Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1987 Mar;55(3):233–238. doi: 10.1038/bjc.1987.45

The effects of melphalan and misonidazole on the vasculature of a murine sarcoma.

J C Murray, V Randhawa, J Denekamp
PMCID: PMC2001746  PMID: 3552014

Abstract

A method for estimating both structural and functional vascular volumes in murine sarcomas is described. Intact vessels were demonstrated by the presence of laminin, a basement membrane-associated antigen, using an immunofluorescent technique, and functional vessels in the same sample by prior injection with the DNA binding dye Hoechst 33342. No significant vascular effects were seen after melphalan but a very pronounced decrease in both functional and structural vascular volume was seen after MISO. Combined chemotherapy of a murine sarcoma with melphalan and MISO induced a rapid decrease in the functional vascular volume, and there was a resumption of blood flow prior to measurable regrowth. The fully regrown tumour retained the vascular characteristics of untreated tumours of similar size.

Full text

PDF
233

Images in this article

234Figure 1
on p.234

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ackerman N. B. Experimental studies on the circulation dynamics of intrahepatic tumor blood supply. Cancer. 1972 Feb;29(2):435–439. doi: 10.1002/1097-0142(197202)29:2<435::aid-cncr2820290227>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  2. Albertsson M., Mercke C., Håkansson C. H. Reaction of the vascular system in the trachea of the rabbit exposed to fractionated irradiation with and without the addition of misonidazole. Radiother Oncol. 1985 Apr;3(3):267–277. doi: 10.1016/s0167-8140(85)80035-9. [DOI] [PubMed] [Google Scholar]
  3. Barsky S. H., Baker A., Siegal G. P., Togo S., Liotta L. A. Use of anti-basement membrane antibodies to distinguish blood vessel capillaries from lymphatic capillaries. Am J Surg Pathol. 1983 Oct;7(7):667–677. doi: 10.1097/00000478-198310000-00007. [DOI] [PubMed] [Google Scholar]
  4. Birembaut P., Caron Y., Adnet J. J., Foidart J. M. Usefulness of basement membrane markers in tumoural pathology. J Pathol. 1985 Apr;145(4):283–296. doi: 10.1002/path.1711450402. [DOI] [PubMed] [Google Scholar]
  5. Brown J. M. Cytotoxic effects of the hypoxic cell radiosensitizer Ro 7-0582 to tumor cells in vivo. Radiat Res. 1977 Dec;72(3):469–486. [PubMed] [Google Scholar]
  6. Chaplin D. J., Durand R. E., Olive P. L. Cell selection from a murine tumour using the fluorescent probe Hoechst 33342. Br J Cancer. 1985 Apr;51(4):569–572. doi: 10.1038/bjc.1985.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chin J. B., Rauth A. M. The metabolism and pharmacokinetics of the hypoxic cell radiosensitizer and cytotoxic agent, misonidazole, in C3H mice. Radiat Res. 1981 May;86(2):341–357. [PubMed] [Google Scholar]
  8. Denekamp J., Hill S. A., Hobson B. Vascular occlusion and tumour cell death. Eur J Cancer Clin Oncol. 1983 Feb;19(2):271–275. doi: 10.1016/0277-5379(83)90426-1. [DOI] [PubMed] [Google Scholar]
  9. Durand R. E. Use of Hoechst 33342 for cell selection from multicell systems. J Histochem Cytochem. 1982 Feb;30(2):117–122. doi: 10.1177/30.2.6174559. [DOI] [PubMed] [Google Scholar]
  10. Falk P. Patterns of vasculature in two pairs of related fibrosarcomas in the rat and their relation to tumour responses to single large doses of radiation. Eur J Cancer. 1978 Mar;14(3):237–250. doi: 10.1016/0014-2964(78)90187-1. [DOI] [PubMed] [Google Scholar]
  11. Gomer C. J., Johnson R. J. Relationship between misonidazole toxicity and core temperature in C3H mice. Radiat Res. 1979 May;78(2):329–333. [PubMed] [Google Scholar]
  12. Hall E. J., Roizin-Towle L. Hypoxic sensitizers: radiobiological studies at the cellular level. Radiology. 1975 Nov;117(2):453–457. doi: 10.1148/117.2.453. [DOI] [PubMed] [Google Scholar]
  13. Hilmas D. E., Gillette E. L. Morphometric analyses of the microvasculature of tumors during growth and after x-irradiation. Cancer. 1974 Jan;33(1):103–110. doi: 10.1002/1097-0142(197401)33:1<103::aid-cncr2820330116>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  14. Hirst D. G., Denekamp J., Hobson B. Proliferation kinetics of endothelial and tumour cells in three mouse mammary carcinomas. Cell Tissue Kinet. 1982 May;15(3):251–261. doi: 10.1111/j.1365-2184.1982.tb01044.x. [DOI] [PubMed] [Google Scholar]
  15. MARGULIS A. R., CARLSSON E., McALISTER W. H. Angiography of malignant tumors in mice. Acta radiol. 1961 Sep;56:179–192. doi: 10.3109/00016926109172575. [DOI] [PubMed] [Google Scholar]
  16. McNally N. J. Enhancement of chemotherapy agents. Int J Radiat Oncol Biol Phys. 1982 Mar-Apr;8(3-4):593–598. doi: 10.1016/0360-3016(82)90691-5. [DOI] [PubMed] [Google Scholar]
  17. Millar B. C. Hypoxic cell radiosensitizers as potential adjuvants to conventional chemotherapy for the treatment of cancer. Biochem Pharmacol. 1982 Aug 1;31(15):2439–2445. doi: 10.1016/0006-2952(82)90051-x. [DOI] [PubMed] [Google Scholar]
  18. Olive P. L., Chaplin D. J., Durand R. E. Pharmacokinetics, binding and distribution of Hoechst 33342 in spheroids and murine tumours. Br J Cancer. 1985 Nov;52(5):739–746. doi: 10.1038/bjc.1985.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Randhawa V. S., Stewart F. A., Denekamp J., Stratford M. R. Factors influencing the chemosensitization of melphalan by misonidazole. Br J Cancer. 1985 Feb;51(2):219–228. doi: 10.1038/bjc.1985.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reinhold H. S., Visser J. W. In vivo fluorescence of endothelial cell nuclei stained with the dye Bis-benzamide H 33342. Int J Microcirc Clin Exp. 1983;2(2):143–146. [PubMed] [Google Scholar]
  21. Rubin P., Casarett G. Microcirculation of tumors. I. Anatomy, function, and necrosis. Clin Radiol. 1966 Jul;17(3):220–229. doi: 10.1016/s0009-9260(66)80027-2. [DOI] [PubMed] [Google Scholar]
  22. Rubin P., Casarett G. Microcirculation of tumors. II. The supervascularized state of irradiated regressing tumors. Clin Radiol. 1966 Oct;17(4):346–355. doi: 10.1016/s0009-9260(66)80052-1. [DOI] [PubMed] [Google Scholar]
  23. Révész L., Siracka E. A morphometric study of vascularization in uterine cervix cancers. Cytometry. 1984 Jul;5(4):442–444. doi: 10.1002/cyto.990050424. [DOI] [PubMed] [Google Scholar]
  24. Shipley W. U., Stanley J. A., Steel G. G. Tumor size dependency in the radiation response of the Lewis lung carcinoma. Cancer Res. 1975 Sep;35(9):2488–2493. [PubMed] [Google Scholar]
  25. Siemann D. W. Potentiation of chemotherapy by hypoxic cell radiation sensitizers--a review. Int J Radiat Oncol Biol Phys. 1982 Jun;8(6):1029–1034. doi: 10.1016/0360-3016(82)90172-9. [DOI] [PubMed] [Google Scholar]
  26. Smith K. A., Begg A. C., Denekamp J. Differences in chemosensitivity between subcutaneous and pulmonary tumours. Eur J Cancer Clin Oncol. 1985 Feb;21(2):249–256. doi: 10.1016/0277-5379(85)90180-4. [DOI] [PubMed] [Google Scholar]
  27. Solesvik O. V., Rofstad E. K., Brustad T. Vascular changes in a human malignant melanoma xenograft following single-dose irradiation. Radiat Res. 1984 Apr;98(1):115–128. [PubMed] [Google Scholar]
  28. Song C. W. Effect of local hyperthermia on blood flow and microenvironment: a review. Cancer Res. 1984 Oct;44(10 Suppl):4721s–4730s. [PubMed] [Google Scholar]
  29. Steel G. G., Adams K. Stem-cell survival and tumor control in the Lewis lung carcinoma. Cancer Res. 1975 Jun;35(6):1530–1535. [PubMed] [Google Scholar]
  30. Stratford I. J., Adams G. E. Effect of hyperthermia on differential cytotoxicity of a hypoxic cell radiosensitizer, Ro-07-0582, on mammalian cells in vitro. Br J Cancer. 1977 Mar;35(3):307–313. doi: 10.1038/bjc.1977.44. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. THOMLINSON R. H., GRAY L. H. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br J Cancer. 1955 Dec;9(4):539–549. doi: 10.1038/bjc.1955.55. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tannock I. F. Population kinetics of carcinoma cells, capillary endothelial cells, and fibroblasts in a transplanted mouse mammary tumor. Cancer Res. 1970 Oct;30(10):2470–2476. [PubMed] [Google Scholar]
  33. Tannock I. F., Steel G. G. Quantitative techniques for study of the anatomy and function of small blood vessels in tumors. J Natl Cancer Inst. 1969 May;42(5):771–782. [PubMed] [Google Scholar]
  34. Thomlinson R. H., Craddock E. A. The gross response of an experimental tumour to single doses of x-rays. Br J Cancer. 1967 Mar;21(1):108–123. doi: 10.1038/bjc.1967.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Timpl R., Rohde H., Robey P. G., Rennard S. I., Foidart J. M., Martin G. R. Laminin--a glycoprotein from basement membranes. J Biol Chem. 1979 Oct 10;254(19):9933–9937. [PubMed] [Google Scholar]
  36. VOGEL A. W. INTRATUMORAL VASCULAR CHANGES WITH INCREASED SIZE OF A MAMMARY ADENOCARCINOMA: NEW METHOD AND RESULTS. J Natl Cancer Inst. 1965 May;34:571–578. [PubMed] [Google Scholar]
  37. Vaupel P. Hypoxia in neoplastic tissue. Microvasc Res. 1977 May;13(3):399–408. doi: 10.1016/0026-2862(77)90106-6. [DOI] [PubMed] [Google Scholar]
  38. Wickersham J. K., Barrett W. P., Furukawa S. B., Puffer H. W., Warner N. E. An evaluation of the response of the microvasculature in tumors in C3H mice to vasoactive drugs. Bibl Anat. 1977;(15 Pt 1):291–293. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES