Therapeutic administration of recombinant human granulocyte colony-stimulating factor accelerates hemopoietic regeneration and enhances survival in a murine model of radiation-induced myelosuppression

1990 ◽  
Vol 8 (2) ◽  
pp. 107-122 ◽  
Author(s):  
Myra L. Patchen ◽  
Thomas J. Macvittie ◽  
Brian D. Solberg ◽  
Larry M. Souza
Keyword(s):  
Murine Model ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Radiation Induced ◽  
Stimulating Factor ◽  
Therapeutic Administration

scholarly journals Granulocyte Colony-Stimulating Factor Treatment Before Radiotherapy Protects Against Radiation-Induced Liver Disease in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Isalira Peroba Rezende Ramos ◽  
Marlon Lemos Dias ◽  
Alan Cesar Nunes De Moraes ◽  
Fernanda Guimarães Meireles Ferreira ◽  
Sergio Augusto Lopes Souza ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Disease Model ◽  
Survival Rates ◽  
Radiotherapy Planning ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Before And After ◽  
Radiation Induced ◽  
Stimulating Factor

Radiation-induced liver disease (RILD) remains a major problem resulting from radiotherapy. In this scenario, immunotherapy with granulocyte colony-stimulating factor (G-CSF) arises as an attractive approach that might improve the injured liver. Here, we investigated G-CSF administration’s impact before and after liver irradiation exposure using an association of alcohol consumption and local irradiation to induce liver disease model in C57BL/6 mice. Male and female mice were submitted to a previous alcohol-induced liver injury protocol with water containing 5% alcohol for 90 days. Then, the animals were treated with G-CSF (100 μg/kg/d) for 3 days before or after liver irradiation (18 Gy). At days 7, 30, and 60 post-radiation, non-invasive liver images were acquired by ultrasonography, magnetic resonance, and computed tomography. Biochemical and histological evaluations were performed to verify whether G-CSF could prevent liver tissue damage or reverse the acute liver injury. Our data showed that the treatment with G-CSF before irradiation effectively improved morphofunctional parameters caused by RILD, restoring histological arrangement, promoting liver regeneration, preserving normal organelles distribution, and glycogen granules. The amount of OV-6 and F4/80-positive cells increased, and α-SMA positive cells’ presence was normalized. Additionally, prior G-CSF administration preserved serum biochemical parameters and increased the survival rates (100%). On the other hand, after irradiation, the treatment showed a slight improvement in survival rates (79%) and did not ameliorate RILD. Overall, our data suggest that G-CSF administration before radiation might be an immunotherapeutic alternative to radiotherapy planning to avoid RILD.

scholarly journals Actions of colony-stimulating factor 3 on the maturing oocyte and developing embryo in cattle

2020 ◽  
Vol 98 (4) ◽  
Author(s):  
Elizabeth A Jannaman ◽  
Yao Xiao ◽  
Peter J Hansen
Keyword(s):  
Transcript Abundance ◽  
Blastocyst Stage ◽  
Bovine Oocyte ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Serum Free Medium ◽  
Rt Pcr ◽  
Oocyte Competence ◽  
Stimulating Factor ◽  
Therapeutic Administration

Abstract Colony-stimulating factor 3 (CSF3), also known as granulocyte colony-stimulating factor, is used to reduce the incidence of mastitis in cattle. Here, we tested whether recombinant bovine CSF3 at 1, 10, or 100 ng/mL acts on the bovine oocyte during maturation or on the developing embryo to modify competence for development and characteristics of the resultant blastocyst. For experiment 1, oocytes were matured with or without CSF3. The resultant embryos were cultured in a serum-free medium for 7.5 d. There was no effect of CSF3 on cleavage or on development to the blastocyst stage except that 100 ng/mL reduced the percent of putative zygotes and cleaved embryos becoming blastocysts. Expression of transcripts for 93 genes in blastocysts was evaluated by RT-PCR using the Fluidigm platform. Transcript abundance was affected by one or more concentrations of CSF3 for four genes only (CYP11A1, NOTCH2, RAC1, and YAP1). For experiment 2, cumulus-oocyte complexes (COC) were fertilized with either X- or Y-sorted semen. Putative zygotes were cultured in medium containing CSF3 treatments added at the beginning of culture. There was no effect of CSF3, sex, or the interaction on the percent of putative zygotes that cleaved or on the percent of putative zygotes or cleaved embryos becoming a blastocyst. For experiment 3, CSF3 was added from day 4 to 7.5 of development. There was no effect of CSF3 on development to the blastocyst stage. Transcript abundance of 10 genes was increased by 100 ng/mL CSF3, including markers of epiblast (NANOG, SOX2), hypoblast (ALPL, FN1, KDM2B, and PDGFRA), epiblast and hypoblast (HNF4A) and trophectoderm (TJAP1). Results are indicative that concentrations of CSF3 higher than typical after therapeutic administration can reduce oocyte competence and act on the embryo to affect characteristics of the blastocyst.

scholarly journals Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamide-treated primates.

1987 ◽  
Vol 165 (4) ◽  
pp. 941-948 ◽  
Author(s):  
K Welte ◽  
M A Bonilla ◽  
A P Gillio ◽  
T C Boone ◽  
G K Potter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
White Blood Cells ◽  
Chemotherapeutic Agents ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Radiation Induced ◽  
Peripheral White Blood Cells ◽  
In Vivo Effects ◽  
Stimulating Factor

We examined the in vivo effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in primates (cynomolgus monkeys) treated with subcutaneous doses of rhG-CSF for 14-28 d. A dose-dependent increase in the peripheral white blood cells (WBC) was seen, reaching a plateau after 1 wk of rhG-CSF treatment. The elevation of WBC was due to an increase in the absolute neutrophil count. These results demonstrate that rhG-CSF is a potent granulopoietic growth and differentiation factor in vivo. In cyclophosphamide (CY)-induced myelosuppression, rhG-CSF was able to shorten the time period of WBC recovery in two treated monkeys to 1 wk, as compared to more than 4 wk for the control monkey. Its ability to significantly shorten the period of chemotherapy-induced bone marrow hypoplasia may allow clinicians to increase the frequency or dosage of chemotherapeutic agents. In addition, the increase in absolute numbers of functionally active neutrophils may have a profound effect in the rate and severity of neutropenia-related sepsis. Furthermore, the activities reported here indicate a potential role for rhG-CSF in the treatment of patients with myelodysplastic syndrome, congenital agranulocytosis, radiation-induced myelosuppression, and bone marrow transplantation.

scholarly journals Not all hematopoietic growth factors are created equal: should we gain information for their use with immunotherapy?

2021 ◽  
Vol 9 (8) ◽  
pp. e003154
Author(s):  
Paolo Bossi ◽  
Cristina Gurizzan ◽  
Luigi Lorini ◽  
Pierluigi di Mauro ◽  
Chiara Sardini ◽  
...  
Keyword(s):  
Growth Factors ◽  
The Novel ◽  
Granulocyte Colony Stimulating Factor ◽  
Negative Consequences ◽  
Colony Stimulating Factor ◽  
Hematopoietic Growth Factors ◽  
Chemotherapy Induced Neutropenia ◽  
Stimulating Factor ◽  
Therapeutic Administration ◽  
Novel Therapeutic

Myeloid growth factors, either granulocyte colony-stimulating factor (CSF) or granulocyte-macrophage CSF, are widely used to reduce the incidence and severity of chemotherapy-induced neutropenia by prophylactic or therapeutic administration. However, their activity in the novel therapeutic regimens, which often rely on the association between immunotherapy and chemotherapy, has not been thoroughly characterized yet. This paper presents some of the preclinical and clinical research regarding the putative interplay between myeloid growth factors and the immune system, advocating further studies to elucidate their potential positive or negative consequences on the outcomes when administered with immunotherapeutic agents.

Reversal of radiation-induced neutropenia by granulocyte colony-stimulating factor

1992 ◽  
Vol 20 (3) ◽  
pp. 240-242 ◽  
Author(s):  
Lawrence B. Marks ◽  
Henry S. Friedman ◽  
Joanne Kurtzberg ◽  
W. Jerry Oakes ◽  
Beverly M. Hockenberger
Keyword(s):  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Radiation Induced ◽  
Stimulating Factor

scholarly journals Effect of human recombinant granulocyte colony-stimulating factor on induction of myeloid leukemias by X-irradiation in mice

Blood ◽  
1993 ◽  
Vol 82 (7) ◽  
pp. 2163-2168 ◽  
Author(s):  
Y Kawase ◽  
M Akashi ◽  
H Ohtsu ◽  
Y Aoki ◽  
A Akanuma ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Whole Body ◽  
Leukemia Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Myeloid Leukemias ◽  
Fab Classification ◽  
Radiation Induced ◽  
Stimulating Factor

Hematopoietic suppression is one of the serious problems induced by whole body irradiation. Granulocyte colony-stimulating factor (G-CSF) stimulates the progenitors of granulocytes and accelerates their recovery from bone marrow suppression induced by cytotoxic chemotherapy or radiation. On the other hand, G-CSF stimulates proliferation of myeloid leukemia cells as well as normal granulocytes in vitro. We designed a method to determine if G-CSF affects the incidence of myeloid leukemias induced by irradiation and the types of leukemias induced according to the French-American-British (FAB) classification in RFM/MsNrs mice. Administration of G-CSF (2 micrograms/d for 7 days) after a single 3-Gy irradiation significantly increased the number of peripheral blood neutrophils as compared with those in control mice. Even after discontinuation of G-CSF, both the total leukocyte and neutrophil counts increased to day 10, and their levels remained elevated until day 14. The incidence of myeloid leukemia in mice exposed to a single 3-Gy irradiation was 18.6% (38 of 204), and treatment with G-CSF did not increase the incidence (15.7% [32 of 204]). In the mice with radiation-induced leukemia, those receiving G- CSF had a mean survival time of 357 days, whereas those not receiving the factor survived for 349 days. There was no significant difference of survivals between the two groups. Most of the radiation-induced leukemias in the two groups were M1 or M2, according to the FAB classification; no characteristic difference was observed among the types of leukemias. Although G-CSF stimulated the leukemia cells in vitro, G-CSF administration after irradiation did not increase the occurrence of radiation-induced myeloid leukemias. Our results show that administration of G-CSF effectively accelerates neutrophil recovery from irradiation-induced hematopoietic injury and does not enhance the induction of myeloid leukemia in RFM/MsNrs mice by irradiation.

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