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Cell kinetic studies of endothelial cells in the adenocarcinoma EO 771 and the effect of cyclophosphamide

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Virchows Archiv B

Summary

Cell kinetic studies of endothelial cells in the adenocarcinoma EO 771 growing in C57bl/6j mice and after transplantation into Balb/c-nu/nu mice, as well as of the effect of cyclophosphamide treatment have been carried out. The3H-thymidine labelling index of endothelial cells decreases from about 8% 3–6 days after tumour inoculation to about 3% at 18 days. This decrease parallels that of the labelling index of tumour cells, i.e. there is a positive correlation between the labelling index of endothelial cells and that of tumour cells. The labelling index of endothelial cells in the tumour periphery is two to three times as high as that in the tumour centre reflecting corresponding differences in the rate of proliferation. There is no difference in the proliferation of endothelial cells whether the tumour grows in C57bl/6j or in Balb/c-nu/nu mice. After treatment with cyclophosphamide the labelling index of endothelial cells decreases within 2 days to 1–2% and remains that low despite regrowth of the tumour with increased tumour cell proliferation, indicating that tumour relapse does not depend on tumour angiogenesis.

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References

  • Bassukas ID, Maurer-Schultze B (1987) Mechanism of growth retardation of the adenocarcinoma EO 771. Radiat Environ Biophys 26:125–141

    Article  PubMed  CAS  Google Scholar 

  • Bassakus ID, Maurer-Schultze B (1988) The recursion formula of the Gompertz function: A simple method for the estimation and comparison of tumor growth curves. Growth Dev Aging 52:113–122

    Google Scholar 

  • Bassukas ID, van Seil B, Maurer-Schultze B (1989) Cell kinetics of solid tumor cells sublethally damaged by cyclophosphamide. Cell Tissue Kin 22:175

    Google Scholar 

  • Benckhuysen C, van der Steen J, Spanjersberg EJ (1986) Two stable fenton oxidation products of cyclophosphamide as precursors of 4-hydroxycyclophosphamide under physiologic conditions. Cancer Treat Rep 60:369–372

    Google Scholar 

  • Cataland S, Cohen C, Sapirstein LA (1962) Relationship between size and perfusion rate of transplanted tumors. J Natl Cancer Inst 29:389–394

    PubMed  CAS  Google Scholar 

  • Clark RAF, DellaPelle P, Manseau E, Lanigan JM, Dvorak HF, Colvin RB (1982) Blood vessel fibronectin increases in conjuction with endothelial cell proliferation and capillary ingrowth during wound healing. J Invest Dermatol 79:269–276

    Article  PubMed  CAS  Google Scholar 

  • Connors TA (1974) Alkylating Agents. Topics in Curr Chem 52:141–171

    CAS  Google Scholar 

  • Cox PJ, Phillips PJ, Thomas P (1976) Studies on the selective action of cyclophosphamide: Inactivation of the hydroxylated metabolite by tissue-soluble enzymes. Cancer Treat Rep 60:321–326

    PubMed  CAS  Google Scholar 

  • Davies MG, Marks R (1978) Dermo-epidermal relationships in pyogenic granulomata. Br J Dermatol 99:503–512

    Article  PubMed  CAS  Google Scholar 

  • Denekamp J (1982) Endothelial cell proliferation as a novel approach to targeting tumour therapy. Br J Cancer 45:136–139

    PubMed  CAS  Google Scholar 

  • Denekamp J, Hobson B (1982) Endothelial-cell proliferation in experimental tumours. Br J Cancer 46:711–720

    PubMed  CAS  Google Scholar 

  • Dunham LJ, Stewart HL (1953) A survey of transplantable and transmissible tumors. J Natl Cancer Inst 13:1299–1377

    PubMed  CAS  Google Scholar 

  • Folkman J (1971) Tumor angiogenesis: Therapeutic implications. N Engl J Med 285:1182–1186

    PubMed  CAS  Google Scholar 

  • Folkman J (1974) Tumor angiogenesis factor. Cancer Res 34:2109–2113

    PubMed  CAS  Google Scholar 

  • Folkman J (1984) Angiogenesis. In: Biology of endothelial cells. EA Jaffe, ed. (Boston: Nijhoff). pp 412–428

    Google Scholar 

  • Folkman J (1985) Tumor angiogenesis. Adv Cancer Res 43:175–204

    PubMed  CAS  Google Scholar 

  • Folkman J (1986) How is blood vessel growth regulated in normal and neoplastic tissue? GHA Clows memorial award lecture. Cancer Res 46:467–473

    PubMed  CAS  Google Scholar 

  • Folkman J (1987) What is the role of angiogenesis in metastasis of cutaneous melanoma? Eur J Cancer Clin Oncol 23:361–363

    Article  PubMed  CAS  Google Scholar 

  • Folkman J, Cotran R (1976) Relation of vascular proliferation to tumor growth. Int Rev Exp Pathol 16:207–248

    PubMed  CAS  Google Scholar 

  • Folkman J, Klagsbrun M (1987) Angiogenic factors. Science 235:442–447

    Article  PubMed  CAS  Google Scholar 

  • Folkman J, Watson K, Ingber D, Hanahan D (1989) Induction of angiogenesis during the transition from hyperplasia to neoplasia. Nature 339:58–61

    Article  PubMed  CAS  Google Scholar 

  • Gospodarowicz D, Ferrara N, Schweigerer L, Neufeld G (1987) Structural characterization and biological functions of fibroblast growth factors. Endocrine Rev 8:95–116

    Article  CAS  Google Scholar 

  • Groothuis DR, Pasternak JF, Fisher JM, Blasberg RG, Bigner DD, Vick NA (1983) Regional measurements of blood flow in experimental RG-2 rat gliomas. Cancer Res 43:3362–3367

    PubMed  CAS  Google Scholar 

  • Gunduz N (1981) Cytokinetics of tumour and endothelial cells and vascularization of lung metastases in C3H/He mice. Cell Tissue Kin 14:343–363

    CAS  Google Scholar 

  • Heller V, Bassukas ID, Grups JW, Wirth MP (1987) Growth of human renal cell carcinoma in nude mice. Invest Urol 2:75–80

    Google Scholar 

  • Hill DL (1975) Antitumor effects in experimental animals. In: A review of cyclophosphamide. Springfield Ill: CC Thomas Publ, pp 198–241

    Google Scholar 

  • Hirst DG, Denekamp J, Hobson B (1980) Proliferation studies of the endothelial and smooth muscle cells of the mouse mesentery after irradiation. Cell Tissue Kin 13:91–104

    CAS  Google Scholar 

  • Hirst DG, Denekamp J, Hobson B (1982) Proliferation kinetics of endothelial and tumour cells in three mouse mammary carcinomas. Cell Tissue Kin 15:251–261

    CAS  Google Scholar 

  • Hobson B, Denekamp J (1984) Endothelial proliferation in tumours and normal tissues: continuous labelling studies. Br J Cancer 49:405–113

    PubMed  CAS  Google Scholar 

  • Jones B, Camplejohn RS (1983) Stathmokinetic measurement of tumour cell proliferation in relation to vascular proximity. Cell Tissue Kin 16:351–355

    CAS  Google Scholar 

  • Maciag T (1984) Angiogenesis. Prog Hemostasis Thromb 7:167–182

    CAS  Google Scholar 

  • Moore JV, Hasleton PS, Buckley CH (1985) Tumour cords in 52 human bronchial and cervical squamous cell carcinomas: Inferences for their cellular kinetics and radiobiology. Br J Cancer 51:407–113

    PubMed  CAS  Google Scholar 

  • Polverini PJ, Cotran RS, Sholley MM (1977) Endothelial proliferation in the delayed hypersensitivity reaction: an autoradiographic study. J Immunol 118:529–532

    PubMed  CAS  Google Scholar 

  • Rastinejad F, Polverini PJ, Bouck NP (1989) Regulation of the activity of a new inhibitor of angiogenesis by a cancer suppressor gene. Cell 56:345–355

    Article  PubMed  CAS  Google Scholar 

  • Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS (1986) Transforming growth-factor type-β: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci 83:4167–4171

    Article  PubMed  CAS  Google Scholar 

  • Ryan TJ (1969) A study of the epidermal capillary unit in psoriasis. Dermatologica 138:459–472

    Article  PubMed  CAS  Google Scholar 

  • Sachs L (1984) Angewandte Statistik, 6. Auflage. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Schreiber AB, Winkler ME, Derynck R (1986) Transforming growth factor-α: A more potent angiogenic mediator than epidermal growth factor. Science 232:1250–1253

    Article  PubMed  CAS  Google Scholar 

  • Schultze B, Fietkau R, Schäfer E, Bassukas I (1985) Cell kinetic studies of the effect of cytotoxic drugs on survival and proliferation of ascites and solid tumor cells of the mouse. Ann NY Acad Sci 459:278–292

    Article  PubMed  CAS  Google Scholar 

  • Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC, Gospodarowicz D (1987) Capillary endothelial cells express basic fibroblastic growth factor, a mitogen that promotes their own growth. Nature 325:257–259

    Article  PubMed  CAS  Google Scholar 

  • Sholley MM, Cavallo T, Cotran RS (1977) Endothelial proliferation in inflammation. I. Autoradiographic studies following thermal injury to the skin of normal rats. Am J Pathol 89:277–296

    PubMed  CAS  Google Scholar 

  • Sholley MM, Ferguson GP, Seibel HR, Montour JL, Wilson JD (1984) Mechanism of neovascularization. Lab Invest 51:624–634

    PubMed  CAS  Google Scholar 

  • Shubik P (1982) Vascularization of tumors: A review. J Cancer Res Clin Oncol 103:211–226

    Article  PubMed  CAS  Google Scholar 

  • Snell GD, Russell E, Fekete E, Smith P (1953) Resistance of various inbred strains of mice to tumor homoiotransplants, and its relation to the H-2 allele which each carries. J Natl Cancer Inst 14:485–491

    PubMed  CAS  Google Scholar 

  • Srivastava A, Laidler P, Hughes LE, Woodcock J, Shedden EJ (1986) Neovascularization in human cutaneous melanoma: a quantitative morphological and Doppler ultrasound study. Eur J Cancer Clin Oncol 22:1205–1209

    Article  PubMed  CAS  Google Scholar 

  • Steel GG, Lamerton LF (1966) The growth rate of human tumors. Br J Cancer 20:74–86

    PubMed  CAS  Google Scholar 

  • Stolpen AH, Guinan EC, Fiers W, Pober JS (1986) Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers. Am J Pathol 123:16–24

    PubMed  CAS  Google Scholar 

  • Tannock IF (1970) Population kinetics of carcinoma cells, capillary endothelial cells, and fibroblasts in a transplanted mouse mammary tumor. Cancer Res 30:2470–2476

    PubMed  CAS  Google Scholar 

  • Tannock IF, Hayashi S (1972) The proliferation of capillary endothelial cells. Cancer Res 32:77–82

    PubMed  CAS  Google Scholar 

  • Thomas KA (1985) Mechanisms of action of mitogenic growth factors. Comments Mol Cell Biophys 3:1–13

    Google Scholar 

  • Walter J, Maurer-Schultze B (1987) Regrowth, tumor cell proliferation and morphological alterations of the adenocarcinoma EO 771 following a single dose of 30 Gy60Co-rays. Strahlenther Oncol 163:687–694

    CAS  Google Scholar 

  • Ziehe M, Gullino PM (1982) Angiogenesis and neoplastic progression in vitro. J Natl Cancer Inst 69:483–187

    Google Scholar 

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  1. Institut für Medizinische Strahlenkunde der Universität Würzburg, Versbacher Strasse 5, D-8700, Würzburg, Federal Republic of Germany

    I. D. Bassukas, G. Vester & B. Maurer-Schultze

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  1. I. D. Bassukas
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  2. G. Vester
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  3. B. Maurer-Schultze
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Bassukas, I.D., Vester, G. & Maurer-Schultze, B. Cell kinetic studies of endothelial cells in the adenocarcinoma EO 771 and the effect of cyclophosphamide. Virchows Archiv B Cell Pathol 59, 251–256 (1990). https://doi.org/10.1007/BF02899411

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