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rhGM-CSF(Leucogen<sup>ⓡ</sup>)의 비감염성 상처 치유 효과에 관한 연구
한승규,김병수,김애리,서재홍,최철원,신상원,김열홍,김우경,김준석,Han, Seung Kyu,Kim, Byung Soo,Kim, Aeree,Seo, Jae Hong,Choi, Chul Won,Shin, Sang Won,Kim, Yeul Hong,Kim, Woo Kyung,Kim, Jun Suk 대한면역학회 2001 Immune Network Vol.1 No.1
Background: rhGM-CSF has been shown to enhance the migration and proliferation of endothelial cells and to promote keratinocyte growth. This study was tried to evaluate the effect of rhGM-CSF dressing on the uninfected wounds. Methods: Thirty Sprague-dawley white mice(250-300g) were selected in this study. The number of wound with the diameter of 5 mm, was 3 in left and 3 in right at the symmetric sites, respectively. The site of rhGM-CSF dressing was decided by a randomization. rhGM-CSF($Leucogen^{(R)}$) was diluted in the distilled water($5{\mu}g/mL$). The experimental wound group was dressed by l mL of distilled water mixed with rhGM-CSF and control wound group was dressed by l mL of distilled water. The dressing was done, every 24 hours. The criteria of comparison were the duration of wound healing duration, histologic findings and the bacterial culture of wound sites. Results: The duration of wound healing was $10.3{\pm}1.7days$ in experimental group and $10.2{\pm}2.8days$ in control group, without significant difference. There was no specific difference of histologic findings between both groups. The pathogen was not found, at all. Conclusion: It seems to be that rhGM-CSF has no prominent effect on the uninfected wound healing in the mice without immune suppression.
시리안 햄스터 볼주머니 점막에 대한 recombinant human Granulocyte Macrophge-Colony Stimulating Factor의 효과
조선아(Sun-A Cho),박종환(Jong-Hwan Park),석승혁(Seung-Hyeok Seok),전재현(Jae-Hyeon Juhn),김성진(Seong-Jin Kim),지희정(Hyi-Jeong Ji),추연성(Youn-Sung Choo),박재학(Jae-Hak Park) 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.3
This study was aimed to identify the effect of recombinant human Granulocyte Macrophge-Colony Stimulating Factor (rhGM-CSF) on the mucous membrane of hamster cheek pouch. After anesthetized with ketamine and xylazine, hamsters were topically administered with rhGM-CSF at the dose of 0.4 ㎍/㎖, 2㎍/㎖, 10 ㎍/㎖, 50 ㎍/㎖, and 250 ㎍/㎖ for 14 days. The thickness of the sratum basale, stratum spinosum, and stratum corneum was determined in each group. And cell proliferation in mucosal layer was also evaluated by immunohistochemistry. The thickness of stratum spinosum increased in the group administered with rhGM-CSF of 0.4 ㎍/㎖ (1.75㎛±0.69), but decreased in the groups administered with that of over 2 ㎍/㎖. In immunohistochemistry, high Ki-67 positive response was also detected in the hamster administered with rhGM-CSF of 0.4㎍/㎖. This study showed that rhGM-CSF induces the epithelial proliferation at concentration of 0.4㎍/㎖.
허시현,김완종,한규범,이영준,김지현,윤광호,한만덕,신길상 한국통합생물학회 2012 Animal cells and systems Vol.16 No.3
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.
Heo, Si-Hyun,Han, Kyu-Boem,Lee, Young-Jun,Kim, Ji-Hyun,Yoon, Kwang-Ho,Han, Man-Deuk,Shin, Kil-Sang,Kim, Wan-Jong The Korean Society for Integrative Biology 2012 Animal cells and systems Vol.16 No.3
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.
기본 항암 화학요법에 불응 하는 전이성 이행상피 세포암 환자에서 시행한 증량 M-VAC 항암 화학 요법 2례
조용현,권병산,이지열,김세웅,이충범,윤문수 대한화학요법학회 1997 대한화학요법학회지 Vol.15 No.3
1. 목적 전이성 방광 이행 상피 세포암의 경우에 시행될 수 있는 몇가지 전신적 항암 요법 중 M-VAC 병용 투여가 가장 인정받고 있는 항암 요법이긴 하나 일시적 반응 후 재발시 즉 M-VAC 병용투여에 불응하는 경우 증상 완화 요법(palliative therapy) 이외에 다른 치료 방법이 없었다. 저자들은 M-VAC 병용 요법에 불응하는 전이성 방광 이행상피 세포암 환자 2례에서 기존 M-VAC 항암 화학 요법보다 항암제 투여량을 증량한 M-VAC 항암 요법을 시행하였다. 2. 방법 기존 M-VAC 항암 화학요법용량(Methotrexate 30㎎/㎡, Vinblastine 3㎎/㎡, Adriamysin 30㎎/㎡, Cisplatin 70㎎/㎡)보다 항암제 용량을 증량하고(Methotrexate 30㎎/㎡, Vinblastine 4㎎/㎡, Adriamycin 60㎎/㎡, Cisplatin 100㎎/㎡) 이로 인한 골수 저하증을 예방하기 위하여 GM-CSF를 동시에 투여하였다. 3. 결과 증례 1 환자는 중량 항암 화학 요법 1개월 후 추적검사에서 전이된 임파절이 모두 소실된 완전 관해를 보였으며 증례 2 환자는 증량 항암 요법 후 14일째 폐혈증으로 사망하였다. 4. 결론 증량 M-VAC 항암 화학 요법은 아직 시행 기간 및 증례가 많지 않아 완전 관해 기간 및 적절한 항암요법 시행 횟수의 미확립, 항암제 치료 도중의 치사율의 감소등이 문제점으로 지적되고 있으나 기존 M-VAC 항암 요법에 불응하는 전이성 방광이행 상피 세포암 환자에서 우선 고려될 수 있는 치료법으로 사료된다. Background : M-VAC(methotrexate, vinblastine. doxorclbicin, cisplatin) chemotherapy is the most common and effective treatment modality for advanced transitional bladder tumor. However, there is no effective therapy in case of the patients nith bladder tumor refractory to M-VAC chemotherapy. Methods : Two male patients mith metastatic transitional bladder tumors refractory to conventional chemotherapy with methbtrexate, vinblastine, doxorubicim, and cispiatin (M-VAC) were treated with escalate3 dose of M-VAC plus recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF). Formula of escalated M-VAC chemotherapy were 30mg/m^(2) of inethotrexate, 4mg/m^(2) of vinblastine. 60rmg/m^(2) of doxorubicm, and 10Omg/m^(2) of cisplatin, and 250mg/m^(2) rhGM-CSF per day administered subcutaneously (SC) for 10 consecutive days. Result : One of the treated patients mas responded with complete remission and the other one m-as dead by sepsis on post-escalated M-VAC chenctherapy 14 days. Coclusion : We believe escalated M-VAC chemotherapy may be one of the effective alternative treatment for patients with metastatic urothelial tumor refractory to conventional M-VAC chemotherapy.
효모에서 발현된 유전자 재조합 GM-CSF의 일반 약리작용
이은방(Eun Bang Lee),김운자(Oon Ja Kim) 대한약학회 1991 약학회지 Vol.35 No.2
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 3mg/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 1mg/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 1X10-6g/ml. However, this substance was demonstrated to stimulate the formation of leucocytes in rats.