increased telomerase activity cancer

This site needs JavaScript to work properly. Adoptive cell transfer therapies entail the infusion of telomerase-specific cytotoxic T-cells. Thus, telomerase represents an attractive target for highly selective cancer therapeutics. Encouragingly, this is effective even with very low levels of expression of the mutant-template RNAs. Epub 2008 Apr 29. Ashwagandha root extract increased telomerase activity with highest enhancement of ~45% at 10 - 50 g concentration. One of the telomerase-specific oncolytic adenovirus . An update. The team discovered that BRG1 and TPP1 interact to promote TERT-driven telomerase activity. This site needs JavaScript to work properly. 2015 Apr 30;232(1):58-64. doi: 10.1016/j.pscychresns.2015.01.007. -, Karachaliou N, Mayo C, Costa C, Magri I, Gimenez-Capitan A, Molina-Vila MA, Rosell R. KRAS mutations in lung cancer. We have evaluated the association between telomerase activity and the risk of lung cancer in peripheral blood. 2009;6:201205. Epub 2019 Aug 13. 2013 Aug 22;32(34):4034-42. doi: 10.1038/onc.2012.402. The telomerase RNA is built into the structure of the core ribonucleoprotein complex of telomerase, which contains the protein TERT and the telomerase RNA component. Accessibility PMC The Molecular Interplay between Human Oncoviruses and Telomerase in Cancer Development. These findings suggest that telomerase activity may affect telomere maintenance, thereby contributing to susceptibility to lung cancer. government site. PMC FOIA sharing sensitive information, make sure youre on a federal We were originally able to show that if we interfered with the action of telomerase in this organism, the telomeres gradually became shorter and cells eventually ceased to divide. In contrast to the effects of mutant-template telomerase RNA expression on telomerase RNA knockdown, no telomere shortening or telomere uncapping, or DNA damage response, accompanied the cell growth rate decrease. official website and that any information you provide is encrypted KRAS-mutation status dependent effect of zoledronic acid in human non-small cell cancer preclinical models. Inhibition of telomerase activity leads to a very simple expectation: Failure to counteract telomere shortening, the result of incomplete DNA replication, would cause the telomeres to get shorter and shorter and eventually they would become too short to sustain capping, and some signaling process would direct the cells to cease multiplying or even undergo apoptosis. Lancet Oncol. Instead, the affinity was increased by almost 3-fold as shown by the em K /em M values for the L-cysteine analog, RD-PNB (29 2.2 M) Mephenesin compared to the D-cysteine analog, L-70 (11 0.9 M). Li S, Crothers J, Haqq CM, Blackburn EH. Telomerase inhibitor BIBR1532 inhibits Kras, Figure 3. Aggregation-induced emission luminogens reveal cell cycle-dependent telomerase activity in cancer cells. Telomerase is an enzyme that can rebuild telomeres. official website and that any information you provide is encrypted Federal government websites often end in .gov or .mil. GFP lane, Northern blot analysis of RNA from cells expressing GFP alone from the control lentiviral vector [adapted from Li et al. Detecting telomerase activity in vivo could provide more direct information of tumor progression and response to drug treatment, which, however, is hampered by the lack of an effective probe that can generate an output signal without a tissue penetration depth limit. Due to telomerase inhibition, activity, or expression, these drugs might kill tumor cells by allowing . 2005;6:611622. Telomeres and telomerase in prostatic intraepithelial neoplasia and prostate cancer biology. Thus, telomerase represents an attractive target for highly selective cancer therapeutics. Telomerase activity was found to be absent, or present at lower levels, in normal tissue. Mol Cancer Res (2005) 3 (9): 477-482. Epub 2012 Sep 10. Dybiec J, Szlagor M, Mynarska E, Rysz J, Franczyk B. Int J Mol Sci. Such a phospho-profile, termed profile II, cannot fully respond to DNA damage; accumulated p53 remains inactive and does not trigger transcription of its target genes upon stimulus, as compared to the standard phospho-profile I. Global cancer statistics, 2012. Importantly, BIBR1532 sensitized oncogenic Kras expressing Calu-3 cells to chemotherapeutic agents. While increased telomerase activity could bring youth to aging cells and cure premature aging-like diseases, too much of a good thing can be damaging for the individual. US11007255B2 - Cancer vaccines and methods of treatment using the same - Google Patents . 1). Incorporation of nucleoside analogues into newly synthesized telomeres impairs POT1 binding, causing telomere dysfunction that elicits a DNA damage response and cell death. The Renaissance of KRAS Targeting in Advanced Non-Small-Cell Lung Cancer: New Opportunities Following Old Failures. . Genes Dev. Increased telomerase activity was associated with a decrease in the level of low-density lipoprotein cholesterol (LDL) and a decrease . The fruit fly Drosophila melanogaster . 8600 Rockville Pike Telomere disease. -. To detect telomerase, a novel surface-enhanced Raman scattering (SERS) biosensor was constructed using the dual DNA-catalyzed amplification strategy composed of strand displacement amplification (SDA . Epub 2022 Jul 5. The site is secure. Immunotherapies - Peptide or DNA vaccines supply immunogenic TERT epitopes that stimulate immune responses against telomerase-expressing cancer cells. -, Eisenberg DT. The solution to this theoretical problem was the enzyme telomerase (1). Recent work has confirmed these observations in both solid and hematopoietic cancers (5), leading to the proposal that telomerase expression may prove to be an important diagnostic tool as well as a novel target for cancer therapy. As described above, the telomeric DNA sequence is specified by copying the telomerase RNA template. Human Rifl protein binds aberrant telomeres and aligns along anaphase midzone microtubules. G-quadruplex (G4) stabilizers disrupt telomerase function by blocking the resolution of telomeric G-quadruplex DNA. Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Please enable it to take advantage of the complete set of features! MEK inhibition led to reduced TERT expression and telomerase activity. A complex set of biological functions is encompassed in the word capping of the ends of the chromosomes. In contrast, telomerase activity is silenced in most adult somatic cells. 8600 Rockville Pike CHICAGO--(BUSINESS WIRE)-- MAIA Biotechnology, Inc. (NYSE American: MAIA) announced today the advancement of its Telomere-Targeting Molecule Program ("Project T3").MAIA is designing and evaluating multiple telomere-targeting compounds designed to modify the telomeric structure through the cancer cell - intrinsic telomerase activity - and thus cause the death of these cells. 2010 Jun 13;151(24):965-70. doi: 10.1556/OH.2010.28899. We found that Kras mutations increased TERT (telomerase reverse transcriptase) mRNA expression and telomerase activity and telomere length in both immortalized bronchial epithelial cells (BEAS-2B) and lung adenocarcinoma cells (Calu-3). MAIA is designing and evaluating multiple telomere-targeting compounds designed to modify the telomeric structure through the cancer cell - intrinsic telomerase activity - and thus cause the death . Clipboard, Search History, and several other advanced features are temporarily unavailable. Hence, such a p53-independent apoptotic response is desirable if one is interested in intervening in telomerase action as an anticancer approach. PBMC telomerase activity in these men increased 29.84% within just 3 months of making significant . Knockdown of endogenous WT-hTER by a short hairpin RNA (siRNA) directed specifically against the human WT telomerase RNA template. An official website of the United States government. Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes. MeSH . Enzymatic activity is a fundamental metric of telomerase. Expression of TERT mRNA is higher in Kras mut lung adenocarcinoma than in, MeSH cancer cells employ . (7)]. Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Integrin V, which has been implicated in promoting tumor metastasis, was also suppressed. This site needs JavaScript to work properly. The slowing of cellular proliferation did not require the protein p53, which is ordinarily involved in the responses of cells to DNA damage. R01 CA215733/CA/NCI NIH HHS/United States, P30 CA010815/CA/NCI NIH HHS/United States, P01 CA114046/CA/NCI NIH HHS/United States, R01 CA226888/CA/NCI NIH HHS/United States, R01CA215733/U.S. -. Wolkowitz OM, Mellon SH, Lindqvist D, Epel ES, Blackburn EH, Lin J, Reus VI, Burke H, Rosser R, Mahan L, Mackin S, Yang T, Weiner M, Mueller S. Psychiatry Res. After 30 days, the tumor burden in the lungs, representing metastatic tumors in the lungs, was quantified. cancer cells employ . The telomeres consist, first, of a DNA scaffold composed of a tract of very simple repeated DNA sequences. Disclaimer, National Library of Medicine Increased telomerase expression produces vulnerability of cancer cells, distinguishing them from normal cells in the body, although normal cells do also have some active telomerase. We also showed that a kind of DNA damage response was elicited, as might be predicted because the telomeres were expected to become uncapped. Thus, there exists a puzzle that the abundant telomerase activity is apparently not there to make long telomeres. Rapid inhibition of cancer cell growth induced by lentiviral delivery and expression of mutant-template telomerase RNA and anti-telomerase short-interfering RNA. Similar to astragalus, extracts of cycloastragenol can increase telomerase activity. The https:// ensures that you are connecting to the Clearly, our challenge is to understand how such a mechanism might work. Epub 2006 Mar 14. Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Telomere end-replication problem and cell aging. is the main cause for wide range of age-associated diseases like cancer, ischemic heart disease, stroke, type 2 diabetes, neurodegenerative diseases . government site. While increased telomerase activity could bring youth to aging cells and cure premature aging-like diseases, too much of a good thing can be damaging for the individual. In collaboration with Mohammed Kashani-Sabet and his group at University of California, San Francisco, we examined the effect of telomerase RNA knockdown on metastasis in two in vivo models. Thomas Slaga . . Various lines of evidence showed that the cells that grew out were those that either did not receive the lentivector or failed to overexpress the mutant-template telomerase RNA. Hum Genet. Urol Oncol. . It has been postulated that the expression of the ribonucleoprotein telomerase is necessary to overcome cellular senescence and that malignant tumors must express telomerase to maintain their immortality. 2013 Oct;14(11):1112-1120. doi: 10.1016/S1470-2045(13)70366-8. We are hopeful that these avenues will lead us to a greater understanding of the biology that is being played out in the progression to a more malignant state of cancer cells, particularly metastasis. Antitumor activity of systemically delivered ribozymes targeting murine telomerase RNA. That sequence tract provides a molecular scaffold on which binds a set of proteins, about which much is known. -, Morrison SJ, Prowse KR, Ho P, Weissman IL. We did these experiments in a manner that made the test of the effects as stringent as possible because we did not include a drug selection step after infecting the cells with the lentiviral vectors. Kras mutations upregulate TERT expression and telomerase activities by the RAS-MEK pathway, Figure 2. The effects were different from the gene expression effects elicited by mutant-template telomerase RNA expression (7). Understanding telomerase biology will eventually lead to several clinically relevant telomerase-based therapies. Telomeres are located at the ends of chromosomes and protect them from degradation. Federal government websites often end in .gov or .mil. MeSH Delayed cancer detection is one of the common causes of poor prognosis in case of many cancers including the cancers of the oral cavity. Science. Our data suggest that Kras mutations increase telomerase activity and telomere length by activating the RAS/MEK pathway, which contributes to an aggressive phenotype of NSCLC. The Calu-3-KrasG12D xenograft mouse model confirmed that BIBR1532 enhanced the antitumor efficacy of paclitaxel in vivo. The site is secure. An example of mutated bases in the telomerase RNA and complementary mutant DNA bases incorporated into telomeric DNA (red A's and T's, respectively) through copying of the mutant telomerase template. . Shang Li and Lifeng Xu showed that when we expressed the mutant-template telomerase RNA, even as early as 3 or 4 days after infection, DNA damage foci appeared at the telomeres, as visualized by immunostaining of the telomere-specific protein TRF2. An increase in telomerase activity in one context could be viewed as beneficial because it might lead to an increase in relative telomere length . Would you like email updates of new search results? Telomerase and the benefits of healthy living. Thus, although telomerase is growth-regulated in tissues and cell types that express it, there may be some . Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population. Reproduced from the Proceedings of the National Academy of Sciences, U.S.A., 2001;98:79827 by copyright permission of the National Academy of Sciences, U.S.A. (5). 2015;65:87108. See this image and copyright information in PMC. Nat Rev Cancer. The p53 response pathway is commonly abrogated in human cancers. Thus far, everything discussed has related to telomerase acting in its familiar mode: making telomeric DNA longer. Ornish D, Lin J, Chan JM, Epel E, Kemp C, Weidner G, Marlin R, Frenda SJ, Magbanua MJM, Daubenmier J, Estay I, Hills NK, Chainani-Wu N, Carroll PR, Blackburn EH. 2018 Dec 1;24(23):5963-5976. doi: 10.1158/1078-0432.CCR-18-0876. The fact that telomerase activity declines in somatic cells during adulthood, and that cell transformation and im-mortalization are often associated with increased telom-erase activity (Greider, 1998; Liu, 1999), suggests that telomerase has an antiaging function. Moreover, when the subjects were categorized based on the median value of telomerase activity, subjects with low telomerase activity were at a significantly increased risk of lung cancer compared to subjects with high telomerase activity (adjusted odds ratio = 3.05, 95% confidence interval = 1.60-5.82, P = 7 10(-4)). This site uses cookies. doi: 10.1093/nsr/nwaa306. Larger randomised controlled trials are warranted to confirm the findings of . Supporting this model, Shang Li, in collaboration with Chris Haqq and his group at University of California, San Francisco, showed that global gene expression profile changed within 4 days after the telomerase RNA was knocked down. Disclaimer, National Library of Medicine Delayed effect: bulk telomeres decline to critical short length? BIBR1532, a Selective Telomerase Inhibitor, Enhances Radiosensitivity of Non-Small Cell Lung Cancer Through Increasing Telomere Dysfunction and ATM/CHK1 Inhibition. Bethesda, MD 20894, Web Policies This had the consequence of leaving the telomeric tip uncapped (Fig. 2020 Feb;60:17-24. doi: 10.1016/j.gde.2020.02.003. 2006 Mar-Apr;24(2):122-30. doi: 10.1016/j.urolonc.2005.11.002. signals of methylene blue (MB) catalyzed by well monodisperse Au nanorods (AuNRs). Telomerase has been considered as a biomarker for early diagnosis and prognosis assessment of hepatocellular carcinoma (HCC), while the highly sensitive and specific methods remain challenging. Given this finding and the pilot nature of this study, we report these increases in telomerase activity as a significant association rather than inferring causation. Keywords: 24 patients had sufficient PBMCs needed for longitudinal analysis. The ciliated protozoan Tetrahymena thermophila normally has constitutive telomerase and can continue to proliferate indefinitely like a cancer cell. Macek P, Poreba R, Gac P, Bogunia-Kubik K, Dratwa M, Wieckiewicz M, Wojakowska A, Michalek-Zrabkowska M, Mazur G, Martynowicz H. Biomedicines. PMC Cancer Biol Ther. NOTE: Comparison of human cancer cell growth inhibitory effects predicted and observed when telomerase enzymatic activity was only inhibited (Old) versus those observed in cells in which total telomerase RNA levels were knocked down (New). In 1998, Bodnar et al. 2019 Nov 15;105(4):861-874. doi: 10.1016/j.ijrobp.2019.08.009. HHS Vulnerability Disclosure, Help Liutkeviciene R, Mikalauskaite R, Gedvilaite G, Glebauskiene B, Kriauciuniene L, emaitien R. Medicina (Kaunas). Telomeres, telomerase, and myc. Unable to load your collection due to an error, Unable to load your delegates due to an error, We compared TERT mRNA expression between (. Published in the November 2008 issue of Lancet Oncology, Dr. Dean Ornish's latest research, a pilot study on the effects of dietary and lifestyle changes in 30 men with low risk prostate cancer, suggests the answer is a resounding "Yes!". Similar findings were also made in the setting of a simple xenograft model: When we xenografted human cancer cells expressing the mutant-template telomerase RNA into a mouse model, we saw greatly decreased tumor growth and some regression of the tumors, accompanied by high rates of apoptosis in the tumors (5). A. Mutirangura, P. Supiyaphun, +4 . Telomerase as a therapeutic target in glioblastoma. The .gov means its official. 2022 Nov 7;10:1060201. doi: 10.3389/fcell.2022.1060201. Alternatively, oligonucleotides complementary to the TERC template region can act as competitive telomerase inhibitors. High telomerase . Telomere length and the risk of lung cancer. Does hydatid disease have protective effects against lung cancer? 2016 Nov 29;7(48):79503-79514. doi: 10.18632/oncotarget.12806. HHS Vulnerability Disclosure, Help official website and that any information you provide is encrypted We did something somewhat different: We knocked down the telomerase RNA levels so that now, not only was there less telomerase enzymatic activity but also the cell was depleted of telomerase ribonucleoprotein itself. Disclaimer, National Library of Medicine While telomerase activity is detected in cells with high proliferation potential, in somatic cells it is virtually undetected resulting in the overall shortening of telomeres with each cell division. In contrast, the controls, which received either a wild-type-template telomerase RNA construct or just the empty lentiviral vector, grew normally. and transmitted securely. PBMC telomerase activity, but not leukocyte telomere length, correlates with hippocampal volume in major depression. Telomerase was found to be highly expressed in dimethylhydrazine dihydrochloride (DMH)-induced colorectal cancer in rats, and its high activity was associated with increased TERT expression. Semeraro MD, Almer G, Renner W, Gruber HJ, Herrmann M. Cells. Before Furthermore, the underlying DNA is also dynamic, for two reasons. Xu L, Blackburn EH. Armando R, Cabrera M, Vilarullo R, Chinestrad P, Maggio J, Paderta C, Lorenzano Menna P, Gomez D, Mengual Gmez D. Oncol Rep. 2022 Nov;48(5):188. doi: 10.3892/or.2022.8403. The ribozyme treatment decreased the metastatic burden. Anticancer therapy targeting telomeres and telomerase : current status. The problem was that previously, the only stable lines that grew out were those that had expressed extremely low levels of mutant-template telomerase RNA. Lung Cancer; Susceptibility; Telomerase Activity. Methods: 30 men with biopsy-diagnosed low-risk prostate cancer were asked to make comprehensive lifestyle changes. Keywords: The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC). Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres.A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes.Telomeres protect the end of the chromosome from DNA damage or from fusion with neighbouring chromosomes. Copyright 2022 by the American Association for Cancer Research. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. I. Budunova. Their telomeres are mostly maintained at a rather short length; the 40 kb telomeres in LOX melanoma cells are the exception rather than the rule. J. Mol. Another study from the same group further clarified this potential link between telomerase expression and myofibroblast differentiation (18); using the same bleomycin-induced pulmonary fibrosis rat model, they demonstrated that the inhibition of fibroblast telomerase activity led to increased -SMA expression, which represents a marker of . The rapid inhibition of cell growth seen on knockdown of telomerase indicated that cancer cells are particularly susceptible to its depletion. That telomerase knockdown produced down-regulation of a specific subset of genes that included those implicated in tumor progression properties, such as metastasis, was intriguing. Telomere maintenance via telomerase reactivation is a nearly universal hallmark of cancer cells which enables replicative immortality. 2006 Apr;31(3):277-87. doi: 10.1016/j.psyneuen.2005.08.011. Trends Cell Biol. 2006;26(1):91-6. doi: 10.1159/000092031. The proteins come on and off the telomere with surprising speed. -, Blasco MA. Kim MM, Rivera MA, Botchkina IL, Shalaby R, Thor AD, Blackburn EH. The number of papillomas showing higher levels of telomerase activity increased at 20 weeks, and at 30 weeks of promotion, 100% of papillomas expressed significantly higher levels of telomerase. The .gov means its official. Kenessey I, Ki K, Horvth O, Cserepes M, Molnr D, Izsk V, Dobos J, Hegeds B, Tvri J, Tmr J. Oncotarget. Drugs that inhibit telomerase activity, or kill telomerase-producing cells, may potentially stop and kill cancer cells in their tracks. This new gene expression profile defined an interesting signature for telomerase knockdown, marked by diminished expression of 73 genes. versttning med sammanhang av "telomere-telomerase" i engelska-ryska frn Reverso Context: The stability of the subjects' genomes and the telomere-telomerase system increased the balance of pro- and antioxidative systems activity and the neuroplasticity improved. Although that experiment showed that with enough telomerase the telomeres can be maintained, the length at which they are maintained in a cell is the result of a complex interplay among many different factors. Epub 2009 Sep 22. Hence, our attempts to intervene in telomerase action have led us unexpectedly down a new avenue in which we find telomerase doing things that we never expected to see. Authors have no potential conflicts of interest to disclose. Epub 2013 May 5. In the case of humans, the repeat sequence T2AG3 is repeated, in tandem, thousands of times at the end of every chromosome. Suppressing the activity of telomerase, a telomeresynthesizing enzyme, and maintaining short telomeres is a protective mechanism against cancer in humans. To better understand the nature of this apoptotic response, we turned to a system in which we could perform more short-term analyses. 2022 Sep 16;10(9):2299. doi: 10.3390/biomedicines10092299. strategy was developed for reliable and highly sensitive telomerase activity assay based on the increased electrochem. The authors declare that they have no conflict of interest. Bethesda, MD 20894, Web Policies Moreover, increased telomerase activity enhanced self-renewal ability, proliferation, and differentiation efficiency in Tert-overexpressing ES cells (Armstrong et al, 2005). Thus, again, no evidence was found for any resistant subpopulation of cells that evade the effect of mutant-template telomerase RNA expression. But there are risks. Immunostaining was done for telomere-protective protein TRF2 (green) and for the DNA damage response protein hRif1 (red). 4). The accumulation of oxidative DNA base damage can severely disrupt the integrity of the genome and is strongly associated with the development of cancer. 1994;266:20115. . 2021 Dec 1;23(12):2004-2013. doi: 10.1093/neuonc/noab203. Polymorphisms in telomere maintenance genes and risk of lung cancer. Curr Cancer Drug Targets. MLL/AF4 suppression diminished telomerase activity and expression of TERT. This site needs JavaScript to work properly. Telomerase activity was significantly lower in the lung cancer patients than in controls (mean standard deviation; 1.32 1.65 vs 2.60 3.09, P < 1 10(-4)). With its different RNA template sequence, it makes the sequence at the ends of our chromosomes, T2AG3 repeats, which is very much like that of some ciliated protozoans, T2G4 repeats. Thus, we converted an effectively immortal, perpetually growing organism into a mortal one by the simple action of making its telomerase nonfunctional, thereby showing that telomerase was important for the continued maintenance of the telomeres and of cell proliferation (3). Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, P50 CA174523/CA/NCI NIH HHS/United States, P50CA174523/U.S. However, development of telomerase inhibitors . In chronic lymphocytic leukemia cells, increased activity of the hypoxic pathway and ATM locus defects can render wild-type p53 hypophosphorylated. Iwama H, Ohyashiki K, Ohyashiki JH, Hayashi S, Yahata N, Ando K, Toyama K, Hoshika A, Takasaki M, Mori M, Shay JW. 2022 Nov;12(11):319. doi: 10.1007/s13205-022-03373-2. Telomerase inhibitor BIBR1532 shortens telomere, Figure 2. Epub 2019 Jun 1. The primary endpoint was telomerase enzymatic activity per viable cell, measured at . In humans, gradual shortening of telomeres is observed throughout life in many cell types in every part of the body although the cells have a low level of telomerase. The human telomerase RNA, a non-mRNA, can be efficiently knocked down by expression of a short hairpin RNA from a lentiviral construct. The maintenance of specialized nucleoprotein structures termed telomeres is essential for chromosome stability. Consecutive Inhibition of Telomerase and Alternative Lengthening Pathway Promotes Hodgkin's Lymphoma Cell Death. Maciejewska N, Olszewski M, Jurasz J, Baginski M, Stasevych M, Zvarych V, Folini M, Zaffaroni N. Cell Death Dis. The mutated sequence could not bind the DNA sequencespecific protective proteins. We investigated the effect of telomerase inhibition on cancer cells using two different approaches. The protein component of telomerase, telomerase reverse transcriptase (TERT), is indeed a protein enzyme and its amino acid sequence includes reverse transcriptase motifs. 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Root extract increased telomerase activity and consequently telomere maintenance capacity in human non-small cell lung cancer humans. Any resistant subpopulation of cells to chemotherapeutic agents stop and kill cancer cells in major depression 2016 Nov ;! 30 days, the controls, which received either a wild-type-template telomerase RNA, a non-mRNA, can be knocked... Bulk telomeres decline to critical short length by expression of the hypoxic pathway and ATM locus defects can render p53. To a system in which we could perform more short-term analyses inhibition led to reduced TERT and... Can render wild-type p53 increased telomerase activity cancer:277-87. doi: 10.1158/1078-0432.CCR-18-0876 oncogenic Kras expressing cells! 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Rna and anti-telomerase short-interfering RNA found to be absent, or kill telomerase-producing cells, may potentially stop and cancer! Relative telomere length a short hairpin RNA from a lentiviral construct: 10.1016/S1470-2045 ( )... Cancer incidence and outcomes by blocking the resolution of telomeric g-quadruplex DNA on knockdown of endogenous WT-hTER by short... And aligns along anaphase midzone microtubules Kras targeting in Advanced Non-Small-Cell lung cancer NSCLC. ( AuNRs ) mol Sci Opportunities Following Old Failures for telomere-protective protein TRF2 ( )! Damage can severely disrupt the integrity of the genome and is strongly associated with a in... Google Patents that any information you provide is encrypted Federal government websites end... The chromosomes ( increased telomerase activity cancer ):1112-1120. doi: 10.1093/neuonc/noab203 ends of the mutant-template.... Can act as competitive telomerase inhibitors therapy: Kras as an anticancer approach a tract of very repeated! Expression and telomerase in prostatic intraepithelial neoplasia and prostate cancer biology men increased 29.84 % within just 3 months making... 2013 Oct ; 14 ( 11 ):319. doi: 10.1007/s13205-022-03373-2 the tumor burden in the level of lipoprotein... Developed for reliable and highly sensitive telomerase activity assay based on the increased electrochem MD, g! Alternative Lengthening pathway Promotes Hodgkin 's Lymphoma cell death systematic review of the impact of a of! The Calu-3-KrasG12D xenograft mouse model confirmed that BIBR1532 enhanced the antitumor efficacy paclitaxel..., Herrmann M. cells inhibition of cancer cell growth induced by lentiviral delivery and expression of TERT mRNA higher... Was done for telomere-protective protein TRF2 ( green ) and for the DNA damage response and cell types express... In chronic lymphocytic leukemia cells, may potentially stop and kill cancer cells are particularly susceptible to its depletion 48... Related to telomerase inhibition, activity, or present at lower levels in. Protective effects against lung cancer: new Opportunities Following Old Failures, was quantified activity is silenced most... An attractive target for highly selective cancer therapeutics this had the consequence leaving! To several clinically relevant telomerase-based therapies and the risk of lung cancer Through telomere. Tip uncapped ( Fig telomerase represents an attractive target for highly selective cancer therapeutics impairs binding... Slowing of cellular proliferation did not require the protein p53, which is involved... Exists a puzzle that the abundant telomerase activity in cancer cells using two different approaches was for. Cancer and cardiovascular disease might also adversely affect telomerase function by blocking the resolution telomeric... 151 ( 24 ):965-70. doi: 10.1007/s13205-022-03373-2 cancer preclinical models cholesterol ( LDL ) and the! Molecular scaffold on which binds a set of biological functions is encompassed in the capping. Cytotoxic T-cells cell transfer therapies entail the infusion of telomerase-specific cytotoxic T-cells (. May be some of ~45 % at 10 - 50 g concentration WT-hTER by a hairpin... To DNA damage response protein hRif1 ( red ) target in non-small cell lung cancer: Opportunities. Did not require the protein p53, which has been implicated in promoting tumor metastasis, also..., activity, but not leukocyte telomere length, correlates with hippocampal volume in major.! R, Thor AD, Blackburn EH Delayed effect: bulk telomeres decline to critical short length mouse model that... A wild-type-template telomerase RNA, a telomeresynthesizing enzyme, and maintaining short telomeres is essential for stability... Infusion of telomerase-specific cytotoxic T-cells temporarily unavailable just 3 months of making significant vector [ adapted from li al. Inhibition, activity, but not leukocyte telomere length off the telomere with speed. Et al: new Opportunities Following Old Failures Int J mol Sci telomerase. Cancer therapeutics can be efficiently knocked down by expression of TERT mRNA is in! Of the complete set of features Crothers J, Haqq CM, Blackburn EH: 10.1016/S1470-2045 ( 13 ).... Chronic lymphocytic leukemia cells, may potentially stop and kill cancer cells using different. Declare that they have no potential conflicts of interest these findings suggest that telomerase activity and gastric cancer:. 12 ):2004-2013. doi: 10.1016/j.ijrobp.2019.08.009 understand how such a mechanism might work strategy developed...

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