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( Hye Jung Chang ),( Jae Hoon Lee ),( Young Rok Do ),( Sung Hwa Bae ),( Jung Lim Lee ),( Seung Hyun Nam ),( Sung Soo Yoon ),( Soo Mee Bang1 ) 대한내과학회 2011 The Korean Journal of Internal Medicine Vol.26 No.4
Background/Aims: The clinical efficacy and safety of a three-drug combination of melphalan, prednisone, and thalidomide were assessed in patients with multiple myeloma who were not candidates for high-dose therapy as a firstline treatment. Because the side effects of thalidomide at a dose of ≥ 100 mg daily can be a barrier to effective treatment for these patients, we evaluated the efficacy and safety of a reduced dose of thalidomide, 50 mg, for non-transplant candidates. Methods: Twenty-one patients were treated in 4-week cycles, receiving 4 mg/m2 melphalan and 40 mg/m2 prednisone on days 1-7 and 50 mg thalidomide daily. The primary efficacy outcome was the overall response rate. Aspirin (100 mg daily) was also provided as prophylactic treatment for thromboembolism. Results: The overall response rate was 57.1%; a complete response was seen in 23.8% of patients, a partial response in 33.3%, and stable disease in 9.5%. After a median follow-up time of 16.1 months, the median time to progression was 11.4 months (95% confidence interval, 2.1 to 20.6); the median overall survival was not reached. Grades 3 and 4 adverse events included infection (10%), peripheral neuropathy (5%), diarrhea (5%), thrombosis (10%), and loss of consciousness (10%). Two patients discontinued treatment due to loss of consciousness and neuropathy. Conclusions: Low-dose thalidomide (50 mg) plus melphalan and prednisone is an effective combination drug therapy option for newly diagnosed myeloma patients who are ineligible for high-dose chemotherapy.
Development of a Test Method for the Evaluation of DNA Damage in Mouse Spermatogonial Stem Cells
Hye Lyun Jeon,Jung-Sun Yi,Tae Sung Kim,Youkyung Oh,Hye Jeong Lee,Minseong Lee,Jin Seok Bang,Kinarm Ko,Il Young Ahn,Kyungyuk Ko,Joohwan Kim,Hye-Kyung Park,Jong Kwon Lee,Soo Jung Sohn 한국독성학회 2017 Toxicological Research Vol.33 No.2
Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration (IC50) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.
Prevalence of Clostridium tetani isolated from cattle farms in Korea
Jin Sung Seo(Jin Sung Seo),Young Min Son(Young Min Son),Kwang-Ho Choi(Kwang-Ho Choi),Mi-Hye Hwang(Mi-Hye Hwang),Kichan Lee(Kichan Lee),Bang-Hun Hyun(Bang-Hun Hyun),Young-Ju Lee(Young-Ju Lee),Byeong Ye 한국예방수의학회 2018 한국예방수의학회 학술대회자료집 Vol.2018 No.-
Development of a Test Method for the Evaluation of DNA Damage in Mouse Spermatogonial Stem Cells
Jeon, Hye Lyun,Yi, Jung-Sun,Kim, Tae Sung,Oh, Youkyung,Lee, Hye Jeong,Lee, Minseong,Bang, Jin Seok,Ko, Kinarm,Ahn, Il Young,Ko, Kyungyuk,Kim, Joohwan,Park, Hye-Kyung,Lee, Jong Kwon,Sohn, Soo Jung Korean Society of ToxicologyKorea Environmental Mu 2017 Toxicological Research Vol.33 No.2
Although alternative test methods based on the 3Rs (Replacement, Reduction, Refinement) are being developed to replace animal testing in reproductive and developmental toxicology, they are still in an early stage. Consequently, we aimed to develop alternative test methods in male animals using mouse spermatogonial stem cells (mSSCs). Here, we modified the OECD TG 489 and optimized the in vitro comet assay in our previous study. This study aimed to verify the validity of in vitro tests involving mSSCs by comparing their results with those of in vivo tests using C57BL/6 mice by gavage. We selected hydroxyurea (HU), which is known to chemically induce male reproductive toxicity. The 50% inhibitory concentration ($IC_{50}$) value of HU was 0.9 mM, as determined by the MTT assay. In the in vitro comet assay, % tail DNA and Olive tail moment (OTM) after HU administration increased significantly, compared to the control. Annexin V, PI staining and TUNEL assays showed that HU caused apoptosis in mSSCs. In order to compare in vitro tests with in vivo tests, the same substances were administered to male C57BL/6 mice. Reproductive toxicity was observed at 25, 50, 100, and 200 mg/kg/day as measured by clinical measures of reduction in sperm motility and testicular weight. The comet assay, DCFH-DA assay, H&E staining, and TUNEL assay were also performed. The results of the test with C57BL/6 mice were similar to those with mSSCs for HU treatment. Finally, linear regression analysis showed a strong positive correlation between results of in vitro tests and those of in vivo. In conclusion, the present study is the first to demonstrate the effect of HU-induced DNA damage, ROS formation, and apoptosis in mSSCs. Further, the results of the current study suggest that mSSCs could be a useful model to predict male reproductive toxicity.