Hematopoietic and therapeutic properties of bestatin in normal and myelosuppressed mice

J. E. Talmadge, Louis Pelus, P. L. Black, F. Abe

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Bestatin is a potent inhibitor of aminopeptidase B, an enzyme which is found in abundance in the membrane of monocytes and macrophages. Binding of Bestatin to cells in the histiocylic linage upregulates colony stimulating activity (both in vitro and in vivo), which subsequently increases hematopoietic and hematologic values. We report that the treatment of mice with Bestatin upregulates the frequency and absolute numbers of colony forming unit - granulocyte-macrophage (CFU-GM), as well as the entry of CFU-GM into S phase (a measure of progenitor cell activity). As a result, there is an increase in bone marrow cellularity in cyclophosphamidc myelosuppressed mice and an increase in the absolute neutrophil count in normal and myelosuppressed mice. The therapeutic application of this hematopoietic modulator has been demonstrated in combination cyclophosphamide and Bestatin protocols. While Bestatin has significant therapeutic activity for minimal metastatic disease, therapy models in which the hosts have greater metastatic tumor burdens requires combination chemoimmunotherapy for a significant therapeutic effect. Because myelosuppression as a therapeutic indication for Bestatin has only recently been recognized, few clinical studies have been undertaken with appropriate surrogates of hematopoietic activity. However, the preliminary clinical evidence of hematopoietic activity by this non-toxic dipeptide, as reviewed here, suggests that this may be an appropriate drug for the treatment of myelosuppressed patients. Thus, Bestatin as an orally active biological response modifier (BRM) has significant therapeutic activity for metastatic disease via multiple mechanisms including hematopoietic stimulation and macrophage activating properties. Bestatin/hemopoietic stimulation/macrophage activation.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalBiomedicine and Pharmacotherapy
Volume45
Issue number2-3
DOIs
StatePublished - 1991
Externally publishedYes

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Granulocyte-Macrophage Progenitor Cells
Therapeutics
Up-Regulation
Macrophages
Macrophage Activation
ubenimex
Dipeptides
Immunologic Factors
Therapeutic Uses
Tumor Burden
S Phase
Cyclophosphamide
Monocytes
Neutrophils
Stem Cells
Bone Marrow
Membranes
Enzymes
Pharmaceutical Preparations
In Vitro Techniques

ASJC Scopus subject areas

  • Pharmacology

Cite this

Hematopoietic and therapeutic properties of bestatin in normal and myelosuppressed mice. / Talmadge, J. E.; Pelus, Louis; Black, P. L.; Abe, F.

In: Biomedicine and Pharmacotherapy, Vol. 45, No. 2-3, 1991, p. 61-69.

Research output: Contribution to journalArticle

Talmadge, J. E. ; Pelus, Louis ; Black, P. L. ; Abe, F. / Hematopoietic and therapeutic properties of bestatin in normal and myelosuppressed mice. In: Biomedicine and Pharmacotherapy. 1991 ; Vol. 45, No. 2-3. pp. 61-69.
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