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Goralatide (AcSDKP), a negative growth regulator, protects the stem cell compartment during chemotherapy, enhancing the myelopoietic response to GM‐CSF
Author(s) -
Bogden Arthur E.,
Moreau JacquesPierre,
GambaVitalo Christina,
Deschamps de Paillette Evelyne,
Tubiana Maurice,
Frindel Emilia,
Carde Patrice
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980330)76:1<38::aid-ijc8>3.0.co;2-z
Subject(s) - regulator , chemotherapy , compartment (ship) , stem cell , cell growth , cancer research , medicine , oncology , biology , microbiology and biotechnology , biochemistry , oceanography , gene , geology
The aim of our study was to investigate the protection afforded to the bone marrow by Goralatide (AcSDKP), an inhibitor of hemopoietic stem cell proliferation, when administered alone or in combination with a growth factor (granulocyte/macrophage colony‐stimulating factor [GM‐CSF]) during iterative cycles of Ara‐C (cytarabine) treatment. In control mice receiving the inhibitor alone without Ara‐C, the number of granulocytes was reduced during treatment, and a surge in number of peripheral blood cells was observed after its completion. Peripheral hematological responses were monitored during 3 consecutive cycles of Ara‐C chemotherapy and the resultant nadir and recoveries. Analysis of variance of the treatment effects pooled over the 3 cycles showed that a treatment regimen in which the inhibitor was administered during the myelotoxic periods of chemotherapy confirmed the existence of a surge after completion of administration of the inhibitor and showed a significant protective effect. When the cycles of chemotherapy plus Goralatide were followed by GM‐CSF, the recovery from leukopenic nadirs was accelerated and the white blood cells and granulocyte levels were markedly increased over those observed in control mice and in mice treated either with Goralatide alone or with GM‐CSF alone. The differences were highly significant. A consistent and significant increase ( p < 0.001) in platelet count was also noted in animals given Goralatide in conjunction with Ara‐C or Ara‐C + GM‐CSF. After three treatment cycles, this response to the CSF was far better in mice treated by the inhibitor than when CSF was given alone, suggesting a protection of the stem cell pool. Int. J. Cancer 76:38–46, 1998.© 1998 Wiley‐Liss, Inc.