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Lung Cancer pp 171–191Cite as

In vitro models for testing of cytostatic agents in small cell lung cancer

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Part of the book series: Cancer Treatment and Research ((CTAR,volume 72))

Abstract

Small cell lung cancer (SCLC) is one of the solid tumors most responsive to chemotherapy. Despite the apparent initial sensitivity of SCLC, acquired drug resistance is the major problem; only a small proportion of patients will remain in remission beyond two years [1]. The overall treatment results have not changed markedly in the last decade, despite the application of numerous combination regimens, late intensification regimens, high-dose chemotherapy with autologous bone-marrow rescue, and various types of adjuvant radiotherapy. Resistance in SCLC may be associated with the concomitant occurrence of a less chemosensitive histological tumor type, such as adenocarcinoma or squamous cell carcinoma, but only in a minority of cases. The large majority (over 85%) of SCLC patients who after treatment die with disease still have SCLC histology at autopsy [2]. Although drug resistance in SCLC may have a pharmacological basis or be due to changes in cell kinetics during therapy, the resistance appears to be due primarily to cellular factors.

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References

  1. Hansen HH. 1992. Management of small-cell cancer of the lung. Lancet 339:846–849.

    Article  PubMed  CAS  Google Scholar 

  2. Sehested M, Hirsch FR, Østerlind K, Olsen JE. 1986. Morphologic variations of small cell lung cancer. A histopathologic study of pretreatment and posttreatment specimens in 104 patients. Cancer 57:804–807.

    Article  PubMed  CAS  Google Scholar 

  3. Goldie JH, Coldman AJ. 1984. The genetic origin of drug resistance in neoplasms: Implications for systemic therapy. Cancer Res 44:3643–3653.

    PubMed  CAS  Google Scholar 

  4. Borst P. 1991. Genetic mechanisms of drug resistance. A review. Rev Oncol 4:87–105.

    Google Scholar 

  5. Cullen M. 1990. The design of phase II trials. Lung Cancer 5:214–220.

    Article  Google Scholar 

  6. Grant SC, Gralla RJ, Kris MG, Orazem J, Kitsis EA. 1992. Single-agent chemotherapy trials in small-cell lung cancer, 1970 to 1990: The case for studies in previously treated patients. J Clin Oncol 10:484–498.

    PubMed  CAS  Google Scholar 

  7. Monks A, Scudiero D, Skehan P, Shoemaker R, Pauli K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A, Gray-Goodrich M, Campbell H, Mayo J, Boyd M. 1991. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst 83:757–766.

    Article  PubMed  CAS  Google Scholar 

  8. Nitiss J, Wang JC. 1988. DNA-topoisomerase-targeting antitumor drugs can be studied in yeast. Proc Natl Acad Sci USA 85:7501–7505.

    Article  PubMed  CAS  Google Scholar 

  9. Elsea SH, Osheroff N, Nitiss JL. 1992. Cytotoxicity of quinolones toward eukaryotic cells. Identification of topoisomerase II as the primary cellular target for the quinolone CP-15, 953 in yeast. J Biol Chem 267:13150–13153.

    PubMed  CAS  Google Scholar 

  10. Nitiss JL, Liu Y-X, Harbury P, Jannatipour M, Wasserman R, Wang JC. 1992. Amsacrine and etoposide hypersensitivity of yeast cells overexpressing DNA topoisomerase II. Cancer Res 52:4467–4472.

    PubMed  CAS  Google Scholar 

  11. Kawada S, Yamashita Y, Fujii N, Nakano H. 1991. Induction of a heat-stable topoisomerase II-DNA cleavable complex by nonintercalative terpenoides, terpentecin and clerocidin. Cancer Res 51:2922–2925.

    PubMed  CAS  Google Scholar 

  12. Yamashita Y, Kawada S, Fujii N, Nakano H. 1991. Induction of mammalian DNA topoisomerase I and II mediated DNA cleavage by saintopin, a new antitumor agent from fungus. Biochemistry 30:5838–5845.

    Article  PubMed  CAS  Google Scholar 

  13. Cole SPC. 1992. Multidrug resistance in small cell lung cancer. Cancer J Physiol Pharmacol 70:313–329.

    Article  CAS  Google Scholar 

  14. Giaccone G, Gazdar AF, Beck H, Zunino F, Capranico G. 1992. Multidrug sensitivity phenotype of human lung cancer cells associated with topoisomerase II expression. Cancer Res 52:1666–1674.

    PubMed  CAS  Google Scholar 

  15. Bai R, Pauli KD, Herald CL, Malspeis L, Pettit GR, Hamel E. 1991. Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. J Biol Chem 266:15882–15889.

    PubMed  CAS  Google Scholar 

  16. Pauli KD, Lin CM, Malspeis L, Hamel E. 1992. Identification of novel antimitotic agents acting at the tubulin level by computer-assisted evaluation of differential cytotoxicity data. Cancer Res 52:3892–3900.

    Google Scholar 

  17. Kristjansen PEG, Hirsch FR. 1989. A review of the 5th World Congress on Lung Cancer held by the International Association for the Study of Lung Cancer. Eur Respir J 2:275–279.

    PubMed  CAS  Google Scholar 

  18. Bork E, Ersbøll J, Dombernowsky P, Bergman B, Hansen M, Hansen HH. 1991. Teniposide and etoposide in previously untreated small-cell lung cancer: A randomized study. J Clin Oncol 9:1627–1631.

    PubMed  CAS  Google Scholar 

  19. Hirsch FR, Hansen HH, Hansen M, Østerlind K, Vindeløv LL, Dombernowsky P, Sørensson S. 1987. The superiority of combination chemotherapy including etoposide based on in vivo cell cycle analysis in the treatment of extensive small cell lung cancer: A randomized trial of 288 consecutive patients. J Clin Oncol 5:585–591.

    PubMed  CAS  Google Scholar 

  20. Roper PR, Drewinko B. 1976. Comparison of in vitro methods to determine drug-induced cell lethality. Cancer Res 36:2182–2188.

    PubMed  CAS  Google Scholar 

  21. Freshney RI. 1987. Culture of Animal Cells: A Manual of Basic Technique (2nd ed.). Wiley-Liss: New York, pp. 245–256.

    Google Scholar 

  22. Roed H, Christensen IJ, Vindeløv LL, Spang-Thomsen M, Hansen HH. 1987. Inter-experiment variation and dependence on culture conditions in assaying the chemosensitivity of human small cell lung cancer cell lines. Eur J Cancer Clin Oncol 23:177–186.

    Article  PubMed  CAS  Google Scholar 

  23. Jensen PB, Roed H, Vindeløv L, Christensen IJ, Hansen HH. 1989. Reduced variation in the clonogenic assay obtained by standardization of the cell culture conditions prior to drug testing on small cell lung cancer cell lines. Invest New Drugs 7:307–315.

    Article  PubMed  CAS  Google Scholar 

  24. Jensen PB, Christensen IJ, Sehested M, Hansen HH, Vindeløv L. 1993. Differential cytotoxicity of 19 anticancer agents in wild type and etoposide resistant small cell lung cancer cell lines. Br J Cancer 67:311–320.

    Article  PubMed  CAS  Google Scholar 

  25. Roed H, Vindeløv LL, Christensen IJ, Spang-Thomsen M, Hansen HH. 1987. The effect of the two epipodophyllotoxin derivatives etoposide (VP-16) and teniposide (VM-26) on cell lines established from patients with small cell carcinoma of the lung. Cancer Chemother Pharmacol 19:16–20.

    Article  PubMed  CAS  Google Scholar 

  26. Sehested M, Skovsgaard T, Jensen PB, Demant EJF, Friche E, Bindslev N. 1990. Transport of the multidrug resistance modulators verapmil and azidopine in wild type and daunorubicin resistant Ehrlich ascites tumor cells. Br J Cancer 62:37–41.

    Article  PubMed  CAS  Google Scholar 

  27. Friche E, Jensen PB, Nissen NI. 1992. Comparison of cyclosporin A and SDZ PSC 833 as multidrug resistance modulators in a daunorubicin resistant Ehrlich ascites tumor. Cancer Chemother Pharmacol 30:235–237.

    Article  PubMed  CAS  Google Scholar 

  28. Jensen PB, Sørensen BS, Demant EJF, Sehested M, Jensen PS, Vindeløv L, Hansen HH. 1990. Antagonistic effect of aclarubicin on the cytotoxicity of etoposide and 4′-(9-acridinylamino) methanesulfon-m-anisidide in human small cell lung cancer cell lines and on topoisomerase II mediated DNA cleavage. Cancer Res 50:3311–3316.

    PubMed  CAS  Google Scholar 

  29. Jensen PB, Jensen PS, Demant EJF, Friche E, Sørensen BS, Sehested M, Wasserman K, Vindeløv L, Westergaard O, Hansen HH. 1991. Antagonistic effect of aclarubicin on daunorubicin-induced cytotoxicity in human small cell lung cancer cells: relationship to DNA integrity and topoisomerase II. Cancer Res 51:5093–5099.

    PubMed  CAS  Google Scholar 

  30. Roed H, Vindeløv LL, Christensen IJ, Spang-Thomsen M, Hansen HH. 1988. The cyto-toxic activity of cisplatin, carboplatin and teniposide alone and combined determined on four human small cell lung cancer cell lines by the clonogenic assay. Eur J Clin Oncol 24:247–253.

    Article  CAS  Google Scholar 

  31. Carmichael J, Mitchell JB, Degraff WG, Gamson J, Gazdar AF, Johnson BE, Glatstein E, Minna JD. 1988. Chemosensitivity testing of human lung cancer cell lines using the MTT assay. Br J Cancer 57:540–547.

    Article  PubMed  CAS  Google Scholar 

  32. Kohn KW. 1991. Principles and practice of DNA filter elution. Pharmac Ther 49:55–77.

    Article  Google Scholar 

  33. Jensen PB, Sørensen BS, Sehested M, Demant EJF, Kjeldsen E, Friche E, Hansen HH. 1993. Different modes of anthracycline interaction with topoisomerase II: separate structures critical for DNA-cleavage, and for overcoming topoisomerase II related drug resistance. Biochem Pharmacol 45:2025–2035.

    Article  PubMed  CAS  Google Scholar 

  34. Liu LF. 1989. DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem 58:351–371.

    Article  PubMed  CAS  Google Scholar 

  35. Hsiang Y, Herzberg R, Hect S, Liu LF. 1985. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 260:14873–14878.

    PubMed  CAS  Google Scholar 

  36. Sørensen BS, Sinding J, Andersen AH, Alsner J, Jensen PB, Westergaard O. 1992. Mode of action of topoisomerase II targeting agents at a specific DNA sequence: uncoupling the DNA binding, cleavage, and religation events. J Mod Biol 228:778–786.

    Article  Google Scholar 

  37. Osheroff N. 1989. Biochemical basis for the interactions of type I and type II topoisomerases with DNA. Pharmacol Ther 41:223–241.

    Article  PubMed  CAS  Google Scholar 

  38. Andersen HA, Christiansen K, Zechiedrich EL, Jensen PS, Osheroff N, Westergaard O. 1989. Strand specificity of the topoisomerase II mediated double-stranded DNA cleavage reaction. Biochemistry 28:6237–6244.

    Article  PubMed  CAS  Google Scholar 

  39. Danks MK, Schmidt CA, Cirtain MC, Suttle DP, Beck WT. 1988. Altered catalytic activity of and DNA cleavage by DNA topoisomerase It from human leukemic cells selected for resistance to VM-26. Biochemistry 27:8861–8869.

    Article  PubMed  CAS  Google Scholar 

  40. Bugg BY, Danks MK, Beck WT, Suttle DP. 1991. Expression of a mutant DNA topoisomerase II CCRF-CEM human leukemic cells selected for resistance to teniposide. Proc Natl Acad Sci (USA) 88:7654–7658.

    Article  CAS  Google Scholar 

  41. Hayes JD, Wolf CR. 1990. Molecular mechanisms of drug resistance. Biochem J 272: 281–295.

    PubMed  CAS  Google Scholar 

  42. Dan0 K. 1973. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta 323:466–483.

    Article  PubMed  Google Scholar 

  43. Juliano RL, Ling V. 1976. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162.

    Article  PubMed  CAS  Google Scholar 

  44. Endicott JA, Ling V. 1989. The biochemistry of p-glycoprotein mediated multidrug resistance. Annu Rev Biochem 58:137–171.

    Article  PubMed  CAS  Google Scholar 

  45. Skovsgaard T. 1978. Mechanism of cross-resistance between vincristine and daunorubicin in Ehrlich ascites tumor cells. Cancer Res 38:4722–4727.

    PubMed  CAS  Google Scholar 

  46. Sehested M, Friche E, Jensen PB, Demant EJF. 1992. Relationship of VP-16 to the classical multidrug resistance phenotype. Cancer Res 52:2874–2879.

    PubMed  CAS  Google Scholar 

  47. Chen AY, Yu C, Potmesil M, Wall ME, Wani MC, Liu LF. 1991. Camptothecin overcomes MDR1-mediated resistance in human KB carcinoma cells. Cancer Res 51:6039–6044.

    PubMed  CAS  Google Scholar 

  48. Ballinari D, Pezzoni G, Giuliani FC, Grandi M. 1989. Biological profile of 13-OH-iododoxorubicin: preclinical data. Proc Am Assoc Cancer Res 30:482.

    Google Scholar 

  49. Sehested M, Skovsgaard T, van Deurs B, Winther-Nielsen H. 1987. Increased plasma membrane traffic in daunorubicin resistant P388 leukaemic cells. Effect of daunorubicin and verapamil. Br J Cancer 56:747–751.

    Article  PubMed  CAS  Google Scholar 

  50. Demant EJF, Sehested M, Jensen PB. 1990. A model for computer simulation of P-glycoprotein and transmembrane delta pH mediated anthracycline transport in multidrug resistant tumor cells. Biochim Biophys Acta 1055:117–125.

    Article  PubMed  CAS  Google Scholar 

  51. Cole SPC, Chanda ER, Dicke FP, Gerlach JH, Mirski SEL. 1991. Non-P-glycoprotein-mediated multidrug resistance in a small cell lung cancer cell line: evidence for decreased susceptibility to drug-induced DNA damage and reduced levels of topoisomerase II. Cancer Res 51:3345–3352.

    PubMed  CAS  Google Scholar 

  52. Cole SPC, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AMV, Deeley RG. 1992. Overexpression of a transporter gene in a multi-drug-resistant human lung cancer cell line. Science 258:1650–1654.

    Article  PubMed  CAS  Google Scholar 

  53. Versantvoort CHM, Broxterman HJ, Pinedo HM, de Vries EGE, Feller N, Kuiper CM, Lankelma J. 1992. Energy-dependent processes involved in reduced drug accumulation in multidrug-resistant lung cancer cell lines without P-glycoprotein expression. Cancer Res 52:17–23.

    PubMed  CAS  Google Scholar 

  54. Scheper RJ, Broxterman HJ, Scheffer GL, Kaaijk P, Dalton WS, van Heijningen THM, van Kalken CK, Slovak ML, de Vries EGE, van der Valk P, Meijer CJLM, Pinedo HM. 1993. Overexpression of a Mr 110,000 vesicular protein in non-P-glycoprotein-mediated multidrug resistance. Cancer Res 53:1475–1479.

    PubMed  CAS  Google Scholar 

  55. Nooter K, Herweijer H. 1991. Multidrug resistance (mdr) genes in human cancer. Br J Cancer 63:663–669.

    Article  PubMed  CAS  Google Scholar 

  56. Pirker R, Walner RJ, Geissler K, Linkesch W, Haas OA, Bettelheim P, Hopfner M, Scherrer R, Valent P, Havelec L, Ludwig H, Lechner K. 1991. MDR1 gene expression and treatment outcome in acute myeloid leukemia. J Natl Cancer Inst 83:708–712.

    Article  PubMed  CAS  Google Scholar 

  57. Sehested M, Ersbøl J, Friche E, Jensen PB, Demant EJF. 1993. Detection of P-glycoprotein in adult AML. In The Clinical Value of Drug Resistance Assays in Leukemia and Lymphoma, P Twentyman and G Kaspars (eds.). Harwood Academic Publishers, pp. 49–54.

    Google Scholar 

  58. Lai SL, Goldstein LJ, Gottesman MM, Pastan I, Tsai CM, Johnson BE, Mulshine JL, Ihde DC, Kayser K, Gazar AF. 1989. MDR1 gene expression in lung cancer. J Natl Cancer Inst 81:1144–1145.

    Article  PubMed  CAS  Google Scholar 

  59. Holzmayer TA, Hilsenbeck S, Vonhoff DD, Roninson IB. 1992. Clinical correlates of mdrl (P-glycoprotein) gene expression in ovarian and small-cell lung carcinomas. J Natl Cancer Inst 84:1486–1491.

    Article  PubMed  CAS  Google Scholar 

  60. Jensen PB, Vindeløv L, Roed H, Demant EJF, Sehested M, Skovsgaard T, Hansen HH. 1989. In vitro evaluation of the potential of aclarubicin in the treatment of small cell carcinoma of the lung (SCCL). Br J Cancer 60:838–844.

    Article  PubMed  CAS  Google Scholar 

  61. Reeve JG, Rabbitts PH, Twentyman PR. 1989. Amplification and expression of mdr1 gene in a multidrug resistant variant of small cell lung cancer cell line NCI-H69. Br J Cancer 60:339–342.

    Article  PubMed  CAS  Google Scholar 

  62. Minato K, Kanzawa F, Nishio K, Nakagawa K, Fujiwara Y, Saijo N. 1990. Characterization of an etoposide-resistant human small-cell lung cancer cell line. Cancer Chemother Pharmacol 26:313–317.

    Article  PubMed  CAS  Google Scholar 

  63. Jensen PB, Roed H, Sehested M, Demant EJF, Vindeløv L, Christensen IJ, Hansen HH. 1992. Doxorubicin sensitivity pattern in a panel of small cell lung cancer cell lines: Correlation to etoposide and vincristine and inverse correlation to carmustine sensitivity. Cancer Chemother Pharmacol 31:46–52.

    Article  PubMed  CAS  Google Scholar 

  64. Wu L, Smythe AM, Stinson SF, Mullendore LA, Monks A, Scudiero DA, Pauli KD, Koutsoukos AD, Rubinstein LV, Boyd MR, Shoemaker RH. 1992. Multidrug-resistant phenotype of disease-oriented panels of human tumor cell lines used for anticancer drug screening. Cancer Res 52:3029–3034.

    PubMed  CAS  Google Scholar 

  65. Tewey KM, Rowe TC, Yang L, Halligan BD, Liu LF. 1984. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science 226:466–468.

    Article  PubMed  CAS  Google Scholar 

  66. Bodley A, Liu LF, Israel M, Seshadri R, Koseki Y, Giuliani FC, Kirschenbaum R, Silber R, Potmesil M. 1989. DNA topoisomerase II-mediated interaction of doxorubicin and daunorubicin congeners with DNA. Cancer Res 49:5969–5978.

    PubMed  CAS  Google Scholar 

  67. Holm B, Jensen PB, Sehested M, Hansen HH. In vivo inhibition of etoposide (VP-16) mediated apoptosis, toxicity, and antitumor effect by the topoisomerase II uncoupling anthracycline aclarubicin. Cancer Chemother Pharmacol (in press).

    Google Scholar 

  68. Jensen PB, Roed H, Skovsgaard T, Friche E, Vindeløv L, Hansen HH, Spang-Thomsen M. 1990. Antitumor activity of the two epipodophyllotoxin derivatives VP-16 and VM-26 in preclinical systems: a comparison of in vitro and in vivo drug evaluation. Cancer Chemother Pharmacol 27:194–198.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Peter Buhl Jensen
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  2. Maxwell Sehested
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Editors and Affiliations

  1. Department of Oncology 5074, Rigshospitalet, 9 Blegdamsvej, DK-2100, Copenhagen, Denmark

    Heine H. Hansen

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Buhl Jensen, P., Sehested, M. (1994). In vitro models for testing of cytostatic agents in small cell lung cancer. In: Hansen, H.H. (eds) Lung Cancer. Cancer Treatment and Research, vol 72. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-2630-8_9

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  • DOI: https://doi.org/10.1007/978-1-4615-2630-8_9

  • Publisher Name: Springer, Boston, MA

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