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 Teniposide

teniposide is a semisynthetic derivative of podophyllotoxin with antineoplastic activity. Teniposide forms a ternary complex with the enzyme topoisomerase II and DNA, resulting in dose-dependent single- and double-stranded breaks in DNA, DNA: protein cross-links, inhibition of DNA strand religation, and cytotoxicity. This agent acts in the late S or early G phase of the cell cycle. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

DRUG DESCRIPTION

VUMON® (teniposide injection) (also commonly known as VM-26), is supplied as a sterile nonpyrogenic solution in a nonaqueous medium intended for dilution with a suitable parenteral vehicle prior to intravenous infusion. VUMON is available in 50 mg (5 mL) ampules. Each mL contains 10 mg teniposide, 30 mg benzyl alcohol, 60 mg N,N-dimethylacetamide, 500 mg purified Cremophor® EL (polyoxyethylated castor oil)*, and 42.7% (v/v) dehydrated alcohol. The pH of the clear solution is adjusted to approximately 5 with maleic acid. Teniposide is a semisynthetic derivative of podophyllotoxin. The chemical name for teniposide is 4′-demethylepipodophyllotoxin 9-[4,6-0-(R)-2-thenylidene-β-D-glucopyranoside]. Teniposide differs from etoposide, another podophyllotoxin derivative, by the substitution of a thenylidene group on the glucopyranoside ring. Teniposide is a white to off-white crystalline powder with the empirical formula C32H32O13S and a molecular weight of 656.66. It is a lipophilic compound with a partition coefficient value (octanol/water) of approximately 100. Teniposide is insoluble in water and ether. It is slightly soluble in methanol and very soluble in acetone and dimethylformamide.

CLINICAL PHARMACOLOGY

Teniposide is a phase-specific cytotoxic drug, acting in the late S or early G2 phase of the cell cycle, thus preventing cells from entering mitosis. Teniposide causes dose-dependent single- and double-stranded breaks in DNA and DNA-protein cross-links. The mechanism of action appears to be related to the inhibition of type II topoisomerase activity since teniposide does not intercalate into DNA or bind strongly to DNA. The cytotoxic effects of teniposide are related to the relative number of double-stranded DNA breaks produced in cells, which are a reflection of the stabilization of a topoisomerase II-DNA intermediate. Teniposide has a broad spectrum of in vivo antitumor activity against murine tumors, including hematologic malignancies and various solid tumors. Notably, teniposide is active against sublines of certain murine leukemias with acquired resistance to cisplatin, doxorubicin, amsacrine, daunorubicin, mitoxantrone, or vincristine.

 1: Verma RP, Hansch C. A QSAR study on the cytotoxicity of podophyllotoxin analogues against various cancer cell lines. Med Chem. 2010 Mar;6(2):79-86. PubMed PMID: 20470250.

2: Lata H, Mizuno CS, Moraes RM. The role of biotechnology in the production of the anticancer compound podophyllotoxin. Methods Mol Biol. 2009;547:387-402. PubMed PMID: 19521861.

3: Hirpara KV, Aggarwal P, Mukherjee AJ, Joshi N, Burman AC. Quercetin and its derivatives: synthesis, pharmacological uses with special emphasis on anti-tumor properties and prodrug with enhanced bio-availability. Anticancer Agents Med Chem. 2009 Feb;9(2):138-61. Review. PubMed PMID: 19199862.

4: Xu H, Lv M, Tian X. A review on hemisynthesis, biosynthesis, biological activities, mode of action, and structure-activity relationship of podophyllotoxins: 2003-2007. Curr Med Chem. 2009;16(3):327-49. Review. PubMed PMID: 19149581.

5: Giri A, Lakshmi Narasu M. Production of podophyllotoxin from Podophyllum hexandrum: a potential natural product for clinically useful anticancer drugs. Cytotechnology. 2000 Oct;34(1-2):17-26. PubMed PMID: 19003377.

6: Lamblin F, Hano C, Fliniaux O, Mesnard F, Fliniaux MA, Lainé E. [Interest of lignans in prevention and treatment of cancers]. Med Sci (Paris). 2008 May;24(5):511-9. Review. French. PubMed PMID: 18466729.

7: Wang HK. Plant-derived anticancer agents currently in clinical use or in clinical trials. IDrugs. 1998 May;1(1):92-102. PubMed PMID: 18465513.

8: Srivastava SK, Jha A, Agarwal SK, Mukherjee R, Burman AC. Synthesis and structure-activity relationships of potent antitumor active quinoline and naphthyridine derivatives. Anticancer Agents Med Chem. 2007 Nov;7(6):685-709. Review. PubMed PMID: 18045063.

9: Moraes-Cerdeira RM, Burandt CL Jr, Bastos JK, Nanayakkara NP, McChesney JD. In vitro propagation of Podophyllum peltatum. Planta Med. 1998 Feb;64(1):42-5. PubMed PMID: 17253216.

10: Chen H, Shao C, Shi H, Mu Y, Sai K, Chen Z. Single nucleotide polymorphisms and expression of ERCC1 and ERCC2 vis-à-vis chemotherapy drug cytotoxicity in human glioma. J Neurooncol. 2007 May;82(3):257-62. Epub 2006 Dec 7. PubMed PMID: 17151930.

11: Aneja R, Vangapandu SN, Lopus M, Chandra R, Panda D, Joshi HC. Development of a novel nitro-derivative of noscapine for the potential treatment of drug-resistant ovarian cancer and T-cell lymphoma. Mol Pharmacol. 2006 Jun;69(6):1801-9. Epub 2006 Mar 3. Erratum in: Mol Pharmacol. 2007 Aug;72(2):486. PubMed PMID: 16517755.

12: Moinuddin SG, Youn B, Bedgar DL, Costa MA, Helms GL, Kang C, Davin LB, Lewis NG. Secoisolariciresinol dehydrogenase: mode of catalysis and stereospecificity of hydride transfer in Podophyllum peltatum. Org Biomol Chem. 2006 Mar 7;4(5):808-16. Epub 2006 Jan 30. PubMed PMID: 16493463.

13: Marchion DC, Bicaku E, Turner JG, Daud AI, Sullivan DM, Munster PN. Synergistic interaction between histone deacetylase and topoisomerase II inhibitors is mediated through topoisomerase IIbeta. Clin Cancer Res. 2005 Dec 1;11(23):8467-75. PubMed PMID: 16322310.

14: Wang T, Chen FY, Gu CH, Zhong H, Teng Y, Ouyang RR. [Transfection of HL-60 cells with CYP3A5 gene induces drug-resistant phenotype]. Zhonghua Zhong Liu Za Zhi. 2005 Aug;27(8):461-4. Chinese. PubMed PMID: 16188140.

15: Srivastava V, Negi AS, Kumar JK, Gupta MM, Khanuja SP. Plant-based anticancer molecules: a chemical and biological profile of some important leads. Bioorg Med Chem. 2005 Nov 1;13(21):5892-908. Review. PubMed PMID: 16129603.

16: Rickardson L, Fryknäs M, Dhar S, Lövborg H, Gullbo J, Rydåker M, Nygren P, Gustafsson MG, Larsson R, Isaksson A. Identification of molecular mechanisms for cellular drug resistance by combining drug activity and gene expression profiles. Br J Cancer. 2005 Aug 22;93(4):483-92. PubMed PMID: 16012520; PubMed Central PMCID: PMC2361589.

17: You Y. Podophyllotoxin derivatives: current synthetic approaches for new anticancer agents. Curr Pharm Des. 2005;11(13):1695-717. Review. PubMed PMID: 15892669.

18: Youn B, Moinuddin SG, Davin LB, Lewis NG, Kang C. Crystal structures of apo-form and binary/ternary complexes of Podophyllum secoisolariciresinol dehydrogenase, an enzyme involved in formation of health-protecting and plant defense lignans. J Biol Chem. 2005 Apr 1;280(13):12917-26. Epub 2005 Jan 13. PubMed PMID: 15653677.

19: Farkya S, Bisaria VS, Srivastava AK. Biotechnological aspects of the production of the anticancer drug podophyllotoxin. Appl Microbiol Biotechnol. 2004 Oct;65(5):504-19. Epub 2004 Jul 28. Review. PubMed PMID: 15378293.

20: Le Garrec D, Gori S, Luo L, Lessard D, Smith DC, Yessine MA, Ranger M, Leroux JC. Poly(N-vinylpyrrolidone)-block-poly(D,L-lactide) as a new polymeric solubilizer for hydrophobic anticancer drugs: in vitro and in vivo evaluation. J Control Release. 2004 Sep 14;99(1):83-101. PubMed PMID: 15342183.

21: Mo YY, Yu Y, Ee PL, Beck WT. Overexpression of a dominant-negative mutant Ubc9 is associated with increased sensitivity to anticancer drugs. Cancer Res. 2004 Apr 15;64(8):2793-8. PubMed PMID: 15087395.

22: Umemura K, Yanase K, Suzuki M, Okutani K, Yamori T, Andoh T. Inhibition of DNA topoisomerases I and II, and growth inhibition of human cancer cell lines by a marine microalgal polysaccharide. Biochem Pharmacol. 2003 Aug 1;66(3):481-7. PubMed PMID: 12907247.

23: Chattopadhyay S, Bisaria VS, Srivastava AK. Enhanced production of podophyllotoxin by Podophyllum hexandrum using in situ cell retention bioreactor. Biotechnol Prog. 2003 May-Jun;19(3):1026-8. PubMed PMID: 12790673.

24: Gao H, Yamasaki EF, Chan KK, Shen LL, Snapka RM. DNA sequence specificity for topoisomerase II poisoning by the quinoxaline anticancer drugs XK469 and CQS. Mol Pharmacol. 2003 Jun;63(6):1382-8. PubMed PMID: 12761349.

25: Kaaijk P, Kaspers GJ, Van Wering ER, Broekema GJ, Loonen AH, Hählen K, Schmiegelow K, Janka-Schaub GE, Henze G, Creutzig U, Veerman AJ. Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia. Br J Cancer. 2003 Mar 10;88(5):775-81. PubMed PMID: 12618889; PubMed Central PMCID: PMC2376358.

26: Rousseau A, Marquet P. Application of pharmacokinetic modelling to the routine therapeutic drug monitoring of anticancer drugs. Fundam Clin Pharmacol. 2002 Aug;16(4):253-62. Review. PubMed PMID: 12570013.

27: Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD. Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 2002 Nov 1;62(21):6172-7. PubMed PMID: 12414644.

28: Fernando LP, Kurian PJ, Fidan M, Fernandes DJ. Quantitation of gene-specific DNA damage by competitive PCR. Anal Biochem. 2002 Jul 15;306(2):212-21. PubMed PMID: 12123658.

29: Asami Y, Jia DW, Tatebayashi K, Yamagata K, Tanokura M, Ikeda H. Effect of the DNA topoisomerase II inhibitor VP-16 on illegitimate recombination in yeast chromosomes. Gene. 2002 May 29;291(1-2):251-7. PubMed PMID: 12095698.

30: Moraes RM, Bedir E, Barrett H, Burandt C Jr, Canel C, Khan IA. Evaluation of Podophyllum peltatum accessions for podophyllotoxin production. Planta Med. 2002 Apr;68(4):341-4. PubMed PMID: 11988859.

31: Hu S, Huang C, Chen B. [Enhanced cytotoxicity of VM-26 in human malignant glioma cells by calcium channel blocker nicardipine in vitro]. Hunan Yi Ke Da Xue Xue Bao. 1999;24(2):143-6. Chinese. PubMed PMID: 11938773.

32: Baumhäkel M, Kasel D, Rao-Schymanski RA, Böcker R, Beckurts KT, Zaigler M, Barthold D, Fuhr U. Screening for inhibitory effects of antineoplastic agents on CYP3A4 in human liver microsomes. Int J Clin Pharmacol Ther. 2001 Dec;39(12):517-28. PubMed PMID: 11770832.

33: Pang S, Zheng N, Felix CA, Scavuzzo J, Boston R, Blair IA. Simultaneous determination of etoposide and its catechol metabolite in the plasma of pediatric patients by liquid chromatography/tandem mass spectrometry. J Mass Spectrom. 2001 Jul;36(7):771-81. PubMed PMID: 11473400.

34: Gordaliza M, Miguel del Corral JM, Angeles Castro M, García-García PA, San Feliciano A. Cytotoxic cyclolignans related to podophyllotoxin. Farmaco. 2001 Apr;56(4):297-304. PubMed PMID: 11421258.

35: Felix CA. Leukemias related to treatment with DNA topoisomerase II inhibitors. Med Pediatr Oncol. 2001 May;36(5):525-35. Review. PubMed PMID: 11340607.

36: Sánchez-Alcázar JA, Khodjakov A, Schneider E. Anticancer drugs induce increased mitochondrial cytochrome c expression that precedes cell death. Cancer Res. 2001 Feb 1;61(3):1038-44. PubMed PMID: 11221830.

37: Solary E, Mannone L, Moreau D, Caillot D, Casasnovas RO, Guy H, Grandjean M, Wolf JE, André F, Fenaux P, Canal P, Chauffert B, Wotawa A, Bayssas M, Genne P. Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes. Leukemia. 2000 Dec;14(12):2085-94. PubMed PMID: 11187897.

38: Gordaliza M, Castro MA, del Corral JM, Feliciano AS. Antitumor properties of podophyllotoxin and related compounds. Curr Pharm Des. 2000 Dec;6(18):1811-39. Review. PubMed PMID: 11102564.

39: Relling MV, Pui CH, Sandlund JT, Rivera GK, Hancock ML, Boyett JM, Schuetz EG, Evans WE. Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia. Lancet. 2000 Jul 22;356(9226):285-90. PubMed PMID: 11071183.

40: Rousseau A, Marquet P, Debord J, Sabot C, Lachâtre G. Adaptive control methods for the dose individualisation of anticancer agents. Clin Pharmacokinet. 2000 Apr;38(4):315-53. Review. PubMed PMID: 10803455.

41: Morgan SE, Cadena RS, Raimondi SC, Beck WT. Selection of human leukemic CEM cells for resistance to the DNA topoisomerase II catalytic inhibitor ICRF-187 results in increased levels of topoisomerase IIalpha and altered G(2)/M checkpoint and apoptotic responses. Mol Pharmacol. 2000 Feb;57(2):296-307. PubMed PMID: 10648639.

42: Holden JA, Townsend JJ. DNA topoisomerase II-alpha as a proliferation marker in astrocytic neoplasms of the central nervous system: correlation with MIB1 expression and patient survival. Mod Pathol. 1999 Dec;12(12):1094-100. PubMed PMID: 10619260.

43: Bun H, Disdier B, Aubert C, Catalin J. Interspecies variability and drug interactions of clozapine metabolism by microsomes. Fundam Clin Pharmacol. 1999;13(5):577-81. PubMed PMID: 10520731.

44: Mo YY, Beck WT. DNA damage signals induction of fas ligand in tumor cells. Mol Pharmacol. 1999 Feb;55(2):216-22. PubMed PMID: 9927611.

45: Hande KR. Etoposide: four decades of development of a topoisomerase II inhibitor. Eur J Cancer. 1998 Sep;34(10):1514-21. Review. PubMed PMID: 9893622.

46: Mo YY, Ameiss KA, Beck WT. Overexpression of human DNA topoisomerase II alpha by fusion to enhanced green fluorescent protein. Biotechniques. 1998 Dec;25(6):1052-7. PubMed PMID: 9863061.

47: Duffy CP, Elliott CJ, O'Connor RA, Heenan MM, Coyle S, Cleary IM, Kavanagh K, Verhaegen S, O'Loughlin CM, NicAmhlaoibh R, Clynes M. Enhancement of chemotherapeutic drug toxicity to human tumour cells in vitro by a subset of non-steroidal anti-inflammatory drugs (NSAIDs). Eur J Cancer. 1998 Jul;34(8):1250-9. PubMed PMID: 9849488.

48: Hande KR. Clinical applications of anticancer drugs targeted to topoisomerase II. Biochim Biophys Acta. 1998 Oct 1;1400(1-3):173-84. Review. PubMed PMID: 9748560.

49: McLeod HL. Clinically relevant drug-drug interactions in oncology. Br J Clin Pharmacol. 1998 Jun;45(6):539-44. Review. PubMed PMID: 9663808; PubMed Central PMCID: PMC1873644.

50: Dolan ME, Frydman B, Thompson CB, Diamond AM, Garbiras BJ, Safa AR, Beck WT, Marton LJ. Effects of 1,2-naphthoquinones on human tumor cell growth and lack of cross-resistance with other anticancer agents. Anticancer Drugs. 1998 Jun;9(5):437-48. PubMed PMID: 9660542.

51: Imbert TF. Discovery of podophyllotoxins. Biochimie. 1998 Mar;80(3):207-22. PubMed PMID: 9615861.

52: Reber U, Wüllner U, Trepel M, Baumgart J, Seyfried J, Klockgether T, Dichgans J, Weller M. Potentiation of treosulfan toxicity by the glutathione-depleting agent buthionine sulfoximine in human malignant glioma cells: the role of bcl-2. Biochem Pharmacol. 1998 Feb 1;55(3):349-59. PubMed PMID: 9484802.

53: Holden JA. Human deoxyribonucleic acid topoisomerases: molecular targets of anticancer drugs. Ann Clin Lab Sci. 1997 Nov-Dec;27(6):402-12. PubMed PMID: 9433537.

54: Catapano CV, Carbone GM, Pisani F, Qiu J, Fernandes DJ. Arrest of replication fork progression at sites of topoisomerase II-mediated DNA cleavage in human leukemia CEM cells incubated with VM-26. Biochemistry. 1997 May 13;36(19):5739-48. PubMed PMID: 9153414.

55: Furukawa M, Harada T, Tanaka T, Kuwano M. [DNA topoisomerases targeting anticancer agents and mechanism for acquirement of drug resistance]. Nippon Rinsho. 1997 May;55(5):1096-102. Review. Japanese. PubMed PMID: 9155159.

56: Pezzuto JM. Plant-derived anticancer agents. Biochem Pharmacol. 1997 Jan 24;53(2):121-33. Review. PubMed PMID: 9037244.

57: Cornarotti M, Tinelli S, Willmore E, Zunino F, Fisher LM, Austin CA, Capranico G. Drug sensitivity and sequence specificity of human recombinant DNA topoisomerases IIalpha (p170) and IIbeta (p180). Mol Pharmacol. 1996 Dec;50(6):1463-71. PubMed PMID: 8967966.

58: Coustan-Smith E, Kitanaka A, Pui CH, McNinch L, Evans WE, Raimondi SC, Behm FG, Aricò M, Campana D. Clinical relevance of BCL-2 overexpression in childhood acute lymphoblastic leukemia. Blood. 1996 Feb 1;87(3):1140-6. PubMed PMID: 8562940.

59: Faure P, Madelaine I. [Topoisomerases: therapeutic value]. Ann Pharm Fr. 1996;54(1):40-4. French. PubMed PMID: 8702194.

60: Hirohashi Y, Hidaka K, Sato S, Kuwano M, Kohno K, Hisatsugu T. Biomodulation by hyperthermia of topoisomerase II-targeting drugs in human colorectal cancer cells. Jpn J Cancer Res. 1995 Nov;86(11):1097-105. PubMed PMID: 8567402.

61: Spitzner JR, Chung IK, Gootz TD, McGuirk PR, Muller MT. Analysis of eukaryotic topoisomerase II cleavage sites in the presence of the quinolone CP-115,953 reveals drug-dependent and -independent recognition elements. Mol Pharmacol. 1995 Aug;48(2):238-49. PubMed PMID: 7651357.

62: Liliemark E, Pettersson B, Peterson C, Liliemark J. High-performance liquid chromatography with fluorometric detection for monitoring of etoposide and its cis-isomer in plasma and leukaemic cells. J Chromatogr B Biomed Appl. 1995 Jul 21;669(2):311-7. PubMed PMID: 7581907.

63: Kanzawa F, Nishio K, Kubota N, Saijo N. Antitumor activities of a new indolocarbazole substance, NB-506, and establishment of NB-506-resistant cell lines, SBC-3/NB. Cancer Res. 1995 Jul 1;55(13):2806-13. PubMed PMID: 7796407.

64: Middel O, Woerdenbag HJ, van Uden W, van Oeveren A, Jansen JF, Feringa BL, Konings AW, Pras N, Kellogg RM. Synthesis and cytotoxicity of novel lignans. J Med Chem. 1995 Jun 9;38(12):2112-8. PubMed PMID: 7783142.

65: Tortora G, Ciardiello F, Damiano V, Pepe S, Bianco C, di Isernia G, Davies SL, North P, Harris AL, Hickson ID, et al. Cyclic AMP-dependent protein kinase type I is involved in hypersensitivity of human breast cells to topoisomerase II inhibitors. Clin Cancer Res. 1995 Jan;1(1):49-56. PubMed PMID: 9815886.

66: Fernandes DJ, Qiu J, Catapano CV. DNA topoisomerase II isozymes involved in anticancer drug action and resistance. Adv Enzyme Regul. 1995;35:265-81. PubMed PMID: 7572348.

67: Permana PA, Snapka RM, Shen LL, Chu DT, Clement JJ, Plattner JJ. Quinobenoxazines: a class of novel antitumor quinolones and potent mammalian DNA topoisomerase II catalytic inhibitors. Biochemistry. 1994 Sep 20;33(37):11333-9. PubMed PMID: 7727384.

68: Kim R, Beck WT. Differences between drug-sensitive and -resistant human leukemic CEM cells in c-jun expression, AP-1 DNA-binding activity, and formation of Jun/Fos family dimers, and their association with internucleosomal DNA ladders after treatment with VM-26. Cancer Res. 1994 Sep 15;54(18):4958-66. PubMed PMID: 8069863.

69: Long BH, Fairchild CR. Paclitaxel inhibits progression of mitotic cells to G1 phase by interference with spindle formation without affecting other microtubule functions during anaphase and telephase. Cancer Res. 1994 Aug 15;54(16):4355-61. PubMed PMID: 7913875.

70: Jensen PB, Sørensen BS, Sehested M, Grue P, Demant EJ, Hansen HH. Targeting the cytotoxicity of topoisomerase II-directed epipodophyllotoxins to tumor cells in acidic environments. Cancer Res. 1994 Jun 1;54(11):2959-63. PubMed PMID: 8187081.

71: Gottesman MM, Germann UA, Aksentijevich I, Sugimoto Y, Cardarelli CO, Pastan I. Gene transfer of drug resistance genes. Implications for cancer therapy. Ann N Y Acad Sci. 1994 May 31;716:126-38; discussion 138-43. PubMed PMID: 7912913.

72: Kubota N, Nishio K, Takeda Y, Ohmori T, Funayama Y, Ogasawara H, Ohira T, Kunikane H, Terashima Y, Saijo N. Characterization of an etoposide-resistant human ovarian cancer cell line. Cancer Chemother Pharmacol. 1994;34(3):183-90. PubMed PMID: 7911742.

73: Bachur NR, Johnson R, Yu F, Hickey R, Applegren N, Malkas L. Antihelicase action of DNA-binding anticancer agents: relationship to guanosine-cytidine intercalator binding. Mol Pharmacol. 1993 Nov;44(5):1064-9. PubMed PMID: 8246909.

74: Galpin AJ, Evans WE. Therapeutic drug monitoring in cancer management. Clin Chem. 1993 Nov;39(11 Pt 2):2419-30. Review. PubMed PMID: 8222253.

75: Zhou-Pan XR, Sérée E, Zhou XJ, Placidi M, Maurel P, Barra Y, Rahmani R. Involvement of human liver cytochrome P450 3A in vinblastine metabolism: drug interactions. Cancer Res. 1993 Nov 1;53(21):5121-6. PubMed PMID: 8221648.

76: Hamaguchi K, Godwin AK, Yakushiji M, O'Dwyer PJ, Ozols RF, Hamilton TC. Cross-resistance to diverse drugs is associated with primary cisplatin resistance in ovarian cancer cell lines. Cancer Res. 1993 Nov 1;53(21):5225-32. PubMed PMID: 8106143.

77: Ohtsu T, Sasaki Y. [Pharmacodynamics of anticancer agents]. Gan To Kagaku Ryoho. 1993 Sep;20(12):1741-9. Review. Japanese. PubMed PMID: 8379667.

78: Wasserman RA, Austin CA, Fisher LM, Wang JC. Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast. Cancer Res. 1993 Aug 1;53(15):3591-6. PubMed PMID: 8393377.

79: D'Argenio DZ, Rodman JH. Targeting the systemic exposure of teniposide in the population and the individual using a stochastic therapeutic objective. J Pharmacokinet Biopharm. 1993 Apr;21(2):223-51. PubMed PMID: 8229682.

80: Matsuo K, Kohno K, Sato S, Uchiumi T, Tanimura H, Yamada Y, Kuwano M. Enhanced expression of the DNA topoisomerase II gene in response to heat shock stress in human epidermoid cancer KB cells. Cancer Res. 1993 Mar 1;53(5):1085-90. PubMed PMID: 8382554.

81: Zhou XJ, Zhou-Pan XR, Gauthier T, Placidi M, Maurel P, Rahmani R. Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions. Biochem Pharmacol. 1993 Feb 24;45(4):853-61. PubMed PMID: 8452560.

82: Lorico A, Long BH. Biochemical characterisation of elsamicin and other coumarin-related antitumour agents as potent inhibitors of human topoisomerase II. Eur J Cancer. 1993;29A(14):1985-91. PubMed PMID: 8280493.

83: Neumann M, Wilisch A, Diddens H, Probst H, Gekeler V. MDR hamster cells exhibiting multiple altered gene expression: effects of dexniguldipine-HCl (B859-35), cyclosporin A and buthionine sulfoximine. Anticancer Res. 1992 Nov-Dec;12(6B):2297-302. PubMed PMID: 1284202.

84: McLeod HL, Relling MV, Crom WR, Silverstein K, Groom S, Rodman JH, Rivera GK, Crist WM, Evans WE. Disposition of antineoplastic agents in the very young child. Br J Cancer Suppl. 1992 Aug;18:S23-9. Review. PubMed PMID: 1503923; PubMed Central PMCID: PMC2149660.

85: Takano H, Kohno K, Matsuo K, Matsuda T, Kuwano M. DNA topoisomerase-targeting antitumor agents and drug resistance. Anticancer Drugs. 1992 Aug;3(4):323-30. Review. PubMed PMID: 1330080.

86: Wolverton JS, Danks MK, Granzen B, Beck WT. DNA topoisomerase II immunostaining in human leukemia and rhabdomyosarcoma cell lines and their responses to topoisomerase II inhibitors. Cancer Res. 1992 Aug 1;52(15):4248-53. PubMed PMID: 1322239.

87: Pommier Y, Orr A, Kohn KW, Riou JF. Differential effects of amsacrine and epipodophyllotoxins on topoisomerase II cleavage in the human c-myc protooncogene. Cancer Res. 1992 Jun 1;52(11):3125-30. PubMed PMID: 1317259.

88: Clark PI. Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives. Semin Oncol. 1992 Apr;19(2 Suppl 6):20-7. Review. PubMed PMID: 1411635.

89: Evans WE, Rodman JH, Relling MV, Petros WP, Stewart CF, Pui CH, Rivera GK. Differences in teniposide disposition and pharmacodynamics in patients with newly diagnosed and relapsed acute lymphocytic leukemia. J Pharmacol Exp Ther. 1992 Jan;260(1):71-7. PubMed PMID: 1731053.

90: Petros WP, Rodman JH, Relling MV, Christensen M, Pui CH, Rivera GK, Evans WE. Variability in teniposide plasma protein binding is correlated with serum albumin concentrations. Pharmacotherapy. 1992;12(4):273-7. PubMed PMID: 1518726.

91: Huot J, Roy G, Lambert H, Chrétien P, Landry J. Increased survival after treatments with anticancer agents of Chinese hamster cells expressing the human Mr 27,000 heat shock protein. Cancer Res. 1991 Oct 1;51(19):5245-52. PubMed PMID: 1913647.

92: Kohno K, Takano H, Kuwano M. [Mechanisms of resistance to DNA topoisomerase II inhibitors]. Gan To Kagaku Ryoho. 1991 Aug;18(10):1568-73. Review. Japanese. PubMed PMID: 1651684.

93: Hongo T, Fujii Y. In vitro chemosensitivity of lymphoblasts at relapse in childhood leukemia using the MTT assay. Int J Hematol. 1991 Jun;54(3):219-30. PubMed PMID: 1747457.

94: Ratain MJ, Schilsky RL, Conley BA, Egorin MJ. Pharmacodynamics in cancer therapy. J Clin Oncol. 1990 Oct;8(10):1739-53. Review. PubMed PMID: 2213109.

95: Qian XD, Beck WT. Binding of an optically pure photoaffinity analogue of verapamil, LU-49888, to P-glycoprotein from multidrug-resistant human leukemic cell lines. Cancer Res. 1990 Feb 15;50(4):1132-7. PubMed PMID: 1967551.

96: Wright SE, White JC, Huang L. Partitioning of teniposide into membranes and the role of lipid composition. Biochim Biophys Acta. 1990 Jan 29;1021(2):105-13. PubMed PMID: 2302390.

97: Wright SE, Hines LH, White JC. Effects of the lipophilic anticancer drug teniposide (VM-26) on membrane transport. Chem Biol Interact. 1990;75(1):31-48. PubMed PMID: 2364457.

98: Fesen M, Pommier Y. Mammalian topoisomerase II activity is modulated by the DNA minor groove binder distamycin in simian virus 40 DNA. J Biol Chem. 1989 Jul 5;264(19):11354-9. PubMed PMID: 2544590.

99: Wright SE, White JC. Effects of the anticancer agent VM-26 on hexose uptake in Ehrlich cells. Cancer Biochem Biophys. 1989 May;10(3):185-96. PubMed PMID: 2776116.

100: Relling MV, Evans WE, Fonné-Pfister R, Meyer UA. Anticancer drugs as inhibitors of two polymorphic cytochrome P450 enzymes, debrisoquin and mephenytoin hydroxylase, in human liver microsomes. Cancer Res. 1989 Jan 1;49(1):68-71. PubMed PMID: 2908853.

101: Evans WE, Relling MV, Rodman JH, Crom WR. Anticancer therapy as a pediatric pharmacodynamic paradigm. Dev Pharmacol Ther. 1989;13(2-4):85-95. Review. PubMed PMID: 2693007.

102: Miki T, Kotake T. [Anti-cancer drug sensitivity test against human testicular cancer xenograft--comparison with clinical results of chemotherapy]. Hinyokika Kiyo. 1988 Nov;34(11):1903-9. Japanese. PubMed PMID: 3242364.

103: Zamora JM, Pearce HL, Beck WT. Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells. Mol Pharmacol. 1988 Apr;33(4):454-62. PubMed PMID: 3162758.

104: Sawada M, Ozaki M, Hongo J, Hirota Y, Inagaki M. [Assessment of the establishing individual protocol for effective chemotherapy of ovarian cancer--fundamental research using human tumor-nude mouse system]. Nippon Sanka Fujinka Gakkai Zasshi. 1987 Oct;39(10):1776-83. Japanese. PubMed PMID: 3429976.

105: Ali-Osman F, Giblin J, Dougherty D, Rosenblum ML. Application of in vivo and in vitro pharmacokinetics for physiologically relevant drug exposure in a human tumor clonogenic cell assay. Cancer Res. 1987 Jul 15;47(14):3718-24. PubMed PMID: 2954633.

106: Rodman JH, Abromowitch M, Sinkule JA, Hayes FA, Rivera GK, Evans WE. Clinical pharmacodynamics of continuous infusion teniposide: systemic exposure as a determinant of response in a phase I trial. J Clin Oncol. 1987 Jul;5(7):1007-14. PubMed PMID: 3598607.

107: el-Yazigi A, Martin CR. Improved assay for etoposide in plasma by radial-compression liquid chromatography with electrochemical detection. Clin Chem. 1987 Jun;33(6):803-5. PubMed PMID: 3594819.

108: Gupta RS, Bromke A, Bryant DW, Gupta R, Singh B, McCalla DR. Etoposide (VP16) and teniposide (VM26): novel anticancer drugs, strongly mutagenic in mammalian but not prokaryotic test systems. Mutagenesis. 1987 May;2(3):179-86. PubMed PMID: 3325741.

109: Wright SE, White JC. Membrane ordering effects of the anticancer agent VM-26. Biochim Biophys Acta. 1986 Dec 16;863(2):297-304. PubMed PMID: 3024721.

110: Zamora JM, Beck WT. Chloroquine enhancement of anticancer drug cytotoxicity in multiple drug resistant human leukemic cells. Biochem Pharmacol. 1986 Dec 1;35(23):4303-10. PubMed PMID: 3466591.

111: Wright SE, White JC. Teniposide-induced changes in the physical properties of phosphatidylcholine liposomes. A calorimetric study. Biochem Pharmacol. 1986 Aug 15;35(16):2731-5. PubMed PMID: 3741467.

112: Long BH, Musial ST, Brattain MG. DNA breakage in human lung carcinoma cells and nuclei that are naturally sensitive or resistant to etoposide and teniposide. Cancer Res. 1986 Aug;46(8):3809-16. PubMed PMID: 3015377.

113: Long BH, Musial ST, Brattain MG. Single- and double-strand DNA breakage and repair in human lung adenocarcinoma cells exposed to etoposide and teniposide. Cancer Res. 1985 Jul;45(7):3106-12. PubMed PMID: 3839166.

114: Gupta RS. Cross-resistance of vinblastine- and taxol-resistant mutants of Chinese hamster ovary cells to other anticancer drugs. Cancer Treat Rep. 1985 May;69(5):515-21. PubMed PMID: 2860971.

115: Matsushima Y, Kanzawa F, Hoshi A, Shimizu E, Nomori H, Sasaki Y, Saijo N. Time-schedule dependency of the inhibiting activity of various anticancer drugs in the clonogenic assay. Cancer Chemother Pharmacol. 1985;14(2):104-7. PubMed PMID: 3971474.

116: Ross W, Rowe T, Glisson B, Yalowich J, Liu L. Role of topoisomerase II in mediating epipodophyllotoxin-induced DNA cleavage. Cancer Res. 1984 Dec;44(12 Pt 1):5857-60. PubMed PMID: 6094001.

117: Minocha A, Long BH. Inhibition of the DNA catenation activity of type II topoisomerase by VP16-213 and VM26. Biochem Biophys Res Commun. 1984 Jul 18;122(1):165-70. PubMed PMID: 6331440.

118: Gupta RS, Singh B. 4'-Demethylepipodophyllotoxin-beta-D-glucoside: a new podophyllotoxin derivative with VM-26-like and VP-16-213-like activities. J Natl Cancer Inst. 1984 Jul;73(1):241-8. PubMed PMID: 6588229.

119: McNiel NO, Morgan LR Jr. Effects of sodium warfarin and sodium heparin plus anticancer agents on growth of rat C6 glioma cells. J Natl Cancer Inst. 1984 Jul;73(1):169-76. PubMed PMID: 6588223.

120: Sinkule JA, Stewart CF, Crom WR, Melton ET, Dahl GV, Evans WE. Teniposide (VM26) disposition in children with leukemia. Cancer Res. 1984 Mar;44(3):1235-7. PubMed PMID: 6581866.

121: Sinkule JA, Evans WE. High-performance liquid chromatographic analysis of the semisynthetic epipodophyllotoxins teniposide and etoposide using electrochemical detection. J Pharm Sci. 1984 Feb;73(2):164-8. PubMed PMID: 6707876.

122: Lieber MM. Soft agar colony formation assay for in vitro chemotherapy sensitivity testing of human renal cell carcinoma: Mayo Clinic experience. J Urol. 1984 Feb;131(2):391-3. PubMed PMID: 6199522.

123: Gupta RS. Genetic, biochemical, and cross-resistance studies with mutants of Chinese hamster ovary cells resistant to the anticancer drugs, VM-26 and VP16-213. Cancer Res. 1983 Apr;43(4):1568-74. PubMed PMID: 6831403.

124: Fuerst ML. New anticancer drug class. JAMA. 1983 Mar 25;249(12):1539, 1543. PubMed PMID: 6827733.

125: Dorr RT, Alberts DS. Skin ulceration potential without therapeutic anticancer activity for epipodophyllotoxin commercial diluents. Invest New Drugs. 1983;1(2):151-9. PubMed PMID: 6678864.

126: Evans WE, Crom WR, Sinkule JA, Yee GC, Stewart CF, Hutson PR. Pharmacokinetics of anticancer drugs in children. Drug Metab Rev. 1983;14(5):847-86. Review. PubMed PMID: 6197269.

127: Issell BF. The podophyllotoxin derivatives VP16-213 and VM26. Cancer Chemother Pharmacol. 1982;7(2-3):73-80. Review. PubMed PMID: 7044593.

128: Strife RJ, Jardine I, Colvin M. Analysis of the anticancer drugs etoposide (VP 16-213) and teniposide (VM 26) by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1981 Jun 12;224(1):168-74. PubMed PMID: 7263816.

129: Reich SD. Toxicity of anticancer drugs used in children. Cancer Nurs. 1980 Oct;3(5):385-6. PubMed PMID: 6902677.

130: Strife RJ, Jardine I, Colvin M. Analysis of the anticancer drugs VP 16-213 and VM 26 and their metabolites by high-performance liquid chromatography. J Chromatogr. 1980 May 9;182(2):211-20. PubMed PMID: 7380913.

131: Chiuten DF, Bennett JM, Creech RH, Glick J, Falkson G, Brodovsky HS, Begg CB, Muggia FM, Carbone PP. VM-26, a new anticancer drug with effectiveness in malignant lymphoma: an Eastern Cooperative Oncology Group Study (EST 1474). Cancer Treat Rep. 1979 Jan;63(1):7-11. PubMed PMID: 369693.

132: Rao AP, Rao PN. The cause of G2-arrest in Chinese hamster ovary cells treated with anticancer drugs. J Natl Cancer Inst. 1976 Nov;57(5):1139-43. PubMed PMID: 137324.

133: Gosalvez M, García-Cañero R, Reinhold H. Delayed pyridine nucleotide reoxidation induced by the anticancer agent VM-26 as measured in vivo and in situ by NADH microfluorimetry. Eur J Cancer. 1975 Oct;11(10):709-15. PubMed PMID: 173557.