scholarly journals Granulocyte Colony Stimulating Factor I. Response to Acute Granulocytopenia

Blood ◽  
1971 ◽  
Vol 38 (5) ◽  
pp. 559-568 ◽  
Author(s):  
RICHARD K. SHADDUCK ◽  
N. G. NAGABHUSHANAM
Keyword(s):  
In Vitro Growth ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Humoral Factors ◽  
Factor I ◽  
Csf Levels ◽  
The Relationship ◽  
Increased Activity ◽  
Stimulating Factor

Abstract The in vitro growth of hemopoietic colonies, in the presence of an active colony stimulating factor (CSF), provides a useful model for evaluation of potential humoral factors controlling granulopoiesis. The present investigations were undertaken to assess the relationship between rapidly induced granulocytopenia in rats and the presence of heightened CSF activity. Sera from control animals showed virtually no activity (0-3 colonies). Significant levels of CSF (40-60 colonies) were demonstrated within 2-6 hr after rabbit antirat neutrophil serum (ANS). The increased activity corresponded with the phase of rapid neutrophil destruction. However, in animals rendered neutropenic by pretreatment with cyclophosphamide, ANS administration was also associated with a prompt rise in CSF levels; the magnitude of this response approximated that seen in animals treated with ANS alone. These results suggest that heightened CSF may accompany destruction of relatively small numbers of neutrophils. The temporal appearance of heightened CSF activity in relation to induced granulocytopenia is consistent with the concept that this factor may be a regulator of granulopoiesis.

scholarly journals Close Association between Clearance of Recombinant Human Granulocyte Colony-Stimulating Factor (G-CSF) and G-CSF Receptor on Neutrophils in Cancer Patients

1999 ◽  
Vol 43 (1) ◽  
pp. 21-24 ◽  
Author(s):  
Kenji Terashi ◽  
Mikio Oka ◽  
Shigehiro Ohdo ◽  
Taku Furukubo ◽  
Chizuko Ikeda ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Bolus Dose ◽  
Close Association ◽  
Inverse Correlation ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Csf Levels ◽  
Chemotherapy Induced Neutropenia ◽  
The Relationship ◽  
Stimulating Factor

ABSTRACT Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is used to counter chemotherapy-induced neutropenia. Our previous study showed an inverse correlation between serum rhG-CSF levels and the number of circulating neutrophils in cancer patients (H. Takatani, H. Soda, M. Fukuda, M. Watanabe, A. Kinoshita, T. Nakamura, and M. Oka, Antimicrob. Agents Chemother. 40:988–991, 1996). The aim of this study was to clarify the relationship between rhG-CSF clearance and G-CSF receptors on circulating neutrophils. In five cancer patients receiving chemotherapy, a bolus dose of rhG-CSF (5 μg/kg) was injected intravenously during defined phases of posttreatment neutropenia and neutrophilia. Serum rhG-CSF levels were measured by a chemiluminescence enzyme immunoassay and analyzed by moment analysis. G-CSF receptors on neutrophils were detected by flow cytometry with biotinylated rhG-CSF. rhG-CSF clearance was significantly higher at neutrophilia than at neutropenia (1,497 ± 132 versus 995 ± 266 ml/h; P < 0.01). The percentage of G-CSF receptor-positive neutrophils, reflecting the number of G-CSF receptors per cell, was low at neutropenia without rhG-CSF therapy (44.5% ± 22.1%) and high at neutrophilia with rhG-CSF therapy (73.0% ± 11.4%; P < 0.01). rhG-CSF clearance closely correlated with the percentage of G-CSF receptor-positive neutrophils (r 2 = 0.91; P < 0.0001) and neutrophil count (r 2 = 0.72; P < 0.005). Our results indicate that, in cancer patients receiving chemotherapy, rhG-CSF increases the number of G-CSF receptors per cell as well as circulating neutrophil counts, resulting in modulation of its own clearance.

scholarly journals Glucocorticoids Dose-Dependently Increase Plasma Levels of Granulocyte Colony Stimulating Factor in Man

1998 ◽  
Vol 83 (3) ◽  
pp. 1037-1040 ◽  
Author(s):  
Bernd Jilma ◽  
Petra Stohlawetz ◽  
Thomas Pernerstorfer ◽  
Hans-Georg Eichler ◽  
Claudia Müllner ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Low Dose ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Double Blind ◽  
Healthy Men ◽  
Gm Csf ◽  
Csf Levels ◽  
Stimulating Factor

Glucocorticoids increase neutrophil counts by decreasing the margination of neutrophils and mobilizing neutrophils from the bone marrow pool. The mechanisms for these effects however are not fully elucidated, but it has been demonstrated that dexamethasone enhances release of colony stimulating factor (G-CSF) in-vitro. We therefore hypothesized, that dexamethasone may increase plasma levels of G-CSF. A double blind, randomized, placebo-controlled, three-way cross-over trial was conducted in nine healthy men. Every subject received four identical infusions of saline, 0.04 mg/kg or 1.0 mg/kg dexamethasone during three observation periods of 48 hours each. The low dose of dexamethasone increased G-CSF levels from a baseline of 15.5 ng/L (CI: 10.6–20.4) by 240% (CI: 115–366%) at 24 hours. The high dexamethasone dose increased G-CSF levels from a baseline of 12.3 ng/L (CI: 9.7–14.9) by 871% (CI: 592–1149%) at 24 hours (P = 0.008 for all comparisons). No further increase was observed at 48 hours but the effect was less pronounced (P &lt; 0.008 and P = 0.08 for the high and the low dose of dexamethasone, respectively). Granulocyte-macrophage-CSF (GM-CSF) levels were below the assay’s detection limit of 0.36 ng/L in all subjects. In conclusion, dexamethasone dose dependently increases G-CSF levels in healthy men, an effect which may account for some of its effects on neutrophils.

scholarly journals Levels of recombinant human granulocyte colony-stimulating factor in serum are inversely correlated with circulating neutrophil counts.

1996 ◽  
Vol 40 (4) ◽  
pp. 988-991 ◽  
Author(s):  
H Takatani ◽  
H Soda ◽  
M Fukuda ◽  
M Watanabe ◽  
A Kinoshita ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Time Curve ◽  
Myelosuppressive Chemotherapy ◽  
Concentration Time ◽  
Csf Levels ◽  
Chemotherapy Induced Neutropenia ◽  
The Relationship ◽  
Stimulating Factor

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is effective in countering chemotherapy-induced neutropenia. However, serum rhG-CSF levels cannot be maintained throughout the course of rhG-CSF therapy. The drop in serum rhG-CSF levels may vary with the duration of rhG-CSF administration or with the circulating neutrophil counts. We investigated the relationship between serum G-CSF levels and circulating neutrophil counts and the pharmacokinetics of rhG-CSF for patients with lung cancer who had been treated with myelosuppressive chemotherapy and then with subcutaneous rhG-CSF (lenograstim, 2 micrograms per kg of body weight per day). Twelve patients were randomly assigned to four groups with different rhG-CSF therapy schedules. Serum G-CSF levels were measured by an enzyme immunoassay method. Serum G-CSF levels during the rhG-CSF therapy greatly exceeded endogenous G-CSF levels and were mainly due to the presence of exogenous rhG-CSF rather than increased levels of endogenous G-CSF. Despite the duration of rhG-CSF administration, serum G-CSF levels during rhG-CSF therapy were inversely correlated with circulating neutrophil counts (r2 = 0.73, P < 0.0001). The value for the area under the concentration-time curve of rhG-CSF on the day of neutrophilia was lower than that on the day of neutropenia (P < 0.05). Our results suggest that the fall in serum G-CSF levels during rhG-CSF therapy may result from increased clearance and/or decreased absorption of rhG-CSF, two processes related to circulating neutrophil counts.

scholarly journals G-CSF receptor activation of the Src kinase Lyn is mediated by Gab2 recruitment of the Shp2 phosphatase

Blood ◽  
2011 ◽  
Vol 118 (4) ◽  
pp. 1077-1086 ◽  
Author(s):  
Muneyoshi Futami ◽  
Quan-sheng Zhu ◽  
Zakary L. Whichard ◽  
Ling Xia ◽  
Yuehai Ke ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Src Kinase ◽  
Receptor Activation ◽  
Phosphorylation Sites ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
In Cells

Abstract Src activation involves the coordinated regulation of positive and negative tyrosine phosphorylation sites. The mechanism whereby receptor tyrosine kinases, cytokine receptors, and integrins activate Src is not known. Here, we demonstrate that granulocyte colony-stimulating factor (G-CSF) activates Lyn, the predominant Src kinase in myeloid cells, through Gab2-mediated recruitment of Shp2. After G-CSF stimulation, Lyn dynamically associates with Gab2 in a spatiotemporal manner. The dephosphorylation of phospho-Lyn Tyr507 was abrogated in Shp2-deficient cells transfected with the G-CSF receptor but intact in cells expressing phosphatase-defective Shp2. Auto-phosphorylation of Lyn Tyr396 was impaired in cells treated with Gab2 siRNA. The constitutively activated Shp2E76A directed the dephosphorylation of phospho-Lyn Tyr507 in vitro. Tyr507 did not undergo dephosphorylation in G-CSF–stimulated cells expressing a mutant Gab2 unable to bind Shp2. We propose that Gab2 forms a complex with Lyn and after G-CSF stimulation, Gab2 recruits Shp2, which dephosphorylates phospho-Lyn Tyr507, leading to Lyn activation.

Granulocyte-colony stimulating factor promotes invasion by human lung cancer cell lines in vitro

1996 ◽  
Vol 14 (4) ◽  
pp. 351-357 ◽  
Author(s):  
Xin-Hai Pei ◽  
Yoichi Nakanishi ◽  
Koichi Takayama ◽  
Jun Yatsunami ◽  
Feng Bai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Lung Cancer Cell ◽  
Stimulating Factor

scholarly journals Granulocyte-colony stimulating factor-producing malignant phyllodes tumor of the breast: a rare case

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Kimihisa Mizoguchi ◽  
Kazuhisa Kaneshiro ◽  
Makoto Kubo ◽  
Yoshihiko Sadakari ◽  
Yoshizo Kimura ◽  
...  
Keyword(s):  
Rare Case ◽  
Phyllodes Tumor ◽  
Left Breast ◽  
Lymph Node Biopsy ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Malignant Phyllodes Tumor ◽  
Csf Levels ◽  
Wbc Count ◽  
Stimulating Factor

Abstract Background Granulocyte-colony stimulating factor (G-CSF)-producing tumors can cause leukocytosis despite an absence of infection. G-CSF-producing tumors have been reported in various organs such as the lung, esophagus, and stomach but rarely in the breast. We report a case of G-CSF-producing malignant phyllodes tumor of the breast. Case presentation An 84-year-old woman visited our hospital complaining of a lump in her left breast without fever and pain. Laboratory tests revealed elevated white blood cell (WBC) count and G-CSF levels. A malignant tumor of the breast was diagnosed by core needle biopsy. We performed a total mastectomy and sentinel lymph node biopsy. The tumor was identified as a G-CSF-producing malignant phyllodes tumor. Within 7 days after surgery, the patient’s WBC count and G-CSF level had decreased to normal levels. She is alive without recurrence 13 months after surgery. Conclusions We encountered a rare case of G-CSF-producing malignant phyllodes tumor of the breast. PET–CT revealed diffuse accumulation of FDG in the bone. Phyllodes tumors need to be differentiated from bone metastasis, lymphoma, and leukemia. We must be careful to not mistake this type of tumor for bone marrow metastasis.

scholarly journals Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury

2009 ◽  
Vol 296 (3) ◽  
pp. H823-H832 ◽  
Author(s):  
Yoshimi Hiraumi ◽  
Eri Iwai-Kanai ◽  
Shiro Baba ◽  
Yoshihiro Yui ◽  
Yuri Kamitsuji ◽  
...  
Keyword(s):  
Diastolic Function ◽  
Early Phase ◽  
Cardiac Injury ◽  
Left Ventricular ◽  
Cardiac Mitochondria ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Cellular Fate

Although granulocyte colony-stimulating factor (G-CSF) reportedly plays a cardioprotective role in several models of cardiac injury, clinical use of this drug in cardiac patients has been controversial. Here, we tested, in vivo and in vitro, the effect of G-CSF on cardiac mitochondria, which play a key role in determining cardiac cellular fate and function. Mild stimulation of C57/BL6 mice with doxorubicin (Dox) did not induce cardiac apoptosis or fibrosis but did induce damage to mitochondrial organization of the myocardium as observed through an electron microscope. Cardiac catheterization and echocardiography revealed that Dox did not alter cardiac systolic function or left ventricular size but did reduce diastolic function, an early sign of cardiac damage. Treatment with G-CSF attenuated significantly the damage to mitochondrial organization and rescued diastolic function. In an in vitro model for rat neonatal cardiomyocytes, a subapoptotic dose of Dox induced severe mitochondrial damage, including marked swelling of the cardiac mitochondria and/or decreased mitochondrial membrane potential. These mitochondrial changes were completely blocked by pretreatment with G-CSF. In addition, G-CSF dramatically improved ATP generation, which rescued Dox-impaired mitochondrial electron transport and oxygen consumption mainly through complex IV. These findings clearly indicate that G-CSF protects cardiac mitochondria, which are key organelles in the determination of cardiac cellular fate, in the early phase of cardiac injury.

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