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.

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.

직장 카르시노이드 종양에서 Ki-67 발현의 예후적 중요성

홍수민 ( Su Min Hong ),김유선 ( You Sun Kim ),문정섭 ( Jung Seop Moon ),김진남 ( Jin Nam Kim ),오명기 ( Myoung Ki Oh ),권선옥 ( Sun Ok Kwon ),정성연 ( Seong Yeon Jeong ),홍성우 ( Seong Woo Hong ),강윤경 ( Yun Kyung Kang ) 대한소화기학회 2013 대한소화기학회지 Vol.61 No.2

Background/Aims: Rectal carcinoid tumors can be resected with endoscopy, and it is important to assess their prognostic factors. We evaluated the potential of Ki-67 expression as a prognostic factor in rectal carcinoid tumors. Methods: We retrospectively reviewed the medical records of 37 patients with rectal carcinoid tumors who got endoscopic resection from January 2001 to January 2011 at Inje University Seoul Paik Hospital. We analyzed their endoscopic and histologic findings, Ki-67 expression, clinical outcome, and prognosis. Results: The mean age (±SD) of the patients was 56.3±10.7 years, and the male : female ratio was 3.6:1. The mean tumor size was 0.5±0.4 cm, 33 patients showed grade 1 tumors (89.2%) and the average Ki-67 expression was 0.7±1.2%. Thirty five patients underwent endoscopic mucosal resection, and two required endoscopic submucosal dissection. Eight patients had positive margins after resection, but no cases of lymphovascular invasion were identified. The median follow-up duration was 21.4±25.4 months, and no recurrences were observed. Conclusions: In low grade rectal carcinoid tumors which are lack of central depression on colonoscopy, the expression of a molecular marker of malignant potential, Ki-67, was low. Therefore, endoscopic resection seemed to be a safe and effective treatment for these tumors.

크롬을 처리한 마우스비장세포에서 초기에 발현되는 유전자분석

고재기,백기룡,김우형,정금분,우기민,이상한 순천향대학교 의학연구소 2006 Journal of Soonchunhyang Medical Science Vol.12 No.1

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역행적 골수정 삽입술을 이용한 대퇴골 과상부 골절의 치료

권진우,신승호,조원호,성기호,김기환,손경태,이상훈,박세원,배종문,권태우 대한골절학회 2003 대한골절학회지 Vol.16 No.4

한의진단명과 진단요건의 표준화 연구 II (표준화 실례) : 2차년도 연구결과 중간 보고

양기상,최선미,최승훈,안규석,박경모,박종현,김성우,신승호,정우열,전병훈,고현,김정범,신상우,김성훈,김동희,권영규,엄현섭,장혜옥 한국한의학연구원 1996 한국한의학연구원논문집 Vol.2 No.1

The diagnostic requirements were suggested and explained regarding the systems of differentiation of symptoms and signs in the second year study of standardization and unification of the terms and conditions used for diagnosis in oriental medicine. The systems were as follows; - differential diagnosis according to condition of body fluid, differentiation of syndromes according to the state of qi and blood, differential diagnosis according to relative excessiveness or deficiency of yin and yang(氣血陰陽津液辨證) - differentiation of diseases according to pathological changes of the viscera and their interrelation - analyzing and differentiating of febrile diseases in accordance with the theory of the six channels(傷寒辨證) The individual diagnosis pattern was arranged by the diagnostic requirements in the following order : another name(異名), notion of diagnosis pattern, index of differentiation of symptoms and signs(辨證指標), the main point of diagnosis, analysis of diagnosis pattern(證候分析), discrimination of diagnosis pattern(證候鑑別), a way of curing a diseases(治法), prescription(處方), herb in common use(常用藥物), diseases appearing the diagnosis pattern(常見疾病), documents(文獻調査). This study was carried out on the basis of the Chinese documents and references.

논쟁사를 통해서 본 한국 서양사학의 자기이해 ― 한국 독일사학회 현황과 방향을 중심으로 ―

황기우 ( Hwang Ki Woo ) 수선사학회 2020 史林 Vol.0 No.71

Clearly, big data-based digital technology is the main industry of the Republic of Korea and the leading field of the world. Nevertheless, a new historical methodology based on digital technology is being tried in Western history. History based on digital technology at the beginning stage has yet to produce accurate methodologies or tangible results. But it is only a matter of time and is expected to change the paradigm of history in the near future. Under these circumstances, digital technology, which is leading the fourth industrial revolution, is expected to make new breakthroughs in Korean and German studies as well as Korean Western history. Of course, digital technology cannot be the only key to solving the problems faced by Korean Western history. However, none of the new attempts to transcend existing methodologies in times of historical crisis are more extensive than those based on digital technology and are most suitable for changing the times. In particular, the fact that this field is on the starting line all over the world gives us a lot of meaning. Just as the boundaries between studies in the humanities have become meaningless, the boundaries between natural sciences and humanities are also about to be broken down. At this point, Korean Western history may be forced to recognize itself for its future. The stable environment of university has even become suspicious of its existence, and new digital technology is disabling the function of history as ‘knowledge’. Whatever it may be, the future of Western history is not so bright. Therefore, it is time to start anew the self-awareness of Western history. Such recognition means destroying existing regionalism and reconstructing it from a huge framework called “history,” as emphasized by Kim Ki-bong. And the paradigm shift brought by the fourth industrial revolution is forcing new changes in history as well.

筋小胞體의 ATPase Kinetics에 關한 硏究

朴映淳,李承兩,朴泰水,庾基洙,李 弘,金允坤 圓光大學校 1982 論文集 Vol.16 No.2

본 연구에서는 토끼 골격근 소포체에서 분리한 근소포체의 ATPase활성에 대한 일반적 특성과 수종의 2가 양이온(??)의 영향에 관한 연구를 하였다. ATPase활성과 Ca uptake에 미치는 2가 양이온의 저해 효과와 저해기작은 Dixon plot, Lineweaver-Burk plot, Hanes-Woolf plot, Woolf-Augustinsson-Hofstee plot, Eadie-Scatchard plot, Arrhenius plot등을 이용하여 분석하였으며 그 결과는 다음과 같다. 1. 근소포체의 ATPase는 ??과 ??의 존재하에서 활성화 되어지며 ??의 농도가 4mM일 때 ??의 최적 농도는 0.1mM이었다. 2. 근소포체의 ATPase는 ??-ATPase와 (??)-ATPase로 구성되어 있고 (??) - ATPase의 활성은 ??-ATPase의 활성보다 높았다. 3. ATPase의 활성화 에너지는 약 19Kcal/mol이었다. 4. ATPase 활성에 미치는 2가 양이온은 12.5㎛과 400㎛의 범위 내에서 이온 농도가 증가됨에 따라서 활성도는 점점 감소되었다. 5. ATPase활성율 50% 저해시키는데 2가 양이온의 농도는 Ki값과 같아서 ??, ??, ?? Pd ??에 대한 각각의 농도는 10㎛, 30㎛, 130㎛ 및 350㎛이었다. 특히 ??은 저 농도에서 (12.5-100㎛)는 활성제로, 고농도에서 (200-400㎛)는 저해제로 작용하는 것 같다. 6. 2가 양이온은 ATPase의 Km에는 변화를 주지 않으나 Vmax의 저하를 일으키는 것으로 보아 비경쟁 저해제임이 판정되었다. 7. 2가 양이온은 가역적 저해제임이 판명되었다. 8. Ca 吸收能에 대한 CuCl₂의 阻害는 50~500㎛의 CuCl₂농도에서 현저히 나타났으며 이 현상은 Ca 吸收能과 ATPase 活性과 밀접한 관계를 보여주는 것이다. General properties of the ATPase and the effects of the divalent cations (??) on the total ATPase activity of the fragmented sarcoplasmic reticulum (FSR) isolated from rabbit skeletal muscle were investigated in the present resent research. The inhibitory effect of divalent cations on the FSR ATPase activity and its mechanism were analyzed by various plots such as Dixon plot, Lineweaver-Burk plot, Hanes-woolf plot, Eadie-Scatchard plot and Arrhenius plot. The results obtained were as follows: 1. The FSR ATPase is activated by ?? and ??; the optimum concentration of is 0.1 mM in the presence of 4 mM MgCl₂. 2. The FSR ATPase could be distinguished as ??-ATPase and (??)-ATPase. The activity of (??)-ATPase predomiant over that of ??-ATPase. 3. The apparent energies of activation for total ATPase was approximately 19Kcal/mole. 4. The inhibitory effects of the divalent cations on the enzyme activity increased as the concentrations of the divalent cations increased in the concentrations between 12.5 and 400㎛. 5. Concentration of 50% inhibition for each divalent cation was almost identical with the inhibition constant (ki). The Ki's were 10,30,130, and 350㎛ for ??, ??, ??, and ??, respectively. ?? seemed to be anactivator at lower concentrations and an inhibior at higher concentratios. 6. The divalent cations did not change the Km but decreased the Vmax of the FRS ATPase, suggesting that they are noncompetitive inhibitors on the FSR ATPase. 7. The divalent cations were also found to be revesible inhibitors on the FSR ATPase. 8. The inhibitory effect of CuCl₂on a uptake increased as the concentration CuCl₂increased in the range between 50㎛.

AMP-activated Protein Kinase 활성체인 Metformin의 모발 성장에 미치는 영향

문혜림 ( Hye-rim Moon ),박기영 ( Ki-young Park ),강현지 ( Hyun Ji Kang ),이우진 ( Woo Jin Lee ),원종현 ( Chong Hyun Won ),장성은 ( Sung Eun Chang ),이미우 ( Mi Woo Lee ),최지호 ( Jee Ho Choi ),박경훈 ( Gyeong-hun Park ) 대한피부과학회 2019 대한피부과학회지 Vol.57 No.4

Background: AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that plays a pivotal role in the balance of cellular energy metabolism. Recent studies have reported that AMPK has numerous roles in physiological conditions, and dysregulation of AMPK induces pathological processes and diseases. However, the role of AMPK and its activators have not yet been studied in the context of hair growth regulation. Objective: To investigate the effects of metformin on dermal papilla (DP) and outer root sheath (ORS) cells, as well as the role of the AMPK pathway in hair growth. Methods: We evaluated whether metformin, a well-known AMPK activator, had any beneficial effects on hair growth. In addition, to evaluate the molecular and cellular mechanisms that were involved, protein levels of AMPK and β-catenin were analyzed. Results: Metformin increased the cellular proliferation of human DP and ORS cells. Ki-67 expression was also significantly increased after metformin treatment in the ex vivo hair follicle organ culture. Furthermore, DP and ORS cells treated with metformin had a significant increase in AMPK phosphorylation, which in turn suppressed β-catenin degradation and enhanced its nuclear accumulation. Conclusion: We demonstrated that metformin promoted hair growth via the AMPK/β-catenin signaling pathway in vitro with DP and ORS cells. The hair-promoting effects of AMPK activators may potentially be used for the treatment of alopecia, and further investigation will be needed in the future. (Korean J Dermatol 2019;57(4):175∼ 181)

Expression of Wnt Target Genes in Solid Pseudopapillary Tumor of the Pancreas: A Pilot Study

Kang, Chang Moo,Kim, Hyun Ki,Kim, Hoguen,Choi, Gi Hong,Kim, Kyung Sik,Choi, Jin Sub,Lee, Woo Jung Lippincott Williams Wilkins, Inc. 2009 PANCREAS Vol.38 No.2

OBJECTIVES:: Solid pseudopapillary tumor (SPT) of the pancreas is very rare. This study was performed to analyze the expression of Wnt signal target genes (matrix metalloproteinase-7 [MMP-7], cyclin-D1, and c-myc) and Ki-67 in resected SPTs to determine their clinicopathologic characteristics according to their expression. METHODS:: From January 1995 to December 2005, 23 patients underwent pancreatic resections for SPT of the pancreas. Among 23 formalin-fixed, paraffin-embedded tissues, 12 were evaluated as a pilot study. Immunohistochemistry was performed using various detection and antigen retrieval methods to detect MMP-7, cyclin-D1, c-myc, and Ki-67. The expression of Wnt target genes was correlated with clinicopathologic features of the patients. RESULTS:: Solid pseudopapillary tumors of the pancreas always showed cytoplasmic/nuclear accumulation of &bgr;-catenin, frequent expression of cyclin-D1, and low proliferation index. MMP-7, cyclin-D1, c-myc, and Ki-67 were not correlated with microscopic features suggesting malignant potential (P > 0.05). Tumor size was closely related to microscopic features of malignant potential and apparently has an inverse relationship with the expression of cyclin-D1 and Ki-67 (P < 0.05). CONCLUSIONS:: Low proliferative index and associated MMP-7 expression may cause an unpredictable clinical course in this tumor. Subtle changes in the intracellular environment, not pathologic (morphologic) changes, may elucidate the unpredictable clinical course of this tumor.