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. 1988 Jul;58(1):64–69. doi: 10.1038/bjc.1988.163

In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients.

M H Bronchud 1, M R Potter 1, G Morgenstern 1, M J Blasco 1, J H Scarffe 1, N Thatcher 1, D Crowther 1, L M Souza 1, N K Alton 1, N G Testa 1, et al.
PMCID: PMC2246501  PMID: 2458748

Abstract

Twelve patients with small cell lung cancer were treated with recombinant human granulocyte colony-stimulating factor, rhG-CSF, given by continuous infusion at doses ranging from 1 to 40 micrograms kg-1 day-1. Patients received the rhG-CSF before the start of intensive chemotherapy and after alternate cycles of chemotherapy. Several in vitro assays were performed using peripheral blood neutrophils and marrow progenitor cells collected from patients prior to and after infusion of the growth factor. Peripheral blood neutrophils were tested for mobility and phagocytic activity. In addition, in vitro clonogenic assays of marrow haemopoietic progenitor cells and analysis of bone marrow trephines and aspirates were carried out. We found that rhG-CSF in vivo has at least two main effects: (a) an early fall in peripheral neutrophils, within the first hour, followed by a rapid influx of mature neutrophils into the circulatory pool; (b) stimulation of proliferation and differentiation of neutrophil precursors in the bone marrow. Neutrophils released into the circulation were normal in tests of their mobility and phagocytic activity.

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Selected References

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

  1. Aisner J. Identification of new drugs in small cell lung cancer: phase II agents first? Cancer Treat Rep. 1987 Dec;71(12):1131–1133. [PubMed] [Google Scholar]
  2. BECKER A. J., MCCULLOCH E. A., SIMINOVITCH L., TILL J. E. THE EFFECT OF DIFFERING DEMANDS FOR BLOOD CELL PRODUCTION ON DNA SYNTHESIS BY HEMOPOIETIC COLONY-FORMING CELLS OF MICE. Blood. 1965 Sep;26:296–308. [PubMed] [Google Scholar]
  3. Begley C. G., Lopez A. F., Nicola N. A., Warren D. J., Vadas M. A., Sanderson C. J., Metcalf D. Purified colony-stimulating factors enhance the survival of human neutrophils and eosinophils in vitro: a rapid and sensitive microassay for colony-stimulating factors. Blood. 1986 Jul;68(1):162–166. [PubMed] [Google Scholar]
  4. Bishop C. R., Athens J. W., Boggs D. R., Warner H. R., Cartwright G. E., Wintrobe M. M. Leukokinetic studies. 13. A non-steady-state kinetic evaluation of the mechanism of cortisone-induced granulocytosis. J Clin Invest. 1968 Feb;47(2):249–260. doi: 10.1172/JCI105721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bronchud M. H., Scarffe J. H., Thatcher N., Crowther D., Souza L. M., Alton N. K., Testa N. G., Dexter T. M. Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Br J Cancer. 1987 Dec;56(6):809–813. doi: 10.1038/bjc.1987.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Donahue R. E., Wang E. A., Stone D. K., Kamen R., Wong G. G., Sehgal P. K., Nathan D. G., Clark S. C. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. 1986 Jun 26-Jul 2Nature. 321(6073):872–875. doi: 10.1038/321872a0. [DOI] [PubMed] [Google Scholar]
  7. Easmon C. S., Cole P. J., Williams A. J., Hastings M. The measurement of opsonic and phagocytic function by Luminol-dependent chemiluminescence. Immunology. 1980 Sep;41(1):67–74. [PMC free article] [PubMed] [Google Scholar]
  8. Fleischmann J., Golde D. W., Weisbart R. H., Gasson J. C. Granulocyte-macrophage colony-stimulating factor enhances phagocytosis of bacteria by human neutrophils. Blood. 1986 Sep;68(3):708–711. [PubMed] [Google Scholar]
  9. Groopman J. E., Mitsuyasu R. T., DeLeo M. J., Oette D. H., Golde D. W. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med. 1987 Sep 3;317(10):593–598. doi: 10.1056/NEJM198709033171003. [DOI] [PubMed] [Google Scholar]
  10. Metcalf D. The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood. 1986 Feb;67(2):257–267. [PubMed] [Google Scholar]
  11. Moore M. A., Warren D. J. Synergy of interleukin 1 and granulocyte colony-stimulating factor: in vivo stimulation of stem-cell recovery and hematopoietic regeneration following 5-fluorouracil treatment of mice. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7134–7138. doi: 10.1073/pnas.84.20.7134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Morstyn G., Campbell L., Souza L. M., Alton N. K., Keech J., Green M., Sheridan W., Metcalf D., Fox R. Effect of granulocyte colony stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet. 1988 Mar 26;1(8587):667–672. doi: 10.1016/s0140-6736(88)91475-4. [DOI] [PubMed] [Google Scholar]
  13. Myers C. D., Katz F. E., Joshi G., Millar J. L. A cell line secreting stimulating factors for CFU-GEMM culture. Blood. 1984 Jul;64(1):152–155. [PubMed] [Google Scholar]
  14. Nelson R. D., Quie P. G., Simmons R. L. Chemotaxis under agarose: a new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes. J Immunol. 1975 Dec;115(6):1650–1656. [PubMed] [Google Scholar]
  15. Nicola N. A. Granulocyte colony-stimulating factor and differentiation-induction in myeloid leukemic cells. Int J Cell Cloning. 1987 Jan;5(1):1–15. doi: 10.1002/stem.5530050102. [DOI] [PubMed] [Google Scholar]
  16. RUTENBURG M., ROSALES C. L., BENNETT J. M. AN IMPROVED HISTOCHEMICAL METHOD FOR THE DEMONSTRATION OF LEUKOCYTE ALKALINE PHOSPHATASE ACTIVITY: CLINICAL APPLICATION. J Lab Clin Med. 1965 Apr;65:698–705. [PubMed] [Google Scholar]
  17. SAMUELS A. J. Primary and secondary leucocyte changes following the intramuscular injection of epinephrine hydrochloride. J Clin Invest. 1951 Sep;30(9):941–947. doi: 10.1172/JCI102515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sieff C. A. Hematopoietic growth factors. J Clin Invest. 1987 Jun;79(6):1549–1557. doi: 10.1172/JCI112988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vadhan-Raj S., Keating M., LeMaistre A., Hittelman W. N., McCredie K., Trujillo J. M., Broxmeyer H. E., Henney C., Gutterman J. U. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N Engl J Med. 1987 Dec 17;317(25):1545–1552. doi: 10.1056/NEJM198712173172501. [DOI] [PubMed] [Google Scholar]
  20. Vincent P. C. Granulocyte kinetics in health and disease. Clin Haematol. 1977 Oct;6(3):695–717. [PubMed] [Google Scholar]
  21. Welte K., Bonilla M. A., Gillio A. P., Boone T. C., Potter G. K., Gabrilove J. L., Moore M. A., O'Reilly R. J., Souza L. M. Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates. J Exp Med. 1987 Apr 1;165(4):941–948. doi: 10.1084/jem.165.4.941. [DOI] [PMC free article] [PubMed] [Google Scholar]

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