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.

일반논문 1 : 김종익의 유언과 경성여자의학전문학교 설립과정

백운기 ( Woon Ki Paik ),김상덕 ( Sang Duk Kim ) 연세대학교 의과대학 의사학과 의학사연구소 2011 연세의사학 Vol.14 No.1

Dr. Rosetta Hall, an American missionary physician, and Dr. Jeong-hee Gil, a young Korean physician, founded the Joseon (Keijo) Women`s Training Institute in 1928. Between 1933 and 1937, Dr. Gil and her husband, Dr. Kim Tak-won, maintained and financed the medical institute. Supporting the institute placed a heavy burden on the young doctors who were just establishing their private medical practice. Despite this burden, they undertook the work necessary to elevate the institute to a full medical college. In order to generate the substantial funds needed to establish the medical college, they created a foundation for the “creation of a women`s medical college” in 1934 and solicited funding. In 1937, a philanthropist interested in furthering education, Mr. Kim Jong-ik, agreed to donate the funding necessary to elevate the institute to a medical college. Mr. Kim, however, unexpectedly contracted dysentery and died. In his will, Mr. Kim bequeathed a portion of his estate to upgrading the institute to a medical college. The executor, contrary to Mr. Kim`s intent as set forth in his will, however, did not use the funds to elevate the institute, but rather established a completely new women`s medial college. The executor`s actions were a clear violation of Drs. Kim`s and Gil`s legal rights as beneficiaries under the will. They, nonetheless, accepted the outcome, because challenging the executor`s actions under Japanese rule would have been futile as Dr. Kim was a noted anti-Japanese patriot well known to the Japanese. Moreover, Sato Gozo had been Dr. Kim`s teacher at the Keijo Medical College. Most importantly, their dream of establishing a women`s medical college in Korea had been realized regardless of how. Regardless of whether the institute had been elevated to a medical college or not, Drs. Kim Tak-won and Gil Jeong-hee made great sacrifices to further the education of women medical doctors in Korea and should be recognized for their great contributions to the creation of Korea Women`s Medical College.

尹炳奭 교수의 학문과 梅軒 尹奉吉 연구

김상기(Kim, Sang-ki) 충남대학교 충청문화연구소 2024 충청문화연구 Vol.30·31 No.-

윤병석 교수는 평생동안 독립운동사 연구에 전념하였다. 연구 범위는 한말 의병에서부터 3.1운동, 만주와 연해주, 그리고 미주에서의 독립운동, 간도와 독도문제 등 폭이 넓다. 아울러 윤봉길을 비롯하여 안중근, 이한응, 장인환, 전명운, 강우규, 김상옥 등 의열사와 안창호, 김구, 이승만, 박은식, 신채호, 이동휘 등 임시정부 요인들, 그리고 미주와 러시아 지역에서 활동한 박용만, 홍진, 이동휘, 계봉우, 김정규의 활동상을 학술적으로 실증하였다. 선생님의 학문은 실사구시의 태도를 견지하였다. 그리고 그 속에서 한국의 현 단계에서의 문제점, 그중에서 일본, 중국, 러시아, 미국 등 주변 4강과의 관계 정립을 위한 올바른 방향을 제시하고자 하였다. 일본에 대해서는 역사적 심판을 망각한 단견을 비판하고, 중국에 대해서는 영토문제를 새롭게 규명해야 함을, 러시아에 대하여는 고려인의 강제 이주와 숙청한 사실을 사실대로 밝혀야 한다고 하였다. 윤병석 교수는 윤봉길에 대한 연구와 홍보에도 심혈을 기우렸다. 1998년부터 19년간 매헌연구원 원장을 맡아 윤봉길을 주제로 한 학술대회를 주관하였으며, 윤봉길 기념사업도 수행하여 윤봉길의 활동과 독립정신을 홍보하는데 앞장섰다. 2007년에는『민족의 영웅 윤봉길의사』를 저술하였으며, 2012년에는『매헌윤봉길전집』을 편찬하여 윤봉길 연구의 지평을 넓혀주었다. 필자가 이 편찬사업에 참여한 것이 계기가 되어 윤봉길 연구를 하게 되었으니 윤 선생님께서 필자를 윤봉길 연구자로 이끌어주었다 할 수 있다. 또한 선생님의 후임으로 매헌연구원 원장을 맡기도 하였으니 선생님의 지도와 배려에 큰 감사를 드린다. Professor Yun Pyong-suk devoted his entire life to the Korean Independence Movement Studies. The scope of studies are broad, ranging from the Righteous Armies in the Great Han Empire to the March 1st 1919 Movement, the independence movements in Manchuria, Primorie and America, and the issues of Kando(間島) and Dokdo(獨島). In addition, the heroic activities of Yun Bong-gil, An Jung-geun, Lee Han-Eung, Chang In-Whan, Jeon Myeong-Woon, Kang Woo-kyu, Kim Sang-Ohk, and the leading figures of the Korean Provisional Government such as Ahn Chang-ho, Kim Gu, Rhee Syngman, Park Eun-Sik, Shin Chae-ho, Yi Dong-Whi, and the activities of Park Yong-man, Hong Jin, Yi Dong-Whi, Gye Bong-U who worked in the Americas and Russia, were academically demonstrated. The teachers studies maintained an attitude of Shilsagushi(實事求是). And among them, teacher tried to suggest the problems of Korea in the present stages, and also suggest the right direction for establishing relations with the surrounding four powers, including Japan, China, Russia, and the United States. He criticized that Japan has short-sightedness for forgetting historical judgment, said that China should clarify the territorial issue, and Russia should investigate the forced migration and purging of the Goryeo people. Professor Yun Pyong-suk also devoted to researching and promoting Yun Bong-gil. For 19 years from 1998, he served as the director of the Maeheon Yun Bong-gil Research Institute and organized an academic conference on the subject of Yun Bong-gil. He also took the lead in promoting Yun Bong-gils activities and the spirit of independence by carrying out the Yun Bong-gil Memorial Project. In 2007, he wrote the 『Maeheon Yun Bong-gil, a Patriot and National Hero』. In 2012, he compiled the 『The Complete Works of Patriot Maeheon Yun Bong-gil』 to broaden the horizons of Yun Bong-gils research. This compilation project led me to started researching Yun Bong-gil, so it can be said that teacher led me to become a researcher of Yun Bong-gil. I also served as the head of the Maeheon Yun Bong-gil Research Institute as a successor to the teacher. I greatly appreciate the teachers guidance and consideration.

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)

Low Dose Exposure to Di-2-Ethylhexylphthalate in Juvenile Rats Alters the Expression of Genes Related with Thyroid Hormone Regulation

Kim, Minjeong,Jeong, Ji Seong,Kim, Hyunji,Hwang, Seungwoo,Park, Il-Hyun,Lee, Byung-Chul,Yoon, Sung Il,Jee, Sun Ha,Nam, Ki Taek,Lim, Kyung-Min The Korean Society of Applied Pharmacology 2018 Biomolecules & Therapeutics(구 응용약물학회지) Vol.26 No.5

Phthalates widely used in the manufacture of plastics have deeply penetrated into our everyday lives. Recently, a concern over the toxicity of phthalates on thyroid, has been raised but in most of cases, the doses employed were unrealistically high. To investigate the effects of phthalates on thyroid, we investigated the effects of the repeated oral exposure to low to high doses (0.3, 3, 30 and 150 mg/kg) di-2-ethylhexylphthalate (DEHP) from weaning to maturity for 90 days in juvenile rats on the thyroid. The histological examination revealed that DEHP significantly induced hyperplasia in the thyroid from the doses of 30 mg/kg, which was confirmed with Ki67 staining. In line with this finding, increased mRNA expression of thyrotropin releasing hormone (Trh) was observed in the thyroid of female at 0.3 mg/kg and 150 mg/kg as determined by RNAseq analysis. Moreover, significantly increased expression of parathyroid hormone (Pth) in the female at 0.3 mg/kg, and thyroglobulin (Tg) and thyroid hormone responsive (Thrsp) in the male at 0.3 mg/kg were noted in the blood, of which changes were substantially attenuated at 150 m/kg, alluding the meaningful effects of low dose DEHP on the thyroid hormone regulation. Urinary excretion of mono-2-ethylhexyl-phthalate (MEHP), a major metabolite of DEHP was determined to be 4.10 and 12.26 ppb in male, 6.65 and 324 ppb in female at 0.3 and 30 mg/kg DEHP, respectively, which fell within reported human urine levels. Collectively, these results suggest a potential adverse effects of low dose phthalates on the thyroid.

Four Poems of Kim Ki-rim

Kim Ki-rim,Lee Sung Il(번역자) The Academy of Korean Studies 1990 Korea Journal Vol.30 No.6

Effects of High Cholesterol Diet on Newly Generated Cells in the Dentate Gyrus of C57BL/6N and C3H/HeN Mice

KIM, Il Yong,HWANG, In Koo,CHOI, Ji Won,YOO, Ki-Yeon,KIM, Yo Na,YI, Sun Shin,WON, Moo-Ho,LEE, In Se,YOON, Yeo Sung,SEONG, Je Kyung Japanese Society of Veterinary Science 2009 The Journal of veterinary medical science Vol.71 No.6

<P>In this study, we observed and compared the effects of a high cholesterol diet (HCD) on cell proliferation and differentiation in the subgranular zone of the dentate gyrus of C57BL/6N (B6, susceptible strain) and C3H/HeN (C3H, resistant strain) mice. Ki67 (a marker for cell proliferation) positive cells) were significantly decreased in HCD-fed B6 mice compared to those in B6 (49.7%) and C3H mice fed a low cholesterol diet (LCD). In addition, doublecortin (DCX, a marker for cell differentiation or neuroblasts)-immunoreactive cells in HCD-fed B6 mice were significantly decreased compared to those in LCD-fed B6 and C3H mice. These results suggest that B6 strains are sensitive to HCD, which impairs cell proliferation and differentiation.</P>

Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer

Jung, So-Youn,Han, Wonshik,Lee, Jong Won,Ko, Eunyoung,Kim, Eunkyu,Yu, Jong-Han,Moon, Hyeong-Gon,Park, In Ae,Oh, Do-Youn,Im, Seock-Ah,Kim, Tae-You,Hwang, Ki-Tae,Kim, Sung-Won,Noh, Dong-Young Springer - Society of Surgical Oncology 2009 Annals of Surgical Oncology Vol.16 No.5

Relationship Between Biological Marker Expression and Fluorine-18 Fluorodeoxyglucose Uptake in Incidentally Detected Thyroid Cancer

Kim, Bo Hyun,Kim, In Joo,Kim, Sang Soo,Kim, Seong-Jang,Lee, Chang Hun,Kim, Yong-Ki Mary Ann Liebert 2010 Cancer Biotherapy & Radiopharmaceuticals Vol.25 No.3

<P>The aim of this study was to investigate the underlying mechanisms associated with fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in an incidentally detected thyroid cancer during nonthyroid cancer evaluation. Among 92 patients (10 men and 82 women; mean age, 56.2 +/- 10.9 years; age range, 26-78 years) with focal thyroid FDG uptake during nonthyroid cancer evaluation, 14 patients with cytologically confirmed papillary thyroid cancer were included. For semiquantitative analysis, the maximal standardized uptake value was calculated. Immunohistochemical studies were performed for hypoxia inducible factor 1 alpha (HIF1alpha), HIF2alpha, glucose transporter 1 (GLUT1), GLUT3, carbonic anhydrase IX (CA-IX), hexokinase type II (HK II), and vascular endothelial growth factor (VEGF). The significant findings of this study were as follows: (1) a lack of HIF1alpha and HIF2alpha expression; (2) low-degree expression of GLUT1 (1 patient), GLUT3 (5 of 14 patients), HK II (3 of 14 patients), and CA-IX (1 patient); and (3) high degree expression of VEGF (all 14 patients). The data presented in this study indicate that F-18 FDG uptake in incidentally detected thyroid cancer was not related to hypoxia-induced upregulation of GLUT1, GLUT3, CA-IX, and HK II. Ki-67 expression was not associated with F-18 FDG uptake. However, all incidentally detected thyroid cancers showed a high degree of expression of VEGF.</P>

A subpopulation of cancer stem cells identifies radiographic characteristics in glioblastoma

Kim, Ja Eun,Kim, Sung Kwon,Shin, Jaekyung,Se, Young-Bem,Choi, Seung Hong,Park, Sung-Hye,Choi, Seung Ah,Lee, Ji Yeoun,Phi, Ji Hoon,Wang, Kyu-Chang,Park, Chul-Kee,Kim, Seung-Ki D.A. Spandidos 2017 Oncology letters Vol.13 No.3

<P>Cancer stem cells (CSCs), defined by CD133 expression, harbor heterogeneous subpopulations of cells, including endothelial progenitor cells (EPCs). This study aimed to investigate whether a subpopulation of CSCs could affect the radiographic characteristics of glioblastoma. Tissue samples from 10 patients newly diagnosed with glioblastoma were selected according to the radiographic characteristics of their tumors. The patients were divided into two groups based on preoperative magnetic resonance imaging demonstrating contrast enhancement, necrosis and infiltrative patterns: the enhancement/necrosis group (E/N, n=5) and the non-enhancement/infiltration group (NE/I, n=5). Flow cytometry was used to assess the CSCs while immunohistochemistry was used to study microvessel density and the proliferation index. The EPC (CD34<SUP>+</SUP>/CD133<SUP>+</SUP>) fraction in CSCs (CD133<SUP>+</SUP>) was larger in the NE/I group. However, there was little difference in the angiogenic activity assessed using microvessel density between the two groups. The proliferation index (assessed using the antibody Ki-67) was higher in the E/N group and was negatively correlated with the EPC fraction. The non-EPC (CD34<SUP>−</SUP>/CD133<SUP>+</SUP>) fraction is a major factor responsible for radiographic characteristics of contrast enhancement, thus establishing an association between a subpopulation fraction of CSCs and radiographic characteristics in glioblastoma. Therefore, the simple non-invasive assessment of studying contrast enhancement lesions in glioblastomas may be used to estimate CSC subpopulations.</P>