• Par oncojornal02 dans Accueil le 9 Juin 2020 à 13:36

    Rapamycin for life: A step to immortality. Zoya N Demidenko

     
    June 09, 2020

    Rapamycin for life: A step to immortality


      Tumor suppression is admittedly the moststudied feature of p53. Nevertheless, numerous studies have portrayed p53 as key regulator of several normal biological processes, such as tissue homeostasis, development, differentiation and fertility.1 A seminal work by Hu and colleagues revealed that p53 regulates maternal reproduction through leukemia inhibitory factor (LIF) induction in mice.2 A recent report by Sohr and Engeland extends this observation and suggests a role for p53 in the blastocyst implantation process in humans as well.3 The authors show that CGB7, one of the genes encoding the b subunit of human chorionic gonadotropin (hCG), is transcriptionally induced by p53. hCG is a primate-specific hormone that is crucial for blastocyst implantation and early propagation of pregnancy. Interestingly, the other hCG-b-encoding genes were not induced by p53, thus implying a specific regulation leading to different  functions of these closely related genes. Several studies have connected the p53 pathway to human reproduction at large. In regards to implantation, we know now that both the gene encoding LIF, which is an endometrial cytokine (maternal source) important for blastocyst implantation,4 and CGB7, which is secreted by trophoblasts (blastocyst source), are regulated by p53.3 This implies that p53 has a major role in balancing hormone production at the implantation site, and thus secures proper implantation (Fig. 1). Furthermore, in addition to p53, estrogen receptor (ER) also regulates LIF in the implantation stage.5 Concordantly, we found that the promoter of the human CGB7 gene contains two putative ER responsive elements (-833/-811 bp and -525/-503 bp upstream of the transcription start site of CGB7— NM_033142). Therefore, it is tempting to speculate that ER and p53 cooperate in the regulation of blastocyst implantation through the induction of LIF and CGB7 (Fig. 1). Although some p53 target genes are initially described in other biological processes, they might also be related to the transformation process. For example, LIF was reported to play a vital role in cancer, although its endpoint effect seems to be tumor-specific. For example, secretion of LIF seems to promote tumor growth,6 while, on the other hand, it is transcriptionally repressed in cancer-associated stroma7 and might be located near a tumor suppressor locus in meningiomas.8 As p53 counteracts transformation, one might speculate that CGB7, being a genuine p53 target, has antitumor activity as well. Hitherto, merely one study examined CGB7 in the context of cancer. The mRNA expression of all CGB family members in invasive breast tumors samples were examined, and no significant change in CGB7 expression was found.9 Future research should be aimed at uncovering the full details of p53’s mode of action in the implantation process in both blastocyst and maternal tissue and perhaps tie CGB7 to the transformation process as well.
    https://www.tandfonline.com/doi/pdf/10.4161/cc.10.24.18562?needAccess=true
    impact factor of 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 .
    https://www.scienceopen.com/user/e7fc54ba-94fb-4b90-b8e3-fc61dfb69240


    oncotarget journal impact factor
    When people mention today’s medicine, accuracy plays one of the most significant roles and people’s lives are directly dependent on it. Hence, any researches related to medicine are required to meet the highest standards. The challenge nowadays is that any outcomes of researches can be published online and used as a reference without being properly verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget perfectly understood this problem and attempted 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 main principle of this journal is based on 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 has a complete publications list with corresponding scores above 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it creates the required 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 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 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 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 used for citations in various news articles 69 times. Moreover, 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 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 seen a short overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get helpful scientific facts. Oncotarget is glad 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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  • Par oncojornal02 dans Accueil le 9 Juin 2020 à 13:22

    Chronological lifespan in stationary culture: from yeast to human cells. Zoya N. Demidenko

     
    June 09, 2020
    Chronological lifespan in stationary culture: from yeast to human cells
    A decade ago, Mikhail Blagosklonny predicted that cellular senescence is driven by mitogenic pathways, when the cell cycle is blocked and actual growth is impossible [1]. In particular, the mitogen- and nutrientsensing mTOR (Target of Rapamycin) pathway drives either cell mass growth or aging [2]. Rapamycin prevents conversion of reversible cell cycle arrest to senescence [3-11]. When the cell cycle is blocked, but mTOR is still active, then cells become senescent. This process was named gerogenic conversion or simply geroconversion [12]. Rapamycin did not by-pass arrest but suppress geroconversion. Cells remained resting but not senescent. The discovery of mTOR-dependent geroconversion allowed Blagosklonny to connect cellular aging to age-related diseases and organismal aging [13, 14]. Furthermore, this predicted that rapamycin is a gerosuppressant, which could be used to prevent age-related diseases by slowing down the aging process [14]. Independently, it was discovered that rapamycin suppresses chronological aging of yeast cells [15]. Chronological lifespan of yeast cells in stationary culture is the most fruitful model in aging research and dozens of papers have been published in Nature, Science, Cell and Cell Cycle. Although yeast model was so useful to identify genes involved in mammalian aging, the reason remained unclear. Yeast only loosely resemble post-mitotic cells in human tissues. Unfortunately, there was no model of mammalian chronological aging in cell culture. In one model developed by Fabrizio and Valter Longo [16] as well as by Matt Kaeberlein and Brian K. Kennedy [17], yeast chronological senescence (CS) is caused by acidosis due to overproduction of acetic acid. Obviously, neither replicative nor accelerated senescence of human cells resembles yeast CS in the stationary culture. Surprisingly, the exact replica was so well known and so trivial that it was overlooked by decades. Here Leontieva and Blagosklonny describe the mammalian cellular model: a neglected flask with overgrown cancer cells that turn medium “yellow” (due to lactate accumulation). Such flasks left and forgotten over weekend could be found in any CO2-incubator. The paper is simultaneously startling and obvious. It is obvious from an everyday experience that highly glycollytic cells can destroy cell culture. But like it was known to most researches (90 years ago) that fungi can destroy bacterial culture, it took a special insight to recognize the potential of this seemingly useless phenomenon. There is an intriguing parallel between penicillin and rapamycin. As described in this issue of Aging, mTOR pathway is involved in glycolytic phenotype, causing self-poisoning due to overproduction of lactic acid. By decreasing lactate production, rapamycin prevents chronological senescence (CS). CS can be manipulated genetically and pharmacologically. Most importantly, the same agents that suppress geroconversion, organismal aging and cancer also suppress CS. This study does not break any dogma because there was no dogma as the field did not exist. This paper opens a new filed in both aging and cancer research. Blagosklonny and collaborators are currently preparing follow-up papers with special emphasis to cancer research: the ability of rapamycin to decrease lactate production independently of respiration, selection of highly glycolytic cancer cell clones, tumor progression and resistance to therapy. Many questions will be answered. But this first paper defines the field, providing description of the phenomenon, its mechanism and the ways of pharmacological manipulation. It illuminates the place of yeast CS in aging research and its indirect (via common signaling pathways) relevance to cancer and organismal aging. It also rules out altruistic (programmed) aging of yeast because no one would suspect altruistic nature of cancer cells. I invite the readers to enjoy this first paper in the filed of mammalian cell chronological senescence.

    oncotarget submission 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 .
    https://www.semanticscholar.org/author/Zoya-N.-Demidenko/4772760


    oncotarget impact factor 2021
    When public mention today’s medicine, accuracy plays one of the most important roles and human lives are literally dependent on it. Hence, any researches pertaining to medicine are required to comply with the highest standards. The problem today is that any outcomes of researches can be posted online and used as a reference without being properly verified and validated. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this challenge and attempted to generate an alternative solution. That’s how a weekly oncology-focused research journal called “Oncotarget” has been founded 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 provides a full publications list with respective scores higher than 100 as well as reports discussed previously. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it creates 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 article 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 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 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 indicates “how many people have been exposed to and engaged with a scholarly output.” Hence, the publication about melanoma, was utilized for citations in different news articles 69 times. Moreover, it was mentioned 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 research 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 seen a concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive helpful scientific facts. Oncotarget is glad to have the chance to share with online readers this highly appreciated and top-quality information, that is trustworthy and reliable.
    http://www.impactjournals.com/oncoscience/index.php?abs=14

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  • Par oncojornal02 dans Accueil le 9 Juin 2020 à 12:51

    Elimination of Proliferating Cells Unmasks the Shift from Senescence to Quiescence Caused by Rapamycin

    Abstract

    Background

    Depending on cellular context, p53-inducing agents (such as nutlin-3a) cause different outcomes including reversible quiescence and irreversible senescence. Inhibition of mTOR shifts the balance from senescence to quiescence. In cell lines with incomplete responses to p53, this shift may be difficult to document because of a high proportion of proliferating cells contaminating arrested (quiescent and senescent) cells. This problem also complicates the study of senescence caused by minimal levels of p21 that are capable to arrest a few cells.

    Methodology

    During induction of senescence by low levels of endogenous p53 and ectopic p21, cells were co-treated with nocodazole, which eliminated proliferating cells. As a result, only senescent and quiescent cells remained.

    Results and Discussion

    This approach revealed that rapamycin efficiently converted nutlin-induced-senescence into quiescence. In the presence of rapamycin, nutlin-arrested MCF-7 cells retained the proliferative potential and small/lean morphology. Using this approach, we also unmasked senescence in cells arrested by low levels of ectopic p21, capable to arrest only a small proportion of HT1080-p21-9 cells. When p21 did cause arrest, mTOR caused senescent phenotype. Rapamycin and high concentrations of nutlin-3a, which inhibit the mTOR pathway in these particular cells, suppressed senescence, ensuring quiescence instead. Thus, p21 causes senescence passively, just by causing arrest, while still active mTOR drives senescent phenotype. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026126

    oncotarget journal impact factor 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 .
    https://www.pnas.org/user/logout?current=node/616329 


    oncotarget impact
    When public mention contemporary medicine, precision plays one of the most significant roles and human lives are directly dependent on it. Likewise, any researches related to medicine are required to comply with the top standards. The problem nowadays is that any results of researches can be posted online and used as a reference without being thoroughly verified and approved. Mikhail (Misha) Blagosklonny of Oncotarget clearly understood this challenge and decided to develop an alternative solution. That’s how a weekly oncology-focused research journal called “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 allows both readers and authors to verify publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a complete publications list with respective scores higher than 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny glad to share his new approach and hopes it provides the required 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 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 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 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 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.” Hereby, the publication about melanoma, was used for citations in different news articles 69 times. Moreover, it was mentioned 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 research with a top score of 476, is “Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moon-shot,”. This study has appeared in 60 news stories, 1 online blog post and 6 Twitter posts. The majority of public may have seen a brief overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do get useful scientific facts. Oncotarget is glad to have the ability to share with online viewers this highly appreciated and top-quality information, that is trustworthy and reliable.
    https://medicalxpress.com/journals/oncotarget/


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  • Par oncojornal02 dans Accueil le 9 Juin 2020 à 11:56

    Oncotarget. Zoya N. Demidenko

     
    June 09, 2020
    Oncotarget. Zoya N. Demidenko 
    Welcome to oncotarget.net, a website about Oncotarget, a peer-reviewed open access research journal focusing on all topics surrounding cancer research. Oncotarget is published by Impact Journals of Orchard Park, New York. Impact Journals meets the standards established Wellcome Trust Publisher Requirements and is included on the Wellcome Trust List of Compliant Publishers. Oncotarget is proud to have multiple Nobel Prize winning members on its editorial board, in addition to editors who have won the Lasker Prize and other prestigious recognitions. The open-access model employed by Oncotarget allows for free dissemination of thoroughly vetted peer-reviewed research material to the general public, leading to bigger and more frequent scientific breakthroughs. Because of Oncotarget’s uniquely varied scope, the journal has consistently published research on a wide range of subject areas, allowing readers to access an unparalleled diversity of knowledge in only one publication. The founding editors of Oncotarget are Mikhail (Misha) Blagosklonny and Andrei Gudkov. Dr. Blagosklonny is well-known for his research in the field of aging, having published numerous papers on the subject. Mikhail is credited for advancing groundbreaking research of the drug Rapamycin, an anti-aging medicine that has shown to slow down the aging process. Having been featured in numerous publications on aging including a Scientific American article titled “A New Path to Longevity” (link: https://www.scientificamerican.com/article/a-new-path-to-longevity/), Mikhail continues to provide meaningfully important contributions to the scientific community. Dr. Blagosklonny can be followed on twitter @Blagosklonny and you can visit his website at www.mikhailblagosklonny.com.To get in touch with Oncotarget, please visit our website at www.oncotarget.com. The journal’s ISSN is 1949-2553 and is indexed and/or archived in PubMed, Scopus, PMC, and the Chan Zuckerberg Meta initiative.Follow us on Twitter @Oncotarget!www.twitter.com/oncotarget

    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 .
    https://mcb.asm.org/content/23/3/1014.abstract


    oncotarget impact factor
    When people refer to modern medicine, precision plays one of the most important roles and human lives are directly dependent on it. Hence, any researches related to medicine are necessary to meet the top standards. The issue today 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 clearly understood this issue and decided to come up with 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 measure. That helps both readers and authors to verify publications with Altmetric Article Reports that generate “real-time feedback containing data summary related to a particular publication.” Oncotarget website demonstrates a complete publications list with corresponding scores higher than 100 as well as reports mentioned above. Mikhail (Misha) Blagosklonny proud 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 study 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 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. 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 research 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 concise overview only, however those who visit Mikhail (Misha) Blagosklonny at Oncotarget, do receive useful scientific facts. Oncotarget is happy to have the ability to share with online readers this highly appreciated and top-quality information, that is trustworthy and reliable.
    https://www.livercenter.pitt.edu/news/2019-02/dr-mongas-group-publishes-oncotarget

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  • Par oncojornal02 dans Accueil le 9 Juin 2020 à 11:43

    Contact inhibition and high cell density deactivate the mammalian target of rapamycin pathway, thus suppressing the senescence program. Zoya N. Demidenko

     
    June 09, 2020

    Contact inhibition and high cell density deactivate the mammalian target of rapamycin pathway, thus suppressing the senescence program

    Significance

    This work solves longstanding mysteries in the field of contact inhibition (CI), cancer, and aging. As shown here during CI, cells do not undergo senescence, thus resuming proliferation after replating. We found that CI was associated with inhibition of the mammalian target of rapamycin (mTOR) pathway, which is required for the senescence program. In cancer cells, lacking CI, mTOR was still inhibited in high cell density by an alternative mechanism. Our work explains why CI is reversible and how cells can avoid senescence in vivo, allowing the organism to last for decades. Implications for cancer therapy are discussed.

    Abstract

    During cell cycle arrest caused by contact inhibition (CI), cells do not undergo senescence, thus resuming proliferation after replating. The mechanism of senescence avoidance during CI is unknown. Recently, it was demonstrated that the senescence program, namely conversion from cell cycle arrest to senescence (i.e., geroconversion), requires mammalian target of rapamycin (mTOR). Geroconversion can be suppressed by serum starvation, rapamycin, and hypoxia, which all inhibit mTOR. Here we demonstrate that CI, as evidenced by p27 induction in normal cells, was associated with inhibition of the mTOR pathway. Furthermore, CI antagonized senescence caused by CDK inhibitors. Stimulation of mTOR in contact-inhibited cells favored senescence. In cancer cells lacking p27 induction and CI, mTOR was still inhibited in confluent culture as a result of conditioning of the medium. This inhibition of mTOR suppressed p21-induced senescence. Also, trapping of malignant cells among contact-inhibited normal cells antagonized p21-induced senescence. Thus, we identified two nonmutually exclusive mechanisms of mTOR inhibition in high cell density: (i) CI associated with p27 induction in normal cells and (ii) conditioning of the medium, especially in cancer cells. Both mechanisms can coincide in various proportions in various cells. Our work explains why CI is reversible and, most importantly, why cells avoid senescence in vivo, given that cells are contact-inhibited in the organism. https://www.pnas.org/content/early/2014/05/29/1405723111

    oncotarget research
    When general population speak of modern medicine, accuracy plays one of the most important roles and human lives are directly dependent on it. Likewise, any researches pertaining to medicine are required to comply with the highest standards. The issue nowadays is that any recommendations of researches can be shared online and used as a reference without being precisely checked 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 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 respective scores higher than 100 as well as reports mentioned previously. Mikhail (Misha) Blagosklonny proud to share his new approach and hopes it creates the required 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 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 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 publication about melanoma, was used for citations in different news articles 69 times. Moreover, 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 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 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 ability to share with online customers this highly appreciated and high-quality information, that is trustworthy and reliable.
    https://soundcloud.com/oncotarget
     

     


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