Recombinant human granulocyte-macrophage colony-stimulating factor in septic neutropenic pediatric cancer patients: Detection of circulating hematopoietic precursor cells correlates with rapid granulocyte recovery

1995 ◽  
Vol 25 (5) ◽  
pp. 365-371 ◽  
Author(s):  
Franz-Martin Fink ◽  
Kathrin Maurer-Dengg ◽  
Gerhard Fritsch ◽  
Georg Mann ◽  
Andreas Zoubek ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Pediatric Cancer ◽  
Precursor Cells ◽  
Colony Stimulating Factor ◽  
Hematopoietic Precursor Cells ◽  
Pediatric Cancer Patients ◽  
Hematopoietic Precursor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

scholarly journals The zinc finger transcription factor Egr-1 potentiates macrophage differentiation of hematopoietic cells.

1995 ◽  
Vol 15 (10) ◽  
pp. 5499-5507 ◽  
Author(s):  
K Krishnaraju ◽  
H Q Nguyen ◽  
D A Liebermann ◽  
B Hoffman
Keyword(s):  
Ectopic Expression ◽  
Hematopoietic Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Granulocytic Differentiation ◽  
Hematopoietic Precursor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Macrophage Lineage

Previously we have shown that the zinc finger transcription factor Egr-1 is essential for and restricts differentiation of hematopoietic cells along the macrophage lineage, raising the possibility that Egr-1 actually plays a deterministic role in governing the development of hematopoietic precursor cells along the monocytic lineage. To test this hypothesis, we have taken advantage of interleukin-3-dependent 32Dcl3 hematopoietic precursor cells which, in addition to undergoing granulocytic differentiation in response to granulocyte colony-stimulating factor, were found to be induced for limited proliferation, but not differentiation, by granulocyte-macrophage colony-stimulating factor. It was shown that ectopic expression of Egr-1 blocked granulocyte colony-stimulating factor-induced terminal granulocytic differentiation, consistent with previous findings. In addition, ectopic expression of Egr-1 endowed 32Dcl3 cells with ability to be induced by granulocyte-macrophage colony-stimulating factor for terminal differentiation exclusively along the macrophage lineage. Thus, evidence that Egr-1 potentiates terminal macrophage differentiation has been obtained, suggesting that Egr-1 plays a deterministic role in governing the development of hematopoietic cells along the macrophage lineage.

Randomized, placebo-controlled, multicenter trial of granulocyte-macrophage colony-stimulating factor as infection prophylaxis in oncologic surgery. Leukine Surgical Prophylaxis Research Group.

1998 ◽  
Vol 16 (3) ◽  
pp. 1167-1173 ◽  
Author(s):  
N J Meropol ◽  
D E Wood ◽  
J Nemunaitis ◽  
N J Petrelli ◽  
B J Lipman ◽  
...  
Keyword(s):  
High Risk ◽  
Cancer Patients ◽  
Infection Prophylaxis ◽  
Colony Stimulating Factor ◽  
Postoperative Infections ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
To Receive ◽  
Stimulating Factor

PURPOSE Postoperative infections are a frequent source of preventable morbidity and mortality in the oncologic population. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent modulator of immune effector cells in vitro and in vivo. This study was conducted to determine whether GM-CSF, when administered perioperatively, could reduce the incidence of surgical infections in cancer patients. METHODS This was a prospective, randomized, placebo-controlled, multicenter study. Cancer patients at high risk of infectious surgical morbidity were randomized to receive GM-CSF 125 microg/m2 per day or placebo subcutaneously for 8 days beginning 3 days preoperatively. Routine antibiotic prophylaxis was administered to all patients. RESULTS Three hundred ninety-nine patients were enrolled, with 198 randomized to receive GM-CSF. Twenty-one percent of patients experienced infections during the first 2 weeks postoperatively, and there was no difference in infection rate between the study groups. The most common sites of infection were respiratory tract (53%) and surgical wound (25%). The duration of operation and American Society of Anesthesiology (ASA) physical status classification were the most significant predictors of infection in multivariate analysis. GM-CSF was well tolerated and was not associated with fever. CONCLUSION The eligibility criteria for this study were successful at defining a patient subgroup at high risk for postoperative infections. At an immunomodulatory dose of 125 microg/m2 per day, GM-CSF was safe and well tolerated, but did not reduce the incidence of postoperative infections in this high-risk oncologic population. Infectious morbidity in surgical oncology remains an important subject for continued clinical investigation.

scholarly journals The Expression of Bcl-x Is Downregulated During Differentiation of Human Hematopoietic Progenitor Cells Along the Granulocyte But Not the Monocyte/Macrophage Lineage

Blood ◽  
1997 ◽  
Vol 89 (9) ◽  
pp. 3199-3204 ◽  
Author(s):  
Cristina Sanz ◽  
Adalberto Benito ◽  
Maite Silva ◽  
Beatriz Albella ◽  
Carlos Richard ◽  
...  
Keyword(s):  
Leukemia Cell ◽  
Leukemia Cell Line ◽  
Colony Stimulating Factor ◽  
Inhibitory Protein ◽  
Cd34 Cells ◽  
Hematopoietic Precursor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Macrophage Lineage

Abstract Expression of the apoptosis inhibitory protein Bcl-x was studied in CD34+ hematopoietic precursor cells and in the promyelocytic leukemia cell line HL-60. The enriched population of CD34+ cells (more than 95%) was cultured in the presence of stem cell factor, interleukin-3 (IL-3), IL-6, and either granulocyte colony-stimulating factor or macrophage colony-stimulating factor to achieve granulocyte or monocyte/macrophage differentiation, respectively. The expression of Bcl-x increased in the early stages of both differentiation pathways. However, by day 21 of culture mature granulocytes were Bcl-x–negative, whereas monocytes/macrophages either maintained or increased the expression of Bcl-x. The pattern of Bcl-x expression in the differentiated CD34+ cells was similar to that observed in HL-60 cells differentiated along the granulocyte lineage (induced by incubation with retinoic acid), or along the monocyte/macrophage lineage (induced by incubation with phorbol diester). The bcl-x transcript predominant in HL-60 and CD34+ cells differentiated into monocytes/macrophages was bcl-xL . Although little is yet known regarding the functional significance of Bcl-x within the granulomonocytic compartment, marked changes in the pattern of its expression, as observed during granulomonocytic differentiation of HL-60 and CD34+ cells, are likely to alter the life span of mature granulocytes and monocytes/macrophages.

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