The DOI matches its Crossref record; 47 of the 48 references it cites were found in a registry or an index; none of the 49 sources its claims cite is checked for support yet.
Inhibition of human telomerase in immortal human cells leads to progressive telomere shortening and cell death
Open accessAbstract
The correlation between telomerase activity and human tumors has led to the hypothesis that tumor growth requires reactivation of telomerase and that telomerase inhibitors represent a class of chemotherapeutic agents. Herein, we examine the effects of inhibition of telomerase inside human cells. Peptide nucleic acid and 2′ -O- MeRNA oligomers inhibit telomerase, leading to progressive telomere shortening and causing immortal human breast epithelial cells to undergo apoptosis with increasing frequency until no cells remain. Telomere shortening is reversible: if inhibitor addition is terminated, telomeres regain their initial lengths. Our results validate telomerase as a target for the discovery of anticancer drugs and supply general insights into the properties that successful agents will require regardless of chemical type. Chemically similar oligonucleotides are in clinical trials and have well characterized pharmacokinetics, making the inhibitors we describe practical lead compounds for testing for an antitelomerase chemotherapeutic strategy.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Inhibiting telomerase in immortal human cells with 2′-O-MeRNA or PNA oligonucleotides caused progressive telomere shortening, apoptosis, and eventual loss of proliferation. Telomere shortening and growth arrest were reversible when inhibitor treatment was stopped.
Key findings
- Complementary 2′-O-MeRNA inhibited >95% of telomerase activity 1 day after transfection and >70% at 3 days. HME50-5E proliferation slowed after 15–25 days, and no treated cells remained after 110 days; apoptosis rose from <5% during the first 60 days to 14% at 80 days and 56% at 100 days, versus 2–3% in controls.
- DU145 cells began slowing after 60 days and had undergone 20 fewer population doublings than mismatch-treated cells by 120 days. HME50-hTERT cells, with longer telomeres, showed no significant growth reduction over 120 days.
- Mean telomere restriction fragment length decreased from 2,000 to 1,700 bp in HME50-5E cells by 60 days, from 3,600 to 2,200 bp in DU145 cells by 76 days, and from 7,600 to 6,800 bp in HME50-hTERT cells after 75 days. A template-directed PNA inhibited >90% of telomerase activity at 1 day and shortened telomeres, whereas a nontemplate PNA inhibited only 50% and did not shorten telomeres.
- After inhibitor withdrawal at 76 days, eroded telomeres returned to approximately initial lengths within 3 weeks, and previously static HME50-5E cells regained growth within 3 weeks. No evidence for an ALT pathway was observed.
Methods
- Immortal human cell lines HME50-5E, DU145, and HME50-hTERT were transfected with 2′-O-MeRNA or PNA/DNA complexes using cationic lipids; treatment was repeated every 3–4 days for 120 days, with mismatch oligomers, lipid alone, or nontemplate PNA as controls.
- Telomerase activity was measured by TRAP, mean telomere length by telomere restriction fragment Southern analysis, apoptosis by Annexin V flow cytometry, and proliferation by cell counts/population doublings.
- Effects of matched versus mismatched or nontemplate inhibitors were compared over time to test sequence-specific, telomerase-dependent mechanisms.
Limitations
- Stated in the paper: the TRF assay does not monitor subtelomeric erosion and may underestimate total telomeric DNA loss; 5–30% of telomerase activity remained after treatment; systemic telomerase inhibition would also affect normal stem cells; the long lag before phenotypic effects complicates drug development; and no ALT pathway was observed in these cell types, leaving applicability to ALT-positive tumors uncertain.
- Evident from the text: findings are in vitro in a small number of immortal cell lines, including p53-mutant lines, with no animal or human efficacy/toxicity data; the 120-day culture experiments required stringent precautions against contamination but remain vulnerable to long-term culture artifacts.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 49 cited sources checked · 0 supported · 0 flagged
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and this percentage increased to 56% after 100 days”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Within 60 days of treatment, the mean telomere length of HME50-5E cells treated with 2′-O-MeRNA complementary to hTR was reduced from 2,000 to 1,700 bp (Fig. 4a).”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“leading to progressive telomere shortening”
- Also stated in: § Abstract · plain
“cause telomeres to shorten”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The growth of cells treated with the control oligomer containing mismatch bases was not affected.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By 80 days, however, 14% of cells treated with the match oligomer were observed to undergo apoptosis”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Peptide nucleic acid and 2′-O-MeRNA oligomers inhibit telomerase”
- Also stated in: § Abstract · plain
“We observe that 2′-O-MeRNA and peptide nucleic acid (PNA) oligomers complementary to the template region of hTR inhibit telomerase”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By the end of the experiment (after 120 days), these cells had undergone 20 fewer population doublings than had cells treated with mismatch-containing oligomer.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By contrast, cells treated with lipid alone or the 2′-O-MeRNA oligomer containing mismatched bases underwent apoptosis at a rate of 2–3% throughout the entire experiment.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“HME50-hTERT cells have a much longer mean TRF length (7.6 kilobases) than either HME50-5E or DU145 cells”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Telomere shortening is reversible: if inhibitor addition is terminated, telomeres regain their initial lengths.”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear? Based: unclear
- It may state two separate claims as one. 14
- Probably not a substantial claim. 23
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The TRF length of cells treated with 2-O-MeRNA containing mismatches relative to hTR remained at 2,000 bp, and the signal intensity of probe hybridization was undiminished.”
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observe telomere shortening and decreased cell proliferation, even though between 5% and 30% of telomerase activity remained after treatment with inhibitor.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Telomerase activity has been found in almost all human tumors but not in adjacent normal cells (3, 4).”
What the sources say
- Not checked yetcites [3] Kim N W, Piatyszek M A, Prowse K R, Harley C B, West M D, Ho P L C, Coviello G M, Wright W E, Weinrich S L, Shay J W. Science. 1994;266:2011–2015. doi: 10.1126/science.7605428. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [4] Counter C M, Hirte H W, Bachetti S, Harley C B. Proc Natl Acad Sci USA. 1994;91:2900–2904. doi: 10.1073/pnas.91.8.2900. [DOI] [PMC free article] [PubMed] [Google Scholar] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Human telomerase is a ribonucleoprotein that adds repeated units of TTAGGG to the ends of telomeres (1, 2).”
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“The levels of telomerase activity were within the linear range of the TRAP assay (40).”
What the sources say
- Not checked yetcites [40] Holt S E, Norton J C, Wright W E, Shay J W. Methods Cell Sci. 1996;18:237–248. [Google Scholar] source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“or tumor aggressiveness (11, 12).”
What the sources say
- Not checked yetcites [11] Ohyashiki J H, Ohyashiki K, Iwama I, Hayashi S, Toyama K, Shay J W. Clin Cancer Res. 1997;3:619–625. [PubMed] [Google Scholar]
- Not checked yetcites [12] Hoos A, Hepp H H, Kaul S, Ahlert T, Bastert G, Wallwiener D. Int J Cancer. 1998;79:8–12. doi: 10.1002/(sici)1097-0215(19980220)79:1<8::aid-ijc2>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“recent reports of the effect of the mTR deletion in different genetic backgrounds (17, 18) suggest that the role of telomerase in cancer development could be highly context dependent (19).”
What the sources say
- Not checked yetcites [17] Greenberg R, Chin L, Femino A, Lee K, Gottlieb G J, Greider C W, DePinho R A. Cell. 1999;97:515–525. doi: 10.1016/s0092-8674(00)80761-8. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [18] Chin L, Artandi S E, Shen Q, Tam A, Lee S L, Gottlieb G J, Greider C W, DePinho R A. Cell. 1999;97:527–538. doi: 10.1016/s0092-8674(00)80762-x. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [19] de Lange T, Jacks T. Cell. 1999;98:273–275. doi: 10.1016/s0092-8674(00)81955-8. [DOI] [PubMed] [Google Scholar] source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The cells divide normally until telomeres shorten sufficiently to affect proliferation. At this stage, most cells die”
What the sources say
- Not checked yetcites [31] Lunblad V, Blackburn E H. Cell. 1993;73:347–360. doi: 10.1016/0092-8674(93)90234-h. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“expression of telomerase in conjunction with expression of simian virus 40 large T oncoprotein and an oncogenic allele of H-ras has been shown to promote tumorigenic conversion of normal human cells (28).”
What the sources say
- Not checked yetcites [28] Hahn W C, Counter C M, Lundberg A S, Beijersbergen R L, Brooks M W, Weinberg R A. Nature (London) 1999;400:464–468. doi: 10.1038/22780. [DOI] [PubMed] [Google Scholar] source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“whereas the late-stage disease has high telomerase activity and correlates with a poor outcome (6).”
What the sources say
- Not checked yetcites [6] Hiyama E, Hiyama K, Yokoyama T, Matsuura Y, Piatyszek M A, Shay J W. Nat Med. 1995;1:249–255. doi: 10.1038/nm0395-249. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This decrease in measured TRF length may be an underestimate of the total loss of chromosomal DNA, because the TRF assay does not monitor erosion of subtelomeric regions and because relatively little telomeric DNA remained to hybridize with radiolabeled probe.”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“The 2′-O-MeRNA inhibitor contained four phosphorothioate linkages, a chemical moiety noted for its propensity to produce misleading cellular effects that seem sequence-specific but are actually unrelated to binding to the intended target (42).”
What the sources say
- Not checked yetcites [42] Stein C A. Antisense Res Dev. 1997;7:207–209. [Google Scholar]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the lack of telomerase expression seems to curb growth of rapidly proliferating cells eventually, whereas an increase in telomerase permits indefinite proliferation.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Mutation of the RNA component of telomerase of Tetrahymena (20), Kluyveromyces lactis (21), Saccharomyces cerevisiae (22)”
What the sources say
- Not checked yetcites [20] Yu G-L, Bradley J D, Attardi L D, Blackburn E H. Nature (London) 1990;344:126–132. doi: 10.1038/344126a0. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [21] McEachern M J, Blackburn E H. Nature (London) 1995;376:403–409. doi: 10.1038/376403a0. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [22] Singer M S, Gottschling D E. Science. 1994;266:404–409. doi: 10.1126/science.7545955. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, although telomerase activity can confer extended life span to cells, other mechanisms may also exist.”
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Telomerase will be an unusually challenging target for drug development because of the long lag period expected before telomeres would shorten sufficiently to produce detrimental effects on cell growth and because of the possibility of alternate mechanisms for maintenance of telomeres.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“other studies have suggested that telomerase activity is correlated with the pathologic stage (8–11)”
What the sources say
- Not checked yetcites [8] Albanell J, Lonardo F, Rusch V, Engelhardt M, Langenfeld J, Han W, Klimstra D, Venkatraman E, Moore M A S, Dmitrovsky E. J Natl Cancer Inst. 1997;89:1609–1615. doi: 10.1093/jnci/89.21.1609. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [9] Tahara H, Kuniyasu H, Yokozaki H, Yasui W, Shay J W, Ide T, Tahara E. Clin Cancer Res. 1995;1:1245–1251. [PubMed] [Google Scholar]
- Not checked yetcites [10] Engelhardt M, Drullinsky P, Guillem J, Moore M A. Clin Cancer Res. 1997;3:1931–1941. [PubMed] [Google Scholar]
- Not checked yetcites [11] Ohyashiki J H, Ohyashiki K, Iwama I, Hayashi S, Toyama K, Shay J W. Clin Cancer Res. 1997;3:619–625. [PubMed] [Google Scholar]
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“but some rare survivors continue to proliferate through a recombination mechanism to maintain telomere length.”
What the sources say
- Not checked yetcites [31] Lunblad V, Blackburn E H. Cell. 1993;73:347–360. doi: 10.1016/0092-8674(93)90234-h. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“a few rare tumors (29) and some experimentally immortalized cell lines (30) lack detectable telomerase activity.”
What the sources say
- Not checked yetcites [29] Gupta J, Han L P, Wang P, Bacchetti S. J Natl Cancer Inst. 1996;88:1152–1157. doi: 10.1093/jnci/88.16.1152. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [30] Bryan T M, Englezou A, Dalla-Pozza L, Dunham M A, Reddel R R. Nat Med. 1997;3:1271–1274. doi: 10.1038/nm1197-1271. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To confirm that the effects of inhibitor addition were reproducible, treatment of HME50-5E cells with 2′-O-MeRNA was repeated, and a similar decrease in proliferation was observed.”
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Because of the extreme length of these experiments, stringent precautions were taken to avoid contamination of cultured cells, and all experiments were completed successfully without interruption.”
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Recent work with PNAs introduced into cells by electroporation has shown decreased cell viability, supporting our findings (49).”
What the sources say
- Not checked yetcites [49] Shammas M A, Simmons C S, Corey D R, Shmookler-Reis R J. Oncogene. 1999;18:6191–6200. doi: 10.1038/sj.onc.1203069. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This inhibition may result in few side effects, because the relatively short telomeres of tumors may erode to a critical length before irreversible harm is done to other cells.”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Telomerase is an ideal target for oligonucleotides, because its RNA template is essential for activity and is intrinsically accessible to binding by nucleic acids.”
- Also stated in: § Discussion · plain
“The exposed RNA template of hTR makes telomerase an ideal target for oligonucleotides”
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Also stated in: § Discussion · plain
None of the sources cited for this claim have been checked yet.
In the paper
“In addition, 2′-O-MeRNA and other 2′-O-alkyl-derivatized oligomers bind more tightly to complementary RNA sequences than do analogous DNA oligomers”
What the sources say
- Not checked yetcites [45] Agrawal S, Jiang Z, Zhao Q, Shaw D, Cai Q, Roskey A, Channavajjala L, Saxinger C, Zhang R. Proc Natl Acad Sci USA. 1997;94:2620–2625. doi: 10.1073/pnas.94.6.2620. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [46] Zhou W, Agrawal S. Bioorg Med Chem Lett. 1998;8:3269–3274. doi: 10.1016/s0960-894x(98)00591-5. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Systemic administration of telomerase inhibitors will also inhibit telomerase in normal stem cells.”
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“Oligonucleotides are being tested in 13 ongoing clinical trials (43)”
What the sources say
- Not checked yetcites [43] Hogrefe R I. Antisense Nucleic Acid Drug Dev. 1999;9:351–357. doi: 10.1089/oli.1.1999.9.351. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Tu et al. (47) have performed a comprehensive survey of the literature, leading Stein (48) to estimate that non-sequence-selective effects may be at least partially implicated in results reported in 94% of the 2,026 studies published through 1997.”
What the sources say
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“and have improved resistance to degradation by nucleases, reducing the need for phosphorothioate linkages and improving the selectivity of antisense effects (45, 46)”
What the sources say
- Not checked yetcites [45] Agrawal S, Jiang Z, Zhao Q, Shaw D, Cai Q, Roskey A, Channavajjala L, Saxinger C, Zhang R. Proc Natl Acad Sci USA. 1997;94:2620–2625. doi: 10.1073/pnas.94.6.2620. [DOI] [PMC free article] [PubMed] [Google Scholar] source
- Not checked yetcites [46] Zhou W, Agrawal S. Bioorg Med Chem Lett. 1998;8:3269–3274. doi: 10.1016/s0960-894x(98)00591-5. [DOI] [PubMed] [Google Scholar] source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Indeed, we have previously observed that oligonucleotides that contain uniform phosphorothioate oligonucleotides inhibit telomerase in a non-sequence-specific fashion, presumably through binding to hTERT (38).”
What the sources say
- Not checked yetcites [38] Pitts A E, Corey D R. Proc Natl Acad Sci USA. 1998;95:11549–11554. doi: 10.1073/pnas.95.20.11549. [DOI] [PMC free article] [PubMed] [Google Scholar] source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“one oligonucleotide, Fomivirsen, has been approved for the treatment of cytomegalovirus retinitis (44).”
What the sources say
- Not checked yetcites [44] Marwick C. J Am Med Assoc. 1998;280:871. [Google Scholar] source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The mice used in these experiments possessed much longer telomeres than those found in cancerous human cells.
“the mice used in these experiments possessed much longer telomeres than those found in cancerous human cells”
The paper relies on this without support.
Chemically similar oligonucleotides are in clinical trials and have well characterized pharmacokinetics.
“Chemically similar oligonucleotides are in clinical trials and have well characterized pharmacokinetics”
The paper relies on this without support.
HME50-5E cells were derived from HME50 preimmortal cells that had one mutant p53 allele and lost the second allele during spontaneous immortalization.
“HME50-5E cells were derived from HME50 preimmortal cells that had one mutant p53 allele and lost the second allele during spontaneous immortalization”
The paper relies on this without support.
DU145 cells have two mutant p53 alleles.
“whereas DU145 cells have two mutant alleles”
The paper relies on this without support.
The genetic background of HME50-hTERT cells is similar to that of HME50-5E cells.
“even though the genetic background of HME50-hTERT cells is similar to that of HME50-5E cells”
The paper relies on this without support.
HME50-5E cells have shorter telomeres than DU145 cells.
“which have shorter telomeres than DU145 cells”
The paper relies on this without support.
HME50-hTERT cells have an initial telomere length approximately 4,000 bp longer than that of HME50-5E cells.
“their initial telomere length of HME50-hTERT cells is approximately 4,000 bp longer.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Induction of ALT has also never been reported in previous publications using other means of telomerase inhibition (Hahn et al., 1999b;Herbert et al., 1999;Zhang et al., 1999).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Herbert et al., 1999
In the citing paper
“Several strategies to inhibit telomerase activity have been reported.These include peptide nucleic acids and 2¢-O-MeRNA oligonucleotides directed towards the telomerase RNA template (Herbert et al., 1999), compounds that target telomeric DNA such as cationic porphyrins or anthraquinones (Sun et al., 1997) and nucleosidic reverse transcriptase inhibitors (Strahl and Blackburn, 1996).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Herbert et al., 1999
In the citing paper
“In contrast to previous results employing anti-sense oligonucleotides or the expression of dominant-negative hTERT alleles (Hahn et al., 1999b;Herbert et al., 1999;Zhang et al., 1999) we saw no evidence for an increased rate of apoptosis in the inhibitor-treated cells.”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Herbert et al., 1999
Citations
Cites
Specific Association of Human Telomerase Activity with Immortal Cells and Cancer
Kim, N. W., Piatyszek, M. A., Prowse, K. R., Harley, C. B., West, M. D., Ho, P. L. C., Coviello, G. M., Wright, W. E., Weinrich, S. L., & Shay, J. W. (1994) · Science · doi:10.1126/science.7605428 · Cited by 7,091
Self-citationExtension of Life-Span by Introduction of Telomerase into Normal Human Cells
Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chiu, C.-P., Morin, G. B., Harley, C. B., Shay, J. W., Lichtsteiner, S., & Wright, W. E. (1998) · Science · doi:10.1126/science.279.5349.349 · Cited by 4,975
Self-citationSequence-Selective Recognition of DNA by Strand Displacement with a Thymine-Substituted Polyamide
Nielsen, P. E., Egholm, M., Berg, R. H., & Buchardt, O. (1991) · Science · doi:10.1126/science.1962210 · Cited by 3,332
Creation of human tumour cells with defined genetic elements
Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999) · Nature · doi:10.1038/22780 · Cited by 2,345
The RNA Component of Human Telomerase
Feng, J., Funk, W. D., Wang, S.-S., Weinrich, S. L., Avilion, A. A., Chiu, C.-P., Adams, R. R., Chang, E., Allsopp, R. C., Yu, J., et al. (1995) · Science · doi:10.1126/science.7544491 · Cited by 2,227
Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA
Blasco, M. A., Lee, H.-W., Hande, M. P., Samper, E., Lansdorp, P. M., DePinho, R. A., & Greider, C. W. (1997) · Cell · doi:10.1016/s0092-8674(01)80006-4 · Cited by 2,108
Morin, G. B. (1989) · Cell · doi:10.1016/0092-8674(89)90035-4 · Cited by 1,495
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice
Rudolph, K. L., Chang, S., Lee, H.-W., Blasco, M., Gottlieb, G. J., Greider, C., & DePinho, R. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80580-2 · Cited by 1,349
Bryan, T. M., Englezou, A., Dalla-Pozza, L., Dunham, M. A., & Reddel, R. R. (1997) · Nature Medicine · doi:10.1038/nm1197-1271 · Cited by 1,292
Essential role of mouse telomerase in highly proliferative organs
Lee, H.-W., Blasco, M. A., Gottlieb, G. J., Horner, J. W., Greider, C. W., & DePinho, R. A. (1998) · Nature · doi:10.1038/33345 · Cited by 1,270
Flagged first, then by citations
1 of the 48 references couldn’t be matched to a known paper.
Research works printed but not linked: 5
- H Tahara, H Kuniyasu, H Yokozaki, W Yasui, J W Shay, T Ide, E Tahara Clin Cancer Res 1, 1245–1251 (1995).
- M Engelhardt, P Drullinsky, J Guillem, M A Moore Clin Cancer Res 3, 1931–1941 (1997).
- J H Ohyashiki, K Ohyashiki, I Iwama, S Hayashi, K Toyama, J W Shay Clin Cancer Res 3, 619–625 (1997).
- J W Shay, D Brasiskyte, M Ouellette, M A Piatyszek, H Werbin, Y Ying, W E Wright Methods Mol Genet 5, 263–268 (1994).
- C A Stein Antisense Res Dev 7, 207–209 (1997).
Cited by
Sorted by citations
Items 101–200 of 541
On the road to immortality: hTERT upregulation in cancer cells
Janknecht, R. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00356-4 · Cited by 118
Telomerase inhibition as cancer therapy
Saretzki, G. C. (2003) · Cancer Letters · doi:10.1016/s0304-3835(02)00708-5 · Cited by 114
Parkhurst, M. R., Riley, J. P., Igarashi, T., Li, Y., Robbins, P. F., & Rosenberg, S. A. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-0325 · Cited by 111
Total Synthesis of Dictyodendrin B
Fürstner, A., Domostoj, M. M., & Scheiper, B. (2005) · Journal of the American Chemical Society · doi:10.1021/ja0541175 · Cited by 108
Treating Cancer by Targeting Telomeres and Telomerase
Ivancich, M., Schrank, Z., Wojdyla, L. M., Leviskas, B., Kuckovic, A., Sanjali, A., & Puri, N. (2017) · Antioxidants · doi:10.3390/antiox6010015 · Cited by 109
From bench to bedside: the growing use of translational research in cancer medicine.
Goldblatt, E. M., & Lee, W. (2010) · PubMed Central · Cited by 106
de Magalhães, J. P. (2004) · Experimental Cell Research · doi:10.1016/j.yexcr.2004.07.006 · Cited by 108
Regulation of Telomerase and Telomeres: Human Tumor Viruses Take Control
Bellon, M., & Nicot, C. (2008) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djm269 · Cited by 104
Horner, S. M., DeFilippis, R. A., Manuelidis, L., & DiMaio, D. (2004) · Journal of Virology · doi:10.1128/jvi.78.8.4063-4073.2004 · Cited by 102
Vonderheide, R. H., Anderson, K. S., Hahn, W. C., Butler, M. O., Schultze, J. L., & Nadler, L. M. (2001) · PubMed · Cited by 102
Inhibition of telomerase activity and induction of apoptosis by curcumin in K-562 cells
Chakraborty, S., Ghosh, U., Bhattacharyya, N. P., Bhattacharya, R. K., & Roy, M. (2006) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.12.007 · Cited by 101
Meeker, A. K., & Argani, P. (2004) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/b:jomg.0000048775.04140.92 · Cited by 100
Dası́, F., Lledó, S., García‐Granero, E., Ripoll, R., Marugán, M., Tormo, M., García-Conde, J., & Aliño, S. F. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780285 · Cited by 100
Domchek, S. M., Recio, A., Mick, R., Clark, C. E., Carpenter, E. L., Fox, K. R., DeMichele, A. M., Schuchter, L. M., Leibowitz, M. S., Wexler, M. H., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2765 · Cited by 103
The length of telomeric G-rich strand 3'-overhang measured by oligonucleotide ligation assay
Cimino-Reale, G. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.7.e35 · Cited by 98
Saretzki, G. C., Ludwig, A., von Zglinicki, T., & Runnebaum, I. B. (2001) · Cancer Gene Therapy · doi:10.1038/sj.cgt.7700383 · Cited by 100
Telomerase inhibition, oligonucleotides, and clinical trials
Corey, D. R. (2002) · Oncogene · doi:10.1038/sj.onc.1205063 · Cited by 97
Self-citationTelomeres and Age-Related Diseases
Gruber, H., Semeraro, M. D., Renner, W., & Herrmann, M. (2021) · Biomedicines · doi:10.3390/biomedicines9101335 · Cited by 102
Pizzimenti, S., Toaldo, C., Pettazzoni, P., Dianzani, M. U., & Barrera, G. (2010) · Cancers · doi:10.3390/cancers2020338 · Cited by 98
Ren, J., Xia, H., Just, T., & Dai, Y. (2001) · FEBS Letters · doi:10.1016/s0014-5793(00)02377-2 · Cited by 96
Telomerase in Cancer: Function, Regulation, and Clinical Translation
Robinson, N. J., & Schiemann, W. P. (2022) · Cancers · doi:10.3390/cancers14030808 · Cited by 105
Choi, S. H., Lyu, S. Y., & Park, W. B. (2004) · Archives of Pharmacal Research · doi:10.1007/bf02980049 · Cited by 94
The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity
Zhang, D.-H. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl029 · Cited by 97
Anniballo, R. (2000) · Human Reproduction · doi:10.1093/humrep/15.11.2269 · Cited by 94
Massive Telomere Loss Is an Early Event of DNA Damage-induced Apoptosis
Ramı́rez, R., Carracedo, J., Jiménez, R., Canela, A., Herrera, E., Aljama, P., & Blasco, M. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m206818200 · Cited by 94
Telomerase: regulation, function and transformation
Dong, C. K., Masutomi, K., & Hahn, W. C. (2005) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2004.12.005 · Cited by 96
The significance of telomerase activation and cellular immortalization in human cancer
Newbold, R. F. (2002) · Mutagenesis · doi:10.1093/mutage/17.6.539 · Cited by 94
Telomeres and telomerase as targets for anticancer drug development
Olaussen, K. A., Dubrana, K., Dômont, J., Spano, J., Sabatier, L., & Soria, J. (2006) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2005.08.007 · Cited by 96
Telomerase Can Inhibit the Recombination-based Pathway of Telomere Maintenance in Human Cells
Ford, L. P., Zou, Y. S., Pongracz, K., Gryaznov, S. M., Shay, J. W., & Wright, W. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104469200 · Cited by 92
Self-citationBrodyagin, N., Katkevičs, M., Kotikam, V., Ryan, C. A., & Rozners, E. (2021) · Beilstein Journal of Organic Chemistry · doi:10.3762/bjoc.17.116 · Cited by 94
Zhao, Y. B., Abreu, E. B., Kim, J., Stadler, G., Eskiocak, U., Terns, M. P., Terns, R. M., Shay, J. W., & Wright, W. E. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.03.020 · Cited by 92
Self-citationTelomere Maintenance as a Target for Drug Discovery
Sekaran, V. G., Soares, J., & Jarstfer, M. B. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400528t · Cited by 94
Simultaneous targeting of telomeres and telomerase as a cancer therapeutic approach.
Mo, Y., Gan, Y., Song, S., Johnston, J. S., Xiao, X., Wientjes, M. G., & Au, J. L. ‐. (2003) · PubMed · Cited by 90
Telomerase and its potential for therapeutic intervention
Phatak, P., & Burger, A. M. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707374 · Cited by 94
Telomere dysfunction in aging and cancer
Gilley, D. P., Tanaka, H., & Herbert, B. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.09.003 · Cited by 90
Self-citationTelomerase inhibition and cell growth arrest by G-quadruplex interactive agent in multiple myeloma.
Shammas, M. A., Reis, R. J. S., Akiyama, M., Koley, H., Chauhan, D., Hideshima, T., Goyal, R. K., Hurley, L. H., Anderson, K. C., & Munshi, N. C. (2003) · PubMed · Cited by 88
Kummer, S., Knoll, A., Socher, E. R., Bethge, L., Herrmann, A., & Seitz, O. (2012) · Bioconjugate Chemistry · doi:10.1021/bc300249f · Cited by 88
Cellular Senescence in the Development and Treatment of Cancer
Saretzki, G. C. (2009) · Current Pharmaceutical Design · doi:10.2174/138161210789941874 · Cited by 92
Franco, S., Segura, I., Riese, H. H., & Blasco, M. A. (2002) · PubMed · Cited by 88
Immortalization and Transformation of Human Cells
Hahn, W. C. (2002) · Molecules and Cells · doi:10.1016/s1016-8478(23)15045-x · Cited by 84
Akiyama, M., Hideshima, T., Shammas, M. A., Hayashi, T., Hamasaki, M., Tai, Y., Richardson, P. G. G., Gryaznov, S. M., Munshi, N. C., & Anderson, K. C. (2003) · PubMed · Cited by 84
RetractedWang, E. S., Wu, K., Chin, A. C., Chen‐Kiang, S., Pongracz, K., Gryaznov, S. M., & Moore, M. A. S. (2003) · Blood · doi:10.1182/blood-2003-02-0546 · Cited by 83
Ouchi, H., Ishiguro, H., IKEDA, N., Hori, M., Kubota, Y., & Uemura, H. (2005) · International Journal of Urology · doi:10.1111/j.1442-2042.2004.00973.x · Cited by 81
Ford, L. P., Suh, J. M., Wright, W. E., & Shay, J. W. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.23.9084-9091.2000 · Cited by 82
Self-citationRecognition of Chromosomal DNA by PNAs
Kaihatsu, K., Janowski, B. A., & Corey, D. R. (2004) · Chemistry & Biology · doi:10.1016/j.chembiol.2003.09.014 · Cited by 81
Self-citationUziel, O., Fenig, E., Nordenberg, J., Beery, E., Reshef, H., Sandbank, J., Birenbaum, M., Bakhanashvili, M., Yerushalmi, R., Luria, D., et al. (2005) · British Journal of Cancer · doi:10.1038/sj.bjc.6602592 · Cited by 78
Telomerase as a therapeutic target for malignant gliomas
Komata, T., Kanzawa, T., Kondo, Y., & Kondo, S. (2002) · Oncogene · doi:10.1038/sj.onc.1205072 · Cited by 78
siRNA therapeutics and its challenges: Recent advances in effective delivery for cancer therapy
Paul, A., Muralidharan, A., Biswas, A., Kamath, B. V., Joseph, A., & Alex, A. T. (2022) · OpenNano · doi:10.1016/j.onano.2022.100063 · Cited by 81
Taetz, S., Nafee, N. A., Beisner, J., Piotrowska, K., Baldes, C., Mürdter, T. E., Huwer, H., Schneider, M., Schaefer, U. F., & Klotz, U. E. (2008) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2008.07.011 · Cited by 77
Vonderheide, R. H., Schultze, J. L., Anderson, K. S., Maecker‐Kolhoff, B., Butler, M. O., Xia, Z., Kuroda, M. J., von Bergwelt‐Baildon, M. S., Bedor, M., Hoar, K. M., et al. (2001) · PubMed · Cited by 77
Folini, M., Berg, K., Millo, E., Villa, R., Prasmickaite, L., Daidone, M. G., Benatti, U., & Zaffaroni, N. (2003) · PubMed · Cited by 77
Liu, X., Zhou, Y., Lou, Y., & Zhong, H. (2015) · Gene · doi:10.1016/j.gene.2015.11.009 · Cited by 76
Adding to the ends: what makes telomerase processive and how important is it?
Lue, N. F. (2004) · BioEssays · doi:10.1002/bies.20093 · Cited by 78
Telomerase-independent Regulation of ATR by Human Telomerase RNA
Kedde, M., le Sage, C., Duursma, A. M., Zlotorynski, E., van Leeuwen, B., Nijkamp, W., Beijersbergen, R. L., & Agami, R. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m607676200 · Cited by 78
Telomeres, Telomerase, and Cancer
Buys, C. H. C. M. (2000) · New England Journal of Medicine · doi:10.1056/nejm200004273421710 · Cited by 76
Potent Inhibition of Human Telomerase by Nitrostyrene Derivatives
Kim, J., Kim, J. H., Lee, G. E., Lee, J. E., & Chung, I. K. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.5.1117 · Cited by 75
Therapeutic targeting of replicative immortality
Yaswen, P., MacKenzie, K. L., Keith, W. N., Hentosh, P., Rodier, F., Zhu, J., Firestone, G. L., Matheu, A., Carnero, A., Bilsland, A. E., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.03.007 · Cited by 82
Xia, W., Wang, P., Lin, C., Li, Z., Gao, X., Wang, G., & Zhao, X. (2011) · Journal of Controlled Release · doi:10.1016/j.jconrel.2011.10.011 · Cited by 74
Akiyama, M., Yamada, O., Kanda, N., Akita, S., Kawano, T., Ohno, T., Mizoguchi, H., Eto, Y., Anderson, K. C., & Yamada, H. (2002) · Cancer Letters · doi:10.1016/s0304-3835(01)00838-2 · Cited by 74
Petraccone, L., Erra, E., Esposito, V., Randazzo, A., Mayol, L., Nasti, L., Barone, G., & Giancola, C. (2004) · Biochemistry · doi:10.1021/bi0300985 · Cited by 74
Ren, J., Xia, H., Tian, Y.-M., Just, T., Cai, G., & Dai, Y. (2001) · FEBS Letters · doi:10.1016/s0014-5793(00)02397-8 · Cited by 74
Masutomi, K., & Hahn, W. C. (2003) · Cancer Letters · doi:10.1016/s0304-3835(02)00703-6 · Cited by 75
Dyskeratosis congenita, telomeres and human ageing
Marciniak, R. A., Johnson, F. B., & Guarente, L. (2000) · Trends in Genetics · doi:10.1016/s0168-9525(00)01984-3 · Cited by 74
Gómez‐Millán, J., Goldblatt, E. M., Gryaznov, S. M., Mendonca, M. S., & Herbert, B. (2006) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2006.09.038 · Cited by 74
Self-citationPNA oligomers as tools for specific modulation of gene expression
Pooga, M., Land, T., Bartfai, T., & Langel, Ü. (2001) · Biomolecular Engineering · doi:10.1016/s1389-0344(01)00075-2 · Cited by 74
Allsopp, R., & Weissman, I. L. (2002) · Oncogene · doi:10.1038/sj.onc.1205314 · Cited by 71
In Vivo Regulation of hTERT Expression and Telomerase Activity by Androgen.
Guo, C., Armbruster, B. N., PRICE, D. T., & Counter, C. M. (2003) · The Journal of Urology · doi:10.1097/01.ju.0000074653.22766.c8 · Cited by 70
Cerone, M. A., Londoño‐Vallejo, A., & Autexier, C. (2006) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0033 · Cited by 71
Ji, Z., Ye, W., Liu, G.-G., & Hsiao, W. L. W. (2002) · Life Sciences · doi:10.1016/s0024-3205(02)02176-8 · Cited by 69
Synthesis, Analysis, Purification, and Intracellular Delivery of Peptide Nucleic Acids
Braasch, D. A., & Corey, D. R. (2001) · Methods · doi:10.1006/meth.2000.1111 · Cited by 69
Self-citationTELOMERASE INHIBITORS – OLIGONUCLEOTIDE PHOSPHORAMIDATES AS POTENTIAL THERAPEUTIC AGENTS
Gryaznov, S. M., Pongracz, K., Matray, T. J., Schultz, R. G., Pruzan, R., Aimi, J., Chin, A., Harley, C. B., Herbert, B., Shay, J. W., et al. (2001) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1081/ncn-100002314 · Cited by 67
Self-citationGoldblatt, E. M., Gentry, E. R., Fox, M. J., Gryaznov, S. M., Shen, C., & Herbert, B. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-1188 · Cited by 67
Self-citationTelomeres, telomerase, and tumorigenesis--a review.
Lin, K. W. (2004) · PubMed Central · Cited by 66
Chen, Z., Koeneman, K. S., & Corey, D. R. (2003) · PubMed · Cited by 65
Self-citationTelomeres and Telomerase: From Discovery to Clinical Trials
Corey, D. R. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.12.001 · Cited by 69
Self-citationMCAF1/AM Is Involved in Sp1-mediated Maintenance of Cancer-associated Telomerase Activity
Liu, L., Ishihara, K., Ichimura, T., Fujita, N., Hino, S., Tomita, S., Watanabe, S., Saitoh, N., Ito, T., & Nakao, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m807098200 · Cited by 66
Telomeres, senescence, and hematopoietic stem cells
Zimmermann, S., & Martens, U. M. (2007) · Cell and Tissue Research · doi:10.1007/s00441-007-0469-4 · Cited by 66
Dupont, J., Latouche, J., Ma, C., & Sadelain, M. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-2991 · Cited by 63
Telomeres and telomerase as targets for cancer therapy
Zimmermann, S., & Martens, U. M. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-6481-8 · Cited by 63
Telomerase as a universal tumor antigen for cancer vaccines
Beatty, G. L., & Vonderheide, R. H. (2008) · Expert Review of Vaccines · doi:10.1586/14760584.7.7.881 · Cited by 70
Wang, Y., Cheng, F. X., Yuan, X. L., Tang, W. J., Shi, J., Liao, C., & Liu, X. H. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.02.009 · Cited by 62
Convergent Synthesis of Peptide Nucleic Acids by Native Chemical Ligation
Dose, C., & Seitz, O. (2005) · Organic Letters · doi:10.1021/ol051489+ · Cited by 62
Goodwin, E. C., & DiMaio, D. (2001) · PubMed · Cited by 61
Mechanisms of self-renewal in human embryonic stem cells
Stewart, R., Stojković, M., & Lako, M. (2006) · European Journal of Cancer · doi:10.1016/j.ejca.2006.01.033 · Cited by 71
Kim, H. R., Christensen, R. E., Park, N. H., Sapp, P., Kang, M., & Park, N. H. (2001) · PubMed · Cited by 60
The bovine papillomavirus E5 protein and the PDGF β receptor: It takes two to tango
Talbert‐Slagle, K., & DiMaio, D. (2008) · Virology · doi:10.1016/j.virol.2008.09.033 · Cited by 59
Chemistry and biology of DNA-binding small molecules
Paul, A., & Bhattacharya, S. (2012) · NOT FOUND REPOSITORY (Indian Institute of Science Bangalore) · Cited by 58
Mechanism-based combination telomerase inhibition therapy
Shay, J. W., & Wright, W. E. (2005) · Cancer Cell · doi:10.1016/j.ccr.2004.12.012 · Cited by 58
Self-citationKishi, S., Wulf, G. M., Nakamura, M., & Lu, K. P. (2001) · Oncogene · doi:10.1038/sj.onc.1204229 · Cited by 58
Ford, L. P., Shay, J. W., & Wright, W. E. (2001) · RNA · doi:10.1017/s1355838201010159 · Cited by 58
Self-citationFletcher, T. M., Cathers, B. E., Ravikumar, K. S., Mamiya, B. M., & Kerwin, S. M. (2001) · Bioorganic Chemistry · doi:10.1006/bioo.2000.1194 · Cited by 57
Cell cycle-dependent and -independent telomere shortening accompanies murine brain aging
Ain, Q., Schmeer, C. W., Penndorf, D., Fischer, M., Bondeva, T., Förster, M., Haenold, R., Witte, O. W., & Kretz, A. (2018) · Aging · doi:10.18632/aging.101655 · Cited by 56
Prospects and challenges of building a cancer vaccine targeting telomerase
Vonderheide, R. H. (2007) · Biochimie · doi:10.1016/j.biochi.2007.07.005 · Cited by 59
Beccaria, M. G., Martínez, P., Méndez‐Pertuz, M., Martínez, S., Blanco‐Aparicio, C., Cañamero, M., Mulero, F., Ambrogio, C., Flores, J. M., Megías, D., et al. (2015) · EMBO Molecular Medicine · doi:10.15252/emmm.201404497 · Cited by 57
γ sulphate PNA (PNA S): Highly Selective DNA Binding Molecule Showing Promising Antigene Activity
Avitabile, C., Moggio, L., Malgieri, G., Capasso, D., Gaetano, S. D., Saviano, M., Pedone, C., & Romanelli, A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035774 · Cited by 54
Telomere dysfunction: multiple paths to the same end
Harrington, L. A., & Robinson, M. O. (2002) · Oncogene · doi:10.1038/sj.onc.1205084 · Cited by 54
Molecular regulation of telomerase activity in aging
Nicholls, C., Li, H., Wang, J.-Q., & Liu, J. (2011) · Protein & Cell · doi:10.1007/s13238-011-1093-3 · Cited by 57
Kotsakis, A. P., Vetsika, E., Christou, S., Hatzidaki, D., Vardakis, N., Aggouraki, D., Konsolakis, G., Georgoulias, V., Christophyllakis, C., Cordopatis, P. A., et al. (2011) · Annals of Oncology · doi:10.1093/annonc/mdr396 · Cited by 53
Immunologic approaches to cancer prevention—current status, challenges, and future perspectives
Wojtowicz, M. E., Dunn, B. K., & Umar, A. (2015) · Seminars in Oncology · doi:10.1053/j.seminoncol.2015.11.001 · Cited by 53
Elayadi, A. N. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.8.1683 · Cited by 53
Metadata
- Authors
- Herbert, B.-S., Pitts, A. E., Baker, S. I., Hamilton, S. E., Wright, W. E., Shay, J. W., & Corey, D. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-12-07
- Volume
- 96
- Issue
- 25
- Pages
- 14276-14281
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC24427
- OpenAlex
- W2118228848
- Cited by
- 539
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 11 · 2018: 9 · 2017: 9 · 2016: 5 · 2015: 18 · 2014: 7 · 2013: 12 · 2012: 13
- FWCI
- 27.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Ellison Medical Foundation
- National Institutes of Health
- National Cancer Institute (CA 74908, R01CA074908, CA-85143)
- National Institute of General Medical Sciences (T32GM007062, T32GM07062-23)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- telomerase inhibition, telomere shortening, apoptosis, peptide nucleic acid, 2'-O-methyl RNA, breast epithelial cells, cell immortalization, anticancer drug targets
- MeSH terms
- Antineoplastic Agents, Cell Division, Enzyme Inhibitors, Humans, Oligonucleotides, Telomere, Cell Death, Telomerase, Peptide Nucleic Acids
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
