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Kim, Dong Wook,Min, Woo Sung,Han, Hyun Bok,Kim, Chun Choo,Kim, Dong Jip CATHOLIC MEDICAL CENTER 1992 Bulletin of the Clinical Research Institute Vol.20 No.2
The colony-stimulating factors (CSF) are a family of glycoprotein that regulate the proliferation and maturation of hematopoietic progenitor cells. In addition to their effects on hemopoiesis, CSFs modulate the function of fully mature cells and therefore, play an important role in regulating inflammatory responses vital to host defense. One hematopoietic glycoprotein that appears to specifically control the survival, cycle activation, proliferation and terminal maturation of this myeloid lineage if granulocyte colony-stimulating factor (G-CSF). Preclinical studies of recombinant human granulocyte (rhG-CSF) suggest that it has many potential clinical applications, including enhancing myeloid cells production and functions. But the possible role of CSF of the proliferation in myeloid leukemia is quite conflicting. The purpose of this study was to ditermine the effect of rhG-CSF on normal bone marrow cells and leukemic cell lines. For this experiment, the cells were cultured in medium with rhG-CSF 20, 25 ㎍/ml and without rhG-CSF for 28 days. Leukemic cell lines we used were REH (pre-pre B-acute lymphocytic leukemia), MOLT-3 (T-acute lymphocytic leukemia), HL-60(acute promyelocytic leukemia) and K562 (chronic myelocytic leukemia). And we observed the effects of 2.5 to 30 ㎍/ml rhG-CSF on neutrophilic chemotaxis and phagocytosis. The results were as follows; 1. There were significant proliferations of rhG-CSF 20, 25 ㎍/ml groups compared with those of corresponding control groups in normal bone marrow cell 2. In leukemic cell lines, the proliferations of rhG-CSF 20,25 ㎍/ml group compared with that of control group in K562. 3. Chemotaxis of neutrophils was significantly increased by comparing to control group and correlated with concentration of rhG-CSF. 4. Phagocytosis of neutrophils was significantly enhanced by rhG-CSF 30 ㎍/ml than control group. Phagocytic activity of neutrophil in rhG-CSF with concentreation had tendency to increse without statistical significance when compared with control groups. These findins showed that the proliferation of normal bone marrow cells was increased significantly by rhG-CSF, but not increased significantly in leukemic cell lines at high concentration. Also rhG-CSF promoted neutrophilic chemotaxis and phagocytosis. With these results, we suggest that rhG-CSF is clinically availiable to recovery of bone marrow and reducing the frequency of infection by shortening the period of granulocytopenia after intensive chemotherapy or bone marrow transplantation for the acute leukemia patients.
김지현,지초희,원진희,정해원,문종현,조규완,강병택,정동인 한국임상수의학회 2014 한국임상수의학회지 Vol.31 No.2
The present study evaluated that responses of peripheral and bone marrow depends on the frequency ofrecombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in dogs. The rhG-CSF has beenrevealed that have a beneficial effect for dogs with myelosuppression secondary to chemotherapy or radiation but therewere no studies about the frequency of administration in dogs. In this research, rhG-CSF was administrated 5 μg/kg subcutaneously for each two-dogs group as follows: (1) every day for trial, (2) every other day for trial, (3) everythird day for trial. The peripheral blood analysis including direct microscopic differential counts of one hundred cellswas performed every day. Bone marrow aspiration was performed before administration of rh G-CSF, on the day of0, 3, 9 and when the WBC counts were decreased within the normal range (day 12 or 13). Rh G-CSF was welltoleratedand showed no side effects in all dogs. According to the present study, 5 μg/kg administration of rhG-CSFhave cell-specific, frequency-related effect on bone marrow and peripheral blood. Furthermore, the effects of rhG-CSFadministration on bone marrow sustained during the study and prolonged at least 3 days after discontinuing of rhGCSF treatment. The present study evaluated that responses of peripheral and bone marrow depends on the frequency ofrecombinant human granulocyte colony-stimulating factor (rhG-CSF) administration in dogs. The rhG-CSF has beenrevealed that have a beneficial effect for dogs with myelosuppression secondary to chemotherapy or radiation but therewere no studies about the frequency of administration in dogs. In this research, rhG-CSF was administrated 5 μg/kg subcutaneously for each two-dogs group as follows: (1) every day for trial, (2) every other day for trial, (3) everythird day for trial. The peripheral blood analysis including direct microscopic differential counts of one hundred cellswas performed every day. Bone marrow aspiration was performed before administration of rh G-CSF, on the day of0, 3, 9 and when the WBC counts were decreased within the normal range (day 12 or 13). Rh G-CSF was welltoleratedand showed no side effects in all dogs. According to the present study, 5 μg/kg administration of rhG-CSFhave cell-specific, frequency-related effect on bone marrow and peripheral blood. Furthermore, the effects of rhG-CSFadministration on bone marrow sustained during the study and prolonged at least 3 days after discontinuing of rhGCSFtreatment.
악성림프종 환자에서 복합화학요법으로 유발된 백혈구 감소증에 대한 인형 재조합 과립구 집락형성-촉진인자(rhG-CSF: Neutrogin)의 효과
박성규,전진우,기신영,유병우,김홍수,백승호,원종호,홍대식,박희숙 순천향의학연구소 1995 Journal of Soonchunhyang Medical Science Vol.1 No.1
Clinical effects of rhG-CSF were investigated in 17 patients receiving chemotherapy for non-Hodgkin's lymphoma. Patients were given G-CSF 2㎍/㎏/day after 2nd cycle chemotherapy for least 14 consecutive days, and clinical and laboratory results were compared to results of the first cycle. Treatment with G-CSF resulted in increase of mean WBC count(952.9±152.2㎜³vs 1882.4±350.4/㎜³) and neutrophil count(212.9±53.0/㎜³vs 841.5±238.0/㎜³), reduced the duration of leukocytopenic days(12.4±1.3 days vs 5.5±1.0 days, WBC count less than 4000/㎜³) and neutropenic days(4.5±0.9 days vs 2.3±0.7 days, neutrophil count less than 500/㎜³), and reduced the duration of neutropenic fever(5.8±1.1 days vs 0.9±0.5 days). The side effects of G-CSF were not so significant. These results demonstrated that G-CSF is safe and useful for the treatment of neutropenia induced by anticancer chemotherapy of non-Hodgkin's lymphoma and reducing the incidence of febrile periods and duration of antibiotic administration.
JooBuom Lee,Kyungsun Lee,Keunbum Choe,Hyunseob Jung,Hyunseok Cho,Kiseok Choi,Taegon Kim,Seojin Kim,Hyeong-Seok Lee,Mi-Jin Cha,Si-Whan Song,Chul Kyu Lee,Gie-Taek Chun 한국독성학회 2015 Toxicological Research Vol.31 No.4
TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.
Lee, JooBuom,Lee, Kyungsun,Choe, Keunbum,Jung, Hyunseob,Cho, Hyunseok,Choi, Kiseok,Kim, Taegon,Kim, Seojin,Lee, Hyeong-Seok,Cha, Mi-Jin,Song, Si-Whan,Lee, Chul Kyu,Chun, Gie-Taek Korean Society of ToxicologyKorea Environmental Mu 2015 Toxicological Research Vol.31 No.4
TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.