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Posted

HI all,

Eenzymic/hormone maintence programs.. I've been hearing a lot about these programs for SCLC to keep it in remission and need to start researching them. John or Anyone know anything about it? There are probably posts somewhere on it but I'm not sure where??? Any help would be greatly appreciated... or anyone who has information on these programs.

Thank you!

Laurie

Posted

Laurie,

That sounds interesting...I hope someone else knows the answer.

The only thing I am aware of is something called "chemoprevention" but I am not sure if this has been developed yet or not. I read about in an article on SCLC which was published about 5 years ago and it was still under investigation.

Lynn

Posted

Not sure if this could be something to look into ... BUT

Telomerase is an enzyme and found in 98% of sclc tumors. Telomerase allows a cell to become immortal, thus cancer results.

There is a trial at the NCI though it does not seem to be a telomerase inhibitor. it is a vaccine based on telomerase

http://www.clinicaltrials.gov/ct/show/N ... 40?order=1

Figure 4. Clinical trial design for telomerase inhibitors. (a) Aproposed phase III clinical trial design of telomerase inhibitors asmaintenance therapy in small cell lung cancer (SCLC) afterdebulking chemotherapy. hTERC expression is up-regulated in98% of cases of SCLC [2]. SCLC is extremely sensitive to first-line chemotherapy, but with a relatively short duration ofremission on completion of chemotherapy, with poor responsesto second-line chemotherapy regimens as a result of acquired orintrinsic drug resistance. SCLC is therefore an ideal model formaintenance studies with telomerase inhibitors. (B) A proposedphase III clinical trial design of telomerase inhibitors incombination with cytotoxic chemotherapy in advanced breastcancer, for example, in comparison with chemotherapy alone,with progression-free survival and overall survival (if there is norecognized salvage therapy) as the main endpoints410W. N. Keith et al.Copyright # 2001 John Wiley & Sons, Ltd.J Pathol 2001; 195: 404?14.

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patient population in whom new agents are evaluated.Demonstration of efficacy in `minimal disease state'patient groups requires a phase III-type design withrelatively long follow-up, compared with conventionalphase II studies. In order to justify proceeding to phaseIII studies with trial designs as outlined in Figures 4aand 4b, it will be necessary to demonstrate safety of theagent, to assess pharmacokinetics, and to have somemeasure of desired biological activity, such as inhibi-tion of telomerase activity and shortening of telomerelength within tumour biopsy tissues (Table 1). It isoften not possible to gain pre- and post-therapybiopsies and so it is important either to study a patientgroup where tumour tissue is readily available, or toconsider other surrogate tissue in which telomeraseactivity can be assessed.The challenges presented in the evaluation oftelomerase therapies will therefore require an inte-grated laboratory and clinical approach, with arational clinical trial design incorporating biologicalendpoints. With careful consideration of both tumourbiology and the appropriate clinical scenarios, theintroduction of telomerase-based therapeutics into theclinic is awaited with great anticipation.AcknowledgementsThe Cancer Research Campaign (UK), the Scottish HospitalEndowments Research Trust (SHERT), the European Commis-sion and Glasgow University support research in the authors' lab.References1. Shay JW, Wright WE. Hayflick, his limit, and cellular ageing.Nature Rev Mol Cell Biol 2000; 1: 72?6.2. Reddel RR. A reassessment of the telomere hypothesis ofsenescence. Bioessays 1998; 20: 977?84.3. Reddel RR. The role of senescence and immortalization incarcinogenesis. Carcinogenesis 2000; 21: 477?84.4. Meyerson M. Role of telomerase in normal and cancer cells.J Clin Oncol 2000; 18: 2626?634.5. Holt SE, Shay JW. Role of telomerase in cellular proliferationand cancer. J Cell Physiol 1999; 180: 10?8.6. Shay JW, Zou Y, Hiyama E, Wright WE. Telomerase andcancer. Hum Mol Genet 2001; 10: 677?85.7. Forsythe HL, Jarvis JL, Turner JW, Elmore LW, Holt SE.Stable association of hsp90 and p23, but not hsp70, with activehuman telomerase. J Biol Chem 2001; 276: 15571?5574.8. Holt SE, Aisner DL, Baur J, et al. Functional requirement ofp23 and Hsp90 in telomerase complexes. Genes Dev 1999; 13:817?26.9. Cuthbert AP, Bond J, Trott DA, et al. Telomerase repressorsequences on chromosome 3 and induction of permanentgrowth arrest in human breast cancer cells. J Natl Cancer Inst1999; 91: 37?5.10. Nishimoto A, Miura N, Horikawa I, et al. Functional evidencefor a telomerase repressor gene on human chromosome10p15.1. Oncogene 2001; 20: 828?35.11. Steenbergen RD, Kramer D, Meijer CJ, et al. Telomerasesuppression by chromosome 6 in a human papillomavirus type16-immortalized keratinocyte cell line and in a cervical cancercell line. J Natl Cancer Inst 2001; 93: 865?72.12. Ogoshi M, Le T, Shay JW, Taylor RS. In situ hybridizationanalysis of the expression of human telomerase RNA in normaland pathologic conditions of the skin. J Invest Dermatol 1998;110: 818?23.13. Ramirez RD, Wright WE, Shay JW, Taylor RS. Telomeraseactivity concentrates in the mitotically active segments ofhuman hair follicles. J Invest Dermatol 1997; 108: 113?17.14. Harle-Bachor C, Boukamp P. Telomerase activity in theregenerative basal layer of the epidermis in human skin and inimmortal and carcinoma-derived skin keratinocytes. Proc NatlAcad Sci U S A 1996; 93: 6476?481.15. Liu K, Hodes RJ, Weng N. Cutting edge: telomerase activationin human T lymphocytes does not require increase in telomerasereverse transcriptase (hTERT) protein but is associated withhTERT phosphorylation and nuclear translocation. J Immunol2001; 166: 4826?830.16. Liu K, Schoonmaker MM, Levine BL, June CH, Hodes RJ,Weng NP. Constitutive and regulated expression of telomerasereverse transcriptase (hTERT) in human lymphocytes. ProcNatl Acad Sci U S A 1999; 96: 5147?152.17. Brenner CA, Wolny YM, Adler RR, Cohen J. Alternativesplicing of the telomerase catalytic subunit in human oocytesand embryos. Mol Hum Reprod 1999; 5: 845?50.18. Albanell J, Bosl GJ, Reuter VE, et al. Telomerase activity ingerm cell cancers and mature teratomas. J Natl Cancer Inst1999; 91: 1321?326.19. Yashima K, Maitra A, Rogers BB, et al. Expression of theRNA component of telomerase during human development anddifferentiation. Cell Growth Differentiation 1998; 9: 805?13.20. Wright WE, Piatyszek MA, Rainey WE, Byrd W, Shay JW.Telomerase activity in human germline and embryonic tissuesand cells. Dev Genet 1996; 18: 173?79.21. Soder AI, Going JJ, Kaye SB, Keith WN. Tumour specificregulation of telomerase RNA gene expression visualized byin situ hybridization. Oncogene 1998; 16: 979?83.22. Nowak R, Chrapusta SJ. Regulation of telomerase activity innormal and malignant human cells. Cancer J. Sci. Am 1998; 4:148?54.23. O'Hare MJ, Bond J, Clarke C, et al. Conditional immortaliza-tion of freshly isolated human mammary fibroblasts andendothelial cells. Proc Natl Acad Sci U S A 2001; 98: 646?51.24. Choi D, Whittier PS, Oshima J, Funk WD. Telomeraseexpression prevents replicative senescence but does not fullyreset mRNA expression patterns in Werner syndrome cellstrains. FASEB J 2001; 15: 1014?020.25. Ouellette MM, Aisner DL, Savre-Train I, Wright WE, ShayJW. Telomerase activity does not always imply telomere main-tenance. Biochem Biophys Res Commun 1999; 254: 795?03.26. Counter CM, Meyerson M, Eaton EN, et al. Telomeraseactivity is restored in human cells by ectopic expression ofhTERT (hEST2), the catalytic subunit of telomerase. Oncogene1998; 16: 1217?222.27. Morales CP, Holt SE, Ouellette M, et al. Absence of cancer-associated changes in human fibroblasts immortalized withtelomerase. Nature Genet 1999; 21: 115?18.28. Vaziri H, Benchimol S. Reconstitution of telomerase activity innormal human cells leads to elongation of telomeres andextended replicative life span. Curr Biol 1998; 8: 279?82.29. Bodnar AG, Ouellette M, Frolkis M, et al. Extension of life-span by introduction of telomerase into normal human cells.Science 1998; 279: 349?52.30. Oulton R, Harrington L. Telomeres, telomerase, and cancer:life on the edge of genomic stability. Curr Opin Oncol 2000; 12:74?1.31. Mitchell JR, Wood E, Collins K. A telomerase component isdefective in the human disease dyskeratosis congenita. Nature1999; 402: 551?55.32. Meeker AK, Coffey DS. Telomerase: a promising marker ofbiological immortality of germ, stem, and cancer cells. Areview. Biochemistry 1997; 62: 1323?331.33. Shay JW, Bacchetti S. A survey of telomerase activity in humancancer. Eur J Cancer 1997; 33: 787?91.34. Herbert B, Pitts AE, Baker SI, et al. Inhibition of humantelomerase in immortal human cells leads to progressiveTelomerase and cancer: time to move from a promising target to a clinical reality411Copyright # 2001 John Wiley & Sons, Ltd.J Pathol 2001; 195: 404?14.

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telomere shortening and cell death. Proc Natl Acad Sci U S A1999; 96: 14276?4281.35. Hahn WC, Stewart SA, Brooks MW, et al. Inhibition oftelomerase limits the growth of human cancer cells [seecomments]. Nature Med 1999; 5: 1164?170.36. Dunham MA, Neumann AA, Fasching CL, Reddel RR.Telomere maintenance by recombination in human cells.Nature Genet 2000; 26: 447?50.37. Hoare SF, Bryce LA, Wisman GB, et al. Lack of telomeraseRNA gene hTERC expression in alternative lengthening oftelomere cells is associated with methylation of the hTERCpromoter. Cancer Res 2001; 61: 27?2.38. Reddel RR, Bryan TM, Colgin LM, Perrem KT, Yeager TR.Alternative lengthening of telomeres in human cells. Radiat Res2001; 155: 194?00.39. Lee HW, Blasco MA, Gottlieb GJ, Horner JW, Greider CW,DePinho RA. Essential role of mouse telomerase in highlyproliferative organs. Nature 1998; 392: 569?74.40. Gonzalez-Suarez E, Samper E, Flores JM, Blasco MA.Telomerase-deficient mice with short telomeres are resistant toskin tumorigenesis. Nature Genet 2000; 26: 114?17.41. Greenberg RA, Chin L, Femino A, et al. Short dysfunctionaltelomeres impair tumorigenesis in the INK4a(delta2/3) cancer-prone mouse. Cell 1999; 97: 515?25.42. Hahn WC, Meyerson M. Telomerase activation, cellularimmortalization and cancer. Ann Med 2001; 33: 123?29.43. Blasco MA, Rizen M, Greider CW, Hanahan D. Differentialregulation of telomerase activity and telomerase RNA duringmulti-stage tumorigenesis. Nature Genet 1996; 12: 200?04.44. Blasco MA, Funk W, Villeponteau B, Greider CW. Functional-characterization and developmental regulation of mouse telo-merase RNA. Science 1995; 269: 1267?270.45. Blasco MA, Lee HW, Hande MP, et al. Telomere shorteningand tumor formation by mouse cells lacking telomerase RNA[see comments]. Cell 1997; 91: 25?4.46. Sachsinger J, Gonzalez-Suarez E, Samper E, Heicappell R,Muller M, Blasco MA. Telomerase inhibition in RenCa, amurine tumor cell line with short telomeres, by overexpressionof a dominant negative mTERT mutant, reveals fundamentaldifferences in telomerase regulation between human and murinecells. Cancer Res 2001; 61: 5580?586.47. Broccoli D, Godley LA, Donehower LA, Varmus HE, de LangeT. Telomerase activation in mouse mammary tumors: lack ofdetectable telomere shortening and evidence for regulation oftelomerase RNA with cell proliferation. Mol Cell Biol 1996; 16:3765?772.48. Greenberg RA, Allsopp RC, Chin L, Morin GB, DePinho RA.Expression of mouse telomerase reverse transcriptase duringdevelopment, differentiation and proliferation. Oncogene 1998;16: 1723?730.49. Herrera E, Martinez AC, Blasco MA. Impaired germinal centerreaction in mice with short telomeres. EMBO J 2000; 19:472?81.50. Kemp CJ, Donehower LA, Bradley A, Balmain A. Reductionof p53 gene dosage does not increase initiation or promotionbut enhances malignant progression of chemically induced skintumors. Cell 1993; 74: 813?22.51. Newbold RF. Telomerase as an anti-cancer drug target: will itfulfil its early promise? Anticancer Drug Des 1999; 14: 349?54.52. Niida H, Matsumoto T, Satoh H, et al. Severe growth defect inmouse cells lacking the telomerase RNA component. NatureGenet 1998; 19: 203?06.53. Prowse KR, Greider CW. Developmental and tissue-specificregulation of mouse telomerase and telomere length. Proc NatAcad Sci U S A 1995; 92: 4818?822.54. Rudolph KL, Chang S, Lee HW, et al. Longevity, stressresponse, and cancer in aging telomerase-deficient mice. Cell1999; 96: 701?12.55. Wright WE, Shay JW. Telomere dynamics in cancer progres-sion and prevention: fundamental differences in human andmouse telomere biology. Nature Med 2000; 6: 849?51.56. Zhao JQ, Hoare SF, McFarlane R, et al. Cloning andcharacterization of human and mouse telomerase RNA genepromoter sequences. Oncogene 1998; 16: 1345?350.57. Zhao JQ, Glasspool RM, Hoare SF, Bilsland A, Szatmari II,Keith WN. Activation of telomerase RNA gene promoteractivity by NF-Y, Sp1, and the retinoblastoma protein andrepression by Sp3. Neoplasia 2000; 2: 531?39.58. Morales CP, Lee EL, Shay JW. In situ hybridization for thedetection of telomerase RNA in the progression from Barrett'sesophagus to esophageal adenocarcinoma. Cancer 1998; 83:652?59.59. Yoshida R, Kiyozuka Y, Ichiyoshi H, et al. Change intelomerase activity during human colorectal carcinogenesis.Anticancer Res 1999; 19: 2167?172.60. Fang DC, Young J, Luo YH, Lu R, Jass J. Detection oftelomerase activity in biopsy samples of colorectal cancer.J Gastroenterol Hepatol 1999; 14: 328?32.61. Hiyama E, Hiyama K, Yokoyama T, Shay JW. Immunohisto-chemical detection of telomerase (hTERT) protein in humancancer tissues and a subset of cells in normal tissues. Neoplasia2001; 3: 17?6.62. Wisman GB, De Jong S, Meersma GJ, et al. Telomerase in(pre)neoplastic cervical disease. Hum Pathol 2000; 31: 1304?312.63. Park TW, Riethdorf S, Riethdorf L, Loning T, Janicke F.Differential telomerase activity, expression of the telomerasecatalytic sub-unit and telomerase-RNA in ovarian tumors. IntJ Cancer 1999; 84: 426?31.64. Maitra A, Yashima K, Rathi A, et al. The RNA component oftelomerase as a marker of biologic potential and clinicaloutcome in childhood neuroblastic tumors. Cancer 1999; 85:741?49.65. Hiyama T, Yokozaki H, Kitadai Y, et al. Overexpression ofhuman telomerase RNA is an early event in oesophagealcarcinogenesis. Virchows Arch 1999; 434: 483?87.66. Heine B, Hummel M, Demel G, Stein H. Demonstration ofconstant upregulation of the telomerase RNA component inhuman gastric carcinomas using in situ hybridization. J Pathol1998; 185: 139?44.67. Sarvesvaran J, Going JJ, Milroy R, Kaye SB, Keith WN. Issmall cell lung cancer the perfect target for anti-telomerasetreatment? Carcinogenesis 1999; 20: 1649?651.68. Yoshida K, Sugino T, Tahara H, et al. Telomerase activity inbladder carcinoma and its implication for noninvasive diagnosisby detection of exfoliated cancer cells in urine. Cancer 1997; 79:362?69.69. Ramakumar S, Bhuiyan J, Besse JA, et al. Comparison ofscreening methods in detection of bladder cancer. J Urol 1999;161: 388?94.70. Kavaler E, Landman J, Chang YL, Droller MJ, Liu BCS.Detecting human bladder carcinoma cells in voided urinesamples by assaying for the presence of telomerase activity.Cancer 1998; 82: 708?14.71. Hoshi S, Takahashi T, Satoh M, et al. Telomerase activity ?/nobr>Simplification of assay and detection in bladder tumor andurinary exfoliated cells. Urol Oncol 2000; 5: 25?0.72. Cheng CW, Chueh SC, Chern HD. Diagnosis of bladder cancerusing telomerase activity in voided urine. J Formosan MedAssoc 2000; 99: 920?25.73. Bialkowska-Hobrzanska H, Bowles L, Bukala B, Joseph MG,Fletcher R, Razvi H. Comparison of human telomerase reversetranscriptase messenger RNA and telomerase activity as urinemarkers for diagnosis of bladder carcinoma. Mol Diagn 2000; 5:267?77.74. Muller M, Krause H, Heicappell R, Tischendorf J, Shay JW,Miller K. Comparison of human telomerase RNA andtelomerase activity in urine for diagnosis of bladder cancer.Clin Cancer Res 1998; 4: 1949?954.75. Maitra A, Rathi A, Gazdar AF, Sagalowsky A, Ashfaq R.Expression of the RNA component of human telemorase (hTR)in ThinPrep preparations from bladder washings. Cancer 2001;93: 73?9.76. Itoi T, Shinohara Y, Takeda K, et al. Detection of telomerasereverse transcriptase mRNA in biopsy specimens and bile for412W. N. Keith et al.Copyright # 2001 John Wiley & Sons, Ltd.J Pathol 2001; 195: 404?14.

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diagnosis of biliary tract cancers. Int J Mol Med 2001; 7:281?87.77. Niiyama H, Mizumoto K, Kusumoto M, et al. Activation oftelomerase and its diagnostic application in biopsy specimensfrom biliary tract neoplasms. Cancer 1999; 85: 2138?143.78. Saji M, Xydas S, Westra WH, et al. Human telomerase reversetranscriptase (hTERT) gene expression in thyroid neoplasms.Clin Cancer Res 1999; 5: 1483?489.79. Zeiger MA, Smallridge RC, Clark DP, et al. Human telomerasereverse transcriptase (hTERT) gene expression in FNA samplesfrom thyroid neoplasms. Surgery 1999; 126: 1195?198.80. Morales CP, Burdick JS, Saboorian MH, Wright WE, ShayJW. In situ hybridization for telomerase RNA in routinecytologic brushings for the diagnosis of pancreaticobiliarymalignancies. Gastrointest Endosc 1998; 48: 402?05.81. Niiyama H, Mizumoto K, Kusumoto M, et al. Activation oftelomerase and its diagnostic application in biopsy specimensfrom biliary tract neoplasms. Cancer 1999; 85: 2138?143.82. Itoi T, Ohyashiki K, Yahata N, et al. Detection of telomeraseactivity in exfoliated cancer cells obtained from bile. Int J Oncol1999; 15: 1061?067.83. Itoi T, Shinohara Y, Takeda K, et al. Detection of telomeraseactivity in biopsy specimens for diagnosis of biliary tractcancers. Gastrointest Endosc 2000; 52: 380?86.84. Harada K, Yasoshima M, Ozaki S, Sanzen T, Nakanuma Y.PCR and in situ hybridization studies of telomerase subunits inhuman non-neoplastic livers. J Pathol 2001; 193: 210?17.85. Kobayashi T, Kubota K, Takayama T, Makuuchi M. Telomer-ase activity as a predictive marker for recurrence of hepato-cellular carcinoma after hepatectomy. Am J Surg 2001; 181:284?88.86. Wisman GB, Hollema H, de Jong S, et al. Telomerase activityas a biomarker for (pre)neoplastic cervical disease in scrapingsand frozen sections from patients with abnormal cervical smear.J Clin Oncol 1998; 16: 2238?245.87. Wisman GB, Knol AJ, Helder MN, et al. Telomerase inrelation to clinicopathologic prognostic factors and survival incervical cancer. Int J Cancer 2001; 91: 658?64.88. Hall PA, Going JJ. Predicting the future: a critical appraisal ofcancer prognosis studies. Histopathology 1999; 35: 489?94.89. Dome JS, Chung S, Bergemann T, et al. High telomerasereverse transcriptase (hTERT) messenger RNA level correlateswith tumor recurrence in patients with favorable histologyWilms' tumor. Cancer Res 1999; 59: 4301?307.90. Choi LM, Kim NW, Zuo JJ, et al. Telomerase activity byTRAP assay and telomerase RNA (hTR) expression arepredictive of outcome in neuroblastoma. Med Pediatr Oncol2000; 35: 647?50.91. Clark GM, Osborne CK, Levitt D, Wu F, Kim NW.Telomerase activity and survival of patients with node-positivebreast cancer. J Nat Cancer Inst 1997; 89: 1874?881.92. Rushing EJ, Colvin SM, Gazdar A, et al. Prognostic value ofproliferation index and expression of the RNA componentof human telomerase (hTR) in papillary meningiomas.J Neurooncol 1999; 45: 199?07.93. Sangiorgi L, Gobbi GA, Lucarelli E, et al. Presence oftelomerase activity in different musculoskeletal tumor histo-types and correlation with aggressiveness. Int J Cancer 2001; 95:156?61.94. Tatsumoto N, Hiyama E, Murakami Y, et al. High telomeraseactivity is an independent prognostic indicator of poor outcomein colorectal cancer. Clin Cancer Res 2000; 6: 2696?701.95. Shoji Y, Yoshinaga K, Inoue A, Iwasaki A, Sugihara K.Quantification of telomerase activity in sporadic colorectalcarcinoma: association with tumor growth and venous invasion.Cancer 2000; 88: 1304?309.96. Bieche I, Nogues C, Paradis V, et al. Quantitation of hTERTgene expression in sporadic breast tumors with a real-timereverse transcription-polymerase chain reaction assay. ClinCancer Res 2000; 6: 452?59.97. Mannelli M, Gelmini S, Arnaldi G, et al. Telomerase activity issignificantly enhanced in malignant adrenocortical tumors incomparison to benign adrenocortical adenomas. J Clin Endo-crinol Metab 2000; 85: 468?70.98. Yeh TS, Cheng AJ, Chen TC, et al. Telomerase activity is auseful marker to distinguish malignant pancreatic cystic tumorsfrom benign neoplasms and pseudocysts. J Surg Res 1999; 87:171?77.99. Schneider-Stock R, Rys J, Jaeger V, et al. Prognosticsignificance of telomerase activity in soft tissue sarcomas. IntJ Oncol 1999; 15: 775?80.100. Suda T, Isokawa O, Aoyagi Y, et al. Quantitation of telomeraseactivity in hepatocellular carcinoma: a possible aid for aprediction of recurrent diseases in the remnant liver. Hepatology1998; 27: 402?06.101. Okayasu I, Mitomi H, Yamashita K, et al. Telomerase activitysignificantly correlates with cell differentiation, proliferationand lymph node metastasis in colorectal carcinomas. J CancerRes Clin Oncol 1998; 124: 444?49.102. Streutker CJ, Thorner P, Fabricius N, Weitzman S, ZielenskaM. Telomerase activity as a prognostic factor in neuroblas-tomas. Pediatr Dev Pathol 2001; 3: 62?7.103. Poremba C, Scheel C, Hero B, et al. Telomerase activity andtelomerase subunit gene expression patterns in neuroblastoma:a molecular and immunohistochemical study establishingprognostic tools for fresh-frozen and paraffin-embedded tissues.J Clin Oncol 2000; 18: 2582?592.104. Poremba C, Willenbring H, Hero B, et al. Telomerase activitydistinguishes between neuroblastomas with good and poorprognosis. Ann Oncol 1999; 10: 715?21.105. Poremba C, Hero B, Heine B, et al. Telomerase is a strongindicator for assessing the proneness to progression in neuro-blastomas. Med Pediatr Oncol 2000; 35: 651?55.106. Nozaki C, Horibe K, Iwata H, Ishiguro Y, Hamaguchi M,Takahashi M. Prognostic impact of telomerase activity inpatients with neuroblastoma. Int J Oncol 2000; 17: 341?45.107. Hiyama E, Hiyama K, Yokoyama T, Matsuura Y, PiatyszekMA, Shay JW. Correlating telomerase activity levels withhuman neuroblastoma outcomes. Nature Med 1995; 1: 249?55.108. Hiyama E, Hiyama K, Ohtsu K, et al. Telomerase activity inneuroblastoma: is it a prognostic indicator of clinical beha-viour? Eur J Cancer 1997; 33: 1932?936.109. Bieche I, Nogues C, Paradis V, et al. Quantitation of hTERTgene expression in sporadic breast tumors with a real-timereverse transcription-polymerase chain reaction assay. ClinCancer Res 2000; 6: 452?59.110. Ludwig A, Saretzki G, Holm PS, et al. Ribozyme cleavage oftelomerase mRNA sensitizes breast epithelial cells to inhibitorsof topoisomerase. Cancer Res 2001; 61: 3053?061.111. Naasani I, Seimiya H, Yamori T, Tsuruo T. FJ5002: a potenttelomerase inhibitor identified by exploiting the disease-orientedscreening program with COMPARE analysis. Cancer Res 1999;59: 4004?011.112. Fletcher TM, Salazar M, Chen SF. Human telomerase inhibi-tion by 7-deaza-2k-deoxypurine nucleoside triphosphates. Bio-chemistry 1996; 35: 15611?5617.113. Folini M, Colella G, Villa R, Lualdi S, Daidone MG, ZaffaroniN. Inhibition of telomerase activity by a hammerhead ribozymetargeting the RNA component of telomerase in humanmelanoma cells. J Invest Dermatol 2000; 114: 259?67.114. Glukhov AI, Zimnik OV, Gordeev SA, Severin SE. Inhibitionof telomerase activity of melanoma cells in vitro by antisenseoligonucleotides. Biochem Biophys Res Commun 1998; 248:368?71.115. Hamilton SE, Simmons CG, Kathiriya IS, Corey DR. Cellulardelivery of peptide nucleic acids and inhibition of humantelomerase. Chem Biol 1999; 6: 343?51.116. Harrison JG, Frier C, Laurant R, Dennis R, Raney KD,Balasubramanian S. Inhibition of human telomerase by PNA-cationic peptide conjugates. Bioorg Med Chem Lett 1999; 9:1273?278.117. Hurley LH, Wheelhouse RT, Sun D, et al. G-quadruplexes astargets for drug design [in process citation]. Pharmacol Ther2000; 85: 141?58.Telomerase and cancer: time to move from a promising target to a clinical reality413Copyright # 2001 John Wiley & Sons, Ltd.J Pathol 2001; 195: 404?14.

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118. Kanazawa Y, Ohkawa K, Ueda K, et al. Hammerheadribozyme-mediated inhibition of telomerase activity in extractsof human hepatocellular carcinoma cells. Biochem Biophys ResCommun 1996; 225: 570?76.119. Kanaya T, Kyo S, Hamada K, et al. Adenoviral expression ofp53 represses telomerase activity through down- regulation ofhuman telomerase reverse transcriptase transcription. ClinCancer Res 2000; 6: 1239?247.120. Abdul-Ghani R, Ohana P, Matouk I, et al. Use of transcrip-tional regulatory sequences of telomerase (hTER and hTERT)for selective killing of cancer cells. Mol Ther 2000; 2: 539?44.121. Bisoffi M, Chakerian AE, Fore ML, et al. Inhibition of humantelomerase by a retrovirus expressing telomeric antisense RNA.Eur J Cancer 1998; 34: 1242?249.122. Colgin LM, Wilkinson C, Englezou A, Kilian A, RobinsonMO, Reddel RR. The hTERTalpha splice variant is a dominantnegative inhibitor of telomerase activity. Neoplasia 2000; 2:426?32.123. Kondo Y, Kondo S, Tanaka Y, Haqqi T, Barna BP, CowellJK. Inhibition of telomerase increases the susceptibility ofhuman malignant glioblastoma cells to cisplatin-induced apop-tosis. Oncogene 1998; 16: 2243?248.124. Ku WC, Cheng AJ, Wang TC. Inhibition of telomerase activityby PKC inhibitors in human nasopharyngeal cancer cells inculture. Biochem Biophys Res Commun 1997; 241: 730?36.125. Kusumoto M, Ogawa T, Mizumoto K, et al. Adenovirus-mediated p53 gene transduction inhibits telomerase activityindependent of its effects on cell cycle arrest and apoptosis inhuman pancreatic cancer cells. Clin Cancer Res 1999; 5:2140?147.126. Muller A, Saretzki G, von Zglinicki T. Telomerase inhibition byinduced expression of antisense RNA. Adv Exp Med Biol 1998;451: 23?6.127. Murakami J, Nagai N, Shigemasa K, Ohama K. Inhibition oftelomerase activity and cell proliferation by a reverse transcrip-tase inhibitor in gynaecological cancer cell lines. Eur J Cancer1999; 35: 1027?034.128. Naasani I, Seimiya H, Tsuruo T. Telomerase inhibition,telomere shortening, and senescence of cancer cells by teacatechins. Biochem Biophys Res Commun 1998; 249: 391?96.129. Norton JC, Piatyszek MA, Wright WE, Shay JW, Corey DR.Inhibition of human telomerase activity by peptide nucleicacids. Nature Biotechnol 1996; 14: 615?19.130. Perry PJ, Reszka AP, Wood AA, et al. Human telomeraseinhibition by regioisomeric disubstituted amidoanthracene-9,10-diones. J Med Chem 1998; 41: 4873?884.131. Pitts AE, Corey DR. Inhibition of human telomerase by 2k-O-methyl-RNA. Proc Natl Acad Sci U S A 1998; 95: 11549?1554.132. Shammas MA, Simmons CG, Corey DR, Reis RJ. Telomeraseinhibition by peptide nucleic acids reverses `immortality' oftransformed human cells. Oncogene 1999; 18: 6191?200.133. Sun D, Thompson B, Cathers BE, et al. Inhibition of humantelomerase by a G-quadruplex-interactive compound. J MedChem 1997; 40: 2113?116.134. Tamura Y, Tao M, Miyano-Kurosaki N, Takai K, Takaku H.Inhibition of human telomerase activity by antisense phosphor-othioate oligonucleotides encapsulated with the transfectionreagent, FuGENE6, in HeLa cells. Antisense Nucleic Acid DrugDev 2000; 10: 87?6.135. Villa R, Folini M, Lualdi S, Veronese S, Daidone MG,Zaffaroni N. Inhibition of telomerase activity by a cell-penetrating peptide nucleic acid construct in human melanomacells. FEBS Lett 2000; 473: 241?48.136. Fletcher TM, Cathers BE, Ravikumar KS, Mamiya BM,Kerwin SM. Inhibition of human telomerase by 7-deaza-2k-deoxyguanosine nucleoside triphosphate analogs: potentinhibition by 6-thio-7-deaza-2k- deoxyguanosine 5k-triphosphate.Bioorg Chem 2001; 29: 36?5.137. Mergny JL, Lacroix L, Teulade-Fichou MP, et al. Telomer-ase inhibitors based on quadruplex ligands selected by afluorescence assay. Proc Natl Acad Sci U S A 2001; 98: 3062?/nobr>3067.138. Wan MS, Fell PL, Akhtar S. Synthetic 2k-O-methyl-modifiedhammerhead ribozymes targeted to the RNA component oftelomerase as sequence-specific inhibitors of telomerase activity.Antisense Nucleic Acid Drug Dev 1998; 8: 309?17.139. Mukai S, Kondo Y, Koga S, Komata T, Barna BP, Kondo S.2-5A antisense telomerase RNA therapy for intracranialmalignant gliomas. Cancer Res 2000; 60: 4461?467.140. Mergny JL, Mailliet P, Lavelle F, Riou JF, Laoui A, Helene C.The development of telomerase inhibitors: the G-quartetapproach. Anticancer Drug Des 1999; 14: 327?39.141. Kondo S, Kondo Y, Li G, Silverman RH, Cowell JK. Targetedtherapy of human malignant glioma in a mouse model by 2-5Aantisense directed against telomerase RNA. Oncogene 1998; 16:3323?330.142. Kondo S, Tanaka Y, Kondo Y, et al. Antisense telomerasetreatment: induction of two distinct pathways, apoptosis anddifferentiation. FASEB J 1998; 12: 801?11.143. Gu J, Kagawa S, Takakura M, et al. Tumor-specific transgeneexpression from the human telomerase reverse transcriptasepromoter enables targeting of the therapeutic effects of the Baxgene to cancers. Cancer Res 2000; 60: 5359?364.144. Koga S, Hirohata S, Kondo Y, et al. A novel telomerase-specific gene therapy: gene transfer of caspase-8 utilizing thehuman telomerase catalytic subunit gene promoter. Hum GeneTher 2000; 11: 1397?406.145. Majumdar AS, Hughes DE, Lichtsteiner SP, Wang Z,Lebkowski JS, Vasserot AP. The telomerase reverse transcrip-tase promoter drives efficacious tumor suicide gene therapywhile preventing hepatotoxicity encountered with constitutivepromoters. Gene Ther 2001; 8: 568?78.146. Chang BD, Xuan Y, Broude EV, et al. Role of p53 andp21waf1/cip1 in senescence-like terminal proliferation arrestinduced in human tumor cells by chemotherapeutic drugs.Oncogene 1999; 18: 4808?818.147. Chang BD, Broude EV, Dokmanovic M, et al. A senescence-like phenotype distinguishes tumor cells that undergo terminalproliferation arrest after exposure to anticancer agents. CancerRes 1999; 59: 3761?767.148. Samper E, Goytisolo FA, Slijepcevic P, van Buul PP, BlascoMA. Mammalian Ku86 protein prevents telomeric fusionsindependently of the length of TTAGGG repeats and theG-strand overhang. EMBO Rep 2000; 1: 244?52.149. Teo SH, Jackson SP. Telomerase subunit overexpressionsuppresses telomere-specific checkpoint activation in the yeastyku80 mutant. EMBO Rep 2001; 2: 197?02.150. d'Adda di Fagagna F, Hande MP, Tong WM, Lansdorp PM,Wang ZQ, Jackson SP. Functions of poly(ADP-ribose) poly-merase in controlling telomere length and chromosomalstability. Nature Genet 1999; 23: 76?0.151. van de Vijver MJ. Assessment of the need and appropriatemethod for testing for the human epidermal growth factorreceptor-2 (HER2). Eur J Cancer 2001; 37 (Suppl. 1): S11?/nobr>S17.152. Baselga J. Clinical trials of Herceptin (trastuzumab). EurJ Cancer 2001; 37 (Suppl. 1): S18­S24.153. Schnitt SJ. Breast cancer in the 21st century: neu opportunitiesand neu challenges. Mod Pathol 2001; 14: 213?18.154. Slamon D, Pegram M. Rationale for trastuzumab (Herceptin)in adjuvant breast cancer trials. Semin Oncol 2001; 28: 13?9.155. Yang CT, Lee MH, Lan RS, Chen JK. Telomerase activity inpleural effusions: diagnostic significance. J Clin Oncol 1998; 16:567?73.156. Yahata N, Ohyashiki K, Ohyashiki JH, et al. Telomeraseactivity in lung cancer cells obtained from bronchial washings.J Nat Cancer Inst 1998; 90: 684?90.157. Kleinschmidt-DeMasters BK, Evans LC, Bitter MA, ShroyerAL, Shroyer KR. Part II. Telomerase expression in cerebro-spinal fluid specimens as an adjunct to cytologic diagnosis.J Neurol Sci 1998; 161: 124?34.158. Yokoyama Y, Takahashi Y, Shinohara A, Lian Z, Tamaya T.Telomerase activity in the female reproductive tract andneoplasms. Gynecol Oncol 1998; 68: 145?49.414W. N. Keith et al.Copyright # 2001 John Wiley & Sons, Ltd.J Pathol 2001; 195: 404?14.

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