Recombinant human granulocyte-macrophage colony-stimulating factor as an adjunct to conventional-dose ifosfamide-based chemotherapy for patients with advanced or relapsed germ cell tumors: a randomized trial.

1995 ◽  
Vol 13 (1) ◽  
pp. 79-86 ◽  
Author(s):  
D F Bajorin ◽  
C R Nichols ◽  
H J Schmoll ◽  
P W Kantoff ◽  
C Bokemeyer ◽  
...  
Keyword(s):  
Growth Factor ◽  
Germ Cell ◽  
Germ Cell Tumors ◽  
Infectious Complications ◽  
Colony Stimulating Factor ◽  
Routine Administration ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
The Impact ◽  
Stimulating Factor

PURPOSE Ifosfamide-containing therapy with cisplatin plus either etoposide (VIP) or vinblastine (VeIP) can cure of patients with relapsed germ cell tumors (GCTs), but results in substantial myelotoxicity. This study sought to assess the impact of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the severity of neutropenia and incidence of infectious complications in patients who receive ifosfamide-based chemotherapy for GCT. PATIENTS AND METHODS One hundred and four assessable GCT patients from 20 centers were randomized to receive rhGM-CSF with either cycles 1 and 2 or cycles 3 and 4 of chemotherapy. Standard doses of VIP or VeIP were used. Efficacy data were analyzed using a parallel design for cycles 1 and 2 before the crossover. RESULTS Fewer clinically relevant infections occurred in rhGM-CSF patients (13 of 55, 24%) versus observation patients (22 of 49, 45%) in cycle 1 (P = .01). Decreases were observed in infections during neutropenia (22% v 43%, P = .03), infections requiring intravenous antibiotics (20% v 43%, P = .01), and any infection irrespective of severity (29% v 55%, P = .01) in cycle 1. However, there were no significant differences among the treatment arms in cycle 2 in the proportion of clinically relevant infections (P = .23), infections associated with neutropenia (P = .11), infections requiring antibiotics (P = .22), or any infection (P = .65). rhGM-CSF was discontinued in 14% of cycles because of toxicity related to the growth factor. CONCLUSION rhGM-CSF reduced the incidence of infections in the first cycle of chemotherapy, but no benefit beyond the initial chemotherapy cycle was evident. Based on the limited clinical impact and the high incidence of rhGM-CSF-related toxicity that required growth factor discontinuation, the routine administration of rhGM-CSF to prevent neutropenia and infection after ifosfamide-based chemotherapy for GCT patients is not recommended.

Macrophage Colony-Stimulating Factor as a Marker for Malignant Germ Cell Tumors of the Ovary

1998 ◽  
Vol 68 (1) ◽  
pp. 35-37 ◽  
Author(s):  
Mitsuaki Suzuki ◽  
Hiroshi Kobayashi ◽  
Michitaka Ohwada ◽  
Toshihiko Terao ◽  
Ikuo Sato
Keyword(s):  
Germ Cell ◽  
Germ Cell Tumors ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Malignant Germ Cell Tumors ◽  
Stimulating Factor

Regulation of macrophage colony-stimulating factor in liver fat-storing cells by peptide growth factors

1992 ◽  
Vol 262 (4) ◽  
pp. C876-C881 ◽  
Author(s):  
M. Pinzani ◽  
H. E. Abboud ◽  
L. Gesualdo ◽  
S. L. Abboud
Keyword(s):  
Growth Factor ◽  
Constitutive Expression ◽  
Liver Fat ◽  
Northern Analysis ◽  
Mrna Levels ◽  
Colony Stimulating Factor ◽  
Term Survival ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Macrophage colony-stimulating factor (M-CSF) selectively promotes mononuclear phagocyte survival, proliferation, and differentiation. The production of this factor within the liver may be necessary to support the relatively long-term survival of circulating monocytes as they migrate into tissues and differentiate into macrophages. We studied the constitutive expression and the effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) on M-CSF mRNA levels and secretion of M-CSF in murine liver fat-storing cells (FSC), vascular pericytes likely involved in the development of liver fibrosis. By Northern analysis, using a murine M-CSF cDNA, FSC constitutively express two major transcripts of 4.4 and 2.2 kb, similar to those detected in mouse L cells, used as a control. Exposure to 10 ng/ml PDGF or bFGF increased M-CSF mRNA levels. Peak effects were observed at 3 and 6 h for PDGF and bFGF, respectively, returning to baseline levels by 12 h. Under basal conditions, detectable amounts of M-CSF, measured by radioimmunoassay, were found in cell supernatants conditioned for 8 and 24 h. PDGF and bFGF markedly stimulated the release of M-CSF as early as 8 h, an effect persisting for at least 24 h. These findings suggest that liver FSC release M-CSF upon stimulation by PDGF and bFGF and may contribute to the activation of resident or infiltrating cells in inflammatory liver diseases.

scholarly journals Vascular Smooth Muscle Cell–Derived Transforming Growth Factor-β Promotes Maturation of Activated, Neointima Lesion–Like Macrophages

2014 ◽  
Vol 34 (4) ◽  
pp. 877-886 ◽  
Author(s):  
Allison Ostriker ◽  
Henrick N. Horita ◽  
Joanna Poczobutt ◽  
Mary C.M. Weiser-Evans ◽  
Raphael A. Nemenoff
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Macrophage Activation ◽  
Transforming Growth Factor ◽  
Conditioned Media ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Objective— To define the contribution of vascular smooth muscle cell (SMC)–derived factors to macrophage phenotypic modulation in the setting of vascular injury. Approach and Results— By flow cytometry, macrophages (M4) were the predominant myeloid cell type recruited to wire-injured femoral arteries, in mouse, compared with neutrophils or eosinophils. Recruited macrophages from injured vessels exhibited a distinct expression profile relative to circulating mononuclear cells (peripheral blood monocytes; increased: interleukin-6, interleukin-10, interleukin-12b, CC chemokine receptor [CCR]3, CCR7, tumor necrosis factor-α, inducible nitric oxide synthase, arginase 1; decreased: interleukin-12a, matrix metalloproteinase [MMP]9). This phenotype was recapitulated in vitro by maturing rat bone marrow cells in the presence of macrophage-colony stimulating factor and 20% conditioned media from cultured rat SMC (sMφ) compared with maturation in macrophage-colony stimulating factor alone (M0). Recombinant transforming growth factor (TGF)-β1 recapitulated the effect of SMC conditioned media. Macrophage maturation studies performed in the presence of a pan-TGF-β neutralizing antibody, a TGF-β receptor inhibitor, or conditioned media from TGF-β–depleted SMCs confirmed that the SMC-derived factor responsible for macrophage activation was TGF-β. Finally, the effect of SMC-mediated macrophage activation on SMC biology was assessed. SMCs cocultured with sMφ exhibited increased rates of proliferation relative to SMCs cultured alone or with M0 macrophages. Conclusions— SMC-derived TGF-β modulates the phenotype of maturing macrophages in vitro, recapitulating the phenotype found in vascular lesions in vivo. SMC-modulated macrophages induce SMC activation to a greater extent than control macrophages.

scholarly journals Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 971-979 ◽  
Author(s):  
T Tsuda ◽  
D Wong ◽  
J Dolovich ◽  
J Bienenstock ◽  
J Marshall ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Colony Stimulating Factor ◽  
Nerve Growth ◽  
Basophilic Cell ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose- dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo- CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.

scholarly journals Critical Prosurvival Roles for C/EBPβ and Insulin-Like Growth Factor I in Macrophage Tumor Cells

2004 ◽  
Vol 24 (8) ◽  
pp. 3238-3250 ◽  
Author(s):  
Jennifer Wessells ◽  
Shoshana Yakar ◽  
Peter F. Johnson
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Insulin Like Growth Factor ◽  
Colony Stimulating Factor ◽  
Factor I ◽  
Survival Factor ◽  
Igf I ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

ABSTRACT One of the hallmarks of leukemic cells is their ability to proliferate and survive in the absence of exogenous growth factors (GFs). However, the molecular mechanisms used by myeloid tumor cells to escape apoptosis are not fully understood. Here we report that Myc/Raf-transformed macrophages require the transcription factor C/EBPβ to prevent cell death. In contrast to wild-type cells, C/EBPβ−/− macrophages were completely dependent on macrophage colony-stimulating factor or granulocyte-macrophage colony-stimulating factor for survival and displayed impaired tumorigenicity in vivo. Microarray analysis revealed that C/EBPβ-deficient cells expressed significantly reduced levels of the prosurvival factor insulin-like growth factor I (IGF-I). Overexpression of C/EBPβ stimulated transcription from the IGF-I promoter, indicating that IGF-I is a direct transcriptional target of C/EBPβ. Serological neutralization of IGF-I in C/EBPβ+/+ tumor cell cultures induced apoptosis, showing that IGF-I functions as an autocrine survival factor in these cells. Macrophage tumor cells derived from IGF-I−/− mice were GF dependent, similar to C/EBPβ-deficient cells. Forced expression of either C/EBPβ or IGF-I in C/EBPβ−/− bone marrow cells restored Myc/Raf-induced transformation and permitted neoplastic growth without exogenous GFs. Thus, our findings demonstrate that C/EBPβ is essential for oncogenic transformation of macrophages and functions at least in part by regulating expression of the survival factor IGF-I.

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