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
31 Not checked yet · 31 Own result · 28 Own interpretation · 5 No basis given · 2 Own method · 1 Check pending
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”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“leading to progressive telomere shortening”
- Also stated in: § Abstract · plain
“cause telomeres to shorten”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 80 days, however, 14% of cells treated with the match oligomer were observed to undergo apoptosis”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 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.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“HME50-hTERT cells have a much longer mean TRF length (7.6 kilobases) than either HME50-5E or DU145 cells”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a 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
“Telomere shortening is reversible: if inhibitor addition is terminated, telomeres regain their initial lengths.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
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
“causing immortal human breast epithelial cells to undergo apoptosis with increasing frequency until no cells remain.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“During the first 60 days after initial transfection, less than 5% of cells treated with the fully complementary 2′-O-MeRNA underwent apoptosis.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 observed no significant reduction in their growth rates during the 120-day treatment period (Fig. 2c).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“with the mean TRF length of cells treated with the 2′-O-MeRNA complementary to the template region of hTR decreasing from 3,600 bp to 2,200 bp (Fig. 4b).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 complementary 2′-O-MeRNA oligomer blocked more than 95% of telomerase activity 1 day after transfection”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Addition of complementary 2′-O-MeRNA to DU145 cells caused proliferation of cells to begin to slow after 60 days (Fig. 2b).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“HME50-5E cells have a mean terminal restriction fragment (TRF) length of 2,000 bp”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“whereas DU145 cells possess a mean length of 3,600 bp.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“After 15–25 days, proliferation of HME50-5E cells treated with the complementary oligomer began to slow”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 more than 70% of activity was inhibited 3 days after transfection (Fig. 1).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Addition of a PNA that was complementary to the hTR template to DU145 cells inhibited over 90% of telomerase activity after 1 day (Fig. 1b)”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 after 110 days, no treated cells remained (Fig. 2a).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“A PNA directed to a nontemplate region of hTR inhibited only 50% of telomerase activity after 1 day”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 caused telomere shortening similar to that caused by addition of complementary 2′-O-MeRNA (Fig. 4b).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“After 3 weeks, we noted that the eroded telomeres of cells treated with fully complementary oligomers had returned to approximately their initial lengths (Fig. 5).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Telomeres remained near their initial lengths when measured a second time at 5 weeks.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a 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
“proliferation of treated HME50-hTERT cells did not decrease”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 observed that, within 3 weeks of terminating inhibitor treatment, previously static HME50-5E cells regained the ability to grow at the same rate as cells treated with mismatch-containing 2′-O-MeRNA.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 did not cause telomeres to shorten (results not shown).”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Treatment with match 2′-O-MeRNA and PNA oligomers cause much greater decreases in telomere length and cell proliferation than does treatment with oligomers that contain mismatched bases or treatment with a less efficient PNA inhibitor directed to a nontemplate region of hTR.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a 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
“PNA and 2′-O-MeRNA oligomers cause similar reductions in telomere length”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a 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
“The fact that inhibition of telomerase has a more rapid and pronounced effect on proliferation of HME50-5E cells, which have shorter telomeres than DU145 cells”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: HME50-5E cells have shorter telomeres than DU145 cells.
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
“No evidence for adoption of an ALT (alternative lengthening of telomeres) pathway for telomere maintenance was observed”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“The long lag between loss of telomerase activity and a detrimental phenotype suggests that telomerase will be a difficult target for effective chemotherapy”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Depending on their genetic backgrounds, these mice survived for four to six generations with few detectable phenotypic changes (13, 14);”
What the sources say
- Not checked yetcites [13] Blasco M A, Lee H-W, Hande M P, Samper E, Lansdorp P M, DePinho R A, Greider C W. Cell. 1997;91:25–34. doi: 10.1016/s0092-8674(01)80006-4. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [14] Herrera E, Samper E, Martin-Caballero J, Flores J M, Lee H W, Blasco M A. EMBO J. 1999;18:1172–1181. doi: 10.1093/emboj/18.5.1172. [DOI] [PMC free article] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and the mice were no longer able to reproduce (15).”
What the sources say
- Not checked yetcites [15] Lee H-W, Blasco M A, Gottlieb G J, Horner J W, Greider C W, DePinho R A. Nature (London) 1998;392:569–574. doi: 10.1038/33345. [DOI] [PubMed] [Google Scholar] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Evidence for the existence of this pathway is found in yeast in which the gene for est1, a protein involved in telomere-length maintenance, has been deleted (31).”
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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“the signal intensity of probe hybridization was greatly reduced because of the reduction in telomeric repeats.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“inhibition of telomerase in human cancer would be expected to produce effects more rapidly.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: The mice used in these experiments possessed much longer telomeres than those found in cancerous human cells.
None of the sources cited for this claim have been checked yet.
In the paper
“transfection of cells with the gene encoding the human telomerase reverse transcriptase component (hTERT) and subsequent expression of active telomerase have been shown to extend the life spans of normal human fibroblasts and epithelial cells (25–27).”
What the sources say
- Not checked yetcites [25] Bodnar A G, Oullette M, Frolkis M, Holt S E, Chiu C P, Morin G B, Harley C B, Shay J W, Lichtsteiner S, Wright W E. Science. 1998;279:349–352. doi: 10.1126/science.279.5349.349. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [26] Vaziri H, Benchimol S. Curr Biol. 1998;8:279–282. doi: 10.1016/s0960-9822(98)70109-5. [DOI] [PubMed] [Google Scholar] source
- Not checked yetcites [27] Counter C M, Hahn W C, Wei W, Caddle S D, Beijersbergen R L, Landsdorp P M, Sedivy J M, Weinberg R A. Proc Natl Acad Sci USA. 1998;95:14723–14728. doi: 10.1073/pnas.95.25.14723. [DOI] [PMC free article] [PubMed] [Google Scholar] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A check of a cited source is scheduled, or we don’t hold its full text yet; the claim is checked once it runs.
In the paper
“and a slight increase in spontaneous malignancies (16).”
What the sources say
- Not checked yetcites [16] Rudolph K L, Chang S, Lee H-W, Blasco M, Gottlieb G J, Greider C W, DePinho R A. Cell. 1999;96:701–712. doi: 10.1016/s0092-8674(00)80580-2. [DOI] [PubMed] [Google Scholar] source
A check is scheduled.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not checked yet
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
“Inhibition of cell proliferation suggests that oligonucleotides are a viable approach to antitelomerase therapy”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“an increased incidence of chromosomal abnormalities”
What the sources say
- Not checked yetcites [16] Rudolph K L, Chang S, Lee H-W, Blasco M, Gottlieb G J, Greider C W, DePinho R A. Cell. 1999;96:701–712. doi: 10.1016/s0092-8674(00)80580-2. [DOI] [PubMed] [Google Scholar] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“expression of antisense RNA complementary to the human telomerase RNA component (hTR) caused decreased proliferation of HeLa cells after 23 to 26 doublings (24).”
What the sources say
- Not checked yetcites [24] 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. Science. 1995;269:1236–1241. doi: 10.1126/science.7544491. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“the finding that proliferation of treated HME50-5E cells decreases more dramatically than does cell proliferation of treated DU145 cells may be due to HME50-5E cells possessing shorter telomeres.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“by the seventh generation, highly proliferative organ systems like the testis, bone marrow, and spleen appeared abnormal”
What the sources say
- Not checked yetcites [15] Lee H-W, Blasco M A, Gottlieb G J, Horner J W, Greider C W, DePinho R A. Nature (London) 1998;392:569–574. doi: 10.1038/33345. [DOI] [PubMed] [Google Scholar] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Our results validate telomerase as a target for the discovery of anticancer drugs”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Other studies of these mice revealed shortened life spans”
What the sources say
- Not checked yetcites [16] Rudolph K L, Chang S, Lee H-W, Blasco M, Gottlieb G J, Greider C W, DePinho R A. Cell. 1999;96:701–712. doi: 10.1016/s0092-8674(00)80580-2. [DOI] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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, it is likely that the reduced inhibition is due to dilution of inhibitor as the cell population increases.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In some genetic backgrounds, an increased incidence of neural tube defects limited viability after only four generations (14).”
What the sources say
- Not checked yetcites [14] Herrera E, Samper E, Martin-Caballero J, Flores J M, Lee H W, Blasco M A. EMBO J. 1999;18:1172–1181. doi: 10.1093/emboj/18.5.1172. [DOI] [PMC free article] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and human cells (23) also leads to decreased cell proliferation”
What the sources say
- Not checked yetcites [23] Marusic L, Anton M, Tidy A, Wang P, Villeponteau B, Bacchetti S. Mol Cell Biol. 1997;17:6394–6401. doi: 10.1128/mcb.17.11.6394. [DOI] [PMC free article] [PubMed] [Google Scholar] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“making the inhibitors we describe practical lead compounds for testing for an antitelomerase chemotherapeutic strategy.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Chemically similar oligonucleotides are in clinical trials and have well characterized pharmacokinetics.
In the paper
“The 2′-O-MeRNA oligomers used in these studies are stable to degradation inside cells (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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“supports a mechanism of decreased proliferation involving telomere shortening rather than nonselective toxicity.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“inhibition of telomerase must be maintained at a sustained high level over time to prevent the rapid regrowth of telomeres.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Inhibitors will be most effective against tumor cells with short telomeres”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“suggesting that the effects are caused by Watson–Crick recognition rather than by non-base-pair-mediated contacts with backbone phosphodiester or phosphorothioate linkages.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“If neutral and anionic oligomers produce the same effects, they likely derive from specific Watson–Crick base pairing rather than misleading non-sequence-specific interactions.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“although obtaining a striking phenotypic effect does not require full inhibition of telomerase”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 is an unusually challenging target for drug discovery, because a cellular response that depends on telomere shortening will require weeks to become apparent.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Regrowth to initial telomere length on cessation of inhibitor addition suggests that there is a “set point” for telomere length in human cells”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“suggesting that this pathway may not be readily adopted by some immortal cell types.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“presumably because their initial telomere length of HME50-hTERT cells is approximately 4,000 bp longer.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: HME50-hTERT cells have an initial telomere length approximately 4,000 bp longer than that of HME50-5E cells.
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
“and that the telomeres of stem cells that erode during therapy may recover once treatment is terminated.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Our primary finding is that telomerase is a viable target for synthetic agents aimed at controlling proliferation of immortal human cells.”
- Also stated in: § Discussion · hedged
“Our findings indicate that telomerase is a viable target for chemotherapeutic drugs”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Discussion · hedged
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
“indicating that functional p53 is not necessary for the reduced proliferation of these cell lines on treatment with telomerase inhibitors.”
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: HME50-5E cells were derived from HME50 preimmortal cells that had one mutant p53 allele and lost the second allele during spontaneous immortalization.
- Rests on an assumption: DU145 cells have two mutant p53 alleles.
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
“We offer multiple independent lines of evidence in the present study that the effects we observe are due to Watson–Crick recognition of telomerase.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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]
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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]
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“Thus, the lack of telomerase expression seems to curb growth of rapidly proliferating cells eventually, whereas an increase in telomerase permits indefinite proliferation.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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]
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably 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”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
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
Minotti, G., Menna, P., Salvatorelli, E., Cairo, G., & Gianni, L. (2004) · Pharmacological Reviews · doi:10.1124/pr.56.2.6 · Cited by 3,868
Telomeres and telomerase: three decades of progress
Shay, J. W., & Wright, W. E. (2019) · Nature Reviews Genetics · doi:10.1038/s41576-019-0099-1 · Cited by 924
Self-citationHuman Telomerase and Its Regulation
Cong, Y.-S., Wright, W. E., & Shay, J. W. (2002) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.66.3.407-425.2002 · Cited by 898
Self-citationHayflick, his limit, and cellular ageing
Shay, J. W., & Wright, W. E. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35036093 · Cited by 764
Self-citationChemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs
Shen, X., & Corey, D. R. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1239 · Cited by 654
Self-citation
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
