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.

위 아전절제술 후 십이지장 위 역류성 위염에서 p53 및 Ki-67 단백 발현 양상

최석채 ( Suck Chei Choi ),김용성 ( Yong Sung Kim ),김기훈 ( Ki Hoon Kim ),김헌수 ( Hun Soo Kim ),윤기중 ( Ki Jung Yun ) 대한소화기기능성질환·운동학회 2007 Journal of Neurogastroenterology and Motility (JNM Vol.13 No.2

목적 : 십이지장 위 역류성 위염은 위절제 등에 의해서 발생하는 것으로 후에 암종이 발생할 가능성이 높은 것으로 알려져 왔다. 그러나 사람에서 십이지장 내용물의 역류와 암종 발생 사이의 병인론적 연구가 흔하지 않다. 이에 십이지장 위 역류성 위염을 보이는 환자의 조직과 대조군 환자의 조직을 대상으로 Ki-67 및 p53 단백 발현 정도를 측정하여 상피 세포증식 유도 및 암억제 유전자의 발현 정도를 비교 연구하였다. 대상 및 방법 : 위암종으로 위아전절제술을 받은 총 57예 중 내시경 및 조직학적으로 십이지장 위 역류성 위염으로 진단된 16예의 내시경 조직과 대조군 16예의 내시경 조직을 대상으로 하여 Ki-67 및 p53 단백 발현을 면역조직화학적 염색을 하였고 그 강도를 점수화하였다. 결과 : 십이지장 위 역류성 위염 소견을 보인 환자의 내시경적 추적 기간은 평균 607일, 대조군 556일 그리고 57예의 평균은 471일로 유의한 차이는 없었다. 십이지장 위 역류성 위염 환자의 Ki-67 발현 강도의 중간값은 3.0로 대조군 중간값 2.0보다 의미있게 높았으며, p53 단백의 발현 강도 중간값도 2.0으로 대조군 중간값 1.0 보다 의미있게 높았다. 결론 : 십이지장 위 역류성 위염은 담즙 등이 점막의 상피세포 증식을 유도하고 유전자 이상을 초래할 가능성이 높아 시간 경과 후 암종이 발생할 가능성이 대조군에 비해서 높을 수 있음을 알 수 있었다. Background/Aims: Duodenogastric reflux of bile and other contents of duodenum is one of the main etiologic fators in chronic gastritis, and chronic inflammation has been recognized as a risk factor of human cancer. The aim of this study was therefore to evaluate the expression of p53 and Ki-67 protein in duodenogastric reflux gastritis. Methods: To evaluate the proliferation activity and tumor suppressor gene expression, 16 cases of duodenogastric reflux gastritis and 16 cases of control gastric tissue after subtotal gastrectomy were examined immunohistochemically using the monoclonal antibodies to Ki-67 and p53 protein. Results: The mean duration of follow-up endoscopic biopsy after subtotal gastrectomy was 607 days in duodenogastric reflux gastritis and 556 days in control groups. The mean intensity of Ki-67 in duodenogastric reflux gastritis was significantly higher than that of control tissues (3.0 vs 2.0). The mean intensity of p53 protein in duodenogastric reflux gastritis was significantly higher than that of control tissues (2.0 vs 1.0). Conclusions: The high expressions of Ki-67 and p53 protein in duodenogastric reflux gastritis may be one of the main mechanisms in the development of gastric stump carcinoma. (Kor J Neurogastroenterol Motil 2007;13:118-122)

Effects of Streptozotocin-Induced Type 1 Diabetes on Cell Proliferation and Neuronal Differentiation in the Dentate Gyrus : Correlation with Memory Impairment

Jung Hoon Choi,In Koo Hwang,Sun Shin Yi,Ki-Yeon Yoo,Choong Hyun Lee,Hyung-Cheul Shin,Yeo Sung Yoon,Moo-Ho Won 대한해부학회 2009 Anatomy & Cell Biology Vol.42 No.1

We examined the effects of steptozotocin (STZ)-induced type 1 diabetes on cell proliferation and neuroblasts in the subgranular zone of the hippocampal dentate gyrus (SZDG) of male Wistar rats. Change in memory function was also investigated using the passive avoidance test. In the SZDG, Ki67 (a marker for cell proliferation) positive nuclei were significantly decreased at 2 and 3 weeks and slightly decreased at 4 weeks after STZ treatment. Doublecortin (DCX, a marker for neuronal differentiation)-immunoreactive (+) neuroblasts with tertiary dendrites were significantly decreased in the STZ-treated group compared to those in the vehicle-treated group. However, DCX+ neuroblasts without tertiary dendrites were abundant at 4 weeks after STZ treatment. In addition, retention latency time in STZ-treated group was similar to that of vehicle-treated group at 2 and 3 weeks after STZ treatment. However, the retention latency time was significantly decreased at 4 weeks after STZ treatment. These results suggest that STZ significantly reduced cell proliferation and neuroblasts at 2~3 weeks after STZ treatment, but not at 4 weeks after STZ treatment although memory impairment was detected at 4 weeks after STZ treatment. The gradual reduction of DCX+ neuroblasts with tertiary dendrites may be associated with the impairment of hippocampus-related memory function.

기관지폐 이형성증의 임상 양상: 다기관 연구

성기혜 ( Ki Hye Sung ),김민희 ( Min Hee Kim ),김은령 ( Eun Ryoung Kim ),심재원 ( Jae Won Shim ),이정주 ( Jung Ju Lee ),임재우 ( Jae Woo Im ),진현승 ( Hyun Seung Jin ) 대한주산의학회 2009 Perinatology Vol.20 No.3

목적: 최근 극소 저출생 체중아의 생존율의 개선으로 기관지폐 이형성증(bronchopulmonary dysplasia, BPD)이 늘고 있다. 다기관 연구에 의해 전국적인 BPD의 역학, 임상 양상과 각 병원 간의 차이를 조사하여 향후 우리나라의 BPD 감소와 중증도를 줄이는 것을 목적으로 본 연구를 시행하였다. 방법: 2005년 6월부터 2007년 5월까지 건국대학교병원, 영등포 성애병원, 강북삼성병원, 중앙대학교병원, 건양대학교병원, 강릉아산병원의 신생아 집중 치료실에 입원하였던 신생아 4,476명을 대상으로 하였다. BPD의 진단 기준은 비전형적인 BPD를 포함하여 병인적인 분류를 하고 있는 Ogawa 등의 분류법을 이용하여 신생아 호흡 곤란 증후군(respiratory distress syndrome, RDS)과 전형적 또는 미만성 혼탁의 방사선 소견, 산전 감염의 유무에 따라 6가지 type으로 분류하였다. 또한 전체 신생아의 출생체중 분포와 생존율, 각 출생체중 군별 BPD의 발생률, 병태 비율, 사망률 등을 조사하고, 이 후 재택 산소요법 시행 여부와 미숙아 망막증, 괴사성 장염 등의 합병증 여부를 조사하였다. 결과: 생후 28일째 산소 치료가 필요한 신생아는 89명이었고, 이 중 Ogawa 분류법에 의한 BPD 환아는 70명(1.6%)이었으며, 특히 1,500 g 미만의 환아 237명 중 60명(25.3%)이었다. 생후 28일 이상 생존율은 98.7%이고, 사망 예는 없었으며 평균 재원 기간은 97.8±51.2일(43~405일)이었다. BPD는 900~999 g, 1,000~1,249 g의 체중 군에서 발생률이 각각 15명(21.4%)으로 가장 높았으며, 교정 36주 이후에도 산소투여가 필요한 중증 BPD의 경우 900~999 g의 체중 군에서 7명(23.3%)로 가장 높았다. Ogawa 분류법으로 BPD의 각 병태 비율로는 RDS 이후에 나타나는 I, II형이 각각 전체의 17예(24.3%), 44예(62.9%)로 대다수를 차지하였다. 이외에도 III`형은 2예(2.9%), IV형은 2예(2.9%), V형은 5예(7.1%)이었고, III형, VI형은 없었다. 재택 산소요법은 8예에서 시행되어 전체의 11.4%였으며, 이 중 BPD I형이 7예로 87.5%를 차지하였다. 미숙아 망막증은 35명(50.0%)에서 발생하였으며, 700 g 이하 신생아에서 9예(26.5%)로 가장 많았다. 또한 괴사성 장염은 3명(4.3%)이었다. 결론: 본 연구는 국내에서 처음으로 진행된 BPD의 전국적인 다기관 역학 조사로, 대상 신생아의 Ogawa 분류에 의한 BPD 유병률은 1.6% 이었고 1,500 g 미만 신생아의 25.3%이었으며, 전체 신생아의 BPD 70명 중 Ogawa 분류의 I, II형이 각각 24.3%, 62.9%로 대다수를 차지하였다. Purpose: As the neonatal intensive care advanced, the incidence of neonatal bronchopulmonary dysplasia (BPD) has increased. We conducted a multi-center investigation of the prevalence of BPD in six hospitals to investigate the epidemiology of BPD in Korea. Methods: Retrospective reviews ware performed for survival rate, prevalence of BPD of total 4,476 newborn infants who were admitted to neonatal intensive care unit in Konkuk university hospital, Sung-Ae General hospital, Kangbuk Samsung hospital, Chung-Ang university hospital, Konyang university hospital, and Gangneung Asan hospital between June, 2005 and May, 2007. By Ogawa, BPD was defined as oxygen dependency at 28 days after birth, with respiratory distress symptoms and the change of chest x-ray finding, and classified as 6 subtypes. Classic BPD was defined as oxygen dependency at 36 weeks of postmenstrual age. Results: Survival rate at 28 day after birth was 98.7%. BPD infants by Ogawa classification were 70 (1.6% of overall newborn infants), classic BPD infants were 30 (0.7%). Especially, among 237 preterm infants with birth weight less than 1,500 gram who survived to 28 days of life, 60 (25.3%) had BPD by Ogawa classification and 23 (9.7%) had classic BPD. In Ogawa classification, infants with RDS as type I and II, were 17 infants (24.3%) and 44 infants (62.9%). Home oxygen therapy was performed 8 infants (11.4%). Prevalence of retinopathy of prematurity was 35 infants (50.0%), necrotizing enterocolitis was 3 infants (4.3%), and intraventricular hemorrhage was 6 infants (8.6%). Conclusion: Prevalence of BPD infants was 1.6% of overall newborn, 25.3% of preterm infants with birth weight less than 1,500 gram. Among 70 BPD infants, BPD by Ogawa classification with history of RDS as type I and II were 24.3%, 62.9% as the majority of BPD. This study would be the first report of epidemiology of Korean BPD infants by multi-center study.

동적 그룹에 적합한 안전하고 효율적인 그룹키 동의 프로토콜

김기성(Kim Ki Sung),김정윤(Kim Jung Yoon),최형기(Choi Hyoung Kee) 한국통신학회 2008 한국통신학회 학술대회논문집 Vol.2008 No.7

서울의 PPNG 발생 빈도(1991-1992)

김재홍,윤기범,박평원,김영진,전경민,김영태,김중환,곽호,구상완,송민석,유옥,지혜구,김동원,문상은,박영립,정승호,성범진,성순제,엄주용,황정열,이기홍,이주협,전태진 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.1

The prevalence of PPNG among pretreated gonorrhea cases isolated at the STD clinic of Choong-Ku Public Health Center in Seoul has been studied and reported annually since 1981. In 1991, 123 strains of N.gonorrhoeae were isolated, among which 58(47.1%) were PPNG. In 1992, 98 starains of N.gonorrhoeae were isolated, among which 51(52.0%) were PPNG. In all, 109(49.3%) strains were found to be PPNG among 221 strains isolated between 1991-1992. The prevalence of PPNG in Seoul showed increased tendency till 1989, thereafter, it has been stationary or slightly decreasing.

식도의 원주상피 피복 점막에서 점액유전자 발현 및 세포증식능에 대한 연구

최석채 ( Suck Chei Choi ),김용성 ( Yong Sung Kim ),김기훈 ( Ki Hoon Kim ),김헌수 ( Hun Soo Kim ),조향정 ( Hyang Jeong Jo ),윤기중 ( Ki Jung Yun ) 대한소화기기능성질환·운동학회 2007 Journal of Neurogastroenterology and Motility (JNM Vol.13 No.1

목적 : 바렛식도는 지속적인 위식도역류 등으로 원위부 식도에 정상적으로 존재하는 편평상피세포 대신에 배상세포를 포함하는 장형 원주세포로 식도 점막이 피복되는 것을 말한다. 그리고 이형성을 거쳐 선암종으로 진행할 수 있기 때문에 이형성 이전 단계인 바렛식도의 발암과정에 대한 연구가 필요하다. 이에 바렛식도와 배상세포를 포함하지 않은 원주세포만 있는 식도를 대조군으로 하여 점액유전자 및 세포증식능에 대해 비교 연구하였다. 대상 및 방법 : 임상 및 내시경적으로 바렛식도가 의심되어 원위부 식도에서 생검한 환자들 중에서 배상세포가 있어 조직학적으로 바렛식도로 증명된 25명의 환자와 배상세포가 없었던 환자들 중에서 무작위로 선택한 30예를 대조군으로 하였다. 생검 당시의 나이와 성별 그리고 MUC1, MUC2, Ki-67에 대한 면역조직화학적 염색을 시행하였다. 결과 : 바렛식도의 평균 나이 및 남자 비율은 각각 65.3±10.1세, 76.0%이였고, 대조군의 평균 나이 및 남자 비율은 각각 53.0±14.8세, 60.0%로 바렛식도의 나이가 대조군식도보다 의의있게 높았다. MUC1은 바렛식도 및 대조군 모두에서 100% 발현되었고, MUC2 발현율은 바렛식도 및 대조군에서 각각 92%, 20%이었다. Ki-67 발현율은 바렛식도 및 대조군에서 각각 80.0%, 70.0%이였고, Ki-67 발현 강도의 평균은 바렛식도 1.20±0.76, 대조군 0.77±0.57로 발현 강도에서 바렛식도가 의의있게 높았다. 결론 : 바렛식도는 원주세포만 있는 식도에서 보다 좀더 지속적인 위식도역류 등의 자극으로 생긴다. 그리고 MUC2는 주로 바렛식도에서 발현되고 세포증식능은 바렛식도에서 좀더 높으며 이는 MUC2 발현과 관련될 수 있다고 생각된다. Background/Aims: Barrett`s esophagus is characterized by the presence of metaplastic columnar epithelium with goblet cells in the distal esophagus. Barrett`s esophagus progresses through low grade dysplasia and high grade dysplasia to adenocarcinoma. We studied the patient age, the mucin gene and the proliferation activity of biopsy-proven Barrett`s esophagus and simple columnar epithelium-lined esophagus. Methods: To evaluate the mucin gene expression and proliferation activity, twenty five cases of Barrett`s esophagus and thirty cases of control esophagus were examined immunohistochemically with using the monoclonal antibodies to MUC1, MUC2 and Ki-67. Results: The Barrett`s esophagus patients were older (mean: 65.3±10.1 years) than the control patients (mean: 53.0±14.8 years). The MUC1 expression was 100% in both Barrett`s esophagus and the control esophagus. An MUC2 expression was observed in 92.0% of the Barrett`s esophagus and 20.0% of the control esophagus. The rate and intensity of the Ki-67 expression was higher in the Barrett`s esophagus (80.0%, 1.20±0.76) than that in the control esophagus (70.0%, 0.77±0.57). Conclusions: Barrett`s esophagus is a metaplastic lesion due to the more long-standing gastroesophageal reflux than that in a simple columnar epithelium-lined esophagus. The cause of increased proliferation activity in Barrett`s esophagus may be related to the MUC2 expression. (Kor J Neurogastroenterol Motil 2007;13:21-25)

Focal adhesion kinase and src expression in premalignant and malignant skin lesions

( Ju Yeon Choi ),( Jae Yun Lim ),( Han Saem Kim ),( Jung Min ),( Jung In Kim ),( Hyun Min Seo ),( Sang Hyeon Hwang ),( Chong Won Choi ),( Yoon Hwan Kim ),( Jin Hee Sohn ),( Hyunjoo Lee ),( Won Serk Ki 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Focal adhesion kinase (FAK) and Src are non-receptor tyrosine kinases. FAK and Src play a critical role in inducing malignant transformation in tumor cells. Objectives: We performed immunohistochemical staining for total and phosphorylated forms of FAK and Src, to evaluate the role of FAK and Src in the development of premalignant and malignant skin lesions. Methods: A total of 59 facial skin samples (30 actinic keratoses, 10 Bowen``s diseases, 13 squamous cell carcinomas and six perilesional skins) were immunohistochemically stained for Ki-67, total (t) and phosphorylated (p) form of FAK and Src. Methods: A total of 59 facial skin samples (30 actinic keratoses, 10 Bowen``s diseases, 13 squamous cell carcinomas and six perilesional skins) were immunohistochemically stained for Ki-67, total (t) and phosphorylated (p) form of FAK and Src. Results: Cells positive for t-Src, p-Src-y530, t-FAK and pFAK-s722 were detected in premalignant intra-epithelial lesions (PELs) and squamous cell carcinomas (SCCs), but not in the perilesional skin. There was a tendency towards high correlation between Ki-67 and t-FAK or pFAK-s722, suggestive of the active role of FAK in cell proliferation. Conclusion: Our findings of higher t-Src and p-Src-y530 positive cells in PELs, as compared to SCCs (with higher Ki-67 level), are suggestive of the other role of Src in tumor formation and progression, which requires further investigation.

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

Tetrahydroisoquinoline Alkaloids가 쥐의 동맥과 뇌균등질의 α-Adrenoceptors에 미치는 영향

이현석,백선하,황수현,박인성,김은상,정진명,한종우,장기철,장기철 대한신경외과학회 1999 Journal of Korean neurosurgical society Vol.28 No.1