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.

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.

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.

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.

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>

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>

가토 외고정 모델을 이용한 치밀체형 세라믹스의 골결합능 평가

이재협,이동호,이재학,공현식,안영준,류현승,서준혁,홍국선,김환,장봉순,이춘기 대한정형외과연구학회 2003 대한정형외과연구학회지 Vol.6 No.2

종합검진센터 내원자에서 관상동맥질환 위험요인들의 분포

이충원,이종영,박종원,윤능기,김영조,이현우,이무식,서석권 啓明大學校 醫科大學 1993 계명의대학술지 Vol.12 No.3

1991년3월부터 8월사이에 대구시에 소재한 1개의 대학병원의 종합검진센타에 내원해서 종합검진을 받은 남자 422명(69.9%)과 여자 182명(30.1%)을 대상으로 하여 심헐관계질환의 위험요인들의 전체적인 분포를 보았다. 평균 연령은 남자가 43.3(표준편차, 10.3), 여자가 44.4(표준편차, 10.8)였다. 남자에서 연령에 따라 0.05 수준에서 통계적인 유의성을 보인 위험인자는 혈청 총콜레스테롤(TC). 트리글리세라이드(TC), 고밀도 지단백콜레스테롤(HDL), 저밀도 지단백콜레스테롤(LDL), 수축기혈압, 비체중, A형행동양상이었으며 생활습관으로서는 음주, 흡연, 규칙적인 운동, 우유와 커피섭취, 수면 등이었다. 여자에서는 TC, TG, LDL, 수축기와 확장기혈압, 비체중 그리고 커피섭취와 수면 등이었다. 남자에서 총콜레스테롤의 평균은 181.7mg/dl(표준편차, 32.2), 여자는 182.5mg/이(표준편차, 42.2)였다. 대부분의 위험인자들은 구미의 수준에 미치지 못했으나 남자에서 흡연율이 전체적으로 61.8%로 높으 수준이었으며 특히, 20~29세가 72.9%, 30~39세가 75.2%로서 다른 연령군에 비해 상대적으로 높았다. 여자에서는 전체적으로 6.0%에 지나지 않았다. 확장기혈압 90mmHg 이상을 고혈압자로 정의했을 때의 유병률이 여자 전체대상자에서 24.7%로 높았으며 50-59세는 표본수가 적어서 문제가 되었으나 53.1%였다. 어떤 인구집단내에서 총콜레스테롤의 평균이 200mg/dl 미만이면 고혈압과 흡연의 인구집단의 수준에 관계없이 관상동맥질환(coronary heart disease)의 발생은 드문 것으로 보고가 되고 있으므로 당분간 관상동맥질환 발생률의 급속한 절대적인 증가는 힘드리라 사료된다. 그러나 이러한 결과는 본 연구의 대상자들이 대표성을 지니지 못하며 건강검진센터에 자발적으로 내원한 사람들이므로 해석에 주의를 요한다. Authors examined the distributions of the risk factors for the coronary heart disease in the 422 male (69.9%) and 182 female (30.1%) visitors to the health examination center of a university hospital located in Taegu March to August 1991. Mean age of males was 43.3(standard deviation, SD 10.3) and that of females was 44.4(SD 10.8). Total cholesterol(TC), triglyceride (TG), high-density lipoprotein and low-density lipoprotein cholesterol(LDL), systolic blood pressure, Quetelet index, and Type A Behavior Pattern, and some of life habit variables(alcohol intake, smoking, regular exercise, milk and coffee intake and sleeping) were statistically significant in age groups of the males(P<0.05). In the females, TC, TG and LDL, systolic and diastolic pressure, Quetelet index, coffee intake and sleeping were statistically significant in age groups (P<0.05). Mean of total cholesterol was 181.7㎎/dl(SD,32.2) in males and that of females was 182.5㎎/dl(SD,42.2). Most of the risk factors levels were lower than the Euro-Americans', while smokers were high with 61.8%, especially 72.9% in 20-29 age group and 75.2% in 30-39 age group in males. In females, smokers were just 6.0%. Hypertensives defined by more than 90mmHg diastolic pressure were 24.7% in females, particularly 53.1% in 50-59 age group, but size of the strata was rather small(N=49). In the light of the report that coronary heart disease is uncommon irrespective of population levels of smoking and hypertension, where average total blood cholesterol level in a population is low(<200mg/dl), it is not likely that the absolute increase of the number of the coronary heart disease will increase markedly in the near future. But cautions should be exercised in interpreting the results of this study due to the lack of representativeness and volunteerism. .

크론병에 대한 CoPPLX의 방어효과에 대한 연구

이호학,김유림,문창기,이재일,양병윤,김종수,이정민,정재혁,안석진,박상준,김윤권,김소연,김영중,조민구,최영자,장성조 圓光大學校 醫科學硏究所 2005 圓光醫科學 Vol.20 No.1

흰쥐 시상하부에서 NMDA에 의한 c-fos의 발현

이영기,최기열,이원돈,유영복,이왕재,황덕호,조사선,장가용 대한해부학회 1994 Anatomy & Cell Biology Vol.27 No.3