• Development and Reproduction
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• v.14 no.2
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• pp.43-50
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• 2010

Recently induced pluripotent stem (iPS) cells are derived from somatic cells by ectopic expression of several transcription factors (reprogramming factors) using technology of somatic cell reprogramming. iPS cells are able to selfrenew and differentiate into all type of cells in the body similarly to embryonic stem cells. Because iPS cells have advantages that can avoid immune rejection after transplantation and ethical issues unlike embryonic stem cells, research on iPS has made significant progress since the first report by Yamanaka in 2006. Nevertheless of many advantages of iPS, safer methods to introduce reprogramming factors into somatic cells must be developed due to safety concerns regarding viral vectors, and safer reprogramming factors to substitute the oncogenes should be evaluated for clinical application of iPS. Here we discuss the recent progress in reprogramming factors in embryonic stem cells, oocytes, and embryos, and discuss further research for finding new, more reliable and safer reprogramming factors.

• The Korean Society of Law and Medicine
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• v.16 no.1
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• pp.191-219
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• 2015

The Japanese government has announced that it would invest 30 billion yen in iPS cell research for the next 10 year, and the Japan National Assembly has made an act that supports the iPS cell research. This study analyzes 1) the current trend and application field of stem cell research under Japan; 2) recent policy and regulation change in stem cell research and its application under Japan. This treatise reviews about "Act for Promoting Regenerative Medicine", "Act for Assuring Safety of Regenerative Medicine", and "the Revision of Pharmaceutical Act under Japan. This study may serve as the fundamental reference for the improvements of legal and institutional systems with regard to regulations on the stem cell research under Korea.

• Clinical and Experimental Pediatrics
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• v.45 no.6
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• pp.732-742
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• 2002

Purpose : In order to evaluate the hypoxia-ischemia(H-I) induced neurotoxicity and the protective effect of xanthine oxidase(XO) inhibitor(allopurinol), cell number, cell viability, lactate dehydrogenase(LDH), protein synthesis(PS) and protein kinase C(PKC) activity were measured in cerebral neurons and astrocytes. Methods : Cytotoxic effect was measured by in vitro assay at 12-72 hours after H-I on cerebral neurons and astrocytes derived from 7-day old neonatal rats which were subjected to unilateral common carotid artery occlusion and exposed to hypoxic condition for 3 hours. The protective effect of XO inhibitor was examined by the cell number, cell viability, LDH and PS on 14 days after H-I with allopurinol intraperitoneal injection 15 minutes prior to H-I. In addition, the effect of allopurinol on PKC activity in hypoxic conditions was examined in neurons. Results : 72 hours from H-I, the cell numbers and viability were decreased significantly in time-dependent manner on neurons and those of astrocytes also decreased slightly, compared with control. In neonatal rats treated with H-I, the cell number, cell viability, and PS in neurons were decreased, but LDH was increased significantly compared with control. In neonatal rats pretreated with allopurinol, the cell number and viability, and PS in neurons were increased and LDH was decreased significantly compared with H-I. PKC was increased remarkably after hypoxic condition. But PKC was decreased significantly against hypoxic condition after allopurinol pretreatment. Conclusion : From these results, it is suggested that H-I is more toxic in neurons than astrocytes and allopurinol is very protective with increasing of PS, and decreasing of LDH and PKC in neurons from hypoxic-ischemic condition.

• Journal of Life Science
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• v.20 no.3
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• pp.444-452
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• 2010

The purpose of this study was to investigate the effects of treadmill exercise on $A{\beta}$-42, cytochrome c, SOD-1, 2 and Sirt-3 protein expressions in brain cytosol and mitochondria in mutant (N141I) presenilin-2 transgenic mice with Alzheimer's disease (AD). The mice were divided into four groups (Non-Tg-sedentary, n=5; Non-Tg treadmill exercise, n=5; Tg-sedentary, n=5; Tg treadmill exercise, n=5). To evaluate the neuroprotective effect of treadmill exercise, Non-Tg and Tg mice were subjected to exercise training on a treadmill for 12 wk, after which their brain cytosol and mitochondria were evaluated to determine whether any changes in the cognitive performance, $A{\beta}$-42 protein, cytochrome c protein, anti-oxidant enzymes (SOD-1, SOD-2) and Sirt-3 protein had occurred. The results indicated that treadmill exercise resulted in amelioration in cognitive deficits of Tg mice. In addition, the expressions of mitochondrial $A{\beta}$-42 and cytosolic cytochrome c protein were decreased in the brains of Tg mice after treadmill exercise, whereas antioxidant enzymes, SOD-l and SOD-2 were significantly increased in response to treadmill exercise. Furthermore, treadmill exercise significantly increased the expression of Sirt-3 protein in Non-Tg and Tg mice. Taken together, these results suggest that treadmill exercise is a simple behavioral intervention which can sufficiently improve cognitive performance and inhibit $A{\beta}$-induced oxidative stress in AD.

• Journal of Life Science
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• v.16 no.4
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• pp.632-639
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• 2006

Here we examined the expression patterns and regulation of seven photosynthesis (PS) genes (puf, puc, puhA, bchC, bchE, bchF, and bchI) in the anoxygenic photosynthetic bacterium, Rhodobacter sphaeroides, based on lacZ reporter gene assay. Expression of the tested PS genes, except puhA and bchI, were strongly induced in R. sphaeroides grown under anaerobic conditions relative to that under aerobic conditions. The puhA and bchI genes appear to form the operons together with bchFNBHLM-RSP0290 and crtA, respectively. Expression of the puf, puc, and bchCXYZ operons in R. sphaeroides grown photosynthetically was proportional to the incident light intensity, whereas that of bchFNBHLM(RSP0290-puhA) was inversely related to light intensity. Expression of bchEJG was lowest under medium-light photosynthetic conditions $(10\;W/m^2)$ and highest under high light conditions $(100\;W/m^2)$. The regulation of PS genes by the three major regulatory systems involved in oxygen- and light-sensing in R. sphaeroides is as following: puf and bchC are regulated by both the PpsR repressor and the PrrBA two-component system. The puc operon is under control of PpsR, FnrL, and PrrBA system. Expression of bchE is controlled by FnrL and PrrBA two-component system, whereas bchF is regulated exclusively by PpsR. It was demonstrated that the PpsR repressor is responsible for high-light repression of bchF and that FnrL might be involved in perceiving the cellular redox state in addition to sensing $O_2$ itself.

• Journal of Life Science
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• v.21 no.8
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• pp.1134-1141
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• 2011

Transmembrane protein 21 (TMP21) is a member of the p24 cargo protein family and has been shown to modulate ${\alpha}$-secretase-mediated A${\beta}$ production which was specifically observed in the brains of subjects with Alzheimer's disease (AD). In order to investigate whether TMP21 could affect nerve growth factor (NGF) receptor signaling pathway, the alteration of NGF receptors and their downstream proteins were detected in TMP21 over-expressed cells. CMV/hTMP21 vector used in this study was successfully expressed into TMP21 proteins in B35 cells after lipofectamin transfection. Expressed TMP21 proteins induced the down-regulation of ${\gamma}$-secretase complex components including Presenlin-1 (PS-1), PS-2, Nicastrin (NST), Pen-2 and APH-1. Also, the expression level of NGF receptor $p75^{NTR}$ and RhoA were significantly higher in CMV/hTMP21 transfectants than vehicle transfectants, while their levels returned to vehicle levels after NGF treatment. However, the phosphorylation of NGF receptor TrkA was dramtically decreased in NGF No-treated CMV/hTMP21 transfectants compared with vehicle transfectants, and increased in NGF treated CMV/hTMP21 transfectants. In TrkA downstream signaling pathway, the phosphorylation level of ERK was also decreased in CMV/hTMP21 transfectants, while the phosphorylation of Akt was increased in the same transfectants. Furthermore, NGF treatment induced the increase of phosphorylation level of Akt and ERK in CMV/hTMP21 transfectants. Therefore, these results suggested that over-expression of TMP21may simultaneously induce the up-regulation of $p75^{NTR}$/RhoA expression and the down-regulation of TrkA/ERK phosphorylation through the inhibition of ${\gamma}$-secretase activity.

• Tuberculosis and Respiratory Diseases
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• v.54 no.4
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• pp.415-428
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• 2003

Background : This study assessed the efficacy and toxicity of etoposide and carboplatin(EC) combination regimen as a first line therapy for small cell lung cancer(SCLC), and determined the efficacy and toxicity of topotecan for relapsed SCLC. Methods : One hundred and ten patients with previously untreated SCLC received etoposide($100mg/m^2$ i.v., day 1 to 3) and carboplatin($300mg/m^2$ i.v., day 1) combination chemotherapy every 3 weeks. For patients with relapsed SCLC after EC therapy, topotecan($1.5mg/m^2$) was administered for 5 consecutive days every 3 weeks. Response rate, survival and toxicity profiles were assessed. Response was recorded as CR(complete remission), PR(partial remission), SD(stable disease) and PD(progressive disease). Results : One hundred and one patients were assessed for response to EC. Overall response rate to EC was 57.4%(CR 15.8%, PR 41.6%) with a time to progression of 10.3 months(median). The toxicity was tolerable and there was no treatment-related death. Twenty one relapsed SCLC patients were treated with topotecan. Of those who relapsed within 3 months of EC(refractory relapse, RR), 15.4%(2/13) showed PR, while of those who relapsed after 3 months(sensitive relapse, SR), 25%(2/8) exhibited PR. Grade 4 neutropenia was noted in 9.5% and 14.3% showed thrombocytopenia(G4). Conclusion : The EC regimen showed a moderate response rate for SCLC with minimal toxicity. The use of topotecan for relapsed SCLC warrants further investigation.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.57-64
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• 2006

Background : Recently, there have been several studies showing that irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against extensive disease(ED) small cell lung cancer (SCLC). We conducted a phase II trial to evaluate the efficacy and toxicity of irinotecan plus cisplatin as a 1st line therapy for both limited and extensive disease SCLC. Methods : The study was conducted between January 2002 and June 2004. Patients were treated with $60mg/m^2$ irinotecan on day 1, 8, 15 and $60mg/m^2$ cisplatin on day 1, every 4 weeks. During concurrent thoracic irradiation for limited disease (LD)-SCLC patients, dose of irinotecan was reduced to $40mg/m^2$. Prophylactic cranial irradiation was given to patients with complete remission (CR) after chemotherapy. Results : Median ages of LD- and ED- SCLC were 64 years and performance status (PS) was 0-2. In patients with LD-SCLC, the response rate after concurrent chemoradiotherapy was 85% (CR, 6; Partial response [PR], 11). The median survival was 20 months (95% CIs, 15.6 to 24.4) with 1-and 2-year survival rates of 85% and 35%, respectively. Median progression free survival (PFS) was 12 months (95% CIs, 6.2 to 18.1) with 1- year PFS of 36%. In ED-SCLC, the response rate was 83.4% (CR, 1; PR, 14). The median survival was 14.5 months (95% CIs, 8.8 to 20.1) with 1-year survival rates of 75%. Median PFS was 6.3 months (95% CIs, 5.6 to 7.1) with 1- year PFS of 20%. The major toxicities (grade 3 or 4) of this regimen included leukopenia, anemia, thrombocytopenia, nausea/vomiting, and diarrhea without life threatening complication. Conclusion : Our data shows that the combination of irinotecan plus cisplatin as a first line therapy is effective and tolerable in the treatment of both LD- and ED- SCLC.