic. Preservation of proliferative potential is a sensitive and quantitative measure of suppression of mTOR-driven senescence.
     
    oncotarget impact factor 2020 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 public speak of modern medicine, precision plays one of the most crucial roles and human lives are literally dependent on it. Hereby, any researches pertaining to medicine are necessary to comply with the highest standards. The challenge nowadays is that any outcomes of researches can be posted online and used as a reference without being thoroughly checked and approved. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this issue and tried to develop an alternative solution. That’s how a weekly oncology-focused research journal named “Oncotarget” has been established back in 2010. The key principle of this journal is based on Altmetric scores that are used as a quality measure. That helps both readers and authors to quality-check publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website has a full publications list with corresponding scores higher than 100 as well as reports discussed above. 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 article was released back in 2018 by Oncotarget and completed by diversified 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 relates to “how many people have been exposed to and engaged with a scholarly output.” Likewise, the paper about melanoma, was utilized for citations in different news articles 69 times. Besides that, it was referred to 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 research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This publication 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 readers this highly appreciated and top-quality information, that is trustworthy and reliable.
     

     


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