Modification of Radiosensitivity Following Chemotherapy Exposure: Potential Implications for Combined-Modality Therapy

  • Richard A. Britten
Part of the Cancer Treatment and Research book series (CTAR, volume 112)

Abstract

Treatment protocols for many tumor sites often consist of a combination of poly-chemotherapy with loco-regional radiotherapy. In many instances, these treatments are given in close temporal proximity to each other, either within a few hours (concomitant) or within a few weeks of each other (sequential). In other instances, radiotherapy may be given at some considerable time after completion of chemotherapy to achieve a measure of loco-regional control in tumors that have recurred following front-line chemotherapy. The optimum integration of chemotherapy and radiotherapy in all three situations has yet to be fully established. Careful consideration of the impact of clinically relevant chemoresistance on radiation response in these various scenarios, and appropriate adjustments, may lead to qualitative differences in patient quality of life, and hopefully quantitative improvements in disease free survival

Keywords

Leukemia Glutathione Adduct Sarcoma Doxorubicin 

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References

  1. 1.
    Tannock IF, Goldenberg GG. Drug resistance and experimental chemotherapy. In: The Basic Science of Oncology, 3rd edition, IF Tannock, RP Hill (eds.), McGraw-Hill, New York, NY, 392–419, 1998.Google Scholar
  2. 2.
    Steel GG, Peckham MJ. Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys, 5:85–91, 1979.CrossRefPubMedGoogle Scholar
  3. 3.
    Britten RA, Warenius HM. De novo cisplatinum resistance does not influence cellular radiosensitivity. Eur J Cancer, 29A:1315–1320, 1993.CrossRefPubMedGoogle Scholar
  4. 4.
    Britten RA, Evans AJ, Allalunis-Turner MJ, Pearcey RG. Effect of cisplatin on the clinically relevant radiosensitivity of human cervical carcinoma cell lines. Int J Radiat Oncol Biol Phys, 34:367–374, 1996.CrossRefPubMedGoogle Scholar
  5. 5.
    Warenius HM, Seabra LA, Maw P. Sensitivity to cis-diamminedichloroplatinum in human cancer cells is related to expression of cyclin DI but not c-raf-1 protein. Int J Cancer, 67:224–231, 1996.CrossRefPubMedGoogle Scholar
  6. 6.
    Panis X, Coninx P, Nguyen TD, Legros M. Relation between responses to induction chemotherapy and subsequent radiotherapy in advanced or multicentric squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys, 18:1315–1318, 1990.CrossRefGoogle Scholar
  7. 7.
    Bjork-Eriksson T, West C, Karlsson E, Mercke C. Tumor radiosensitivity (SF2) is a prognostic factor for local control in head and neck cancers. Int J Radiat Oncol Biol Phys, 46:13–19, 2000.CrossRefPubMedGoogle Scholar
  8. 8.
    Eschwege F, Bourhis J, Girinski Tet al.Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: a review of the Institute Gustave Roussy experience. Int J Radiat Oncol Biol Phys, 39:849–853, 1997.CrossRefPubMedGoogle Scholar
  9. 9.
    Stausbol-Gron B, Overgaard J. Relationship between tumour cellin vitroradiosensitivity and clinical outcome after curative radiotherapy for squamous cell carcinoma of the head and neck. Radiother Oncol, 50:47–55, 1999.CrossRefPubMedGoogle Scholar
  10. 10.
    Stadler P, Becker A, Feldmann HJet al.Influence of the hypoxic subvolume on the survival of patients with head and neck cancer. Int J Radiat Oncol Biol Phys, 44:749–754, 1999.CrossRefPubMedGoogle Scholar
  11. 11.
    Liang BC. Effects of hypoxia on drug resistance phenotype and genotype in human glioma cell lines. J Neurooncol, 29:149–155, 1996.CrossRefPubMedGoogle Scholar
  12. 12.
    Walker LJ, Craig RB, Harris AL, Hickson ID. A role for the human DNA repair enzyme HAPI in cellular protection against DNA damaging agents and hypoxic stress. Nucleic Acids Res, 22:4884–4889, 1999.CrossRefGoogle Scholar
  13. 13.
    Hoy CA, Thompson LH, Mooney CL, Salazar EP. Defective DNA cross-link removal in Chinese hamster cell mutants hypersensitive to bifunctional alkylating agents. Cancer Res, 45:1737–1743, 1985.PubMedGoogle Scholar
  14. 14.
    Dabholkar M, Vionnet J, Bostick-Bruton Fet al.Messenger RNA levels of XPAC and ERCCI in ovarian cancer tissue correlate with response to platinum-based chemotherapy. J Clin Invest, 94:703–708, 1994.CrossRefPubMedGoogle Scholar
  15. 15.
    Metzger R, Leichman CG, Danenberg KDet al.ERCCI mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol, 16:309–316, 1998.PubMedGoogle Scholar
  16. 16.
    Murray D, Macann A, Hanson J, Rosenberg E. ERCCI/ERCC4 5’-endonuclease activity as a determinant of hypoxic cell radiosensitivity. Int J Radiat Biol, 69:319–327, 1996.CrossRefPubMedGoogle Scholar
  17. 17.
    Britten RA, Perdue S, Opoku J, Craighead P. Paclitaxel is preferentially cytotoxic to human cervical tumor cells with low Raf-1 kinase activity: implications for paclitaxelbased chemoradiation regimens. Radiother Oncol, 48:329–334, 1998.CrossRefPubMedGoogle Scholar
  18. 18.
    Adjei AA, Erlichman C, Davis JNet al.A phase I trial of the farnesyl transferase inhibitor SCH66336: evidence for biological and clinical activity. Cancer Res, 60:1871–1877, 2000.PubMedGoogle Scholar
  19. 19.
    Cunningham CC, Holmlund JT, Schiller JHet al.A phase I trial of c-Raf kinase antisense oligonucleotide ISIS 5132 administered as a continuous intravenous infusion in patients with advanced cancer. Clin Cancer Res, 6:1626–1631, 2000.PubMedGoogle Scholar
  20. 20.
    Leonetti C, Biroccio A, Candiloro Aet al.Increase of cisplatin sensitivity by c-myc antisense oligodeoxynucleotides in a human metastatic melanoma inherently resistant to cisplatin. Clin Cancer Res, 5:2588–2595, 1999.PubMedGoogle Scholar
  21. 21.
    Dewit L. Combined treatment of radiation and cis-diamminechloroplatinum (II): A review of experimental and clinical data. Int J Radiat Oncol Biol Phys, 13:403–426, 1987.CrossRefPubMedGoogle Scholar
  22. 22.
    Douple EB, Richmond RC. Platinum complexes as radiosensitizers of hypoxic mammalian cells. Br J Cancer, 37 Suppl 111:98–102, 1978.Google Scholar
  23. 23.
    Sorenson CM, Eastman A. Mechanism of cis-diamminedichloroplatinum(II)-induced cytotoxicity: role of G2 arrest and DNA double-strand breaks. Cancer Res, 48:4484–4488, 1988.PubMedGoogle Scholar
  24. 24.
    Bergamo A, Gagliardi R, Scarcia Vet al. In vitrocell cycle arrestin vivoaction on solid metastasizing tumors, and host toxicity of the antimetastatic drug NAMI-A and cisplatin. Pharmacol Exp Ther, 289:559–564, 1999.Google Scholar
  25. 25.
    Yuhas JM, Tarleton AE, Culo F. Tumor line dependent interactions of irradiation and cis-diamminedichloroplatinum in the multicellular tumor spheroid system. Int.1 Radiat Oncol Biol Phys, 5:1373–1375, 1979.CrossRefGoogle Scholar
  26. 26.
    Leith JT, Eun Sun Lee AB, Vayer AJ Jret al.Enhancement of the responses of human colon adenocarcinoma cells to X-irradiation and cis-platinum by n-methylformamide (NMF). Int J Radiat Oncol Biol Phys, 11:1971–1976, 1985.CrossRefPubMedGoogle Scholar
  27. 27.
    Ziegler W, Kopp JM. The effect of combined treatment of HeLa cells with cisplatin and irradiation upon survival and recovery from radiation damage. Radiother Oncol, 8:71–78, 1987.CrossRefPubMedGoogle Scholar
  28. 28.
    Morris M, Eifel PJ, Lu Jet al.Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med, 340:1137–1143, 1999.CrossRefPubMedGoogle Scholar
  29. 29.
    Rose PG, Bundy BN, Watkins EBet al.Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med, 340:1144–1153, 1999.CrossRefPubMedGoogle Scholar
  30. 30.
    Pearcey RG, Mohamed IG, Hanson J. Treatment of high-risk cervical cancer. N Engl J Med, 341:695–696, 1999.CrossRefPubMedGoogle Scholar
  31. 31.
    Fyles A, Keane TJ, Barton M, Simm J. The effect of treatment duration in the local control of cervix cancer. Radiother Oncol, 25:273–279, 1992.CrossRefPubMedGoogle Scholar
  32. 32.
    Withers HR, Taylor JMG, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol, 27:131–146, 1988.CrossRefPubMedGoogle Scholar
  33. 33.
    Britten RA, Liu D, Tessier Aet al.ERCC1 expression as a molecular marker of cisplatin resistance in human cervical tumor cells. Int J Cancer, 89:453–457, 2000.CrossRefPubMedGoogle Scholar
  34. 34.
    Rubin E, Kharbanda S, Gunji Het al.Cis-diamminedichloroplatinum (II) induces c-junexpression in human myeloid leukemia cells: Potential involvement of a protein kinase C-dependent signaling pathway. Cancer Res, 52:878–882, 1992.PubMedGoogle Scholar
  35. 35.
    Eliopoulos AG, Kerr DJ, Maurer HRet al.Induction of the c-myc but not the cH-ras promoter by platinum compounds. Biochem Pharmacol, 50:33–38, 1995.CrossRefPubMedGoogle Scholar
  36. 36.
    Hayakawa J, Ohmichi M, Kurachi Het al.Inhibition of extracellular signal-regulated protein kinase or c-Jun N-terminal protein kinase cascade, differentially activated by cisplatin, sensitizes human ovarian cancer cell line. J Biol Chem, 274:31648–31654, 1999.CrossRefPubMedGoogle Scholar
  37. 37.
    Louie KG, Behrens BC, Kinsella TJet al.Radiation survival parameters of antineoplastic drug-sensitive and -resistant human ovarian cell lines and their modification by buthionine sulfoximine. Cancer Res, 45:2110–2115, 1985.PubMedGoogle Scholar
  38. 38.
    Hida T, Ueda R, Takahashi Tet al.Chemosensitivity and radiosensitivity of small cell lung cancer cell lines studied by a newly developed 3-(4,5-dimethylthiazol-2-y1)-2,5- diphenyltetrazolium bromide (MTT) hybrid assay. Cancer Res, 49:4785–4790, 1999.Google Scholar
  39. 39.
    De Pooter CM, Scalliet PG, Elst HJet al.Resistance patterns between cisdiamminedichloroplatinum(II) and ionizing radiation. Cancer Res, 51:4523–4527, 1991.PubMedGoogle Scholar
  40. 40.
    Twentyman PR, Wright KA, Rhodes T. Radiation response of human lung cancer cells with inherent and acquired resistance to cisplatin. Int J Radiat Oncol Biol Phys, 20:217–220, 1991.CrossRefPubMedGoogle Scholar
  41. 41.
    Britten RA, Warenius HM, White R, Peacock JH. BSO-induced reduction of glutathione levels increases the cellular radiosensitivity of drug-resistant human tumor cells. Int J Radiat Oncol Biol Phys, 22:769–772, 1992.CrossRefPubMedGoogle Scholar
  42. 42.
    Britten RA, Peacock JH, Warenius HM. Collateral resistance to photon and neutron irradiation is associated with acquired cis-platinum resistance in human ovarian tumour cells. Radiother Oncol, 23:170–175, 1992.CrossRefPubMedGoogle Scholar
  43. 43.
    Britten RA, Warenius HM, Masters JRW, Peacock JH. The differential induction of collateral resistance to 62.5 MeV (p-*Be+) neutrons and 4 MeV photons by exposure to cis-platinum. Int J Radiat Oncol Biol Phys, 26:837–843, 1993.CrossRefPubMedGoogle Scholar
  44. 44.
    Britten RA, Warenius HM, Carraway AV, Murray D. Differential modulation of radiosensitivity following induction of cis-platinum resistance in radio-sensitive and -resistant human tumour cells. Radiat Oncol Invest, 2:25–31, 1994.CrossRefGoogle Scholar
  45. 45.
    Poppenborg H, Munstermann G, Knupfer MMet al.C6 cells cross-resistant to cisplatin and radiation. Anticancer Res, 17:2073–2077, 1997.PubMedGoogle Scholar
  46. 46.
    Poppenborg H, Munstermann G, Knupfer MMet al.Cisplatin induces radioprotection in human T98G glioma cells. Anticancer Res, 17:1131–1134, 1997.PubMedGoogle Scholar
  47. 47.
    Raaphorst GP, Wilkins DE, Mao JPet al.Evaluation of cross-resistance between responses to cisplatin, hyperthermia, and radiation in human glioma cells and eight clones selected for cisplatin resistance. Radiat Oncol Invest, 7:153–157, 1999.CrossRefGoogle Scholar
  48. 48.
    Raaphorst GP, Maio J, Ng CE, Stewart DJ. Concomitant treatment with mild hyperthermia, cisplatin and low dose-rate irradiation in human ovarian cancer cells sensitive and resistant to cisplatin. Oncol Rep, 5:971–977, 1998.PubMedGoogle Scholar
  49. 49.
    Frit P, Canitrot Y, Muller Cet al.Cross-resistance to ionizing radiation in a murine leukemic cell line resistant to cis-dichlorodiammineplatinum(II): role of Ku autoantigen. Mol Pharmacol, 56:141–146, 1999.PubMedGoogle Scholar
  50. 50.
    Tebbs RS, Zhao Y, Tucker JDet al.Correction of chromosomal instability and sensitivity to diverse mutagens by a cloned cDNA of the XRCC3 DNA repair gene. Proc Natl Acad Sci USA, 92:6354–6358, 1995.CrossRefPubMedGoogle Scholar
  51. 51.
    McHugh PJ, Sones WR, Hartley JA. Repair of intermediate structures produced at DNA interstrand cross-links in Saccharomyces cerevisiae. Mol Cell Biol, 20:3425–3433, 2000.CrossRefPubMedGoogle Scholar
  52. 52.
    Turchi JJ, Patrick SM, Henkels KM. Mechanism of DNA-dependent protein kinase inhibition by cis-diammine-dichloroplatinum(II)-damaged DNA. Biochem, 36:7586–7593, 1997.CrossRefGoogle Scholar
  53. 53.
    Britten RA, Kuny S, Perdue S. Modification of non-conservative double-strand break (DSB) rejoining activity after the induction of cisplatin resistance in human tumour cells. Br J Cancer, 79:843–849, 1999.CrossRefPubMedGoogle Scholar
  54. 54.
    Britten RA, Liu D, Kuny S, Allalunis-Turner MJ. Differential level of DSB repair fidelity effected by nuclear protein extracts derived from radiosensitive and radioresistant human tumour cells. Br J Cancer, 76:1440–1447, 1997.CrossRefPubMedGoogle Scholar
  55. 55.
    Johnson RE, Brace KC. Radiation response of Hodgkin’s disease recurrent after chemotherapy. Cancer, 19:368–370, 1966.CrossRefGoogle Scholar
  56. 56.
    Ensley JF, Jacobs JR, Weaver Aet al.Correlation between response to cis-platinumcombination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck. Cancer, 54:811–814, 1984.CrossRefPubMedGoogle Scholar
  57. 57.
    Hoskins WJ, Lichter AS, Wittington Ret al.Whole abdominal and pelvic irradiation in patients with minimal and residual disease at second-look surgical reassessment for ovarian carcinoma. Gynecol Oncol, 20:271–280, 1985.CrossRefPubMedGoogle Scholar
  58. 58.
    Ochs JJ, Tester WJ, Cohen MHet al.“Salvage” radiation therapy for intrathoracic small cell carcinoma of the lung progressing on combination chemotherapy. Cancer Treat Rep, 67:1123–1126, 1988.Google Scholar
  59. 59.
    Tattershall MHN, Ramirez C, Coppleson M. A randomized trial comparing platinum-based chemotherapy followed by radiotherapy vs. radiotherapy alone in patients with locally advanced cervical cancer. Int.1 Gynecol Cancer, 2:244–251, 1992.CrossRefGoogle Scholar
  60. 60.
    Lehnert S, Greene D, Batist G. Radiation response of drug-resistant variants of a human breast cancer cell line. Radiat Res, 118:568–580, 1989.CrossRefPubMedGoogle Scholar
  61. 61.
    Lehnert S, Greene D, Batist G. Radiation response of drug-resistant variants of a human breast cancer cell line: The effect of glutathione depletion. Radiat Res, 124:208–215, 1990.Google Scholar
  62. 62.
    Saito Y, Nakada Y, Hotta Tet al.Glutathione and cellular response of ACNU-resistant rat glioma sublines to drugs and radiation. Int J Cancer, 48:861–865, 1991.CrossRefPubMedGoogle Scholar
  63. 63.
    Lau DH, Lewis AD, Ehsan MN, Sikic BI. Multifactorial mechanisms associated with broad cross-resistance of ovarian carcinoma cells selected by cyanomorpholino doxorubicin. Cancer Res, 51:181–187, 1991.Google Scholar
  64. 64.
    Meijer C, Mulder NH, Timmer-Bosscha Het al.Role of free radicals in an adriamycinresistant human small cell lung cancer cell line. Cancer Res, 47:4613–4617, 1987.PubMedGoogle Scholar
  65. 65.
    Pauwels 0, Gozy M, Van butte Pet al. Cross resistance and collateral sensitivity between cytotoxic drugs and radiation in two human bladder cell lines. Radiother Oncol, 39:81–86, 1996.CrossRefPubMedGoogle Scholar
  66. 66.
    Denecke J, Fiedler K, Hacker-Klom Uet al.Multiple drug-resistant C6 glioma cells cross-resistant to irradiation. Anticancer Res, 17:4531–4534, 1997.PubMedGoogle Scholar
  67. 67.
    Budach W, Budach V, Scheulen MEet al.Drug-and radiation-induced resistance in a human neurogenic sarcoma xenografted in nude mice. Cancer Chemother Pharmacol, 31 Suppl 2:S169–173, 1993.Google Scholar
  68. 68.
    Shimm DS, Olson S, Hill AB. Radiation resistance in a multidrug resistant human Tcell leukemia line. Int J Radiat Oncol Biol Phys, 15:931–936, 1988.CrossRefPubMedGoogle Scholar
  69. 69.
    Lehnert S, Vestergaard J, Batist G, Alaoui-Jamali MA. Radiation resistance in a melphalan-resistant subline of a rat mammary carcinoma. Radiat Res, 139:232–239, 1994.CrossRefPubMedGoogle Scholar
  70. 70.
    Barranco SC, Townsend CM Jr, Weintraub Bet al.Changes in glutathione content and resistance to anticancer agents in human stomach cancer cells induced by treatments with melphalan in vitro.Cancer Res, 50:3614–3618, 1990.PubMedGoogle Scholar
  71. 71.
    Britten RA, Warenius HM, White Ret al.Melphalan resistant human ovarian tumour cells are cross-resistant to photons, but not to high LET neutrons. Radiother Oncol, 18:357–367, 1990.CrossRefPubMedGoogle Scholar
  72. 72.
    Martin-Aragon S, Mukherjee SK, Taylor BJet al.Cytosine arabinoside (ara-C) resistance confers cross-resistance or collateral sensitivity to other classes of anti-leukemic drugs. Anticancer Res, 20:139–150, 2000.PubMedGoogle Scholar
  73. 73.
    Wallner KE, Li GC. Effect of cisplatin resistance on cellular radiation response. Int J Radiat Oncol Biol Phys, 13:587–591, 1987.CrossRefPubMedGoogle Scholar
  74. 74.
    Poppenborg H, Knupfer MM, Preiss Ret al.Cisplatin (CDDP)-induced radiation resistance is not associated with CDDP resistance in 86HG39 and A172 malignant glioma cells. Eur J Cancer, 35:1150–1154, 1999.CrossRefPubMedGoogle Scholar
  75. 75.
    Cho J, Lee Y, Lutzky Jet al.Collateral sensitivity to radiation and cis-platinum in a multidrug-resistant human leukemia cell line. Cancer Chemother Pharmacol, 37:168–172, 1995.CrossRefPubMedGoogle Scholar
  76. 76.
    Komori K. Cross-resistance to radiation in human squamous cell carcinoma cells with induced cisplatin resistance. Kokubyo Gakkai Zasshi, 65:202–212, 1998.PubMedGoogle Scholar
  77. 77.
    Oshita F, Fujiwara Y, Saijo N. Radiation sensitivities in various anticancer-drugresistant human lung cancer cell lines and mechanism of radiation cross-resistance in a cisplatin-resistant cell line. J Cancer Res Clin Oncol, 119:28–34, 1992.CrossRefPubMedGoogle Scholar
  78. 78.
    Batist G, Behrens BC, Makuch Ret al.Serial determinations of glutathione levels and glutathione-related enzyme activities in human tumor cells in vitro.Biochem Pharmacol, 35:2257–2259, 1986.CrossRefPubMedGoogle Scholar
  79. 79.
    Scanlon KJ, Kashani-Sabet M. Elevated expression of thymidylate synthase cycle genes in cisplatin-resistant human ovarian carcinoma A2780 cells. Proc Natl Acad Sci USA, 85:650–653, 1988.CrossRefPubMedGoogle Scholar
  80. 80.
    Parker RJ, Eastman A, Bostick-Bruton F, Reed E. Acquired cisplatin resistance in human ovarian cancer cells is associated with enhanced repair of cisplatin-DNA lesions and reduced drug accumulation. J Clin Invest, 87:772–777, 1991.CrossRefPubMedGoogle Scholar
  81. 81.
    Masuda H, Tanaka T, Matsuda H, Kusaba I. Increased removal of DNA-bound platinum in a human ovarian cancer cell line resistant tocis-d iammined ichloroplatinum(II). Cancer Res, 50:1863–1866, 1990.PubMedGoogle Scholar
  82. 82.
    Johnson SW, Perez RP, Godwin AKet al.Role of platinum-DNA adduct formation and removal in cisplatin resistance in human ovarian cancer cell lines. Biochem Pharmacol, 47:689–697, 1994.CrossRefPubMedGoogle Scholar
  83. 83.
    Walker MC, Povey S, Farrington JMet al.Development and characterization of cisplatin-resistant human testicular and bladder tumour cell lines. Eur J Cancer, 26:742–747, 1990.CrossRefPubMedGoogle Scholar
  84. 84.
    Thompson LH, Rubin JS, Cleaver JEet aLA screening method for isolating DNA repair-deficient mutants of CHO cells. Somatic Cell Genet, 6:391–405, 1980.CrossRefPubMedGoogle Scholar
  85. 85.
    Wurschmidt F. Combined modality treatment of the rhabdomyosarcoma RI H of the rat: influence of sequence of cisplatin and fractionated irradiation. Int J Radiat Oncol Biol Phys, 25:73–78, 1993.CrossRefPubMedGoogle Scholar
  86. 86.
    Jackel M, Tausch-Treml R, Kopf-Maier P. Effect of acquired cisplatin resistance on the response of a xenografted human hypopharynx carcinoma to concurrent radiochemotherapy with cisplatin. Laryngoscope, 104:329–334, 1994.CrossRefPubMedGoogle Scholar
  87. 87.
    Mattern J, Bak M Jr, Hoever KH, Volm M. Radiosensitivity of drug-resistant human tumour xenografts. Strahlenther Onkol, 165:870–872, 1989.PubMedGoogle Scholar
  88. 88.
    Looney WB. Alternating chemotherapy and radiotherapy. NCI Monogr, 6:85–94, 1988.PubMedGoogle Scholar
  89. 89.
    Andersson BS, Mroue M, Britten RAet aLMechanisms of cyclophosphamide resistance in a human myeloid leukemia cell line. Acta Oncol, 34:247–251, 1995.CrossRefPubMedGoogle Scholar
  90. 90.
    Nielsen OS, Safwat A, Overgaard J. The effect of sequence and time interval between cyclophosphamide and total body irradiation on lung and bone marrow damage following bone marrow transplantation in mice. Radiother Oncol, 29:51–59, 1993.CrossRefPubMedGoogle Scholar
  91. 91.
    Geara FB, Peters LJ, Ang KKet al.Intrinsic radiosensitivity of normal human fibroblasts and lymphocytes after high-and low-dose-rate irradiation. Cancer Res, 52:6348–6352, 1992.PubMedGoogle Scholar
  92. 92.
    Dahlberg WK, Little JB, Fletcher JAet al.Radiosensitivity in vitroof human soft tissue sarcoma cell lines and skin fibroblasts derived from the same patients. Int J Radiat Biol, 63:191–198, 1993.CrossRefPubMedGoogle Scholar
  93. 93.
    Sersa G, Stabuc B, Cemazar Met al.Electrochemotherapy with cisplatin: clinical experience in malignant melanoma patients. Clin Cancer Res, 6:863–867, 2000.PubMedGoogle Scholar
  94. 94.
    Sersa G, Kranjc S, Cemazar M. Improvement of combined modality therapy with cisplatin and radiation using electroporation of tumors. Int J Radiat Oncol Biol Phys, 46:1037–1041, 2000.CrossRefPubMedGoogle Scholar
  95. 95.
    Fujiwara K, Yamauchi H, Yoshida Tet al.Relationship between peritoneal washing cytology through implantable port system (IPS-cytology) and second-look laparotomy in ovarian cancer patients with unmeasurable residual diseases. Gynecol Oncol, 70:231–235, 1998.CrossRefPubMedGoogle Scholar
  96. 96.
    Britten RA, Evans AJ, Allalunis-Turner MJet al.Intratumoral heterogeneity as a confounding factor in clonogenic assays for tumour radioresponsiveness. Radiother Oncol, 39:145–153, 1996.CrossRefPubMedGoogle Scholar
  97. 97.
    Leith JT, Dexter DL, DeWyngaert JKet al.Differential responses to x-irradiation of subpopulations of two heterogeneous human carcinomas in vitro.Cancer Res, 42:2556–2561, 1982.PubMedGoogle Scholar
  98. 98.
    Tofilon PJ, Vines CM, Meyn REet al.Heterogeneity in radiation sensitivity within human primary tumour cell cultures as detected by the SCE assay. Br J Cancer, 59:54–60, 1989.CrossRefPubMedGoogle Scholar
  99. 99.
    Weichselbaum RR, Beckett MA, Dahlberg W, Dritschilo A. Heterogeneity of radiation response of a parent human epidermoid carcinoma cell line and four clones. Int J Radiat Oncol Biol Phys, 14:907–912, 1988.CrossRefPubMedGoogle Scholar
  100. 100.
    Rasouli-Nia A, Liu D, Perdue S, Britten RA. High Raf-1 kinase activity protects human tumor cells against paclitaxel-induced cytotoxicity. Clin Cancer Res, 4:1111–1116, 1998.PubMedGoogle Scholar
  101. 101.
    Kudelka AP, Winn R, Edwards CLet al.Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res, 2:1285–1288, 1996.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Richard A. Britten
    • 1
  1. 1.Department of Radiation OncologyEastern Virginia Medical SchoolNorfolkUSA

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