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 histiocytic 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 cyclophosphamide 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.

Animals↗

PubMed1991

Deoxyspergualin in lethal murine graft-versus-host disease.

The beneficial effect of deoxyspergualin (DSG, NKT-01) on lethal graft-versus-host disease in mice has been studied in a major histoincompatible donor-recipient combination. Suppression of the effector mechanisms responsible for the lethal outcome in this GVHD model is also noted. This study reveals: (1) DSG has a marked potential for treatment of lethal GVHD; (2) DSG and methotrexate in combination yield longer survival times than DSG or MTX alone; (3) long-term survivors, following DSG treatment, become stable chimeras as evidenced by cell-surface analysis of spleen cells; and (4) high activity of H-2-reactive cytotoxic T lymphocytes is detected in spleens of the mice with lethal GVHD, whereas natural killer activity is only slightly increased. DSG inhibits CTL activity not only in the induction stage but also in the advanced stage of the disease. These findings indicate that DSG might be beneficial in clinical bone marrow transplantation either alone or in combination with MTX.

Animals↗

PubMed1991

Intestinal mucormycosis in a hemodialysis patient treated with desferrioxamine.

A case of fatal intestinal mucormycosis in a 57-year-old female hemodialysis patient who had received desferrioxamine (DFO) for aluminum overload is reported. The focus of fungal infection was not found until the intestine had been resected surgically. DFO is being used with increased frequency in dialysis patients to treat aluminum or iron overload. Recently a possible link between DFO therapy and mucormycosis has been suggested. In the management of hemodialysis patients, the potential risk of mucormycosis with DFO therapy should be considered.

Aluminum↗

PubMed1991