The oncoprotein, gankyrin, is up-regulated in middle ear cholesteatoma

Kim, Ki Hyun,Lim, Hye Jin,Kim, Yeon Ju,Kim, Seung Won,Kim, Young Sun,Tian, Chunjie,Park, Keehyun,Park, Tae Jun,Choung, Yun-Hoon Scandinavian University Press 2014 Acta oto-laryngologica Vol.134 No.3

<P><I>Conclusion:</I> Gankyrin seems to be a better biomarker for cholesteatoma compared with Ki-67. <I>Objective:</I> Gankyrin is an oncoprotein, and occurs in cancers but not in benign diseases. The goal of this study was to compare expression of gankyrin, p53, and a proliferation marker (Ki-67) in cholesteatoma and retroauricular skin (RAS), and to evaluate their significance as clinical parameters. <I>Methods:</I> The levels of expression of gankyrin, Ki-67, and p53 in 10 cholesteatoma and 10 paired samples of normal RAS were evaluated by immunohistochemical staining and Western blot. The results were compared with clinical profiles to investigate a correlation. <I>Results:</I> The expression of gankyrin, Ki-67, and p53 proteins was observed in both basal and suprabasal layers of cholesteatoma. The intensity of gankyrin expression was ‘positive’ in two cases (20%) and ‘strongly positive’ in eight cases (80%); p53 expression in the suprabasal layer was ‘positive’ in 70% of cases; and the Ki-67 staining was ‘focal’ in 80% of cases. In RAS, these proteins were expressed dominantly in the basal layer. Western blot analysis showed that the gankyrin band was more intense in cholesteatoma than in RAS for three of four cases (<I>p</I> < 0.05). However, there was no significant difference in the expression of gankyrin, Ki-67, and p53 according to clinical variables.</P>

인체 대장암 및 자궁경부암에서 PCR-SSCP법을 이용한 Ki-ras 암유전자의 점돌연변이에 관한 연구

박영홍,백낙환,김현찬,김상효,홍관희,김기태,이기영 인제대학교 1994 仁濟醫學 Vol.15 No.2

인체 대장암 20례와 자궁경부암 10례의 암조직을 대상으로 c-Ki-ras 유전자 codon 12와 13에서의 점돌연변이를 알아보고자 polymerase chain reaction(PCR)과 single-strand conformation polymorphism(SSCP) 검사법을 시행하였다. 대장암의 경우 20례중 9례(45%)에서, 자궁경부암의 경우 10례중 1례(10%)에서 양성으로 나왔다. 대장암에서는 codon 12에서 GGT가 TGT로의 치환이 4례로서 가장 많았으며, AGT, CGT로의 치환이 각 1례였고 codon 13에서는 GGC가 GAC로의 치환이 2례, TGC로의 치환이 1례인 것으로 나타났다. 자궁경부암의 경우 codon 12에서 GGT가 AGT로의 치환이 1례인 것으로 나타났다. In an attempt to clarify the role of genetic alteration in the genesis of human colorectal and cervical cancers, tissue specimens from 20 patients with colorectal cancer and 10 patients with cervical cancer were examined for the presence of point mutation in K-ras2 exon 1 by single strand conformation polymorphism analysis of PCR product. Exon I of c-Ki-ras2 was amplified by polymerase chain reaction(PCR) and comparison was made between the normal and mutated genes by nondenaturing polyacrylamide gel electrophoresis(PAGE) of PCR product and nucleotide sequence analysis using asymmetric PCR with direct sequencing. Genomic DNA from white blood cells were used as normal control and those from A427 cell line were used as mutated control. 1.PCR product from A427 cell line showed a distinct migration shift pattern compared to the normal control in PAGE and the direct sequencing indicated that nucleotide sequence of codon 12 was mutated from GGT to GAT. In addition, there was a loss of normal allele in A427 cell line. 2.PCR product from 9 cases(45%) out of a 20 colon cancer patients showed migration shifts in PAGE, and all of these 9 patients invariably demonstrated mutation of ras gene, either in codon 12(6 cases:30%) or 13(3 cases:15%). The base substitutions in codon 12 were: from GGT to AGT(1), CGT(1), or TGT(4). Base changes in codon 13 were from GGC to TGC(1) or GAC(2). 3.PCR product from 1 cases(10%) out of a 10 cervical cancer patients showed migration shrifts in PAGE, Invariably demonstrated mutation of ras gene in codon 12. The base substitutions was from GGT to AGT(1) TQE incidence of point mutation of c-Ki-ras in colon cancer was high, however, it was low in cervical cancer, which showed the relation of ruts gene mutation with colon cancer. PCR -SSCP analysis is a simple, rapid and efficient method of detection of point mutation, especially when dealing with multiple samples.

Comparison of controlled ovarian stimulation outcomes for fertility preservation in women with breast cancer according to KI-67, histologic grade, pathologic type, and cancer stage

( Eun Ji Oh ),( Yeon Hee Hong ),( Seul Ki Kim ),( Jung Ryeol Lee ),( Byung Chul Jee ),( Chang Suk Suh ),( Seok Hyun Kim ) 대한산부인과학회 2020 대한산부인과학회 학술대회 Vol.106 No.-

Objective: This study aims to analyze that specific prognostic factors such as Ki-67 value, histologic grade, pathology type, and cancer stage can affect controlled ovarian stimulation outcomes(COS) for fertility preservation in women with breast cancer. Methods: This retrospective cohort study included 92 patients with breast cancer aged 21-44 who underwent COS from August 2012 to April 2020, excluding patients with previous gonadotoxic therapy history. All COS cycles were conducted letrozole-combined random start GnRH antagonist protocol. COS outcomes were compared according to prognostic factors;Ki-67 (< 30% vs. ≥ 30%), histologic grade (low vs. high), and pathologic type (intraductal carcinoma(IDC) vs. triple-negative breast cancer(TNBC)), and cancer stage (early (I, II) vs. advanced (III, IV)). Multivariate analysis was also conducted to find any parameter that can impact over 10 mature oocytes acquisition. Results: Among the 92 patients, 42 were Ki-67≥30% compared to 49 of Ki-67<30%. The number of oocytes, and initial mature oocytes were comparable between Ki-67<30% and ≥30 group. The maturation rate was significantly higher in Ki-67≥30% group than Ki-67<30% group (57.4±36.8% vs. 44.8±28.3%, p=0.041). The same results were drawn when divided according to IDC or TNBC. The maturation rate was significantly higher in TNBC than the IDC group (73.0±17.6% vs. 47.0±28.1% p=0.001). However, the histologic grade or stage did not show any difference in COS outcomes between high and low grade or early and advanced stages. With multivariate analysis, age and AMH are parameters associated with the acquisition of over 10 mature oocytes (OR 0.863, 95% CI [0.755-0.987], OR 1.408, 95% CI [1.145-1.732], respectively). Conclusion: Either Ki-67 or pathologic type can be a potential reliable marker for predicting COS outcome, especially maturation rate. Further study with larger sample size with specific conditions is necessary to clarify the correlation between breast cancer prognostic factors and COS outcomes.

2003년도 해양스포츠 체험활동을 통한 소아건강교실 사례 발표

김현준,이상엽,이가영,곽현,이남수,김혜선,김윤진,김인주,김용기,대한비만학회 부산분과학회 일동 대한비만학회 2003 The Korean journal of obesity Vol.13 No.4

부산에 소재한 3개 초등학교 청소년단체 소속의 초등하교 3학년부터 6학년까지 구성된 172명을 대상으로 청소년단체 지도자, 초등학교교사, 자원봉사자, 의사와 영양사가 1박 2일간의 해양스포츠 체험활동 을 통한 건강교실을 시행하였다. 대상자의 체질량지수, 체지방량을 측정하여 비만정도를 평가하였으며, 칼로리 섭취에 대한 강의를 시행하였고, 설문지 조사를 통해 대상자의 식이 섭취 습관에 대한 조사를 시행하였고, 본 건강교실에 대한 만족도를 측정하였다. 대상자중 남자에서는 40%, 여자에서는 25.69%에서 비만 경향을 보였다. 대상자의 대부분에서 시행된 건강교실에 긍정적 반응을 보였으며, 향후 체계적인 구성과 철저한 사전계획이 병행되어 본 증례 보고와 같은 건강교실을 시행한다면, 비만아동에서 거부감 없이 비만에 대한 교육을 실시할 수 있으며, 정상 체중 아동군에서도 비만에 대한 예방교육을 시행할 수 있는 프로그램이 될 것이다. 172 elementary school students involved this health program. This subjects were learened about obesity that affect health problem, ideal eating habits, calories that contained in the children's favorite foods by doctors and nutritionist. And this stubjects were checked heights, weight, body fat percent. Obesity is 40% in the boys and 25.69% in the girls. Most subjects were satisfactory with this health program. So we will effectively educate obese children without resistance and prevent normal weight children from obesity through structured and well-designed health program that similar to this program.

목재가 선적된 선창에서 발생한 산소결핍에 의한 질식사

김동훈,김기권,장태정,김정란,이구,김수근,임현술 大韓法醫學會 2001 대한법의학회지 Vol.25 No.1

Oxygen deficiency has been frequent in a clouted space. Wood consumes oxygen and discharges carbon dioxide Instead of photosynthesis in closed space without light, so do some microorganisms on the surface. We experienced a case that a healthy Insect-proofer fell down and died of asphyxia on stair-board at 7 m below the hatch of the cargo-hold shipping wood Analysis of gases in cargo-hold revealed O2; 12.3%, CO; 105 ppm, CH4; 2.7%, and H2S; 1.9% at 1 m below the hatch, and then O2; 6.1%, CO; 220 ppm, CH4; 2.9%, and H2S, 2.3 ppm at 2.5 m below the hatch. Autopsy findings were unremarkable. We justiced the cause of death asphyxia due to oxygen deficiency. As seen in this case, the serious oxygen deficiency was accounted for oxygen consumption by wood and microorganisms.

상행 대동맥을 이환한 대동맥 벽내출혈과 대동맥 박리의 임상적 비교

김현숙,송재관,강덕현,김준,이철환,홍명기,김재중,박성욱,박승정 대한순환기학회 2000 Korean Circulation Journal Vol.30 No.4

한국인 갑상선 수질암 환자에서 RET 원종양유전자 점돌연변이 양상

김형훈,김현진,정윤재,민용기,이명식,이문규,김광원,기창석,김종원,정재훈 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경: 갑상선 수질암의 25∼30%는 유전성으로 발현되는데, MEN 2A, MEN 2B 또는 가족성 수질암의 형태로 나타난다. RET 원종양유전자의 점돌연변이가 유전성 갑상선 수질암의 발생에 중요한 역할을 하므로, 진단 당시의 연령이나 가족력 유무에 관계없이 모든 갑상선 수질암 환자나 또는 RET 변이가 발견된 수질암 환자의 가족 구성원들에서 RET 변이 검색을 하여야 한다. 또한 일부 문헌에서 RET 변이의 양상에따라 임상상이 다르게 표현됨이 보고된 바 있다. 이에 저자들은 한국인 갑상선 수질암 환자에서 RET 원종양유전자의 점돌연변이의 양성률을 알아보고, 변이 양상에 따른 임상상의 차이가 있는지를 알아보고자 본 연구를 시행하였다. 방법: 치근 7년간 본원에서 갑상선절제술을 통해 갑상선 수질암으로 진단받은 29예에서 RET 원종양유전자의 점돌연변이 검사를 시행하였다. 29예의 평균연령은 39세(20∼60세)이었고, 남자 7예, 여자 22예 이었다. 이들의 말초혈액에서 genomic DNA를 분리하고, 특이 시발차를 이용하여 RET 원종양유전자의 exon10, 11, 13, 14, 16부위를 증폭하였다. 증폭된 부위를 자동염기서열분석기를 이용하여 직접 분석하였다. 양성으로 나온 경우는 모든 가족 구성원을 대상으로 RET 변이 유무를 검색하였다. 결과: 대상 환자 29예 중 9예 (31%)에서 RET 원종양유전자 점돌연변이가 발견되었다 RET 변이가 발견된 9예 (남자 3예, 여자 6예)의 평균 연령은 33세 (20∼51세)로 RET 변이가 발견되지 않은 20예의 평균연령 42세(24∼60세)보다 의미 있게 적었다. RET 변이가 발견된 9예 중 MEN 2A가 5예, 가족성 수질암이 1예, 그리고 산발성 수질암이 3예이었고, MEN 2B는단 1예도 진단되지 않았다. MEN 2A 5예 중 4예는 exon 11의 codon 634번(C634R 2예, C634Y 2예)에서, 그리고 나머지 1예는exon 10의 codon 618번 (C618R)에서 변이가 각각 발견되었다. 가족성 수질암 1아는 codon 634번(C634W)에서, 산발성 수질암 3예도 모두 codon 634번 (C634y 2예, C634s 1예)에서 각각 변이가 발견되었다. RET변이 양상 또는 위치에 따른 임상상의 차이는 발견할 수 없었다. 결론: 갑상선 수질암 환자 31%에서 RET 원종양유전자의 점돌연변이를 발견할 수 있었다. 유전성 수질암 중 가족성 수질암 1예를 제외하고 나머지 5예는MEN 2A이었다. 저자들의 5예와 지금까지 국내에서 보고 된 7예를 합친 국내 MEN 2A 12예 중 75% (9/12)는 exon 11의codon 634번(C634R 4예, C634y 4예, C634w 1예)에서, 그리고 나머지 25% (3/12)는 exon 10의 codon618번(C618R 2예, C618s 1예)에서 변이가 발견되었다. 국내에서는 codon 634과 codon 618 두 곳에만 국한된 양상이었고, codon 634에서의 C634R 변이는 1/3에서만 나타났다. 비록 본 연구에서는 제한된 환자 수 때문에 변이 양상과 임상상의 관계를 규명할 수 없었지만, 향후 많은 수의 환자를 대상으로 전향적인 연구를 시행하여 genotype-phenotype 관계 규명을 하는 것이 필요하다. Background: Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 -30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. Methods: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. Results: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. Conclusion: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this (J Kor SOC Endocrinol 18:360-370, 2003).

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.

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>

랫드에서 단일시험법을 이용한 반하 물추출물의 생식독성시험

이기남,유욱준,백인정,연정민,남상섭,이범준,남상윤,김윤배,강현규,안병우,김대중,황방연,노재섭,홍정섭,성하정,김순선,조대현,윤영원 충북대학교 동물의학연구소 2006 Journal of Biomedical and Translational Research Vol.7 No.1

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