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Acta Biologica Hungarica

, Volume 52, Issue 4, pp 403–409 | Cite as

Quantitative Microvascular Changes During Azaserine-Initiated Pancreatic Carcinogenesis

  • Krisztina Nagy
  • Z. Pálfia
  • G. RézEmail author
Article

Abstract

Although angiogenesis is considered to be indispensable for continuous tumour growth, only very few studies have been published performing microvessel quantification during tumour progression. We measured the tumour vascularity in different stages of rat pancreatic carcinogenesis induced by azaserine and promoted by raw soya flour-containing pancreatotrophic diet. Besides the tumour samples taken at 6 (atypical acinar cell nodules), 15 (adenomas) and 20 (localised adenocarcinomas) months after carcinogen initiation, we also investigated 3 control groups: tumour-bearing host tissue of azaserine-treated rats and normal tissue of untreated rats kept on standard or pancreatotrophic diet. In contrast with the usual microvessel counting on hot spots, we determined microvascular surface density (SV) and volume density (VV) by electron microscopic morphometry. There was no significant difference in these respect between the control groups. At month 6 after the azaserine induction SV and VV showed slight, nonsignificant decrease as compared to the host control. Both values remained unchanged until the 15th month and increased significantly by the 20th month. These results may indicate comparable growth rate of tumour and new microvessels in the premalignant stages of carcinogenesis while a more intense angiogenesis than tumour growth afterwards.

Keywords

Microvessel quantitative tumour progression pancreas rat 

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References

  1. 1.
    American Institute of Nutrition (1977) Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies. J. Nutr. 107, 1340–1348.CrossRefGoogle Scholar
  2. 2.
    Barth, P. J., Weingärtner, K., Köhler, H. H., Bittinger, A. (1996) Assessment of the vascularization in prostatic carcinoma: A morphometric investigation. Hum. Pathol. 27, 1306–1310.CrossRefGoogle Scholar
  3. 3.
    Beliën, J. A., Somi, S., de Jong, J. S., van Diest, P. J., Baak, J. P. (1999) Fully automated microvessel counting and hot spot selection by image processing of whole tumour sections in invasive breast cancer. J. Clin. Pathol. 52:3, 184–192.CrossRefGoogle Scholar
  4. 4.
    Bochner, B. H., Cote, R. J., Weidner, N., Groshen, S., Chen, S. C, Skinner, D. G., Nichols, P. W. (1995) Angiogenesis in bladder cancer: relationship between microvessel density and tumour prognosis. J. Natl. Cancer Inst. 87:21, 1603–1612.CrossRefGoogle Scholar
  5. 5.
    De Jaeger, K., Merlo, F. M., Kavanagh, M. C., Fyles, A. W., Hedley, D., Hill, R. P. (1998) Heterogeneity of tumour oxygenation: relationship to tumour necrosis, tumour size, and metastasis. Int. J. Radiat. Oncol. Biol. Phys. 42:4, 717–721.CrossRefGoogle Scholar
  6. 6.
    Folkman, J. (1985) Tumor angiogenesis. Adv. Cancer Res. 43, 175–203.CrossRefGoogle Scholar
  7. 7.
    Fontanini, G., Lucchi, M., Vignati, S., Mussi, A., Ciardiello, F., De Laurentiis, M., De Placido, S., Basolo, F., Angeletti, C. A., Bevilacqua, G. (1997) Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study. J. Natl. Cancer Inst. 89:12, 881–886.CrossRefGoogle Scholar
  8. 8.
    Gasparini, G., Weidner, N., Maluta, S., Pozza, F., Boracchi, P., Mezzetti, M., Testolin, A., Bevilacqua, P. (1993) Intratumoral microvessel density and p53 protein: correlation with metastasis in head and neck squamous-cell carcinoma. Int. J. Cancer 55:5, 739–744.CrossRefGoogle Scholar
  9. 9.
    Hanahan, D., Folkman, J. (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86, 353–364.CrossRefGoogle Scholar
  10. 10.
    Köhler, H. H., Barth, P. J., Siebel, A., Gerharz, E. W., Bittinger, A. (1996) Quantitative assessment of vascular surface density in renal cell carcinomas. Br. J. Urol. 42:4, 717–721.Google Scholar
  11. 11.
    Longnecker, D. S. (1987) The azaserine-induced model of pancreatic carcinogenesis in rats. In: Scarpelli, D. G., Reddy, J. K. and Longnecker, D. S. (eds): Experimental pancreatic carcinogenesis. CRC Press, Boca Raton. pp. 117–132.Google Scholar
  12. 12.
    McGuinness, E. E., Hopwood, D., Wormsley, K. G. (1982) Further studies of the effects of raw soya flour on the rat pancreas. Scand. J. Gastroenterol. 17, 273–277.CrossRefGoogle Scholar
  13. 13.
    Milgross, C. G., Tucker, S. L., Mason, K. A., Hunter, N. R., Peters, L. J., Milas, L. (1997) The effect of tumor size on necrosis and polarographically measured pO2. Acta Oncol. 36:2, 183–189.CrossRefGoogle Scholar
  14. 14.
    Porschen, R., Classen, S., Piontek, M., Borchard, F. (1994) Vascularization of carcinomas of the esophagus and its correlation with tumor proliferation. Cancer Res. 54:2, 587–591.PubMedGoogle Scholar
  15. 15.
    Réz, G., Tóth, S., Pálfia, Z. (1999) Cellular autophagic capacity is highly increased in azaserine-induced premalignant atypical acinar nodule cells. Carcinogenesis 20, 1893–1898.CrossRefGoogle Scholar
  16. 16.
    Rockwell, S., Knisley, J. P. S. (1997) Hypoxia and angiogenesis in experimental tumor models: Therapeutic implications. In Goldberg, I. D. and Rosen, E. M. (eds): Regulation of angiogenesis. Birkhäuser Verlag, Basel. pp. 335–360.CrossRefGoogle Scholar
  17. 17.
    Tanigawa, N., Lu, C., Mitsui, T., Miura, S. (1997) Quantitation of sinusoid-like vessels in hepatocellular carcinoma: its clinical and prognostic significance. Hepathology 26:5, 1216–1223.Google Scholar
  18. 18.
    Toth, S., Nagy, K., Pálfia, Z., Réz, G. Regulation of cellular autophagic capacity: data from the azaserine-induced pancreatic tumor progression (in preparation)Google Scholar
  19. 19.
    Vermeulen, P. B., Libura, M., Libura, J., O’Neill, P. J., van Dam, P., van Marck, E., van Oosterom, A. T., Dirix, L. Y. (1997) Influence of investigator experience and microscopic field size on microvessel density in node-negative breast carcinoma. Breast Cancer Res. Treat. 42:2, 165–172.CrossRefGoogle Scholar
  20. 20.
    Weibel, E. R. (1969) Stereological principles for morphometry in electron microscopic cytology. Int. Rev. Cytol. 26, 235–302.CrossRefGoogle Scholar
  21. 21.
    Weidner, N., Folkman, J., Pozza, F., Bevilacqua, P., Allred, E. N, Moore, D. H., Meli, S., Gasparini, G. (1992) Tumour angiogenesis: a new significant and independent prognostic indicator in earlystage breast carcinoma. J. Natl. Cancer Inst. 84:24, 1875–1887.CrossRefGoogle Scholar
  22. 22.
    Yager, J. D., Roebuck, B. D., Zurlo, J., Longnecker, D. S., Weselcouch, E. O., Wilpone, S. A. (1981) A single-dose protocol for azaserine initiation of pancreatic carcinogenesis in the rat. Int. J. Cancer 28, 601–606.CrossRefGoogle Scholar

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© Akadémiai Kiadó, Budapest 2001

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Department of General ZoologyEötvös Loránd UniversityBudapestHungary

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