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.

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>

Risk of Traumatic Intracranial Hemorrhage From Low-Energy Falls in the Oldest-Old Patients

Sung Kyu Kim,Ki Young Jeong,이종석,Han Sung Choi,홍훈표,고영관 대한노인병학회 2016 Annals of geriatric medicine and research Vol.20 No.4

Background: The population of individuals classified as oldest-old (aged ≥85 years) has increased rapidly in recent years. The rates of morbidity from chronic diseases and physical dependence tend to be higher in the oldest-old compared with individuals classified as young-to-middle-old (aged 65-84 years). Therefore, the classification and evaluation of traumatic injuries in the oldest-old group are necessary. Herein we focused on the risk of traumatic intracranial hemorrhage from low-energy falls in older patients. Methods: Patient medical records from the Emergency Department after low-energy falls that occurred between November 2014 and April 2016 were retrospectively analyzed. Patients were divided into an older group (aged ≥65 years) and an adult group (aged 18-64 years); the older group was subdivided into the oldest-old group (aged ≥85 years) and a young-to-middle-old group (aged 65-84 years). The rate of intracranial hemorrhage and related factors were also investigated. Results: The older group had a greater risk of traumatic intracranial hemorrhage than the adult group (20% vs. 12.6%, p=0.019). Furthermore, more cases of traumatic intracranial hemorrhage were found in the oldest-old group than in the young-to-middle-old group (37.5% vs. 18.0%, p=0.024). Similarly, the risk of traumatic intracranial hemorrhage in the oldest-old was higher than in the young-to-middle-old group (p=0.032). Conclusion: The risk of traumatic intracranial hemorrhage from low-energy falls in the oldest-old patients was higher than in the young-to-middleold patients. Therefore, physicians need to pay particular attention to oldest-old patients, even to those with mental integrity and without neurological deficits.

진공열간가압성형 (VHP) 법 및 압출로 제조한 SiCp/Al 및 SiCp/2024Al 복합재료의 동적탄성계수와 감쇄능 (내부마찰) : 금속기 복합재료의 동적탄성계수 및 감쇄능 측정

김영만,조기현,이경민,홍성길 대한금속재료학회(대한금속학회) 1999 대한금속·재료학회지 Vol.37 No.9

To shorten the processes of MMC fabrication, a number of techniques are being studied. In this study, a new process for MMC's fabrication was developed utilizing vacuum hot pressing and subsequent extrusion. MMC's with pure Al and 2024Al matrices reinforced with various volume fractions of SiC particulates were produced at 400℃ by vacuum hot pressing(VHP), followed by direct extrusion with extrusion ratios of 10:1 at 480℃ at constant ram speed of 2㎜/sec. The effects of extrusion pressure and relative density according to the volume fractions of the reinforcement were compared with the resultant metallurgical microstructures. Young's moduli of the manufactured composites were measured by the sonic resonance method, damping capacity by free decay method. Measured Young's moduli of the composites at room temperature were compared with the predictions based on Rule of Mixtures, Halpin-Tsai and Mean-field models. Measured Young's moduli of the composites are in good agreement with the predictions based on Mean-field model. The composites reinforced with finer particles showed higher damping capacity under the same amount of SiC reinforcement.

남자 알코올 의존 환자의 기질적 특성에 관한 연구

김성곤,민영기,이덕기,김미영,송영상,권도훈,고영훈,박제민,정병선 대한생물치료정신의학회 2003 생물치료정신의학 Vol.9 No.1

목 적: 본 연구의 목적은 한국인 남자 알코올 의존 환자의 기질적 특성을 Temperament and Character Inventory(TCI)를 이용하여 조사하는 것이다. 방 법: DSM-Ⅳ 진단 기준에 맞는 알코올 의존 환자 30명과 정상인 36명을 대상으로 연구학적 특성을 조사하고, 기질적 특성을 한글판 TCI를 이용하여 조사하였다. 모든 대상자의 나이는 30~60세였다. 결 과: 1) 두 군간 평균 나이는 유의한 차이가 없었으나, 교육 정도와 결혼을 유지하고 있는 비율 및 취업률은 알코올 의존군이 정상 대조군에 비해 유의하게 낮았다. 2) 알코올 의존군에서는 정상 대조군에 비해 Harm Avoidance(HA) 점수와 Self-transcendence(ST)점수는 유의하게 높았으며, Self-directiveness(SD)점수는 유의하게 낮았다. 3) 알코올 의존군 내에서의 각 척도들 간의 상관관계는, HA와 SD 점수, HA와 Persistence(PE) 점수, ST와 SD 점수는 각각 유의한 음의 상관관계, ST와 PE 점수, SD 점수와 Cooperativeness(CO) 점수, Reward Dependence(RD)와 CO 점수는 양의 상관관계를 보였다. 결 론: 이러한 본 연구의 결과는 한국인 남성에서 수줍음을 잘 타며, 걱정도 많고, 염세적이고 쉽게 피로해지는 기질적 특성이 알코올 의존과 연관성이 있음을 의미한다. Objectives : The purpose of this study was to assess the temperament of male parients with alcohol dependence. Methods : The subjects were 30 patients who met DSM-Ⅳ criteria for alcohol dependence and 36 normal controls. All subjects completed Temperament and Character Inventory(TCI) which was developed by Cloninger. Results : 1) The educational level, marital status, and occupation in alcohol dependence group were significantly lower than those of normal control group, but there was no difference in the age between two groups. 2) Among the scores of TCI, the score of harm avoidance(HA) and self-transcendence(ST) were significantly higher in the alcohol dependence group than in the normal control group. 3) In the alcohol dependence group, a significant negative correlation among the scores of TCI was between HA and SD, HA and Persistence(PE), ST and SD, and positive correlation between ST and PE, SD and Cooperativeness(CO), Reward Dependence(RD) and CO. Conclusion : These results suggest that shy, fearful, pessimistic and fatigable temperament are related to developing alcohol dependence in Korean males.

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).

제1형 당뇨병 환자에서 췌도세포 동종이식의 반복시행

양태영,정인경,서인아,오은영,조건영,오승훈,김성주,정재훈,민용기,이명식,이문규,김광원,도영수,주성욱 대한당뇨병학회 2002 Diabetes and Metabolism Journal Vol.24 No.4

연구배경:췌도세포 이식은 시술이 간편하고 안전하기 때문에 반복이식이 가능하여 그 동안 여러 센터에서 반복이식의 성공을 보고한 바 있다. 국내에서도 본 병원을 비롯하여 몇몇 센터에서 췌도세포 이식이 활발히 시도되고 있으나 사람에서의 동종이식 및 동종 이식의 반복시행은 보고된 바 없는 실정이다. 저자 등은 국내 최초로 췌도세포 동종이식을 시행하여, 혈청 C­펩타이드가 증가하고 인슐린 요구량이 감소하였으며, 혈당농도와 당화혈색소의 안정을 보였다. 그러나 이식 70일 후 다시 인슐린 요구량이 증가하고 C­펩타이드가 감소하여 췌도세포 이식을 다시 시행한 바 있다. 2차 이식 후 70여일이 지난 현재 다시 혈청 C­펩타이드가 증가하고, 인슐린 요구량이 더 감소되어 췌도세포 이식에서 반복 시행의 유용성을 보고하는 바이다. 방법:환자는 32세 남자로 17년전 당뇨병 진단 후 인슐린 치료 중이었으며, 3년전 부터는 만성신부전증으로 혈액툭석을 하고있었다. 1999년 12월 25일 신장이식을 하였고 3일 후 췌도이식을 하였으며, 두번째 이식은 70일 후 시행하였다. 췌도분리는 변형된 Recordi방법과 비연속성 자당 농도차(discontinuous density gradient)를 이용하였으며 분리한 췌도는 배양 후 환자의 신장기능이 정상화되고 미생물학 검사에서 음성을 확인한 후 경피경간으로 간문맥을 접근하여 16G 폴리 에틸렌 카테터를 이용하여 간실질에 이식하였다. 결과:1차 췌도이식시 순수분리전 췌도수는 210,000개, 순수분리후 획득한 췌도수는 90,000개, 순도 95%, 세포양 1.0mL 이었고, 2차 췌도이식시 순수분리전 췌도수는 420,000개, 순수분리후 획득한 췌도수는 370,000개, 순도 95%, 세포양 1.5mL 이었다. 1,2차 모두 간문맥을 통해 약 20분에 걸쳐 간실질에 주입하였다. 췌도이식전 인슐린요구량은 75∼75U/일, HbA1e 8∼10%, C­펩타이드 0.6ng/mL 였으며, 1차 췌도이식수 7일째 인슐린 요구량은 40U/일, C­펩타이드 1.5ng/mL, FPS 109mg/mL 였고, 40일 추적관찰 후 인슐린 요구량이 36U/일, C­펩타이드 1.8ng/mL, HbA1e 6.5∼7.0%로 안정되었다. 그러나 이식 50일째부터 인슐린 요구량이 50∼56U/일, C­펩타이드 0.6ng/mL, FPS 130∼200mg/dL로 혈당 조절이 불안정하여 다시 췌도이식을 시행하였다. 2차 이식후 50일이 경과한 현재, 인슐린 요구량은 26U/일, C­펩타이드 1.8ng/mL, FPS 90∼120mg/dL로 다시 안정되었다. 결론:췌도이식은 반복이식이 가능하며, 본 환자의 경우 인슐린요구량 감소, 혈당의 안정화 및 C­펩타이드가 상승하여 이식한 췌도의 기능을 확인할 수 있었고, 향후 스테로이드 등 면역억제가 유지 용량으로 감량되면 인슐린 요구량은 더 감소될 것으로 기대된다. Over the past 20 years, significant advances have been made in human islet transplantation. However, cases of prolonged insulin independence after islet allotransplantation have rarely been reported and over time, a slight, gradual decrease in insulin secretion appears to occur, as suggested by the lower C-peptide. Although preliminary clinical success achieved over the past few years has been considerably higher with whole pancreatic transplant than with isolated islet grafts, both approaches remain experimental. Islet grafts might gain, over time, increasing credibility and might eventually provide an easier alternative in terms of grafting procedures and patient management, as compared with the more "traumatizing" whole-pancreas transplantation. Also, using islet, re-transplantation is possible. But it is not known whether re-transplantation of islet could be suitable for those patients who lost grafted islet function. The aim of the present study was to investigate the benefits of re-transplantation of islet in previously simultaneous islets-kidney transplant (SIK) patient who have lost graft function. Methods : The recipient was a 32 year old male. First islet transplantation was underwent at December 25, 1999. However, the grafted islets lost function after 70 days. So we performed re-transplantation of islets. The isolation of islet was conducted sterilely on a laminarflow hood and isolated by a modified Recordimethod. The islet was injected slowly into the liver via a cannular placed in the potalvein for 20 minutes. Results : Transplanted islets were 90,000 IEq at first islet transplantation, 370,000 IEq at second islet transplantation. The insulin requirement was reduced from 75-85 to 35-40 U/day, the basal C-peptide level was 1.5 ng/mL at 7 days posttransplant Unfortunately, the grafted islets lost function after 70 days. After second transplantation, the insulin requirement was reduced to 26 U/day. Conclusions : Despite the continuous need for exogenous insulin therapy, islet transplantation can prevent wide glucose fluctuations, thus resulting in normalization of glycemic control and improvement in HbAlc, and also, show that islets can be successfully and safely re-transplanted intraportally in patients who have lost previously grafted islet function (J Kor Diabetes Asso 457~466, 2000).

부산지역 무균성 뇌막염 원인 바이러스의 분리 및 동정 : 1998년을 중심으로

김영희,정영기,김기순,지영미,윤재득,김병준,구평태,민상기,정구영,김만수,조경순 동의대학교 기초과학연구소 2000 基礎科學硏究論文集 Vol.10 No.1

The incidence of aseptic meningitis infection is ensuing and threatening the health of children. Enteroviruses are the major agents of aseptic meningitis and identification of virus has been a clue to diagnosis and epidemiology. The outbreak of aseptic meningitis occurred in Pusan, 1998. Patients were concentrated from April through November. Children were more susceptible than adults. Among 306 cases of specimens from stool, throat swab tested, only 7.2% were positive on virus isolation, 12 cases from stool and 10 from throat, respectively. All isolated 7 serotypes of viruses represented cytopathic effect on cultured cells. Three types of echovirus 6, 25, 30 and coxsackievirus B2, B3, B4, B6 were identified by neutralizing anti body test. Isolated coxsackievirus and echovirus were observed by an electron microscope with negative staining.

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>