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.

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)

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)

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

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

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>

Associations of serotonergic genes with poststroke emotional incontinence

Kim, Jae‐,Min,Stewart, Robert,Kang, Hee‐,Ju,Bae, Kyung‐,Yeol,Kim, Sung‐,Wan,Shin, Il‐,Seon,Kim, Joon‐,Tae,Park, Man‐,Seok,Cho, Ki‐,Hyun,Yoon, Jin‐ John Wiley Sons, Ltd 2012 INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY Vol.27 No.8

<P><B>Objectives</B></P><P>Poststroke emotional incontinence (PSEI) has been associated with serotonergic dysfunction. Polymorphisms of serotonin transporter (5‐HTT) and serotonin 2a receptor (5‐HTR2a) genes may regulate serotonergic signaling at brain synapses, and this study was to investigate associations with PSEI in an East Asian population.</P><P><B>Methods</B></P><P>In 276 stroke cases, PSEI was diagnosed by Kim's criteria. Covariates included age, gender, education, history of depression or stroke, current depression, and stroke severity and location. Genotypes were ascertained for 5‐HTT gene‐linked promoter region (5‐HTTLPR), serotonin transporter intron 2 variable number tandem repeat, 5‐HTR2a 1438A/G, and 5‐HTR2a 102 T/C. Associations with PSEI were estimated by using logistic regression models, and gene–gene interactions were investigated by using the generalized multifactor dimensionality reduction method.</P><P><B>Results</B></P><P>PSEI was present in 37 (13.4%) patients. The 5‐HTT gene‐linked promoter region <I>s</I>/<I>s</I> genotype was independently associated with PSEI. No associations with STin2 VNTR and 5‐HTR2a genes were found, and no significant gene–gene interactions were identified.</P><P><B>Conclusions</B></P><P>Stroke patients with 5‐HTTLPR <I>s</I> allele had higher susceptibility to PSEI, which underlines the potential role of serotonergic pathways in its etiology. Copyright © 2011 John Wiley & Sons, Ltd.</P>

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.

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>