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Titolo:
MYELOID PROGENITOR-CELL PROLIFERATION AND MOBILIZATION EFFECTS OF BB10010, A GENETICALLY-ENGINEERED VARIANT OF HUMAN MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA, IN A PHASE-I CLINICAL-TRIAL IN PATIENTS WITH RELAPSED REFRACTORY BREAST-CANCER/
Autore:
BROXMEYER HE; ORAZI A; HAGUE NL; SLEDGE GW; RASMUSSEN H; GORDON MS;
Indirizzi:
INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,1044 W WALNUT ST INDIANAPOLIS IN 46202 INDIANA UNIV,SCH MED,DEPT MICROBIOL IMMUNOL INDIANAPOLIS IN 46202 INDIANA UNIV,SCH MED,DEPT MED INDIANAPOLIS IN 46202 WALTHER CANC INST INDIANAPOLIS IN 46208 INDIANA UNIV,SCH MED,DEPT LAB MED & PATHOL INDIANAPOLIS IN 46202 BRITISH BIOTECH INC ANNAPOLIS MD 21401
Titolo Testata:
Blood cells, molecules, & diseases
fascicolo: 2, volume: 24, anno: 1998,
pagine: 14 - 30
SICI:
1079-9796(1998)24:2<14:MPPAME>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLONY-STIMULATING FACTOR; HUMAN-BONE-MARROW; PARAFFIN SECTIONS; CHEMOKINETIC PROPERTIES; RAPID MOBILIZATION; FORMATION INVITRO; CD34(+) CELLS; STEM-CELLS; PROTEIN; MURINE;
Keywords:
CHEMOKINE; MIP-1-ALPHA; BB10010; MYELOPOIESIS; HEMATOPOIETIC PROGENITOR CELLS; CELL CYCLE; CLINICAL TRIAL;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
H.E. Broxmeyer et al., "MYELOID PROGENITOR-CELL PROLIFERATION AND MOBILIZATION EFFECTS OF BB10010, A GENETICALLY-ENGINEERED VARIANT OF HUMAN MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA, IN A PHASE-I CLINICAL-TRIAL IN PATIENTS WITH RELAPSED REFRACTORY BREAST-CANCER/", Blood cells, molecules, & diseases, 24(2), 1998, pp. 14-30

Abstract

Macrophage Inflammatory Protein (MIP)-1 alpha is myelosuppressive in vitro and in vivo for hematopoietic stem and immature subsets of-myeloid progenitor cells, demonstrates some myeloprotective effects in micetreated with Ara-C and hydroxyurea, and has stem/progenitor cell mobilizing activity in mice, Based on these observations, BB10010, a genetic variant of MIP-1 alpha, was assessed for effects on marrow and blood myeloid progenitor cells in patients with relapsed/refractory breastcancer, MIP-1 alpha readily polymerizes, whereas BB10010 has a reduced tendency to form large polymers at physiological pH and ionic strength and retains biological activity, Patients were injected with 5, 10,30 or 100 mu g/kg BB10010 s.c. daily for 3 days, BB10010 significantly reduced the cycling status of marrow myeloid progenitors from pretreatment levels of 39-58% to 0-11% one day after the third and last injection of BB10010, This was associated with significant decreases in frequency of marrow progenitors (number of colonies formed per number ofcells plated) and percent biopsied marrow CD34(+) cells, The suppressive effects were reversible in patients and the rapidity of this reversal demonstrated in mouse studies, BB10010 had no effect on nucleated cellularity or on the proliferation of nucleated cells as assessed in marrow biopsies from the patients. These latter effects may in part reflect the noted decreased apoptosis of nucleated cells by BE 10010. BB10010 also demonstrated significant but modest myeloid progenitor cellmobilizing capacity. Blood progenitors were in a slow or non-cycling state prior to treatment and this did not change after administration of BB10010, The above effects of BB10010 were similar at the four different dosage levels assessed. These results demonstrate in humans the suppressive and mobilizing effects of MIP-1 alpha and BB10010 previously noted in vivo in mice.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 13:21:00