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.

Comparison of Proliferative Activity in Each Histological Subtypes of Benign and Atypical Intracranial Meningiomas by PCNA and Ki-67 Immunolabeling

최승진,장은덕,권성오,계대곤,박춘근,이상원,강준기,Choi, Seung Jin,Chang, Eun Deok,Kwon, Seung Oh,Kye, Dae Kon,Park, Choon Keun,Lee, Sang Won,Kang, Joon Ki The Korean Neurosurgical Society 2000 Journal of Korean neurosurgical society Vol.29 No.9

목 적 : 양성 뇌수막종에 비하여 이형성 및 악성 뇌수막종이 나쁜 임상적인 예후 및 양상을 보이는 것은 잘 알려져 있으나, 양성 뇌수막종에 있어서 각각의 병리조직학적 아형에 따른 생물학적 양상의 차이에 대해서는 잘 알려지지 않거나 일부 논란이 되고있다. 본 연구에서는 이형성 뇌수막종 및 양성 뇌수막종의 각각의 병리조직학적 아형에 따른 증식능의 차이여부를 알아보고자 PCNA와 Ki-67표지지수를 분석하였다. 방 법 : 본원에서 뇌수막종으로 수술을 시행하여 얻은, 재발을 보여 재수술을 시행한 2례를 포함하여, 파라핀에 포매시킨 27개의 조직을 대상으로 병리학적인 증식능을 분석하기 위해, PCNA에 대한 단일항체 및 MIB-1 단일항체를 이용한 면역조직화학적 염색을 시행하였다. 조직학적 분류상 meningothelial type이 8례, transitional type이 9례, fibroblastic type이 5례였으며, 이형성 수막종이 5례였다. 결 과 : PCNA표지지수의 평균값은 양성 수막종에서 meningothelial type이 $4.82{\pm}5.10%$, transitional type이 $9.01{\pm}4.25%$, fibroblastic type이 $5.66{\pm}5.32%$를 보였으나 이형성 수막종에서는 $27.62{\pm}19.67%$의 높은 지수를 나타냈고, Ki-67 표지지수의 평균값은 양성 수막종의 아형에서 각각 $0.43{\pm}0.85%$, $0.44{\pm}1.08%$, $0.24{\pm}0.18%$를 보이고, 역시 이형성 수막종에서는 $0.84{\pm}0.59%$의 높은 지수를 보였다. 즉, 양성 수막종에서 각각의 아형에 따른 PCNA 및 Ki-67 표지지수는 통계학적으로 의미있는 차이는 없었으나(p>0.05), 이형성 수막종에서는 의미있는 높은 표지지수를 보여(p<0.05) 양성 수막종에서 보다 높은 증식능을 보임을 알 수 있었다. 결 론 : PCNA 및 Ki-67 표지지수를 이용한 증식능의 비교결과, 양성 뇌수막종에서는 각각의 아형에 따른 생물학적 양상이나 예후는 차이가 없을것으로 생각되나, 이형성 수막종에서는 높은 증식능을 보여 이에 대한 예후를 예상할 수 있을것으로 생각되며, 또한 이러한 표지지수가 병리조직학적으로 양성과 이형성의 감별에 많은 도움이 될것으로 사료된다. Objective : The clinical prognosis and biological behavior of atypical and especially malignant meningiomas are well known to be worse than benign meningioma, but the degree of biological aggressiveness in each classical subtypes of benign meningioma is controversy. This study was performed to see whether there is a difference in the proliferative activity between each different histological subtypes of benign meningioma as well as atypical meningioma. Methods : Paraffin-embedded surgical specimens of 27 meningiomas, including two recurrent tumors, were studied to evaluate proliferative activity by immunohistochemical method with monoclonal antibodies to proliferating cell nuclear antigen(PCNA) and MIB-1. The specimens consisted of 8 cases of meningothelial, 9 cases of transitional, 5 cases of fibroblastic subtypes and 5 cases of atypical meningiomas. Results : Mean PCNA labeling indices of meningothelial, transitional and fibroblastic meningiomas were $4.82{\pm}5.10%$, $9.01{\pm}4.25%$ and $5.66{\pm}5.32%$, but that of atypical meningiomas was $27.62{\pm}19.67%$, noting a higher value compared to all three subtypes of benign meningiomas. Mean Ki-67 labeling indices of the above 3 subtypes were $0.43{\pm}0.85%$, $0.44{\pm}1.08%$ and $0.24{\pm}0.18%$, and that of atypical meningiomas was also revealed to be of higher value ($0.84{\pm}0.59%$). PCNA and Ki-67 labeling indices were not statistically different between histological subtypes of benign meningioma(p>0.05), but the differences of both immunolabeling between benign and atypical meningiomas were statistically significant(p<0.05). Conclusion : Immunolabeling of PCNA and Ki-67 in intracranial meningiomas reveals no prognostic difference between meningothelial, transitional and fibroblastic subtypes in classical benign meningiomas by measuring expression of PCNA and Ki-67, but it seems to be helpful in differentiating benign and atypical meningioma, later showing more proliferative activity and biological aggressiveness.

소켓 용접부 내부 결함 검사용 초음파 자동 검사 장비 개발

이정기,박문호,박기성,이재호,임성진 한국비파괴검사학회 2003 학술대회 논문집 Vol.- No.1

대구경 배관에서 소구경 배관으로 연결하는 부위 및 배관의 방향 전환을 위해 연결하는 소켓용 접부의 용입 불량 및 사용시간이 경과되면서 내부로부터 진전될 수 있는 균열 검출을 위한 초음파 검사 기법을 확립하였고, 검사를 수행할 수 있는 초음파 탐촉의 개발과 더불어 자동으로 검사할 수 있는 검사 장비와 제어용 운영 프로그램을 개발하였다. 개발된 장비는 컴퓨터를 기반으로 하고 있으며, pulser/receiver를 내장하고 고속 A/D board를 사용하여 초음파 탐상기 역할을 프로그램으로 구현하였으며, ISA interface type으로 4축 제어용 motion controller를 개발하여 자동 검사를 수행하는 scanner를 제어하도록 하였으며, 검사 결과는 소켓용접부 단면을 실시간 영상으로 나타내도록 되어 있다. 개발된 장비는 원자력 발전소나 화학플랜트에 많이 널려 있는 소켓용접부 내의 용입불량, 피로 균열 등을 검출하여 객관적인 검사 결과를 제시할 수 있으므로 설비 안전 관리 및 보수 부위 결정에 기여가 있을 것으로 기대된다.

소켓 용접부 결함 검사용 초음파 자동 검사 장비 개발

이정기,박문호,박기성,이재호,임성진 한국비파괴검사학회 2004 한국비파괴검사학회지 Vol.24 No.3

대구경 배관에서 소구경 배관으로 연결하는 부위 및 배관의 방향 전환을 위해 사용하는 소켓용접부는 용입불량 및 사용기간이 경과되면서 내부로부터 진전될 수 있는 균열 등의 결함을 가질 수 있다. 그러나 지금까지 적용하고 있는 비파괴검사법인 액체침투탐상과 방사선투과검사로는 내부에 존재하는 균열성 결함의 검출이 어렵다. 본 연구에서는 소켓용접부 내부의 균열성 결함 검출을 위한 초음파 검사 기법을 확립하였고, 검사를 수행할 수 있는 초음파 탐촉자를 설계 제작하였으며, 자동으로 검사할 수 있는 검사 장비와 제어용 운영 프로그램을 개발하였다. 개발된 장비는 컴퓨터를 기반으로 하고 있으며, pulser/receiver를 내장하고 100㎒ 고속 A/D board를 사용하여 초음파 탐상기 역할을 프로그램으로 구현하였으며, ISA interface type으로 4축 제어용 motion controller를 개발하여 자동 검사를 수행하는 scanner를 제어하도록 하였으며, 검사 결과는 소켓용접부 단면을 실시간 영상으로 나타내도록 되어 있다. 인공결함 ㅅ험편의 결함을 평가한 결과 결함의 깊이가 1㎜인 결함의 평가 길이는 실제 크기보다 작게 나타내고 있으며, 결함의 깊이가 증가할수록 결함의 길이가 더 크게 평가되었다. 본 연구로 개발한 장비는 원자력 발전소나 화학플랜트에 많이 널려 있는 소켓용접부 내의 용입불량, 피로 균열 등을 검출하여 객관적인 검사 결과를 제시할 수 있으므로 설비 안전 관리 및 보수 부위 결정에 기여할 수 있을 것으로 기대된다. Socket weldment used to change the flow direction of fluid may have flaws such as lack of fusion and cracks. Liquid penetrant testing or Radiography testing have been applied as NDT methods for flaw detection of the socket weldment. But it is difficult to detect the flaw inside of the socket weldment with these methods. In order to inspect the flaws inside the socket weldment, a ultrasonic testing method is established and a ultrasonic transducer and automated ultrasonic testing system are developed for the inspection. The automated ultrasonic testing system is based on the portable personal computer and operated by the program based Windows 98 or 2000. The system has a pulser/receiver, 100 ㎒ high speed A/D board, and basic functions of ultrasonic flaw detector using the program. For the automated testing, motion controller board of ISA interface type is developed to control the 4-axis scanner and a real time iC-scan image of the automated testing is displayed on the monitor. A flaws with the size of less than 1 ㎜ in depth are evaluated smaller than its actual size in the testing, but the flaws larger than 1 ㎜ appear larger than its actual size on the contrary. This tendency is shown to be increasing as the flaw size increases. A reliable and objective testing results are obtained with the developed system, so that it is expected that it can contribute to safety management and detection of repair position of pipe lines of nuclear power plants and chemical plants.

Ki - 1 임파종 1 예

강민모(Min Mo Kang),김경재(Kyoung Jae Kim),이지현(Ji Hyun Lee),최석문(Seog Mun Choi),안기성(Ki Sung Ahn),황기석(Kee Suk Whang),김용진(Yong Jin Kim),박재복(Jae Bok Park) 대한내과학회 1993 대한내과학회지 Vol.45 No.4

A 60-year-old man was admitted to our hospital complaining of fever with chillness and anarexia for 12 weeks. Physical examination revealed supraclavicular lymphadenopathy and left inguinal lymphadenopathy. Abdominal CT scan showed the evidence of maked lymphadenopathy on retraperitoneal, external iliac, obturator, left inguinal, and celiac lymph nodes. A pathologic diagnosis of Ki-1(+) lymphoma was made by the biopsed supraclavicular lymph node because the node consisted of large cells with pleomorphic nuclei, scanty cytoplasm, large basophilic nucleoli, atypical vacuoli and large cells were positive for leukocyte common antigen, Ber-H2, marker, and B-cell marker.

들잔디 성숙종자로부터 캘러스배양 및 식물체 재분화에 미치는 몇 가지 요인의 영향

이상훈,김범수,원성혜,조진기,김기용,박근제,성병렬,이효신,이병현 Plant molecular biology and biotechnology research 2004 Plant molecular biology and biotechnology research Vol.2004 No.-

In an effort to optimize tissue culture responses of zoysiagrass (Zoysia japonica Steud.) for genetic transformation, factors affecting callus induction and plant regeneration were investigated. MS medium containing 3 ㎎/L 2,4-D was optimal for embryogenic callus induction from mature seed. The plant regeneration frequency of 73.3% was observed when embryogenic calli induced in this medium were transferred to N6 medium supplemented with 0.1 ㎎/L 2,4-D and 5 ㎎/L BA. Among several basic media, MS and N6 medium were optimal for callus induction and plant regeneration, respectively. Regenerated plants were grown normally when shoots transplanted to the soil. A rapid and efficient plant regeneration system established in this study will be useful for molecular breeding of turfgrass through genetic transformation.

Gelatin 액화세균의 생장억제에 관한 연구

이기성,崔榮吉,趙賢淑 漢陽大學校 環境科學硏究所 1983 環境科學論文集 Vol.4 No.-

Gelatin 을 재료로 이용하는 식품의 폐기물에서 gelatin 을 액화시키는 능력이 특히 뛰어난 4종의 세균을 분리·동정하였으며, 배지내에 NaCI, KI·I₂, CuSO₄등의 억제제를 농도별로 처리했을때 나타나는 4균주의 생존도 및 액화능의 변화를 비교·검토하였고, 생존도에 미치는 pH의 영향도 조사하였다. 또한 MIC(Minimal Inhibitory Concentration) Test를 시행하여 항생제에 대한 4균주의 MIC도 조사하였다. 그 결과는 다음과 같다. 1. 4균주중 H strain은 Serratia liquefaciens로, Y₁strain은 Enterobacter속으로, Y₂와 Y₃strain 은 Pseudomonas 속으로 동정되었다. 2. 배지내에 억제제로 NaCl을 처리했을 경우, 7% 농도에서 생장이 100% 억제되었으며, KI·I₂처리시에는 20ppm 에서부터 생장이 억제되기 시작하여 100ppm에서는 4개의 균주 모두 100% 생장이 억제되었다. CuSO₄처리시에는 100ppm에서부터 억제효과를 나타내기 시작하여 300ppm에서는 거의 100% 억제 효과를 보였다. 생존도에 미치는 pH의 영향을 살펴본 결과, pH 5.0, 5.5, 6.0에서는 대조군과 동일한 생존도를 나타냈으나 pH 4.0, 4.5 에서는 100% 생장이 억제되었다. 분리 균주들의 액화능 비교에 있어서는 H strain 이 가장 뛰어난 액화능을 나타내었다. CuSO₄와 KI·I₂를 각각 3ppm, 10ppm의 저농도로 처리했을 경우 4균주의 액화능은 대체로 10∼20% 감소되었다. 3. 액화 능력이 가장 뛰어난 H strain 의 MIC 는 Penicillin G; 1∼5 ㎍/ml, Spectinomycin; 12.5∼25㎍/ml, Ampicillin; <0.05㎍/ml, Cefobid; <1㎍/ml, Claforan; 0.02∼0.3㎍/ml, Tetra-cycline; >10㎍/ml로 나타났다. Tetracycline을 제외한 5가지 항생제에 대하여 H strain이 Y strain들에 비해 민감한 것으로 나타났다. 그러나 Tetracycline의 경우에는 H strain이 Y strain들에 비하여 저항성을 갖는 것으로 나타났다. Four strains of gelatin-liquefying bacteria were isolated from the sewage of the food using gelatin as the material. Treated with various concentration of NaCl, KI-I₂and CuSO₄in the culture medium and with various gradient of pH, viability of the four strains was examined and compared with each other. And also, gelatin liquefying ability was investigated in the normal culture condition and in accordance with the concentration of the inhibitor. Morever, MIC(Minimal Inhibitory Concentration) test for these strains was also carried out. The results were as follows: 1. Of the four isolated strains, the H strain was identified as Serratia liquefaciens, Y₁as the genus Enterobacter, Y₂and Y₃strains as the genus Pseudomonas. 2. Treating the culture medium with NaCl as the growth inhibitor, 7% concentration of NaCl inhibited completely the viability of all the isolated strains. Adding KI-I₂solution to the medium at the level of 20ppm, viability began to decrease and the inhibitory effect was shown 100% at 100ppm. Treated with CuSO₄at the level of 10ppm, viability began to decrease, and at 300ppm growth inhibition showed almost 100%. There was no significant difference in viability according to the pH gradient at the range of 5.0-6.0. However, at pH 4.0 and 4.5, 100% inhibitory effect on the growth was shown. Considered with the ability of gelatin liquefaction, the H strain among the four strains had the most rapid and strong ability in gelatin liquefaction. (That is, about 23 times more effective in gelatin liquefaction than that of Y₁strain) 3. Considered the MIC test, the H strain was more sensitive to Penicillin G(1-5 ㎍/ml), Spectinomycin(12.5-25㎍/ml), Ampicillin(<0.05㎍/ml), Cefobid(<1㎍/ml) and Claforan (0.02-0.3㎍/ml) than to those of the strains. Compared with the other strains, the H strain was more insensitive up to the level of 10㎍/ml to the minimal inhibitory concentration of Tetracycline.

새로운 연노출의 효과지표로서의 혈장 δ-aminolevulinic acid 측정의 유용성

이금원,황보영,김용배,리갑수,이성수,장봉기,함정오,안규동,이병국 순천향대학교 산업의학연구소 2001 순천향산업의학 Vol.7 No.1

To evaluate the usefulness of the measurement of plasma δ - aminolevulinic acid (ALAP) as a new effect indicator of lead exposure, the association of ALAP with blood lead, DMSA chelatable lead and bone lead with a special emphasis of genetic interaction of ALAD polymorphism was studied with 419 lead exposed workers and 85 non-lead exposed workers. Lead workers were recruited from storage battery industries, secondary smelting industries and other lead using industries and non-lead workers selected from electronic refrigerator manufacturing industry. Blood lead, DMSA chelatable lead and bone lead were chosen for parameters of lead exposure. Plasma and urinary ALA were selected for the effect parameter of lead intoxication. Information for age, smoking, drinking habit and body mass index were also obtained. Job duration for lead workers was also collected. The overall prevalence of the variant allele, ALAD type 1-2 or 2-2(ALAD2) in lead exposed workers was 10.0% (42 out of 419 lead workers) which was not differed from control workers (9.4% : 8 out of 85). The means blood lead and DMSA chelatable lead of lead workers with ALAD 1(ALAD type 1-1) were lower than those of lead workers with ALAD2, but the differences were not statistically significant. On the other hand, the mean of tibia lead of lead workers with ALADI was higher than that of lead workers with ALAD2, but the difference was not statistically significant. DMSA chelatable lead showed highest correlation with log transformed plasma ALA(LALAP)(r=0.682) and blood lead and tibia lead had r=0.650, r=0,402 correlation coefficient with LALAP respectively On the other hand. log transformed urinary ALA(LALAU) had lower correlation coefficient with all three parameters of lead exposure than LALAP. The equation of robustic simple linear regression of blood lead on LALAP was LALAP=2.0439+0.0165PbB in ALADI lead workers and LALAP=2.031+0.0121PbB in ALAD2 lead workers. ALAD genotype in the multiple regression analysis of blood lead with LALAP after adjusting for possible confounders(sex, ago, BMI, smoking and drinking status and job duration) showed significant main effect on LALAP resulting lower LALAP in ALAD2 lead workers than ALADI lead workers. On the other hand, effect modification of ALAD genotype was observed in the multiple regression analysis of tibia lead with LALAP after adjusting for possible confounders, but there was no significant effect of ALAD genotype in the multiple regression analysis of DMSA chelatable lead with LALAP after covariate adjustment. With above results, plasma ALA was found to be a useful effect parameter of lead exposure compared with urinary ALA. It was also observed that ALAD polymorphism made significant effect on the association of blood and tibia lead with ALAP. Thc lower plasma ALA in ALAD2 lead workers suggested supportive effect of ALAD2 in lead exposure.

조혈모세포이식환자에서 조혈기능의 회복과 관련된 인자들에 관한 연구

정기주,강명수,권기두,김경하,이상철,김현정,배상병,김찬규,이남수,이규택,원종호,홍대식,박희숙 순천향대학교 의학연구소 2007 Journal of Soonchunhyang Medical Science Vol.13 No.1

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