K01AT004199/AT/NCCIH NIH HHS/United States. This site needs JavaScript to work properly. doi: 10.1093/nsr/nwaa306. Cell. Telomerase activity has been detected in 85% of tumors representing 15 cancer types, whereas most benign tumors and somatic tissues have very low levels or lack detectable telomerase activity Furthermore, in special metastatic tumor types such as neuroblastoma stage IVs, in which there is a high rate of spontaneous regression, telomerase . An important conclusion of this work is that telomerase participates in cell responses in ways that do not seem to involve the telomere itself. PMC sharing sensitive information, make sure youre on a federal government site. Disclaimer, National Library of Medicine using human cancer cells showed that TERT is a direct target of the Wnt/-catenin pathway and -catenin/TCF4 complex binds to the TERTp and increases telomerase activity Summary and conclusionsprospects for cancer therapy. That sequence tract provides a molecular scaffold on which binds a set of proteins, about which much is known. Telomeres are protective DNA-protein complexes at the end of linear chromosomes that promote chromosomal stability. Nat Rev Cancer. One of the telomerase-specific oncolytic adenovirus . 2010 Jun 13;151(24):965-70. doi: 10.1556/OH.2010.28899. The response to mutant-template telomerase RNA is highly specific for cells that have high levels of telomerase. eCollection 2021. 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. However, development of telomerase inhibitors has been challenging and thus far there are no clinically approved strategies exploiting this cancer target. Comprehensive lifestyle changes significantly increase telomerase activity and consequently telomere maintenance capacity in human immune-system cells. Humans also have telomerase. Immunotherapies, MeSH Aggregation-induced emission luminogens reveal cell cycle-dependent telomerase activity in cancer cells. Wu X, Wu J, Dai J, Chen B, Chen Z, Wang S, Wu F, Lou X, Xia F. Natl Sci Rev. Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. 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. Accessibility N Engl J Med. We could achieve up to about 90% knockdown either by using short hairpin siRNAs expressed in the cells from a lentiviral vector expression cassette or by treating the cancer cells with the short synthetic siRNA oligonucleotides with or without modified backbones (Fig. Herein, an enzyme-free electroanal. We observed that at 10 weeks of promotion, only one mouse skin papilloma of 11 analyzed showed high levels of telomerase activity. The results are the means SEM (n=3). Unable to load your collection due to an error, Unable to load your delegates due to an error. The site is secure. The site is secure. Which of the following statements is accurate about the activity of the telomerase enzyme in cancer cells? Careers. Alternatively, oligonucleotides complementary to the TERC template region can act as competitive telomerase inhibitors. We used this organism because it has a large number of telomeres and is a relatively rich source of telomerase. Epub 2022 Aug 16. official website and that any information you provide is encrypted Ovals and diamonds, sequence-specific DNA binding proteins that protect telomeric DNA and cap it; red, telomerase; blue Xs, mutated telomerase RNA template and correspondingly mutated telomeric DNA sequence. and transmitted securely. de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Relative Leukocyte Telomere Length and Telomerase Complex Regulatory Markers Association with Leber's Hereditary Optic Neuropathy. 8600 Rockville Pike -. As a result, cancer cells essentially become immortal. The unexpectedly rapid response to telomerase knockdown prompted us to carry out many controls to rule out possibilities such as targets other than the telomerase RNA being responsible for the effects on cell growth. FOIA 2006 Mar-Apr;24(2):122-30. doi: 10.1016/j.urolonc.2005.11.002. cancer cells employ . Xu L, Blackburn EH. Polymorphisms in telomere maintenance genes and risk of lung cancer. Although the mouse telomerase RNA component levels were increased 2-fold and correlated well with proliferation markers, activity levels were increased 10-fold, suggesting a second level of regulation in addition to growth regulation . Keywords: -, Karachaliou N, Mayo C, Costa C, Magri I, Gimenez-Capitan A, Molina-Vila MA, Rosell R. KRAS mutations in lung cancer. Those T2AG3 repeats are the critical binding sites for sequence-specific telomeric protective proteins. This site needs JavaScript to work properly. The findings give new insights into cellular aging and the development of cancer. . -, Shields JM, Pruitt K, McFall A, Shaub A, Der CJ. Lancet Oncol. Liu Y, Betori RC, Pagacz J, Frost GB, Efimova EV, Wu D, Wolfgeher DJ, Bryan TM, Cohen SB, Scheidt KA, Kron SJ. As shortened telomeres inhibit tumor formation and prolong life span in a KrasG12D mouse lung cancer model, we investigated the implications of telomerase in Kras-mutant NSCLC. 2018 Dec 1;24(23):5963-5976. doi: 10.1158/1078-0432.CCR-18-0876. Bookshelf 2021 Dec 16;13(24):6332. doi: 10.3390/cancers13246332. Tieing together loose ends: telomere instability in cancer and aging. Knockdown of endogenous WT-hTER by a short hairpin RNA (siRNA) directed specifically against the human WT telomerase RNA template. Psychoneuroendocrinology. Tumor cells in control . This site needs JavaScript to work properly. https://doi.org/10.1158/1541-7786.MCR-05-0147. 2011;23:149167. Copyright 2022 by the American Association for Cancer Research. Epub 2019 Jun 1. This site needs JavaScript to work properly. Sunaga N, Kaira K, Imai H, Shimizu K, Nakano T, Shames DS, Girard L, Soh J, Sato M, Iwasaki Y, Ishizuka T, Gazdar AF, Minna JD, Mori M. Oncogene. Clipboard, Search History, and several other advanced features are temporarily unavailable. -, Eisenberg DT. 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. Mol Cancer Res (2005) 3 (9): 477-482. Epub 2011 Jul 23. J. Mol. Federal government websites often end in .gov or .mil. We were, however, unable to rule out the possibility that telomerase activation over such a short time was a compensatory mechanism induced by adverse conditions (eg, a worsening of prostate cancer). Larger randomised controlled trials are warranted to confirm the findings of this study. Lima MF, Freitas MO, Hamedani MK, Rangel-Pozzo A, Zhu XD, Mai S. Biomedicines. We interpret these findings to mean that as the cells grew, with some probability they would die by apoptosis. 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. 2006;26(1):91-6. doi: 10.1159/000092031. Unlike viral or retroviral reverse transcriptases, such as that of HIV-1, the cellular enzyme telomerase specializes in making the multiple short tandem repeats that are at the ends of chromosomes. 2000 Jan;462(1):31-47. doi: 10.1016/s1383-5742(99)00091-5. Telomere terminal transferase (telomerase) enzyme activity (not the identification of the genes encoding the components of telomerase) was discovered in 1985 in the single-cell organism Tetrahymena ().Almost a decade later, telomerase was described as an almost universal marker in advanced human cancers (), but it was not until 1997 that the catalytic protein component was isolated, first in . Federal government websites often end in .gov or .mil. We therefore investigated what happens when you knock down the high levels of telomerase in human cancer cells. Telomeres, telomerase, and myc. 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. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/International, P50 CA174523/CA/NCI NIH HHS/United States, P50CA174523/U.S. Jacobs F, Cani M, Malapelle U, Novello S, Napoli VM, Bironzo P. Cancers (Basel). Elizabeth H. Blackburn; Telomerase and Cancer: Kirk A. Landon - AACR Prize for Basic Cancer Research Lecture. Drugs that inhibit telomerase activity, or kill telomerase-producing cells, may potentially stop and kill cancer cells in their tracks. Hiyama, E; Yokoyama, T; Tatsumoto, N; Hiyama, K; Imamura, Y; Murakami, Y; Kodama, T; Piatyszek, M A; Shay, J W . We also address some of the challenges to telomerase-directed therapies including potential therapeutic resistance and considerations for future therapeutic applications and translation into the clinical setting. 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). To determine whether the telomeres had become uncapped, we looked for the appearance of DNA damage foci at telomeres (Fig. Apoptosis was quantified in clonal lines stably expressing low levels of a mutant-template telomerase RNA construct, a control wild-type RNA construct, or parental MCF-7 cells. Note that not all telomeres (TRF2 spots) overlap with DNA damage foci, although each of the large DNA damage focal spots overlaps with one or more telomeres. Without new synthesis of telomeres at chromosome ends the chromosomes shorten with progressive cell division, eventually triggering either replicative senescence or apoptosis when telomere length becomes critically short. Would you like email updates of new search results? 2019 Jun;9(2):219-230. doi: 10.15171/apb.2019.025. As Bernard Weinstein (9) has proposed for other signaling pathways in tumors, cancer cells might be addicted to high levels of telomerase, such that their physiology becomes habituated to it that when telomerase is withdrawn, a cold turkey response is deleterious to the cell. 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. For these immunostaining experiments, we used proteins that are known to accumulate in DNA damage foci at sites of DNA damage, such as the protein hRif1. Progressing next generation of telomere-targeting candidates through proof of concept studies with promising anti-cancer activity Filed provisional new composition of matter patent during fourth . The ciliated protozoan Tetrahymena thermophila normally has constitutive telomerase and can continue to proliferate indefinitely like a cancer cell. Epub 2022 Oct 10. Indeed, that expected result is exactly what is seen when the telomerase activity in cells is inhibited by, for example, expressing an excess of a catalytically dead version of the protein TERT, which, although it can still assemble into the telomerase ribonucleoprotein complex, forms a complex that is not catalytically active. Targeting the "hallmarks of aging" to slow aging and treat age-related disease: fact or fiction? Remember, this enzyme isn't found in . PBMC telomerase activity expressed as natural logarithms increased from 2.00 (SD 0.44) to 2.22 (SD 0.49; p=0.031). Mol. Genetic Variants of the TERT Gene and Telomere Length in Obstructive Sleep Apnea. For example, we could reinfect those outgrowing cells and recapitulate the same growth kinetics compared with the controls for at least three cycles of reinfections. The https:// ensures that you are connecting to the In addition, higher TERT expression was seen in Kras-mutant NSCLC than that with wild-type Kras. The core structure includes a conserved pseudoknot, which is one of the parts of RNA that interact tightly and specifically with the protein TERT in the enzyme complex. 2009 Oct;18(10):2773-81. doi: 10.1158/1055-9965.EPI-09-0323. NCI CPTC Antibody Characterization Program, Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. 2003 Oct 1;289(2):326-34. doi: 10.1016/s0014-4827(03)00281-7. The rapid inhibition of cell growth seen on knockdown of telomerase indicated that cancer cells are particularly susceptible to its depletion. Bethesda, MD 20894, Web Policies Hum Genet. Background: Researchers found that the enzyme telomerase, which is active in most tumor cells, may also protect healthy adult cells from becoming cancerous. That property also makes telomerase a very unusual reverse transcriptase. We investigated the effect of telomerase inhibition on cancer cells using two different approaches. Careers. For example, in the earliest experiments we did, we transfected the mutant template telomerase RNA constructs into human cancer cell lines and selected for cells that stably expressed the mutant-template telomerase RNA (5). Demethylation of the human telomerase catalytic subunit (hTERT) gene promoter reduced hTERT expression and telomerase activity and shortened telomeres. Federal government websites often end in .gov or .mil. In contrast, the controls, which received either a wild-type-template telomerase RNA construct or just the empty lentiviral vector, grew normally. Understanding telomerase biology will eventually lead to several clinically relevant telomerase-based therapies. Reproduced from The Journal of Cell Biology, 2004;167:819830 by copyright permission of The Rockefeller University Press (10). Epub 2022 Jul 5. Hence, all one needed to do was spike the endogenous telomerase in the cancer cells with a little mutant-template telomerase RNA that assembled into the telomerase to make mutant repeats. Valdiani A, Ofoghi H, Akbarizare M, Talei D. 3 Biotech. We found that Kras mutations increased TERT (telomerase reverse transcriptase) mRNA expression and telomerase activity and it was more than a decade ago that researchers showed that TPP1 would increase telomerase activity. 24 patients had sufficient PBMCs needed for longitudinal analysis. FOIA Published in Cancer Research 1996. 4). Thus, incomplete replication of the chromosome ends occurs, which, if left unchecked by any compensatory mechanism, leads to a problem of maintaining the full-length of chromosomal DNA molecules. However, blocking telomerase activity could affect cells where telomerase activity is . GFP lane, Northern blot analysis of RNA from cells expressing GFP alone from the control lentiviral vector [adapted from Li et al. We found that the cellular response to this way of uncapping of telomeres in cancer cells was a very robust apoptotic response (Fig. Although in many normal adult human cell types telomerase is often expressed at very low, sometimes undetectable, levels, it is clear that telomerase has some protective role in such normal cells. 2016 Jul;23(4):346-53. doi: 10.1097/MOH.0000000000000252. The pseudoknot is also critically important for the action of telomerase. One reason is that, as was predicted in the 1970s, the known mechanism of DNA polymerase prevents complete DNA replication all the way to the ends of the chromosome at every round of replication. Clipboard, Search History, and several other advanced features are temporarily unavailable. At various levels, it is also active in other adult human cells, but the levels are often very low and not enough to sustain telomere length over a lifetime. Once again, the effects did not require p53 (7). Clin Cancer Res. Through this work, we learned, somewhat to our surprise, that we might also be able to incur a more rapid effect on cancer cell growth than expected and even change their cancerous properties in ways that were hitherto unsuspected (7). Moreover, increased telomerase activity enhanced self-renewal ability, proliferation, and differentiation efficiency in Tert-overexpressing ES cells (Armstrong et al, 2005). We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). Cancer Epidemiol Biomarkers Prev. Lung Cancer; Susceptibility; Telomerase Activity. 2022 Sep 16;10(9):2299. doi: 10.3390/biomedicines10092299. Accessibility . After much study, it has emerged that the RNAs from evolutionarily diverse eukaryotes share a common core structure (2). An update. Irradiation-induced telomerase activity and gastric cancer risk: a case-control analysis in a Chinese Han population. The template is only a minor part of the entire telomerase RNA molecule. These applications include inhibiting or targeting telomerase as a novel antineoplastic strategy and using cells immortalized by telomerase for therapeutic applications. Approximately 85% of human cancers achieve indefinite cell proliferation and avoidance of telomeric shortening through increased telomerase activity. A low threshold level of expression of mutant-template telomerase RNA inhibits human tumor cell proliferation. -, Morrison SJ, Prowse KR, Ho P, Weissman IL. Kras mutations upregulate TERT expression, Figure 1. The p53 response pathway is commonly abrogated in human cancers. Cynthia Marcelo. Gene Dev. Ashwagandha root extract increased telomerase activity with highest enhancement of ~45% at 10 - 50 g concentration. He X, Qiao Q, Ge N, Nan J, Shen S, Wang Z, Yang Y, Bao G. BMC Cancer. Epub 2022 Jul 5. DNA damage foci accumulate at a subset of telomeres in cells expressing a mutant-template telomerase RNA. Life extension is the concept of extending the human lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled limit of 125 years.. Several researchers in the area, along with "life extensionists", "immortalists" or "longevists" (those who wish to achieve longer lives themselves), postulate that future . Disclaimer, National Library of Medicine Telomerase inhibitor BIBR1532 inhibits Kras, Figure 3. For example, up-regulation of p21 expression was seen, consistent with a DNA damage response. Background Genome-wide association studies (GWAS) have identified genetic susceptibility variants for both leukocyte telomere length (LTL) and lung cancer susceptibility. Telomere maintenance via telomerase reactivation is a nearly universal hallmark of cancer cells which enables replicative immortality. 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). The mutant-template telomerase RNA caused uncapping of the telomeres. 5. Lai K. L and T.Y.W. Federal government websites often end in .gov or .mil. Identification of a specific telomere terminal transferase activity in. 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. Understanding Ras: it ain't over 'til it's over. Yu GL, Bradley JD, Attardi LD, Blackburn EH. Please enable it to take advantage of the complete set of features! Thomas . The https:// ensures that you are connecting to the Introduction. Consecutive Inhibition of Telomerase and Alternative Lengthening Pathway Promotes Hodgkin's Lymphoma Cell Death. doi: 10.1016/j.chembiol.2022.09.002. Would you like email updates of new search results? 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!". Northern blot analysis of RNA extracted from a human cancer cell line, MCF-7. Please enable it to take advantage of the complete set of features! official website and that any information you provide is encrypted An increase in telomerase activity in one context could be viewed as beneficial because it might lead to an increase in relative telomere length . Cellular and gene expression responses involved in the rapid growth inhibition of human cancer cells by RNA interference-mediated depletion of telomerase RNA. Telomerase activity analysis was . Epub 2022 Jul 15. HHS Vulnerability Disclosure, Help Before Epub 2019 Aug 13. Telomere shortness in human beings is emerging as a prognostic marker of disease risk, progression, and premature mortality in many types of cancer, including breast, prostate, colorectal, bladder, head and neck, lung, and renal cell. MEK inhibition led to reduced TERT expression and telomerase activity. Authors have no potential conflicts of interest to disclose. Telomerase inhibitor BIBR1532 inhibits Kras mutations-induced cell transformation and migration capability, Figure 4. 3. Careers. 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. This site needs JavaScript to work properly. An official website of the United States government. Suppressing the activity of telomerase, a telomeresynthesizing enzyme, and maintaining short telomeres is a protective mechanism against cancer in humans. DNA methylation of the TERT promoter and its impact on human cancer. Melanoma, an aggressive form of skin cancer, is highly dependent on telomerase to grow, . Disorders in cell circuitry during multistage carcinogenesis: the role of homeostasis. Not all cellsonly about 90% to 95% of the cellswere infected. Lower left, schematic of the uncapping of telomeres. The solution to this theoretical problem was the enzyme telomerase (1). Bookshelf -, Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, et al. KRAS-mutation status dependent effect of zoledronic acid in human non-small cell cancer preclinical models. Thus, the RNA and the protein of telomerase collaborate in the enzymatic action. Telomerase activity was found to be absent, or present at lower levels, in normal tissue. Front Cell Dev Biol. Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes. Blocking telomerase could impair fertility, wound healing, and production of blood cells and immune system cells. This new gene expression profile defined an interesting signature for telomerase knockdown, marked by diminished expression of 73 genes. 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. -cancer . Does hydatid disease have protective effects against lung cancer? Telomerase is commonly expressed in human cancer cells. Keshavarz M, Xie K, Schaaf K, Bano D, Ehninger D. Mol Psychiatry. These included some intriguing genes, such as cyclin G2 or CDC27genes that have been implicated in cell cycle progression. Mol Cancer Res 1 September 2005; 3 (9): 477482. Unable to load your collection due to an error, Unable to load your delegates due to an error, Therapeutic strategies for targeting telomerase Approaches to targeting telomerase include: 1. Please enable it to take advantage of the complete set of features! The RNA has a short template sequence that is copied into DNA, which extends, and thus lengthens, the chromosomal DNA. Thus far, everything discussed has related to telomerase acting in its familiar mode: making telomeric DNA longer. -. We aimed to assess whether 3 months of intensive lifestyle changes increased telomerase activity in peripheral blood mononuclear cells (PBMC). However, previous studies have not addressed whether improvements in nutrition and lifestyle are associated with increases in telomerase activity. These proteins include DNA sequencespecific binding proteins and other proteins that together, in effect, sheathe the chromosome end. This inactive complex swamps out the endogenous telomerase. 2022 Sep 7;58(9):1240. doi: 10.3390/medicina58091240. Today, many of those factors are known, including proteins that aid in binding to the telomere and protect it from increased by telomerase activity. cancer cells employ . In cell culture, telomere shortening leads to cell senescence as the telomeres no longer can sustain a capping structure at the ends of the chromosomes. Recent studies also suggest that telomerase is implicated in tumor . Epub 2005 Nov 17. Telomerase inhibitor BIBR1532 increases sensitivities of Kras G12D and Kras G12V -Calu-3 cells, Figure 5. The effects were different from the gene expression effects elicited by mutant-template telomerase RNA expression (7). Epub 2018 Aug 2. . The .gov means its official. Moreover, when the subjects were categorized based on the median value of telomerase activity, subjects with low telomerase activity were at a . PMC [The 2009 Nobel Prize in Medicine and its surprising message: lifestyle is associated with telomerase activity]. Telomere maintenance via telomerase reactivation is a nearly universal hallmark of cancer cells which enables replicative immortality. Nuclear telomerase extracts were obtained from human breast cancer PMC42 cells transfected for 15 h with dierent hTERT cDNA expression constructs as indicated. Epigenetics alternation in lung fibrosis and lung cancer. DNA glycosylase is the critical enzyme that initiates the base excision repair (BER) pathway, recognizing and excising damaged bases. -cancer cells show decreased telomerase activity and the telomeres are shortened. The primary endpoint was telomerase enzymatic activity per viable cell, measured at baseline and after 3 months. Similar to astragalus, extracts of cycloastragenol can increase telomerase activity. Bethesda, MD 20894, Web Policies MLL/AF4 suppression diminished telomerase activity and expression of TERT. Telomerase as a therapeutic target in glioblastoma. Therefore, Shang Li developed a short-term expression system for mutant-template telomerase RNA (6). Telomerase contains an RNA component. After 30 days, the tumor burden in the lungs, representing metastatic tumors in the lungs, was quantified. Interestingly, Zhang et al. 1994;266:20115. 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)). Targeting. Tsirpanlis G, Chatzipanagiotou S, Boufidou F, Kordinas V, Alevyzaki F, Zoga M, Kyritsis I, Stamatelou K, Triantafyllis G, Nicolaou C. Am J Nephrol. Genes Dev. The slowing of cellular proliferation did not require the protein p53, which is ordinarily involved in the responses of cells to DNA damage. 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. The .gov means its official. In collaboration with Jerry Cunha's lab at University of California, San Francisco, human bladder tumor cells were xenografted under the renal capsule in a mouse. Lifestyle factors known to promote cancer and cardiovascular disease might also adversely affect telomerase function. Telomerase levels are very highly regulated in normal human cells. 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). Methods: Gupta N, Patel HD, Taylor J, Borin JF, Jacobsohn K, Kenfield SA, Eggener SE, Price C, Davuluri M, Byrne N, Bivalacqua TJ, Loeb S. Prostate Cancer Prostatic Dis. The ribozyme treatment decreased the metastatic burden. Telomerase therapy has been shown to improve healthspan in mice and to increase survival in patients with cancer. These findings suggest that telomerase activity may affect telomere maintenance, thereby contributing to susceptibility to lung cancer. Telomerase activity is essential for the maintenance of critical telomere length, enabling cell replicative immortality, one of the hallmarks of cancer .