Ki-67 labeling index as a prognostic marker in advanced stomach cancer

Sang Hyuk Seo,Kwang Hee Kim,Sang Hoon Oh,Yunseon Choi,Ki Jung Ahn,Ji Young Lee,Sang Min Lee,박지선,Woo Gyeong Kim 대한외과학회 2019 Annals of Surgical Treatment and Research(ASRT) Vol.96 No.1

Purpose: Proliferation marker Ki-67 is widely used in cancer prognosis prediction. We tried to investigate the role of Ki-67 as a prognostic factor in stomach cancer after surgery in this study. Methods: We retrospectively evaluated 251 patients who underwent curative resection for gastric cancer from 2010 to 2015. In pathologic examination, Ki-67 labeling index was defined as the percentage of Ki-67 antigen positive cells. Prognostic significance of Ki-67 for gastric cancer was evaluated. Disease-free survival (DFS) was assessed as a primary end-point. Results: The median follow-up period was 28.0 months. Thirty-one patients (12.4%) showed Ki-67 labeling index (LI) lower than 25%. Sixty-eight patients (26.6%) showed recurrence during follow-up period. Recurrence was associated with Ki- 67 LI level (≤25%, P = 0.016), and lymph node metastasis status (P = 0.002). High Ki-67 LI level (>25%) was also related to p53 positivity (P < 0.001) and poorly cohesive type (P = 0.002). The 3-year DFS was 69.4%. Low Ki-67 LI level (≤25%) was related with low DFS (47.6% vs. 72.6%, P = 0.016). T stage (P < 0.001), N stage (P = 0.006), lymphovascular invasion (P = 0.010), and neuronal invasion (P = 0.001) also affected the DFS. In addition, T stage (P = 0.03) and Ki-67 LI (P = 0.035) were independent prognostic factors for DFS. In patients treated with adjuvant chemotherapy (n = 239, 93.4%), low Ki-67 (≤25%) was a poor prognostic factor for DFS (P = 0.013). Conclusion: Low Ki-67 LI predicts high rate of progression and low DFS of stomach cancer. Ki-67 LI can be a predictive marker in resected stomach cancer treated with surgery and adjuvant chemotherapy.

간내 담석과 동반된 간내 담도암에서의 p53과 Ki-ras의 발현

김명환,이성구,서동완,이승규,남승우,박능화,민영일,김연석,심기남,공경엽 대한소화기학회 1997 대한소화기학회지 Vol.30 No.5

Background/Aims: Hepatolithiasis or primary intrahepatic stones may be accompanied later by intrahepatic cholangiocarcinoma. This cancerous lesion is frequently associated with atypical hyperplastic epithelium that was suspected of being precancerous. To investigate the Ki-ras or p53 mutation may play a role in carcinogenesis, and to determine whether atypical hyperplastic epithelium may be precancerous, this study was performed in intrahepatic cholangiocarcinomas associated with hepatolithiasis. Methods: We examined 12 patients with intrahepatic cholangiocarcinomas associated with hepatolithiasis. Ki-ras point mutations were assessed by direct DNA sequencing. Expressions of p53 protein were immunohistochemically assessed. The overexpression of p53 and point mutation of Ki-ras were examined in normal, hyperplastic, atypical hyperplastic, and can- cerous tissues separately. Results: The expressions of p53 protein were detected in 4 (33%) of 12 cholangiocarcinomas and Ki-ras point mutations at codon 12 were found in 2 (17%) of 12 cholangiocarcinomas. In those two carcinoma cases which contained the mutant sequence of Ki-ras, the same point mutation from wild type GGT (glycine) to GAT (aspartic acid) was. found in the associated atypical hyperplastic epithelium. However, none of the normal and hyperplastic epithelium harbored Ki-ras or p53 mutations. Conclusions: The overexpression of p53 may play a part in the carcinogenesis of some intrahepatic cholangiocarcinomas associated with hepatolithiasis, whereas the role of Ki-ras mutations in those cases is dubious. However, Ki-ras point mutation at codon 12 may be responsible for either cancer or atypical hyperplastic epithelium associated with hepatolithiasis in certain cases, suggesting atypical hyperplastic epithelium may give rise to carcinoma.

개구리 皮膚의 伸張度와 X線 全身照射가 이에 미치는 影響

李基錫,朱永恩 慶北大學校 醫科大學 1975 慶北醫大誌 Vol.16 No.1

개구리皮膚의 伸張度와 X-線照射가 이에 미치는 影響을 알기 爲하여 腹部 및 背部皮膚에서 各各 矢狀 및 橫斷切片을 作成하여 길이-張力曲線中 彈性의 限界內에서 Hooke의 法則에 따르는 部位에서 Young率을 求 하고 1,000R의 X-線全身照射를 한 後 1,3,5,7 및 10日에서 各各 皮膚切片의 伸張度를 求하여 서로 比較 하였던 바 다음과 같은 結果를 얻었다. 1. 正常개구리의 腹部皮膚의 矢狀 및 橫斷切片의 Young率은 各各 4.09×10 exp (7) dyne/㎠ 및 3.99×10 exp (7) dyne/㎠이었다. 背部皮膚에서 얻은 矢狀 및 橫斷切片의 Young率은 各各 3.69×10 exp (7) dyne/㎠ 및 5.81×10 exp (7) dyne/㎠이었다. 2. X-線 全身照射를 한 群에서 腹部皮膚에서는 그 矢狀切片의 Young率은 照射 3日에서 5.38×10 exp (7) dyne/㎠으로서 가장 높고 그 後는 漸次 낮아지는 傾向을 나타내었고 照射 10日에서는 4.20×10 exp (7) dyne/㎠으로서 正常値에 가까워지는 傾向을 나타내었다. 橫斷切片에서는 照射 3日 및 5日에서 Young率이 各各 4.55×10 exp (7) dyne/㎠ 및 4.50×10 exp (7) dyne/㎠으로서 가장 높고 그後는 第10日까지 次次 낮아진듯하나 그 傾向이 矢狀切片에서 처럼 뚜렷하지 않았다. 3. X-線 全身照射로서 背部皮膚에서는 그 矢狀切片의 Young率은 照射 第3日 및 5日에서 各各 4.25×10 exp (7) dyne/㎠ 및 4.30×10 exp (7) dyne/㎠으로서 높아지는 傾向을 나타내고 그後는 漸次 낮아져서 第10日에서는 正常値와 비슷하게 되는 傾向을 나타내었다. 橫斷切片에서의 Young率도 照射後 第3日 및 5日에서 各各 6.02×10 exp (7) dyne/㎠및 6.00×10 exp (7) dyne/㎠으로서 正常値보다 若干 높은듯 하고 그後는 낮아지는 傾向을 보이나 그 程度가 矢狀切片에서 처 럼 뚜렷하지 못하였다. In an attempt to observe the changes of the distensibility of the frog skin by whole body X-irradiation, the sagittal and transverse strips were excised from the abdominal and back skin of the frog (Rana nigromaculata) following whole body X-irradiation with 1,000R. Young Modulus of the strip was calculated from the length-tension curve of each sample, and a comparison was made with the non-irradiated control group. Experiments were performed on 1,3,5,7 and 10 days after the irradiation, and the results thus obtained are summarized as follows: 1. Young Modulus of the sagittal and transverse strips of the abdominal skin of the normal frog was 4.09×10 exp (7) dyne/㎠ and 3.99×10 exp (7) dyne/㎠, respectively. Young Modulus of the back skin of the normal frog was 3.69×10 exp (7) dyne/㎠ in the sagittal strip, and 5.81×10 exp (7) dyne/㎠ in the transverse strip. 2. Young Modulus of the sagittal strip of the abdominal skin in the irradiated group was the highest (5.38×10 exp (7) dyne/㎠) on the 3rd post-irradiation day, and a tendency of gradual decrease to the normal value on the 10th post-irradiation day was observed. In the transverse strip of the abdominal skin in the irradiated group, the highest values of Young Modulus were observed on the 3rd(4.55×10 exp (7) dyne/㎠) and 5th(4.50×10 exp (7) dyne/㎠) post-irradiation day, and a tendency of gradual decrease till 10th day was observed, but the tendency was not as prominent as in the sagittal strip. 3. A tendency of the elevated values of Young Modulus on the 3rd(4.25×10 exp (7) dyne/㎠) and 5th(4.30×10 exp (7) dyne/㎠) post-irradiation day with the decreasing values to the normal value on the 10th day was observed in the sagittal strip of the back skin of the irradiated frog. In the transverse strip of the irradiated frog, Young Modulus showed a slight increase on the 3rd(6.02×10 exp (7) dyne/㎠) and 5th(6.00×10 exp (7) dyne/㎠) day after the irradiation, but a tendency of decrease was observed thereafter.

촉매를 이용한 이산화탄소 고정화 및 고리형 카보네이트 합성반응에 대한 계산화학적 해석

안혜영(Hye Young An),김민경(Min-Kyung Kim),정희철(Hui Cheol Jeong),엄기헌(Ki Heon Eom),원용선(Yong Sun Won) 한국청정기술학회 2016 청정기술 Vol.22 No.1

본 연구에서는 이론화학 또는 분자모델링이라 불리는 계산화학을 기존에 연구된 촉매반응 실험결과를 해석하는 데 접목시켜 보았다. 온실효과의 주범인 이산화탄소를 에폭사이드와 반응을 통해 고정화하고 카보네이트를 생성하는 반응을 선택하였는데 이 반응은 활성화 에너지(55~59 kcal/mol)가 높아 촉매의 사용이 불가피하다. 많은 기존 연구들 중에 ZIF-90/ionic liquid immobilized ZIF-90 (IL-ZIF-90), polystyrene-supported quaternized ammonium salt, KI/KI-glycine, dimethylethanolamine (DMEA)를 촉매로 사용한 경우에 대해 반응의 각 단계를 계산하여 반응의 경로를 예측하고 단계별로 구한 에너지를 바탕으로 에너지도를 구성함으로써 실험결과를 열역학적으로 해석하였다. ZIF-90/IL-ZIF-90과 KI/KI-glycine의 경우는 실험적으로 후자들이 상대적으로 높은 수율을 얻었는데 계산 결과 활성화에너지가 낮아진 이유가 아니라 전자들의 경우 반응 중간체가 높은 에너지를 가져 반응물로 되돌아가는 역반응에 의해 정반응의 진행이 방해를 받은 것으로 밝혀졌다. DMEA를 촉매로 사용하였을 경우는 활성화 에너지를 ~42 kcal/mol로 낮춰줌으로써 금속이나 할로겐염 없이도 촉매의 활성이 잘 일어남을 증명하였다. 폴리스티렌(polystyrene)으로 지지된 quaternized 암모늄염 촉매의 경우 클러스터 가정을 사용하여 계산을 진행하였으며 암모늄염의 -NH기와 에폭사이드의 O 원자 사이의 상호작용의 가능성을 확인할 수 있는 반응경로를 제시하였다. In this study, a computational chemistry methodology called as molecular modeling was been applied to explain several experiment results mechanistically. The reaction chosen for this study was to remove carbon dioxide, known as a primary greenhouse gas, by an epoxide via the carbon dioxide fixation to produce carbonates. This reaction inherently needs the use of catalysts because it has a significantly high activation barrier (55~59 kcal/mol). Among various types of catalysts, we studied in zeolitic imidazolate framework 90 (ZIF-90)/ionic liquid immobilized ZIF-90 (IL-ZIF-90), polystyrene-supported quaternized ammonium salt, KI/KI-glycine, and dimethylethanolamine (DMEA). First, probable reaction pathways were proposed based on calculated energetics by computational chemistry. The energetics was then used for the thermodynamic interpretation on the activity of catalysts. In the case of ZIF-90/IL-ZIF-90 and KI/KI-glycine, IL-ZIF-90 and KI-glycine showed better yields compared to their counterparts. The calculation proposed interesting results that it is not from the lowering of activation energy but from the unstable intermediates of ZIF-90 and KI-glycine. For DMEA, the calculated activation energy was ~42 kcal/mol, much lower than that of the non-catalytic reaction. A possible reaction pathway was located to confirm the interaction between -NH group from ammonium and oxygen from epoxide for polystyrene-supported quaternized ammonium salt.

Comparison of trophic factors changes in the hippocampal CA1 region between the young and adult gerbil induced by transient cerebral ischemia.

Yan, Bing Chun,Park, Joon Ha,Kim, Sung Koo,Choi, Jung Hoon,Lee, Choong Hyun,Yoo, Ki-Yeon,Kwon, Young-Geun,Kim, Young-Myeong,Kim, Jong-Dai,Won, Moo-Ho Kluwer Academic/Plenum Publishers 2012 Cellular and molecular neurobiology Vol.32 No.8

<P>In the present study, we investigated neuronal death/damage in the gerbil hippocampal CA1 region (CA1) and compared changes in some trophic factors, such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF), in the CA1 between the adult and young gerbils after 5 min of transient cerebral ischemia. Most of pyramidal neurons (89%) were damaged 4 days after ischemia-reperfusion (I-R) in the adult; however, in the young, about 59% of pyramidal neurons were damaged 7 days after I-R. The immunoreactivity and levels of BDNF and VEGF, not GDNF, in the CA1 of the normal young were lower than those in the normal adult. Four days after I-R in the adult group, the immunoreactivity and levels of BDNF and VEGF were distinctively decreased, and the immunoreactivity and level of GDNF were increased. However, in the young group, all of their immunoreactivities and levels were much higher than those in the normal young group. From 7 days after I-R, all the immunoreactivities and levels were apparently decreased compared to those of the normal adult and young. In brief, we confirmed our recent finding: more delayed and less neuronal death occurred in the young following I-R, and we newly found that the immunoreactivities of trophic factors, such as BDNF, GDNF, and VEGF, in the stratum pyramidale of the CA1 in the young gerbil were much higher than those in the adult gerbil 4 days after transient cerebral ischemia.</P>

수종의 피부종양에서 Proliferating Cell Nuclear Antigen과 Ki - 67 의 표현에 관한 비교 연구

황선욱(Sun Wook Hwang),원영호(Young Ho Won),전인기(Inn Ki Chun),박창수(Chang Soo Park) 대한피부과학회 1995 大韓皮膚科學會誌 Vol.33 No.3

Background : Both PCNA and Ki-67 have been used as marker for cellular proliferation. The drawback of Ki-67 antibody in immunohistochemistry was that it can be labelled only on fresh tissue, however, MIB1 is a newly developed Ki-67 antiboc which can be labelled on formalin-fixed tissue. Objective : The purpase of the present study is to compir the stainability of the Ki-67 antibody with that of the ICNA antibody on formalin-fixed, para fin embedded tissues. Methods : Using MIE1, the newly developed Ki-67 antibody and PC10(PCNA antibody), speci mens of squamous cell carcinoma(SCC), Bowens disease(BL), actinic keratosis(AK) and basal cell epithelioma(BCE) were stained by one hour immunocytial, mistry using a Microprobe immuno/DNA stainer. Results : The labelling indices (LI) of MIB1 were 82.6%, 37.4%, 38.3% & 81.1% respectively in SCC, BD, AK & BC, while the LI of PC10 were 77.69%, 26.6% & 64.4%. The labelled cells of both antibodies differed in distribution patterns on turmor tissues. Conclusion : MIBI cain be used to be an alternative m.rl r for proliferating cells. MIBI PC10, when used together, will be mutually compensatory the study of proliferating cell kinetics. (Kor J Dermatol 1995;33(3): 453-458)

노화가 인체 중간엽 줄기세포로부터 조골세포로의 증식 및 분화에 미치는 영향

백기현,태현정,오기원,이원영,조정기,권순용,강무일,차봉연,이광우,손호영,강성구,김춘추 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.3

연구배경: 일반적으로 골다공증과 연관된 위험인자로는 연령, 폐경, 약물, 불충분한 칼슘섭취, 만성질환 및 운동부족 등이 있는데, 특히 노화가 진행할수록 골밀도가 감소하는 것은 잘 알려져 있다. 노화와 관련하여 진행되는 골소실은 조골세포 및 전구조골세포의 기능적 결핍에 의한 골형성의 감소가 주요한 요인으로 여겨지고 있다. 그 동안 연령이 조골모 세포의 양과 조골모 세포로부터 성숙조골세포로의 분화 및 증식에 미치는 영향에 대한 일부 보고들이 있었으나 아직 일치된 견해는 없는 형편이다. 방법: 다양한 연령의 사람으로부터 골수를 채취, 중간엽 줄기세포가 포함된 단핵세포를 분리한 후 조골세포로 분화하기 좋은 조건하에서 배양하였다. 대상군은다시 젊은군과 노령군으로 구분하여 다양한 변수를 비교 분석하였다. 일차배양에서는 CFU-F를 계수하여 골수내 중간엽 줄기세포의 수를 추산하였고, 칼슘측정을 통하여 기질의 무기화 정도를 비교하였다. 계대배양후 이차배양에서는 시기별로 알카리성 포스파타제 활성도를 측정하고 오스테오칼신 mRNA의 발현을 관찰하여 젊은군과 노령군 사이의 증식능 차이를 비교하였다. 또한 이차배양 시기별로 MTT 측정을 하여 양군간에 증식능 차이가 있는지 알아보았다. 결과: 1. 일차배양 15일째에 평균 CFU-F의 수는 젊은군에서 유의하게 많았다(젊은군 148.3±28.9, 노령군 54.3±9.1, p=0.02). CFU-F의 평균면적은 젊은군에서 넓은 경향을 보였으나 통계적으로 유의하지는 않았다. 2. 일차배양 17일 경과 후 양군간에 기질 칼슘 침착정도는 유의한 차이를 보이지 않았다(젊은군 103.6±50.6, 노령군: 114.0±56.5, p=NS). 3. 이차배양 10일째에 젊은군에서 알카리성 포스파타제 활성도가 고령군에 비해 유의하게 높았다(젊은군: 935.5±115.0 U/mg, 노령군: 578.4±115.7U/mg,p.0.05). 고령군에서는 시간 경과에 따른 변화가 미약했으며 전반적으로 알카리성 포스파타제의 활성도가 젊은군에 비해 낮았다. 4. 이차배양도중 오스테오칼신 mRNA의 발현은 배양시기별로 젊은군에 비해 고령군에서 더 낮은 경향을 관찰할 수 있었다. 5. 이차배양 10일과 15일에 젊은군에서 노령군보다세포증식이 유의하게 증가된 양상을 보였다(10앓 젊은군 0.73±0.05, 노령군 0.58±0.04, p=0.05, 15일; 젊은군 0.80±0.05, 노령군 0.70±0.03, p=0.05).결론: 이상의 연구에서 저자들은 노령군에서 젊은군보다 골수 내 중간엽줄기세포의 수가 적고, 노령군에서 유래한 전구조골세포의 성숙조골세포로의 증식 및 분화가 젊은군 보다 감소해 있는 것을 관찰할 수 있었다. Background: Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFL-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. Methods: Bone marrow was obtained from the iliac crest of young (n=6, 27.2±8.6 years old) and old (n= 10, 57.4k6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcin expression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. Results: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3±28.9, old: 54.3±9.1, p=0.02) and the mean size of CFL-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6±50.6, old: 114.0±56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5±115.OU/mg, old: 578.4±115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. Conclusion: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging (J Kor SOC Endocrinol 18:296-305, 2003).

The oncoprotein, gankyrin, is up-regulated in middle ear cholesteatoma

Kim, Ki Hyun,Lim, Hye Jin,Kim, Yeon Ju,Kim, Seung Won,Kim, Young Sun,Tian, Chunjie,Park, Keehyun,Park, Tae Jun,Choung, Yun-Hoon Scandinavian University Press 2014 Acta oto-laryngologica Vol.134 No.3

<P><I>Conclusion:</I> Gankyrin seems to be a better biomarker for cholesteatoma compared with Ki-67. <I>Objective:</I> Gankyrin is an oncoprotein, and occurs in cancers but not in benign diseases. The goal of this study was to compare expression of gankyrin, p53, and a proliferation marker (Ki-67) in cholesteatoma and retroauricular skin (RAS), and to evaluate their significance as clinical parameters. <I>Methods:</I> The levels of expression of gankyrin, Ki-67, and p53 in 10 cholesteatoma and 10 paired samples of normal RAS were evaluated by immunohistochemical staining and Western blot. The results were compared with clinical profiles to investigate a correlation. <I>Results:</I> The expression of gankyrin, Ki-67, and p53 proteins was observed in both basal and suprabasal layers of cholesteatoma. The intensity of gankyrin expression was ‘positive’ in two cases (20%) and ‘strongly positive’ in eight cases (80%); p53 expression in the suprabasal layer was ‘positive’ in 70% of cases; and the Ki-67 staining was ‘focal’ in 80% of cases. In RAS, these proteins were expressed dominantly in the basal layer. Western blot analysis showed that the gankyrin band was more intense in cholesteatoma than in RAS for three of four cases (<I>p</I> < 0.05). However, there was no significant difference in the expression of gankyrin, Ki-67, and p53 according to clinical variables.</P>

유아를 위한 환경교육방안 모색

윤기영,조경희 西原大學校 1992 西原大學 論文集 Vol.29 No.-

This Study is to make a environmental education plan for young children for the plan, the objective, substance, method, evaluation of recent environmental education are reviewed in relation with the importance of E.C.E(Early Chilhood Education), young dhild development, E.C.E curriculum sand educational environment. The result shows the needs and possibility for the effective environmental education in the kindergarten. It is also shown some problem in the current situation such as the lack of systematic efforts in developing programs and educational materials. Therefore a plan for the systemic environmental education in the kindergarten is proposed as follows : 1. Appropriateness, integration, and relation must be accomplished. 2. The basic objective is to establish appropriate value and attitude. 3. The substance is to induce the young children to love animals and plants 4. The method is through the experiences in the every day life 5. Physical space, materials, and equipment are needed for cognition of ecological principles. 6. Effective educational materials are needed for young childrens activity. 7. The evaluation has developing skills for emotional area and young children. 8. Teacher education should be reinforced. 9. Kindergarten program must relation with home and society. 10. Kindergarten program should be localized.

Effects of Cu,Zn-superoxide dismutase on cell proliferation and neuroblast differentiation in the mouse dentate gyrus.

Yoo, Dae Young,Shin, Bich Na,Kim, In Hye,Kim, Woosuk,Kim, Dae Won,Yoo, Ki-Yeon,Choi, Jung Hoon,Lee, Choong Hyun,Yoon, Yeo Sung,Choi, Soo Young,Won, Moo-Ho,Hwang, In Koo Kluwer Academic/Plenum Publishers 2012 Neurochem Res Vol.37 No.2

<P>Oxidative stress is one of the most important factors in reducing adult hippocampal neurogenesis in the adult brain. In this study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) on lipid peroxidation, cell proliferation, and neuroblast differentiation in the mouse dentate gyrus using malondialdehyde (MDA), Ki67, and doublecortin (DCX), respectively. We constructed an expression vector, PEP-1, fused PEP-1 with SOD1, and generated PEP-1-SOD1 fusion protein. We administered PEP-1 and 100 or 500 관g PEP-1-SOD1 intraperitoneally once a day for 3 weeks and sacrificed at 30 min after the last administrations. PEP-1 administration did not change the MDA levels compared to those in the vehicle-treated group, while PEP-1-SOD1 treatment significantly reduced MDA levels compared to the vehicle-treated group. In the PEP-1-treated group, the number of Ki67-positive nuclei was similar to that in the vehicle-treated group. In the 100 관g PEP-1-SOD1-treated group, the number of Ki67-positive nuclei was slightly decreased; however, in the 500 관g PEP-1-SOD1-treated group, Ki67-positive nuclei were decreased to 78.5% of the vehicle-treated group. The number of DCX-positive neuroblasts in the PEP-1-treated group was similar to that in the vehicle-treated group. However, the arborization of DCX-positive neuroblasts was significantly decreased in both the 100 and 500 관g PEP-1-SOD1-treated groups compared to that in the vehicle-treated group. The number of DCX-positive neuroblasts with tertiary dendrites was markedly decreased in the 500 관g PEP-1-SOD1-treated group. These results suggest that a SOD1 supplement to healthy mice may not be necessary to modulate cell proliferation and neuroblast differentiation in the dentate gyrus.</P>