Comparison of Proliferative Activity in Each Histological Subtypes of Benign and Atypical Intracranial Meningiomas by PCNA and Ki-67 Immunolabeling

최승진,장은덕,권성오,계대곤,박춘근,이상원,강준기,Choi, Seung Jin,Chang, Eun Deok,Kwon, Seung Oh,Kye, Dae Kon,Park, Choon Keun,Lee, Sang Won,Kang, Joon Ki The Korean Neurosurgical Society 2000 Journal of Korean neurosurgical society Vol.29 No.9

목 적 : 양성 뇌수막종에 비하여 이형성 및 악성 뇌수막종이 나쁜 임상적인 예후 및 양상을 보이는 것은 잘 알려져 있으나, 양성 뇌수막종에 있어서 각각의 병리조직학적 아형에 따른 생물학적 양상의 차이에 대해서는 잘 알려지지 않거나 일부 논란이 되고있다. 본 연구에서는 이형성 뇌수막종 및 양성 뇌수막종의 각각의 병리조직학적 아형에 따른 증식능의 차이여부를 알아보고자 PCNA와 Ki-67표지지수를 분석하였다. 방 법 : 본원에서 뇌수막종으로 수술을 시행하여 얻은, 재발을 보여 재수술을 시행한 2례를 포함하여, 파라핀에 포매시킨 27개의 조직을 대상으로 병리학적인 증식능을 분석하기 위해, PCNA에 대한 단일항체 및 MIB-1 단일항체를 이용한 면역조직화학적 염색을 시행하였다. 조직학적 분류상 meningothelial type이 8례, transitional type이 9례, fibroblastic type이 5례였으며, 이형성 수막종이 5례였다. 결 과 : PCNA표지지수의 평균값은 양성 수막종에서 meningothelial type이 $4.82{\pm}5.10%$, transitional type이 $9.01{\pm}4.25%$, fibroblastic type이 $5.66{\pm}5.32%$를 보였으나 이형성 수막종에서는 $27.62{\pm}19.67%$의 높은 지수를 나타냈고, Ki-67 표지지수의 평균값은 양성 수막종의 아형에서 각각 $0.43{\pm}0.85%$, $0.44{\pm}1.08%$, $0.24{\pm}0.18%$를 보이고, 역시 이형성 수막종에서는 $0.84{\pm}0.59%$의 높은 지수를 보였다. 즉, 양성 수막종에서 각각의 아형에 따른 PCNA 및 Ki-67 표지지수는 통계학적으로 의미있는 차이는 없었으나(p>0.05), 이형성 수막종에서는 의미있는 높은 표지지수를 보여(p<0.05) 양성 수막종에서 보다 높은 증식능을 보임을 알 수 있었다. 결 론 : PCNA 및 Ki-67 표지지수를 이용한 증식능의 비교결과, 양성 뇌수막종에서는 각각의 아형에 따른 생물학적 양상이나 예후는 차이가 없을것으로 생각되나, 이형성 수막종에서는 높은 증식능을 보여 이에 대한 예후를 예상할 수 있을것으로 생각되며, 또한 이러한 표지지수가 병리조직학적으로 양성과 이형성의 감별에 많은 도움이 될것으로 사료된다. Objective : The clinical prognosis and biological behavior of atypical and especially malignant meningiomas are well known to be worse than benign meningioma, but the degree of biological aggressiveness in each classical subtypes of benign meningioma is controversy. This study was performed to see whether there is a difference in the proliferative activity between each different histological subtypes of benign meningioma as well as atypical meningioma. Methods : Paraffin-embedded surgical specimens of 27 meningiomas, including two recurrent tumors, were studied to evaluate proliferative activity by immunohistochemical method with monoclonal antibodies to proliferating cell nuclear antigen(PCNA) and MIB-1. The specimens consisted of 8 cases of meningothelial, 9 cases of transitional, 5 cases of fibroblastic subtypes and 5 cases of atypical meningiomas. Results : Mean PCNA labeling indices of meningothelial, transitional and fibroblastic meningiomas were $4.82{\pm}5.10%$, $9.01{\pm}4.25%$ and $5.66{\pm}5.32%$, but that of atypical meningiomas was $27.62{\pm}19.67%$, noting a higher value compared to all three subtypes of benign meningiomas. Mean Ki-67 labeling indices of the above 3 subtypes were $0.43{\pm}0.85%$, $0.44{\pm}1.08%$ and $0.24{\pm}0.18%$, and that of atypical meningiomas was also revealed to be of higher value ($0.84{\pm}0.59%$). PCNA and Ki-67 labeling indices were not statistically different between histological subtypes of benign meningioma(p>0.05), but the differences of both immunolabeling between benign and atypical meningiomas were statistically significant(p<0.05). Conclusion : Immunolabeling of PCNA and Ki-67 in intracranial meningiomas reveals no prognostic difference between meningothelial, transitional and fibroblastic subtypes in classical benign meningiomas by measuring expression of PCNA and Ki-67, but it seems to be helpful in differentiating benign and atypical meningioma, later showing more proliferative activity and biological aggressiveness.

The impact of pathologic differentiation (well/ poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

Kim, Seung Tae,Lee, Su Jin,Lee, Jeeyun,Park, Joon Oh,Park, Young Suk,Lim, Ho Yeong,Kang, Won Ki Grune & Stratton 2017 Journal of clinical oncology Vol.35 No._suppl15

<P> e15686 </P><P> Background: Herein, we investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum-based therapy. Simultaneously, we evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from etoposide plus platinum (EP)-based therapy. Methods: Among patients pathologically diagnosed with metastatic grade 3 GEP-NECs at Samsung Medical Center between June 2013 and March 2016, 31 GEP-NEC patients receiving etoposide and platinum-based therapy were included in this study. Results: Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. Sixteen unclassified GEP-NECs originated from 7 gall-bladder (GB), 6 liver and 3 unknown primary sites. According to pathologic differentiation, 14 patients had well differentiated and 17 had poorly differentiated grade 3 GEP-NECs. Between well differentiated and poorly differentiated grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between well and poorly differentiated grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67≤60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). There was no significant difference in PFS according to pathologic differentiation (well differentiated vs. poorly differentiated) and Ki67 index ( > 60% vs ≤60%). Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs. </P>

Reversal cell proliferation by exercise in the hippocampal dentate gyrus of offspring born from the stress-exposed maternal rats during pregnancy

Joon-Ki Park,Sam-jun Lee 한국스포츠학회 2015 한국스포츠학회지 Vol.13 No.4

임신중 소음스트레스를 받은 어미 쥐로부터 태어난 새끼 쥐의 뇌의 해마 치상회에서 세포분화의 표식인자인 Ki-67 과 세포분화 촉진요소인 NPY의 발현에 운동이 미치는 영향을 연구하기 위한 목적으로 교미중의 어미 쥐에서 스트레스에 노출시켜 태어난 새끼 쥐를 4집단으로 (통제군, 운동군, 스트레스군, 스트레스 및 운동군)으로 분류하여 각각 집단별 10마리로 분류를 하여 트레드밀 운동을 1주간 실시를 하였다. 운동은 태어난지 3주에서 일주일동안 시키고 희생을 시켰다. 분석은 면역조직화학법을 이용하여 분석을 하였으며, 운동은 1회 30분, 일주일로써 최초 5m/min으로 5분, 다음 8m/min으로 5분 이후 마지막으로 10m/mim으로 20분 동안 경사 없이 중정도의 강도로 실시를 하였다. 통계적인 분석은 일원변량분석을 실시하였으며, 유의수준은 .05로 설정하였다. 결과로는 통제군과 스트레스군보다 운동군과 스트레스 및 운동을 복합한 집단에서 Ki-67 및 NPY의 발현에서 유의한 차이를 보였다. 이러한 유의한 차이가 의미하는 것은 운동이 스트레스를 받고 태어난 새끼 쥐의 뇌의 세포분화의 감소를 운동을 통하여 억제시킴으로써 운동의 긍정적인 효과를 주는 것으로 볼 수가 있다.

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

Bing Chun Yan,Ki-Yeon Yoo,Joon Ha Park,Choong Hyun Lee,Jung Hoon Choi,Moo-Ho Won 대한해부학회 2011 Anatomy & Cell Biology Vol.44 No.3

Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2’-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 ㎎/㎏ EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice.

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus.

Yan, Bing Chun,Yoo, Ki-Yeon,Park, Joon Ha,Lee, Choong Hyun,Choi, Jung Hoon,Won, Moo-Ho Korean Association of Anatomists 2011 Anatomy & Cell Biology Vol.44 No.3

<P>Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 mg/kg EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice.</P>

학교체육 활성화 방안에 대한 연구(Ⅰ) : 강원대학교 교양체육 운영방법의 개선을 중심으로

이광재,문병용,노성규,박기동,홍관이,한상준,유옥재,엄기진,정청자,오수일,김윤래,박장평,부기원 江原大學校附設 體育科學硏究所 1986 江原大學校附設體育科學硏究所論文集 Vol.- No.11

Try to find a scheme for activation to College Physical Education, this Report informs the various kinds of Survey and process those were projected for improvement of management methods on Cultural Physical Education in Kang Weon National University. From experimentally carried out "Sports events Choosing System" not as usual be inforced "Total practical Skill System", Following Positive effects and sujestions were Presented; 1. "Sports events choosing system" gave birth to more students' interesting and more voluntary participation to the sports events they chose, and sports skill and instruction level was elevated due to charge of expert according to each sports events. This system would be managed continuously hereafter for it related to life sports. 2. This System needs to closed cooperations between College and Community, for the facilities of community are utilized by college. 3. To complete the plan for activation of college Physical Education, additionally, the successional study ; namely "autonomous extracurricular sports activity" should be excuted hereafter.

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

완전뇌허혈후 재관류시에 국소뇌혈류, 체성감각유발전위 및 신경학적 회복에 대한 Mannitol과 Thiopental의 효과

박춘근,이상원,박영섭,최승진,허필우,정동섭,강준기,최창락 대한신경외과학회 1996 Journal of Korean neurosurgical society Vol.25 No.2

The cardiopulmonary bypass or cerebral circulation arrest is often used in the treatment of complex aneurysm or of arteriovenous malformation to decrease the risk of intraoperative aneurysm rupture. Although experimental studies have suggested that some drugs may protect the brain from ischemic injury, there are limitations in maintaining cerebral perfusion arrest without incurring neurologic deficits due to the initiation of detrimental processes including excitotoxic neuronal injury, activation of phospholipases, influx of calcium, and generation of damaging free radicals. The purpose of this study is to determine wheter mannitol or thiopental has any favorable effects on the recovery of neurologic deficits and on the regional cerebral blood flow(rCBF), somatosensory evoked potential(SEP) and electroencephalogram(EEG) in cats which underwent 15 minutes-complete global ishcemia-reperfusion. The complete global ischemia was produced in 38 cats by temporary intrathoracic occlusion of the innominate artery and the subclavian artery following ligation of bilateral mammary arteries and simultaneous induction of hypotension. The cats were allocated randomly to one of 4 treatment groups : (1) control group, 8 cats received equal volume of saline solution : (2) thiopental group, 10 cats received 45㎎/㎏ thiopental intravenously, (3) mannitol group, 10 cats received 2g/㎏ mannitol intravenously, (4) combined mannitol and thiopental group, 10 cats received equal dose of mannitol and thiopental intravenously. The drugs were administrated in a equally divided dosage before and after the ischemic episode. The results were as follos : 1) Eight animals which received saline showed the severe postischemic hypoperfusion and poor recovery of SEP and EEG, and 6 of them died within 6 hours after the ischemia. 2) Ten thiopental-treated animals also showed the severe postischemic hypoperfusion and poor recovery of SEP and EEG, and 6 of them died within 6 hours the ischemia. 3) Both mannitol-and combined treated groups showed early recovery of EEG, good recovery of SEP and EEG without the severe postischemic hypoperfusion, and 7 of 10 mannitol-treated animals and 8 of 10 combined treated animals were significantly recovered in all parameters. There were not significant differences in all parameters between the mannitol-and combined treated groups. 4) Thirty-four of 38 animals involved in this 15 minutes-ischemia resulted in the severe neurologic deficits inspite of treatment with mannitol, thiopental or both of them. These results suggest that, in cats, mannitol treatment is effective but not thiopental in preventing severe neurologic injury following complete global ischemia and the duration of complete ischemia should be far less than 15 minutes.

구조화 표본추출을 이용한 핀의 최적설계에 관한 연구

박홍준,김기형 朝鮮大學校 機械技術硏究所 2001 機械技術硏究 Vol.4 No.2

The Taguchi method by orthogonal array, one of the structured sampling methods, has many advantages which are row cost and time saving for experiments and researches. But this method has applied limited area especially about mechanical problems. So, we experimented whether the structured sampling is useful to apply optimal design of mechanical elements. First, we made a mechanical problem to determine optimal parameters of a pin with a hole. The second, we calculated combination of optimal parameters by simulation. At the same time, we seeked optimal combination by structured sampling using orthogonal array and ANOVA. The last, we compared these two results. The experimental result have shown that the structured sampling method seeked optimal parameters exactly. So, we see some possibility in this application.

前腕部 經穴 取穴에서 骨度分寸法과 一夫法의 比較 硏究

박히준,채윤병,차웅석,박종배,이혜정,이향숙,인창식,고형균,김수영,최일환,김강식,문정배,배기태,유경환,육근영,정병주,손인철,임사비나 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2004 東西醫學硏究所 論文集 Vol.2004 No.-

Background : The cun measurement System, an essential and convenient method in locating acupoints, has been widely used in the practice of acupuncture. However, traditional cun measurement has been criticized for its lack of reliability. Objectives : The purposes of this study are to determine if one cun measured by the directional methods have a consistency with that of proportional methods and to investigate which factors are related with these differences, especially in forearm. Methods : The distance between the elbow crease and the wrist crease of forearm was compared to a reference value of one cun obtained by the directional method. In this method, one cun is one third of the distance between index finger and Small finger of a subject, measured at proximal interphalangeal joint. In addition, to investigate the factors influencing the differences between these two methods, we measured the height and body weight and calculated body mass index (BMI). Finally we analyzed the factors correlated with these lengths by linear regression test. Results : The results showed that one cun obtained by the directional methods were significantly different from one cun by the proportional methods in forearm. It was demonstrated that the length acquired with the directional method was more correlated with body weight and body mass index, while the length obtained by the proportional method was more correlated with the height.