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. 1977 Jun;87(3):537–552.

Changes in bone and bone marrow of rabbits bearing the VX-2 carcinoma. A comparison of local and distant effects.

A Hough Jr, H Seyberth, J Oates, W Hartmann
PMCID: PMC2032139  PMID: 869013

Abstract

The VX-2 carcinoma in 32 New Zealand white rabbits was studied morphologically with respect to the osseous effects induced by the innoculation and subsequent growth of tumour in the soft tissues over periods ranging from 1 to 5 weeks. Although more severe changes were noted in bones of tumor-bearing than in non-tumor-bearing limbs, effects could be seen in both experimental situations. Severe bone marrow hyperplasia was noted consistently in tumor-bearing animals. A marked increase in numbers of osteoclasts over control rabbit bones was observed along the surface of bones near and distant from the tumor. Resorptive changes were also noted in the cortex of tumor-bearing rabbits. The increase in osteoclast numbers was related chronologically to the development of hypercalcemia and was proportional to the degree of hypercalcemia at the time the animals died. The number of osteoclasts was inversely proportional to the serum creatinine. A diminution of osteoclast numbers was noted in the latter stages of the disease. These changes may be the morphologic expression of humoral hypercalcemia accompanying the VX-2 carcinoma.

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Selected References

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  1. Azzopardi J. G., Whittaker R. S. Bronchial carcinoma and hypercalcaemia. J Clin Pathol. 1969 Nov;22(6):718–724. doi: 10.1136/jcp.22.6.718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bender R. A., Hansen H. Hypercalcemia in bronchogenic carcinoma. A prospective study of 200 patients. Ann Intern Med. 1974 Feb;80(2):205–208. doi: 10.7326/0003-4819-80-2-205. [DOI] [PubMed] [Google Scholar]
  3. Chopra D., Clerkin E. P. Hypercalcemia and malignant disease. Med Clin North Am. 1975 Mar;59(2):441–447. doi: 10.1016/s0025-7125(16)32045-4. [DOI] [PubMed] [Google Scholar]
  4. Dietrich J. W., Goodson J. M., Raisz L. G. Stimulation of bone resorption by various prostaglandins in organ culture. Prostaglandins. 1975 Aug;10(2):231–240. doi: 10.1016/0090-6980(75)90042-8. [DOI] [PubMed] [Google Scholar]
  5. Ferreira S. H., Vane J. R. Prostaglandins: their disappearance from and release into the circulation. Nature. 1967 Dec 2;216(5118):868–873. doi: 10.1038/216868a0. [DOI] [PubMed] [Google Scholar]
  6. Franklin R. B., Tashjian A. H., Jr Intravenous infusion of prostaglandin E2 raises plasma calcium concentration in the rat. Endocrinology. 1975 Jul;97(1):240–243. doi: 10.1210/endo-97-1-240. [DOI] [PubMed] [Google Scholar]
  7. Gomes B. D., Hausmann E., Wienfeld N., De Luca C. Prostaglandins: bone resorption stimulating factors released from monkey gingiva. Calcif Tissue Res. 1976 Mar 31;19(4):285–293. doi: 10.1007/BF02564011. [DOI] [PubMed] [Google Scholar]
  8. Hamberg M. Inhibition of prostaglandin synthesis in man. Biochem Biophys Res Commun. 1972 Nov 1;49(3):720–726. doi: 10.1016/0006-291x(72)90470-6. [DOI] [PubMed] [Google Scholar]
  9. Hamberg M., Israelsson U. Metabolism of prostaglandin E2 in guinea pig liver. I. Identification of seven metabolites. J Biol Chem. 1970 Oct 10;245(19):5107–5114. [PubMed] [Google Scholar]
  10. Hamberg M. Metabolism of prostaglandins in rat liver mitochondria. Eur J Biochem. 1968 Oct 17;6(1):135–146. doi: 10.1111/j.1432-1033.1968.tb00430.x. [DOI] [PubMed] [Google Scholar]
  11. Klein D. C., Raisz L. G. Prostaglandins: stimulation of bone resorption in tissue culture. Endocrinology. 1970 Jun;86(6):1436–1440. doi: 10.1210/endo-86-6-1436. [DOI] [PubMed] [Google Scholar]
  12. LAPPAT E. J., CAWEIN M. A STUDY OF THE LEUKEMOID RESPONSE TO TRANSPLANTABLE A-280 TUMOR IN MICE. Cancer Res. 1964 Feb;24:302–311. [PubMed] [Google Scholar]
  13. Lupulescu A., Boyd C. B. Lung cancer: a transmission and scanning electron microscopic study. Cancer. 1972 Jun;29(6):1530–1538. doi: 10.1002/1097-0142(197206)29:6<1530::aid-cncr2820290617>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  14. MILCH R. A., CHANGUS G. W. Response of bone to tumor invasion. Cancer. 1956 Mar-Apr;9(2):340–351. doi: 10.1002/1097-0142(195603/04)9:2<340::aid-cncr2820090221>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  15. Moore G. E., Merrick S. B., Woods L. K., Arabasz N. M. A human squamous cell carcinoma cell line. Cancer Res. 1975 Oct;35(10):2684–2688. [PubMed] [Google Scholar]
  16. Mundy G. R., Raisz L. G., Cooper R. A., Schechter G. P., Salmon S. E. Evidence for the secretion of an osteoclast stimulating factor in myeloma. N Engl J Med. 1974 Nov 14;291(20):1041–1046. doi: 10.1056/NEJM197411142912001. [DOI] [PubMed] [Google Scholar]
  17. Obiditsch-Mayer I., Breitfellner G. Electron microscopy in cancer of the lung. Cancer. 1968 May;21(5):945–951. doi: 10.1002/1097-0142(196805)21:5<945::aid-cncr2820210519>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  18. Piper P. J., Vane J. R., Wyllie J. H. Inactivation of prostaglandins by the lungs. Nature. 1970 Feb 14;225(5233):600–604. doi: 10.1038/225600a0. [DOI] [PubMed] [Google Scholar]
  19. Powell D., Singer F. R., Murray T. M., Minkin C., Potts J. T., Jr Nonparathyroid humoral hypercalcemia in patients with neoplastic diseases. N Engl J Med. 1973 Jul 26;289(4):176–181. doi: 10.1056/NEJM197307262890403. [DOI] [PubMed] [Google Scholar]
  20. Robinson W. A. Granulocytosis in neoplasia. Ann N Y Acad Sci. 1974;230:212–218. doi: 10.1111/j.1749-6632.1974.tb14451.x. [DOI] [PubMed] [Google Scholar]
  21. Schooley J. C., Mahlmann L. J. Stimulation of erythropoiesis in plethoric mice by prostaglandins and its inhibition by antierythropoietin. Proc Soc Exp Biol Med. 1971 Nov;138(2):523–524. doi: 10.3181/00379727-138-35931. [DOI] [PubMed] [Google Scholar]
  22. Seyberth H. W., Segre G. V., Morgan J. L., Sweetman B. J., Potts J. T., Jr, Oates J. A. Prostaglandins as mediators of hypercalcemia associated with certain types of cancer. N Engl J Med. 1975 Dec 18;293(25):1278–1283. doi: 10.1056/NEJM197512182932502. [DOI] [PubMed] [Google Scholar]
  23. Strausser H. R., Humes J. L. Prostaglandin synthesis inhibition: effect on bone changes and sarcoma tumor induction in balb/c mice. Int J Cancer. 1975 May 15;15(5):724–730. doi: 10.1002/ijc.2910150503. [DOI] [PubMed] [Google Scholar]
  24. Tashjian A. H., Jr, Voelkel E. F., Goldhaber P., Levine L. Prostaglandins, calcium metabolism and cancer. Fed Proc. 1974 Jan;33(1):81–86. [PubMed] [Google Scholar]
  25. Tashjian A. H., Jr, Voelkel E. F., Levine L., Goldhaber P. Evidence that the bone resorption-stimulating factor produced by mouse fibrosarcoma cells is prostaglandin E 2 . A new model for the hypercalcemia of cancer. J Exp Med. 1972 Dec 1;136(6):1329–1343. doi: 10.1084/jem.136.6.1329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Voelkel E. F., Tashjian A. H., Jr, Franklin R., Wasserman E., Levine L. Hypercalcemia and tumor-prostaglandins: the VX2 carcinoma model in the rabbit. Metabolism. 1975 Aug;24(8):973–986. doi: 10.1016/0026-0495(75)90089-x. [DOI] [PubMed] [Google Scholar]
  27. WILSON J. R., MERRICK H., VOGEL S. D., WOODWARD E. R. HYPERPARATHYROID-LIKE STATE IN RABBITS WITH THE VX-2 CARCINOMA: FURTHER STUDIES. Am Surg. 1965 Feb;31:144–152. [PubMed] [Google Scholar]
  28. Xipell J., Makin H., McKinnon P. A method for the preparation of undecalcified bone sections for light microscopy and microradiography. Stain Technol. 1974 Mar;49(2):69–76. doi: 10.3109/10520297409116944. [DOI] [PubMed] [Google Scholar]
  29. Young D. M., Fioravanti J. L., Prieur D. J., Ward J. M. Hypercalcemic VX-2 carcinoma in rabbits: a clinicopathologic study. Lab Invest. 1976 Jul;35(1):30–46. [PubMed] [Google Scholar]
  30. Zichner L. Die Wirkung des Calcitonins auf das Knochengewebe. Eine licht-, elektronen-, fluorescenzmikroskopische und autoradiographische Untersuchung. Res Exp Med (Berl) 1974;164(4):293–313. doi: 10.1007/BF01851946. [DOI] [PubMed] [Google Scholar]

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