Skip to main content
SpringerLink
Log in

Combined Effects of Radiation, ACNU, and 5-FU on Gliomas: An Experimental Combination Therapy

  • Chapter
Treatment of Glioma

  • 38 Accesses

Abstract

Although surgical removal of the tumor is essential for the treatment of malignant glioma, radiotherapy and chemotherapy have also played important roles in recent years. Improvements in therapeutic results obtained by means of combined therapies continue to be reported [50, 55, 56, 60, 85, 98, 99, 101], but there is a need for further experimental research. We consequently undertook several basic studies on the effectiveness of radiotherapy, l-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), and 5-fluorouracil (5-FU) either alone or in various combinations and report these results in the present chapter. The possibilities for clinical application of the biological results are also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Acker H (1984) Microenvironmental conditions in multicellular spheroids grown under liquid-overlay tissue culture conditions. Recent results in cancer research, spheroids in cancer research. Springer, Berlin—Heidelberg—New York—Tokyo, pp 116–133

    Google Scholar 

  2. Arakawa M, Shimizu F, Okada N (1974) Effect of l-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(chloroethyl)-3-nitrosourea hydrochloride on leukemia L-1210. Jpn J Cancer Res 65:191

    CAS  Google Scholar 

  3. Arima S, Kimura M, Shimizu H (1978) The density in blood and organ of N1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) administered in rectum. Jpn J Cancer Clin 24:613–617 (in Japanese)

    Google Scholar 

  4. Asamura M, Kanamaru R, Sato H, Saito T (1977) Mechanism of ACNU treatment. Saishin-Igaku 32:1417–1419 (in Japanese)

    Google Scholar 

  5. Asamura M, Saito T (1978) Cell synchronization and chemotherapy of cancer. Jpn J Cancer Chemother 5: 737–746 (in Japanese)

    Google Scholar 

  6. Barranco SC, Novak JK, Humphrey RM (1973) Response of mammalian cells following treatment with bleomycin and 1, 3-bis(2-chloroethyl)-l-nitrosourea during plateau phase. Cancer Res 33:691–694

    PubMed  CAS  Google Scholar 

  7. Benda P, Leightbody J, Sato G, Levin L, Sweet WH (1968) Differentiated rat glial cell strain in tissue culture. Science 161:370–371

    PubMed  CAS  Google Scholar 

  8. Benda P, Someda K, Messer J, Sweet WH (1971) Morphological and immunological studies of rat glial tumors and clonal strains propagated in culture. J Neurosurg 34:310–323

    PubMed  CAS  Google Scholar 

  9. Berry RJ (1966) Effect of metabolic inhibition on X-ray dose response curve for the survival of mammalian cells in vitro, and on early recovery between fractionated X-ray doses. Br J Radiol 39:458–463

    PubMed  CAS  Google Scholar 

  10. Bhuyan BK, Blowers CL, Neil GL, Bono VH, Day KJ.(1977) Partial synchronization of L 1210 cells by 5-fluorouracil and its use in drug combinations. Cancer Res 37: 3204–3208

    PubMed  CAS  Google Scholar 

  11. Bhuyan BK, Fraser TJ, Day KJ (1977) Cell proliferation kinetics and drug sensitivity of exponential and stationary populations of cultured L 1210 cells. Cancer Res 37:1057–1963

    PubMed  CAS  Google Scholar 

  12. Bhuyan BK, Scheidt LG, Fraser TJ (1972) Cell-cycle phase specificity of antitumor agents. Cancer Res 32: 398–407

    PubMed  CAS  Google Scholar 

  13. Brown JM (1979) Evidence for acutely hypoxic cells in mouse tumors, and a possible mechanism of reoxygenation. Br J Radiol 52:650–656

    PubMed  CAS  Google Scholar 

  14. Bruce WR, Meeker BE (1967) Comparison of the sensitivity of haematopoietic colony-forming cells in different proliferative status to 5-fluorouracil. J Nat Cancer Inst 38:401–405

    PubMed  CAS  Google Scholar 

  15. Byfield JE, Calabro-Jones P, Klisak I, Kulhanian F (1982) Pharmacologie requirements for obtaining sensitivity of human tumor cells in vitro to combined 5-fluorouracil or futoraful and X-ray. Int J Radiat Oncol Biol Phys 8:1923–1933

    PubMed  CAS  Google Scholar 

  16. Chaplin DJ, Olive PL, Durand RE (1987) Intermittent blood flow in a murine tumor: Radiobiological effects. Cancer Res 47: 597–601

    PubMed  CAS  Google Scholar 

  17. Corbett TH, Griswold DP, Roberts BJ, Peckham JC, Schabel FM Jr (1977) Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas. Cancer 40:2660–2680

    PubMed  CAS  Google Scholar 

  18. Courtenary VD (1976) A soft agar colony assay for Lewis lung tumor and B16 melanoma taken directly from the mouse. Br J Cancer 34:39–45

    Google Scholar 

  19. Deen DF, Hoshino T, Williams ME, Muraoka I, Knebel KE, Baker M (1980) Development of a 9L rat brain tumor cell multicellular spheroid system and its response to l,3-bis(2-chloroethyl)-l-nitrosourea and radiation. J Nat Cancer Inst 64:1373–1382

    PubMed  CAS  Google Scholar 

  20. Deen DF, Williams ME (1979) Isobologram analysis of X-ray-BCNU interactions in vitro. Radiat Res 79:483–491

    PubMed  CAS  Google Scholar 

  21. Durand RE (1976) Cell cycle kinetics in an in vitro tumor model. Cell Tissue Kinet 9:403–412

    PubMed  CAS  Google Scholar 

  22. Durand RE, Biaglow JE (1977) Radiosensitization of hypoxic cells of an in vitro tumor model by respiratory inhibitors. Radiat Res 69:359–366

    PubMed  CAS  Google Scholar 

  23. Elkind MM, Sutton H (1960) Radiation response of mammalian cells grown in culture. I. Repair of X-ray damage in surviving Chinese hamster cells. Radiat Res 13:556–593

    PubMed  CAS  Google Scholar 

  24. Elkind MM, Whitmors GF (1967) The radiobiology of cultured mammalian cells. Gordon and Breach, New York, pp 7–84

    Google Scholar 

  25. Fewer D, Wilson CB, Boldrey EB (1972) The chemotherapy of brain tumors, clinical experience with carmustine (BCNU) and vincristine. JAMA 222:549–552

    PubMed  CAS  Google Scholar 

  26. Fewer D, Wilson CB, Boldrey EB, Enot KJ (1972) A phase II study of 1 -(2-chloroethyl)-3-cyclohexyl-l-nitrosourea (CCNU). Cancer Chemother Res 56:421–427

    CAS  Google Scholar 

  27. Fletcher GH (1980) Textbook of radiotherapy, 3rd edn. Lea and Febiger, Philadelphia, pp 138–144

    Google Scholar 

  28. Fujita H, Ogawa K, Fukabe T, Kimura K (1972) Metabolism of N1(2′-tetrahydro-furyl)-5-fluorouracil (FT-207). Jpn J Cancer Clin 18:917–922 (in Japanese)

    CAS  Google Scholar 

  29. Gerosa MA, Dougherty DV, Wilson CB, Rosenblum MR (1983) Improved treatment of a brain tumor model: II. Sequential therapy with BCNU and 5-fluorouracil. J Neurosurg 58: 368–373

    PubMed  CAS  Google Scholar 

  30. Gerweck LE, Kornblith PL, Burlett P, Wang J, Sweight S (1977) Radiation sensitivity of cultured human glioblastoma. Radiol 125:231–234

    CAS  Google Scholar 

  31. Gray LH (1957) Oxygenation in radiotherapy: I. Radiological consideration. Br J Radiol 30:403–406

    PubMed  CAS  Google Scholar 

  32. Gutin PH, Wilson CB, Kumar ARV, Boldrey EB, Levin VA, Powell M, Enot KJ (1975) Phase II study of procarbazine, CCNU and vincristine combination chemotherapy in the treatment of malignant brain tumors. Cancer 35:1398–1404

    PubMed  CAS  Google Scholar 

  33. Hahn GM (1973) Response of solid tumor cells exposed to chemotherapeutic agents in vivo: Cell survival after 2- and 24-hour exposure. J Nat Cancer Inst 50: 529–533

    PubMed  CAS  Google Scholar 

  34. Hahn GM, Gordon LF, Kurkjian SD (1974) Response of cycling and noncycling cells to 1, 3-bis(2-chloroethyl)-l-nitrosourea and bleomycin. Cancer Res 34:2373–2379

    PubMed  CAS  Google Scholar 

  35. Hall T (1958) Acute and chronic toxicity studies with 5-fluorouracil in man. Proc Am Ass Cancer Res 2: 305

    Google Scholar 

  36. Heal JM, Fox P, Schein PS (1979) A structure-activity study of seven new water soluble nitrosourea. Biochem Pharmacol 28:1301–1306

    PubMed  CAS  Google Scholar 

  37. Hori M, Nakagawa H, Hasegawa H (1978) Chemotherapy of malignant glioma with the new nitrosourea derivative (ACNU). Jpn J Cancer Chemother 5: 773–778 (in Japanese)

    Google Scholar 

  38. Hoshino T (1973) Cell kinetics of brain tumors. Brain and Nerve 1:453–459 (in Japanese)

    Google Scholar 

  39. Hoshino T, Deen DF, Williams ME, Sano Y (1981) Differential response of elutriated 9L cells to treatment with 1, 3-bis-(2-chloroethyl)-l-nitrosourea. Cancer Res 41:4404–4407

    PubMed  CAS  Google Scholar 

  40. Inch WR, McCredie JA, Sutherland RM (1970) Growth of nodular carcinomas in rodents compared with multicell spheroids in tissue culture. Growth 34:271–282

    PubMed  CAS  Google Scholar 

  41. Jones AC, Stratford LJ, Wilson PA, Peckham MJ (1982) In vitro cytotoxic drug sensitivity testing of human tumor xenografts grown as multicellular tumor spheroids. Br J Cancer 46:870–879

    PubMed  CAS  Google Scholar 

  42. Kanazawa H, Miyamoto T (1983) Effect of ACNU, a water-soluble nitrosourea derivative, on survival and cell progression of cultured HeLa S3 cells. Jpn J Cancer Chemother 10:2007–2015 (in Japanese)

    Google Scholar 

  43. Kanamaru R, Asamura M, Sato H, Hayashi Y, Saito T, Saito S (1978) Studies on the effect of ACNU (l-(4-amino-2-methylpyrimidine-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride) for cultured HeLa S3 cells. Kokenshi (Tohoku University) 30:162–170 (in Japanese)

    Google Scholar 

  44. Kaneko S, Allen NJ, Clendenon NR, Kartha M (1983) Treatment schedule of combined radiation and ACNU in combination in experimental brain tumors. Neurol Med Chir (Tokyo) 23: 849–855 (in Japanese)

    CAS  Google Scholar 

  45. Kapp DS, Wagner FC, Lawrence R (1982) Glioblastoma multiforme: Treatment by large dose fraction irradiation and metronidazole. Int J Radiat Oncol Biol Phys 8:351–355

    PubMed  CAS  Google Scholar 

  46. Kaufman N, Bicher HI, Hetzel FW, Brown M (1981) A system for determining the pharmacology of indirect radiation sensitizer drugs on multicellular spheroids. Cancer Clin Trials 4:199–204

    PubMed  CAS  Google Scholar 

  47. Kawano H, Kubota T, Hayashi M (1986) Evaluation of ACNU and 5-Fu in the treatment of gliomas. Neurol Med Chir (Tokyo) 26:140–146 (in Japanese)

    CAS  Google Scholar 

  48. Kitahara M, Katakura R, Mori T, Suzuki J, Sasaki T (1986) Combined effect of ACNU and 5-Fu on rat glioma cells in spheroids and monolayer. Int J Cancer 38:215–222

    PubMed  CAS  Google Scholar 

  49. Kitahara M, Katakura R, Mori T, Sazuki J, Sasaki T (1984) Combined effect of ACNU and 5-fluorouracil on spheroids of rat glioma cells. Neurol Med Chir (Tokyo) 24:745–757 (in Japanese)

    Google Scholar 

  50. Kitahara M, Kuwahara K, Katakura R, Mori T, Suzuki J, Sasaki T (1983) Effect of combined therapy of ACNU and 5-Fu on multicellular spheroids—study of mechanisms and optimal administration. Proceedings of Japan Cancer Association, 42nd Annual Meeting, October 25 (Nagoya), p 228 (in Japanese)

    Google Scholar 

  51. Kogelnik HD, Karcher KH, Szepesi T Schratter AV (1982) High-dose irradiation and misonidazole in the treatment of malignant gliomas—A preliminary report. In: Kärcher KH, Kogelnik HD, Reinartz G (eds) Progress in radio-oncology II. Raven, New York, pp 189–195

    Google Scholar 

  52. Ko vacs CJ, Hopkins HA, Evans MJ, Looney WB (1976) Changes in cellularity induced by radiation in a solid tumor. Int J Radiat Biol 30:101–113

    CAS  Google Scholar 

  53. Kwok TT, Twentyman PR (1985) The relationship between tumour geometry and the response of tumour cells to cytotoxic drugs—An in vitro study using EMT6 multicellular spheroids. Int J Cancer 35:675–682

    PubMed  CAS  Google Scholar 

  54. Leenhouts HP, Chakwick KH (1980) An analysis of the interaction between two nitrosourea compounds and X-irradiation in rat brain tumor cells. Int J Radiat Biol 37:169

    CAS  Google Scholar 

  55. Levin VA, Crafts DC, Wilson CB, Schultz RM, Boldrey EB, Enot KJ, Pischer TL, Seager ML, Elashoff RM (1976) BCNU and procarbazine treatment for malignant brain tumors. Cancer Treat Rep 60:243–249

    PubMed  CAS  Google Scholar 

  56. Levin VA, Edwards MS, Wright D, Seager ML, Pischer TL, Wilson CB (1980) Modified procarbazine, CCNU and vincristine (PCV 3) combination chemotherapy in the treatment of malignant brain tumors. Cancer Treat Rep 64:231–241

    Google Scholar 

  57. Levin VA, Hoffman WF, Pischer TL, Seager ML, Boldrey EB, Wilson CB (1978) BCNU-5-fluorouracil combination therapy for the recurrent malignant brain tumors. Cancer Treat Rep 62:2071–2076

    PubMed  CAS  Google Scholar 

  58. Madoc-Jones H, Bruce WR (1967) Sensitivity of L cells in exponential and stationary phase to 5-fluorouracil. Nature 215: 302–303

    PubMed  CAS  Google Scholar 

  59. Matsumoto K, Tabuchi K, Furuta T (1983) Combined chemotherapy of ACNU and 5-Fu on malignant glioma. Neurol Med Chir (Tokyo) 23:625–632 (in Japanese)

    CAS  Google Scholar 

  60. Mineura K, Mori T, Katakura R, Sasaki T (1981) Therapeutic effects of l-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and radiation on the rat glioma. Neurol Surg (Tokyo) 9:257–265 (in Japanese)

    CAS  Google Scholar 

  61. Mori T, Mineura K, Katakura R (1979) A consideration on pharmacokinetics of a new water-soluble anti-tumor nitrosourea, ACNU, in patients with malignant brain tumor. Brain and Nerve 31:601–606 (in Japanese)

    PubMed  CAS  Google Scholar 

  62. Mori T, Mineura K, Katakura R (1979) Chemotherapy of malignant brain tumor by a water-soluble anti-tumor nitrosourea, ACNU. Neurol Med Chir (Tokyo) 19:1157–1171 (in Japanese)

    CAS  Google Scholar 

  63. Moulder JE, Rocknell S (1984) Hypoxic fraction of solid tumors: Experimental technique, method of analysis, and a survey of existing data. Int J Radiat Oncol Biol Phys 10:695–712

    PubMed  CAS  Google Scholar 

  64. Muller-Klieser, Sutherland EM (1982) Oxygen tensions in multicell spheroid of two cell lines. Br J Cancer 45:256–264

    Google Scholar 

  65. Nakamura K, Asami M, Kawada K (1979) Chromatographic studies on chemical desolation of carcinostatic nitrosourea. J Chromatogr 168:221

    CAS  Google Scholar 

  66. Nakamura K, Asami M, Kawada K, Sasahara K (1977) Quantitative determination of ACNU(l-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride, a new water-soluble antitumor nitrosourea, in biological fluids and tissue of patients by high-performance liquid chromatography: I. Analytical method and pharamatokinetics. Ann Rep Sankyo Res Lab 29:66 (in Japanese)

    CAS  Google Scholar 

  67. Nakamura T, Sasada M, Tashima M (1978) Mechanism of action of l-(4-amino-2-methyl-pyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in leukemia cells. Jpn J Cancer Chemother 5:971–1000 (in Japanese)

    Google Scholar 

  68. Nakajima Y, Miyamoto T, Tanabe M, Watanabe I (1979) Enhancement of mammalian cell killing by 5-fluorouracil in combination with X-ray. Cancer Res 39: 3763–3767

    PubMed  CAS  Google Scholar 

  69. Nederman T, Carlsson J, Malqvist M (1981) Penetration of substances into tumor tissue—A methodological study on cellular spheroids. In Vitro. 17:290–298

    PubMed  CAS  Google Scholar 

  70. Nederman T (1984) Effects of vincristine and 5-fluorouracil on human glioma and thyroid cancer cell monolayers and spheroids. Cancer Res 44:254–258

    PubMed  CAS  Google Scholar 

  71. Ogawa T, Yoneda T, Sakuta M (1984) Activation of FT-207 to 5-Fu in cultured cells of human maxillary cancer (OKK). Proceedings of Japan Cancer Association, 43rd Annual Meeting, October 3 (Fukuoka), p 289 (in Japanese)

    Google Scholar 

  72. Paterson R (1963) The treatment of malignant disease by radiotherapy. Williams and Wilkins, Baltimore, pp 12–15

    Google Scholar 

  73. Phillips H (1973) Dye exclusion tests for cell viability. In: Kruse PF Jr, Patterson MK Jr (eds). Tissue culture, methods and applications. Academic, New York, pp 406–408

    Google Scholar 

  74. Phillips RA, Tolmach LJ (1966) Repair of potentially lethal damage in X-irradiated HeLa cells. Radiat Res 29:413–432

    PubMed  CAS  Google Scholar 

  75. Rosenblum ML, Reynolds AF, Smith KA, Rumack BH, Walker MD (1973) Chloro-ethyl-cyclohexyl-nitrosourea (CCNU) in the treatment of malignant brain tumors. J Neurosurg 39: 306–314

    PubMed  CAS  Google Scholar 

  76. Sakamoto K (1976) Reoxygenation of tumor. Jpn J Cancer Clin 22:116–119 (in Japanese)

    Google Scholar 

  77. Sakamoto K (1974) Radiological significance and limitation of hyperbaric oxygen radiotherapy. Jpn J Cancer Clin 20: 56–58 (in Japanese)

    Google Scholar 

  78. Sakamoto K (1978) Radiobiology of cancer. Chugai-Igakusha, Tokyo, pp 115–118 (in Japanese)

    Google Scholar 

  79. Sasaki T (1981) Implication of tumor cell kinetics in radiotherapy and radiobiology. Jpn J Cancer Clin 27: 1507–1515 (in Japanese)

    Google Scholar 

  80. Sasaki T (1983) Therapeutic ratio in combined radiochemotherapy—Radiobiological consideration. Jpn J Cancer Clin 29:1584–1593 (in Japanese)

    CAS  Google Scholar 

  81. Sasaki T, Sakka M (1981) Implication of thymidine labelling index in the growth kinetics of human solid tumors. Jpn J Cancer Res 72:181–188

    CAS  Google Scholar 

  82. Sasaki T, Sato Y, Sakka M (1980) Cell population kinetics of human solid tumors: A statistical analysis in various histological types. Jpn J Cancer Res 71: 520–529

    CAS  Google Scholar 

  83. Sasaki T, Yamamoto M, Kuwahara K (1984) Lethal effect of bleomycin and peplomy-cin on HeLa cells in multicell tumor spheroids. Cancer Res 44:1374–1379

    PubMed  CAS  Google Scholar 

  84. Sasaki T (1984) Utilization of cultured solid tumor model (spheroid) on tumor-biological research. Radiobiol Res 19:195–208 (in Japanese)

    Google Scholar 

  85. Schabel FM Jr, Laster WR Jr, Trader MW, Corbett TH, Griswold DP Jr (1981) Combination chemotherapy with nitrosourea plus other anticancer drugs against animal tumors. In: Prostayko AW, Grooke ST, Baker LH, Carter SK, Schein PS (eds) Nitrosourea—current status and new development. Academic, New York, pp 9–26

    Google Scholar 

  86. Sheldon PW, Foster JL, Fowler JF (1974) Radiosensitization of C3H mouse mammary tumours by a 2-nitroimidazole drugs. Br J Cancer 30:560–565

    PubMed  CAS  Google Scholar 

  87. Shitara N, Kohno T, Nagamune A, Takakura K, Sano K (1978) Pulse-cytophotometric studies on experimental brain tumor under the effect of chemotherapeutic agents, microwave irradiation and hyperthermia. Neurol Med Chir (Tokyo) 18:199–207 (in Japanese)

    Google Scholar 

  88. Skipper HE, Schabel FM Jr, Mellet LB, Montgomery JA, Welkoft LJ, Lloid HH, Brockman RW (1970) Implication of biochemical, cytokinetic, pharmacologic and toxicologic relationships in the design of optimal therapeutic schedules. Cancer Chemother 54:431–450

    CAS  Google Scholar 

  89. Steel GG (1977) Growth kinetics of tumors. Clarendon, Oxford, pp 23–24

    Google Scholar 

  90. Steel GG (1979) The conceptual basis for the combined uses of radiotherapy and chemotherapy. Radiat Res, Proceedings of 6th International Congress Radiat Res, Tokyo, pp 804–809

    Google Scholar 

  91. Steel GG, Pekham MJ (1979) Exploitable mechanism in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phy 5:85–91

    CAS  Google Scholar 

  92. Sugiyama S, Mori T, Suzuki J, Sasaki T (1984) Lethal effect of X-ray and ACNU on cultured rat glioma cells in multicellular spheroids. Neurol Med Chir (Tokyo) 24:758–766 (in Japanese)

    CAS  Google Scholar 

  93. Sugiyama S, Mori T, Suzuki J, Sasaki T (1985) Effects of combined treatment of X-ray and ACNU on rat glioma cells in monolayer and multicellular spheroids. Neurol Med Chir (Tokyo) 25:707–714 (in Japanese)

    CAS  Google Scholar 

  94. Sutherland RM, McCredie JA, Inch WR (1971) Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J Nat Cancer Inst 46:113–120

    PubMed  CAS  Google Scholar 

  95. Sutherland RM, Durand RE (1976) Radiation response of multicell spheroids. An in vitro tumor model. Curr Top Radiat Res Q 11:87–139

    PubMed  CAS  Google Scholar 

  96. Sutherland RM, Eddy HA, Bareham B, Reich K, Banantwerp D (1979) Resistance to adriamycin in multicellular spheroids. Int J Radiat Oncol Biol Phys 5:1225–1230

    PubMed  CAS  Google Scholar 

  97. Sutton JE, Roos IAG, Hillcoat BL (1982) Combined actions of 5-fluorouracil and l-(2-chloroethyl)-3-(4-methylcyclohexyl)-l -nitrosourea on human colonic carcinoma cells in vitro. Cancer Res 42: 5172–5175

    PubMed  CAS  Google Scholar 

  98. Suzuki M, Hori K, Abe I, Saito S, Sato H (1981) A new approach to cancer chemotherapy: Selective enchancement of tumor blood flow with angiotensine II. J Nat Cancer Inst 67:663–669

    PubMed  CAS  Google Scholar 

  99. Suzuki M, Mori T, Watanabe T, Katakura R, Suzuki J, Wada T (1983) Combined radio-chemo-immunotherapy (RAFP therapy) for medulloblastoma. Neurol Surg (Tokyo) 11:1271–1276 (in Japanese)

    CAS  Google Scholar 

  100. Takakura K, Shitara N, Kohno T, Yamamoto H, Sano K (1979) Cell cycle of brain tumor cells and its combined therapy. Jpn J Cancer Chemother 6:31–40

    Google Scholar 

  101. Takakura K, Abe H, Tanaka R, Kitamura K, Miwa T, Takeuchi K, Yamamoto S, Kageyama N, Handa H, Mogami H, Nishimoto A, Uozumi T, Matsutani M, Nomura K (1986) Effects of ACNU and radiotherapy on malignant glioma. J Neurosurg 64:53–57

    PubMed  CAS  Google Scholar 

  102. Tamura M, Inoue H, Yamasaki H, Kawafuchi J, Niibe H (1983) Evaluation of high dose radiotherapy (500 rads twice weekly) in cerebral glioblastoma. Neurol Med Chir (Tokyo) 23:192–197 (in Japanese)

    CAS  Google Scholar 

  103. Tannock IF (1972) Oxygen diffusion and the distribution of cellular radiosensitivity in tumors. Br J Radiol 45: 515–524

    PubMed  CAS  Google Scholar 

  104. Terashima T, Taolmach LJ (1961) Changes in X-ray sensitivity of HeLa cells during the division cycle. Nature (London) 190: 1210–1211

    Google Scholar 

  105. The committee of brain tumor registry in Japan (1984) Brain Tumor Registry in Japan, vol 5, Tokyo

    Google Scholar 

  106. Thomlinson RH, Gray LH (1955) The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer 9: 539–549

    PubMed  CAS  Google Scholar 

  107. Tobey RA, Crissman HA (1975) Comparative effects of three nitrosourea derivatives on mammalian cell cycle progression. Cancer Res 35:460–470

    PubMed  CAS  Google Scholar 

  108. Toide H, Unemi N, Kawaguchi Y, Taira K (1977) Studies of the mechanism of action of FT-207. Chemother 25: 385–391 (in Japanese)

    CAS  Google Scholar 

  109. Tranum BL, Haut A, Rivkin E, Quagliana JM, Shaw M, Tucker WG, Smith FE, Samson M, Gattlieb J (1975) A phase II study of methyl CCNU in the treatment of solid tumors and lymphomas: A southwest oncology group study. Cancer 35:1148–1153

    PubMed  CAS  Google Scholar 

  110. Valeriote FA, Bruce WR, Meeder BE (1968) Synergistic action of cyclophosphamide on a transplanted murine lymphoma. J Nat Cancer Inst 40: 935–944

    PubMed  CAS  Google Scholar 

  111. Vaupel PW, Frink S, Bicher HI (1981) Heterogenous oxygen partial pressure and pH distribution in C3H mouse mammary adenocarcinoma. Cancer Res 41:2008–2013

    PubMed  CAS  Google Scholar 

  112. Wallen CA, Michaelson S, Wheel KT (1980) Evidence for an unconventional radio-sensitivity of rat 9L subcutaneous tumors. Radiat Res 84: 529–541

    PubMed  CAS  Google Scholar 

  113. Wharam MD, Phillips TL, Kane L, Utley JF (1973) Response of murine solid tumor to in vivo combined chemotherapy and irradiation. Radiol 109:451–455

    CAS  Google Scholar 

  114. Wheeler GP, Bowdon BJ, Adamson DJ, Vali MH (1972) Comparison of the effects of several inhibitors of the synthesis of nucleic acids upon the viability and progression through the cell cycle of cultured H. Ep. No. 2 cells. Cancer Res 32:2661–2669

    PubMed  CAS  Google Scholar 

  115. Wheeler KT, Levin VA, Deen DF (1978) The concept of drug dose for in vitro studies with chemotherapeutic agents. Radiat Res 76:441–458

    PubMed  CAS  Google Scholar 

  116. Wilson CB, Boldrey EB, Enot KJ (1970) BCNU [l,3-bis-2-(chloroethyl)-l-nitrosourea] in the treatment of brain tumors. Cancer Chemother Rep 54:273–281

    PubMed  CAS  Google Scholar 

  117. Yuhas JM, Li AP, Martines AO, Landman AJ (1977) A simplified method for production and growth of multicellular spheroids. Cancer Res 37:3639–3643

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. S. Mashiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Sugiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Kuwahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Kitahara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Neurosurgery, Institute of Brain Diseases, School of Medicine, Tohoku University, Sendai, 980, Japan

    Jiro Suzuki MD

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer-Verlag Tokyo

About this chapter

Cite this chapter

Mashiyama, S., Sugiyama, S., Kuwahara, K., Kitahara, M., Takahashi, K., Sasaki, T. (1988). Combined Effects of Radiation, ACNU, and 5-FU on Gliomas: An Experimental Combination Therapy. In: Suzuki, J. (eds) Treatment of Glioma. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68453-4_3

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-68453-4_3

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68455-8

  • Online ISBN: 978-4-431-68453-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation