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 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 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 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 In vitro killing of neuroblastoma cells by neutrophils derived from granulocyte colony-stimulating factor-treated cancer patients using an anti-disialoganglioside/anti-Fc gamma RI bispecific antibody

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 1124-1130 ◽  
Author(s):  
J Michon ◽  
S Moutel ◽  
J Barbet ◽  
JL Romet-Lemonne ◽  
YM Deo ◽  
...  
Keyword(s):  
Binding Site ◽  
Cancer Patients ◽  
Bispecific Antibody ◽  
Neuroblastoma Cells ◽  
Bispecific Antibodies ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Stimulating Factor

Abstract Neutrophils isolated from cancer patients treated with granulocyte colony-stimulating factor (G-CSF) express high levels of Fc gamma RI. They exhibited an efficient killing of GD2+ neuroblastoma cells in the presence of an antidisialoganglioside (GD2) mouse monoclonal antibody (MoAb; 7A4, IgG3 kappa). However, this cytotoxicity was totally blocked by human monomeric IgG. In contrast, a bispecific antibody (7A4 bis 22/MDX-260), prepared by chemically linking an F(ab') fragment of 7A4 with an F(ab') fragment of an anti-Fc gamma RI MoAb, 22, which binds outside the Fc binding domain, triggered antibody-dependent cell cytotoxicity, even when neutrophils were preincubated with human monomeric IgG. F(ab')2 22 MoAb abrogated the MDX-260 killing without affecting that of 7A4. The 3G8 MoAb, directed against the Fc gamma RIII binding site, did not inhibit the cytotoxicity induced by either antibody. Thus, these results indicate that G-CSF-activated neutrophils exert their cytotoxic effect against neuroblastoma cells through Fc gamma RI and not Fc gamma RIII, and that the saturation of the high affinity Fc gamma RI by monomeric IgG can be overcome by the use of bispecific antibodies binding epitopes outside the IgG Fc gamma RI binding site. A combined administration of such bispecific antibodies and G-CSF may be, therefore, an efficient therapeutic approach to trigger tumor lysis by cytotoxic neutrophils in vivo.

Perturbed Granulopoiesis in Mice With a Targeted Mutation in the Granulocyte Colony-Stimulating Factor Receptor Gene Associated With Severe Chronic Neutropenia

Blood ◽  
1998 ◽  
Vol 92 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Mirjam H.A. Hermans ◽  
Alister C. Ward ◽  
Claudia Antonissen ◽  
Alar Karis ◽  
Bob Löwenberg ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Embryonic Stem ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Targeted Mutation ◽  
Number Of Patients ◽  
Blood Neutrophils ◽  
Csf Levels ◽  
Stimulating Factor ◽  
Chronic Neutropenia

Mutations in the granulocyte colony-stimulating factor (G-CSF) receptor gene are found in a number of patients with severe chronic neutropenia predisposed to acute myeloid leukemia. These mutations result in the absence of the C-terminal domain of the G-CSF-R, a region which has been implicated in differentiation signaling. We generated mice with an equivalent mutation (gcsfr-▵715) by homologous and Cre-mediated recombination in embryonic stem cells. Both wt/▵715 and▵715/▵715 mice have significantly reduced numbers of blood neutrophils compared with their wt/wt littermates. However, under continuous G-CSF administration mutant mice develop peripheral neutrophil counts that significantly exceed those of wild-type littermates. These findings indicate that depending on G-CSF levels in mice, the ▵715 mutation can contribute both to neutropenia and to neutrophilia.

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