• Toxicological Research
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• v.23 no.4
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• pp.383-389
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• 2007

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study we examined the single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to $1000{\mu}g/kg$. The lethal dose ($LD_{50}$) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and $200{\mu}g/kg$ (i. v.) of rhGM-CSF did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.

• Animal cells and systems
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• v.16 no.3
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• pp.207-214
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• 2012

Burns are one of the most devastating forms of trauma and wound healing is a complex and multicellular process, which is executed and regulated by signaling networks involving numerous growth factors, cytokines, and chemokines. Recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) was specifically produced from rice cell culture through use of a recombinant technique in our laboratory. The effect of rhGM-CSF on promotion of deep second-degree burn wound healing on the back skin of a hamster model was evaluated through a randomized and double-blind trial. As macroscopic results, hamster skins of the experimental groups showed earlier recovery by new epidermis than the control groups. Immunohistochemical reactions of proliferating cell nuclear antigen and transforming growth factor-b1, which are indicators of cell proliferation, were more active in the experimental group, compared with the control group. On electron microscopy, basal cells in the epidermis of the experimental group showed oval nuclei, prominent nucleoli, numerous mitochondria and abundant free ribosomes. In addition, fibroblasts contained well-developed rough endoplasmic reticulum with dilated cisternae. Bundles of collagen fibrils filled the extracellular spaces. Particularly, ultrastructural features indicating active metabolism for regeneration of injured skin at 15 days after burn injury, including abundant euchromatin, plentiful free ribosomes, and numerous mitochondria, were observed. These findings suggest that use of rhGM-CSF could result in accelerated deep second-degree burn wound healing in animal models.

• 대한임상약리학회:학술대회논문집
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• 1994.12a
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• pp.45-45
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• 1994

• 대한두경부종양학회:학술대회논문집
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• 1994.11a
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• pp.27-27
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• 1994

• YAKHAK HOEJI
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• v.35 no.2
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• pp.135-141
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• 1991

The general pharmacological tests with rhGM-CSF indicated that it had no influences on rotarod and locomotor activity tests, but shortened hexobarbital-sleeping time at the large dose of 3 mg/kg s.c. in mice. It elicited no hypothermic, analgesic and antiepileptic action. No influences on blood pressure and respiration in rabbits were observed at the dose of 1 mg/kg, i.v. and it did neither affect the receptors of adrenaline, acetylcholine, serotonin, histamine, kinin and oxytocin, nor antagonize the actions of histamine, serotonin and oxytocin at its concentrations of 1$\times$$10^{-6}$g/ml. However, this substance was demonstrated to stimulate the formation of leucocytes in rats.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.314-314
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• 1994

대상환자는 15예로, 14예에서 평가 가능하였으며 남녀비는 8:6, 중앙연령 32세(10-70세) 이었고, 대상질환은 악성골옥종 7예, 악성임파종 2예, 위암 2예, 폐암 2예, 그리고 자궁평활근육종 1예였다. rhGM-CSF 50 $\mu\textrm{g}$/$m^2$ 3예, 100 $\mu\textrm{g}$/$m^2$ 3예, 150 $\mu\textrm{g}$/$m^2$ 3예, 250 $\mu\textrm{g}$/$m^2$ 3예, 350 $\mu\textrm{g}$/$m^2$ 3예, 500 $\mu\textrm{g}$/$m^2$ 6예, 700 $\mu\textrm{g}$/$m^2$ 용량 3예에서 시행되었다. 1주기 시행한 환자는 7예, 2주기 5예, 3주기, 4주기 각각 1예씩 있다. 부작용은 50-150 $\mu\textrm{g}$/$m^2$에서 WHO grade I의 발열, 전신쇠약, 식용부진등이 관찰되었으나 grade II이상의 부작용은 없었다. 250 $\mu\textrm{g}$/$m^2$이상의 용량에서도 grade II의 발열이 관찰되었을 뿐 다른 중증의 부작용은 관찰되지 않았다. 최고용량인 700 $\mu\textrm{g}$/$m^2$ 에서도 grade II의 발열외의 중한 부작용은 관찰되지 않았다. 각 용량에 따른 백혈구 증가율(%투여제2일/투여제1일)은 130-500% 이었다. rhGM-CSF는 투여 2-4 시간후 혈중최고치 (0.42-15.4 ng/ml)가 관찰되었으며 투여 12시간까지 0.2-2 ng/ml 의 농도가 지속되었다. 소변내 rh GM-CSF 배설량은 총투여량의 1% 미만이었다.

• 대한임상약리학회:학술대회논문집
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• 1994.12a
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• pp.44-44
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• 1994

• 대한임상약리학회:학술대회논문집
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• 1993.12a
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• pp.45-45
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• 1993

• 대한임상약리학회:학술대회논문집
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• 1992.11a
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• pp.24-24
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• 1992

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.95-95
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• 1993

대상환자는 15예로, 14예에서 평가가능하였다. 남녀비는 8:6, 중앙연령 32세(10-70세)이었고, 대상질환은 악성골육종 7예, 악성임파종 2예, 위암2예, 폐암 2예, 그리고 자궁악성육종 1예였다. CSF 50 ug/$m^2$ 3예, 100 ug/$m^2$ 3예,150 ug/$m^2$ 3예, 250 ug/$m^2$ 3예,350 ug/$m^2$ 3예, 500 ug/$m^2$ 6예, 700 ug/$m^2$ 용량 3예에서 시행되었다. 1주기 시행한 환자는 7예, 2주기 5예, 3주기, 4주기 각각 1예씩이었다. 부작용은 50-150ug/$m^2$에서 WHO grade I의 발열, 전신쇠약, 식욕부진 등이 관찰되었으나 grade II이상의 부작용은 없었다. 250 ug/$m^2$ 이상의 용량에서도 grade II의 발열이 관찰되었을 뿐 다른 중증의 부작용은 관찰되지 않았다. 최고용량인 700 ug/$m^2$ 에서도 grade II의 발열외의 중한 부작용은 관찰되지 않았다. 각 용량에 따른 백혈구 증가율(%투여제2일/투여제1일)은 130-500% 이었다. 시행된 약동태는 CSF 투여 2-4 시간 후 최고치 (0.42-15.4 ng/ml)를 나타내고 투여 12시간까지 0.2-2 ng/ml의 농도로 지속되었다. 소변내 CSF 배설량은 총투여량의 1% 미만이었다. CSF중화항체는 전예에서 검출되지 않았다.