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.

Inhibition of protein kinase CKII activity by euchrestaflavanone B purified from Cudrania tricuspidata.

Kim, Soon-Hee,Yoon, Soo-Hyun,Lee, Byong Won,Park, Ki Hun,Kim, Young Ho,Bae, Young-Seuk Pergamon Press 2005 Oncology Research Vol.15 No.6

<P>The CKII (EC 2.7.1.37) inhibitory compound was purified from the root barks of Cudrania tricuspidata and identified as (2S)-2-[2,4-dihydroxy-5-(3-methyl-but-2-enyl)-phenyl]-5,7-dihyroxy-6-(3-methyl-but-2-enyl)chroman-4-one (euchrestaflavanone B). Euchrestaflavanone B was shown to inhibit the phosphotransferase activity of CKII with IC50 of about 78 microM. Steady-state studies revealed that euchrestaflavanone B acted as a competitive inhibitor with respect to the substrate ATP. A value of 16.4 microM was obtained for the apparent Ki. Concentration of 0.8 microM euchrestaflavanone B caused 50% growth inhibition of human cancer cells U937 and HeLa. Euchrestaflavanone B-induced cell death was characterized with the cleavage of poly(ADP-ribose) polymerase and procaspase-3, indicating that the inhibitor triggered apoptosis. Because protein kinase CKII is involved in cell proliferation and oncogenesis, these results suggest that euchrestaflavanone B may function by inhibiting oncogenic disease, at least in part, through the inhibition of CKII activity.</P>

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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조직학적 진단된 chronic necrotizing pulmonary aspergillosis 2예

김연숙,정숙인,기현균,김춘관,김신우,한정호,김성민,백경란,송재훈 대한화학요법학회 2000 대한화학요법학회지 Vol.18 No.1

CNPA는 기존의 폐질환 및 폐절제술로 인해 국소방어기전에 저하가 있거나 비특이적 전신면역상태저하를 갖고 있는 환자들에게서 주로 발생하는 만성적인 공동성 폐질환이다. 현재까지 우리나라에서는 CNPA의 보고가 없는 상태이고, 저자들은 최근 조직학적으로 진단된 CNPA 2예를 경험하였기에 보고하는 바이다. 저자들이 경험한 CNPA 환자들은 만성알코올 중독 및 기관지확장증과 같은 기저질환과 폐절제술을 받은 병력이 있었다. Aspergillus가 폐실질을 침윤하고 있는 조직소견과 조직배양에서 Aspergillus가 검출되어 조직학적 진단이 가능하였고, amphotericin B의 정주요법 및 경구 itraconazole 투여와 폐절제술 등으로 성공적으로 치료되었다. 아직 많은 임상의들에게는 낯선 질환인 CNPA의 치료성적은 환자의 동반질환 및 CNPA 자체의 중증도, 진단과 치료 시작의 지연 등에 의해 크게 좌우되므로 만성적으로 진행하는 공동성 폐병변을 갖고 있는 환자에게서 CNPA를 감별하는 것이 중요하다. Chronic necrotizing pulmonary aspergillosis (CNPA) is a chronic cavitary form of pulmonary aspergillosis. Dozens of CNPA cases have been reported in patients with systemic immunologic dysfunction or altered local defense mechanism from preexisting pulmonary disease. Review of literatures revealed that no CNPA cases have been reported in Korea yet. We experienced two cases of CNPA proven by lung biopsy. A 53-year-old alcoholic male in poor nutritional state was admitted with generalized weakness and weight loss. Chest CT revealed a cavitary nodule surrounded with ground-glass attenuation. CT-guided fine needle aspiration and biopsy was done. The biopsy specimen demonstrated dichotomously branching septated hyphae consistent with those of Aspergillus sp. Another case was a 39-year-old man with bronchiectasis who was admitted with persistent hemoptysis. He had a past history of pulmonary tuberculosis. A parahilar lesion with intracavitary soft tissue mass was incidentally detected in high-resolution GT. Left lingular segmentectomy was done due to uncontrolled hemoptysis and CNPA was histologically diagnosed. Both patients were successfully treated with intravenous amphotericin B followed by oral itraconazole. Even though CNPA is unfamiliar to most clinicians, it should be included in differential diagnoses of chronic progressive cavitary pulmonary lesion, especially in patients with immunologic dysfunction.

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.

항암화학요법 중 호중구감소증이 발생한 저위험군 발열 환자들을 대상으로 한 경구 항균제 요법의 임상적 유용성 및 안정성에 대한 연구

김연숙,이혁,기현균,김춘관,김신우,김성민,백경란,김원석,윤성수,이홍기,강원기,박찬형,박근칠,송재훈 대한화학요법학회 2000 대한화학요법학회지 Vol.18 No.1

목적 : 항암화학요법 중 호중구감소증을 동반한 발열이 발생하는 암환자들을 치료하기 위한 다양한 항균제와 여러 가지 방법들이 시도되고 있는 가운데, 합병증과 사망률의 발생가능성이 적은 저위험군 환자들을 대상으로 초기 72시간동안 정주 항균제를 투여한 이후 경구 항균제로 전환하는 요법의 유용성과 안정성을 평가해보고자 본 연구를 시행하였다. 방법 : 1998년 2월부터 1999년 9월까지 본원에서 항암화학요법 중 호중구감소증과 발열이 발생한 환자들 가운데 기저 암질환이 고형암이거나 림프종이고, 입원당시 패혈증의 증후가 없으며 입원 72시간이내에 해열되고 백혈구수치가 증가 추세인 환자들을 대상으로 하여 72시간 동안 정주 항균제를 투여한 이후 경우 ciprofloxacin 750㎎을 하루 2회씩 투여하여 총 4일간 투여하였다. 모든 환자들은 열이 떨어지고 호중구감소증이 회복될 때까지 입원하도록 하였다. 결과 : 총 38명 환자의 40예가 등록이 되었고, 환자들의 기저암 질환은 고형함이 72.5%, 림프종이 27.5%였다. 입원당시 평균 호중구치수는 156/㎕였고, 호중구수치가 100/㎕미만인 경우는 65%였으며, 호중구감소증이 지속된 기간의 평균은 2.4일이었다. 40예 중 39예가 항균제의 변형이나 추가 없이 호중구감소증과 발열로부터 회복이 되어 97.5%의 성공율(95% 신뢰구간: 86.8-99.9%)을 보였다. 부작용으로 피부발진이 있었던 경우가 한 예 있었는데, 증상이 경하여 경구 항균제를 지속할 수 있었다. 심와부의 동통으로 복용을 지속할 수 없어서 대상에서 제외된 예가 또 한 예 있었다. 결론 : 항암요법 중 호중구감소증과 발열을 동반한 환자들 가운데 저위험군 환자들에서 항균제 72시간정주 이후 경구 항균제로의 전환요법은 효과적이고도 안전한 치료방법이라고 할 수 있다. Background : Oral antibiotic therapy following empirical intravenous antibiotics may be effective and safe for febrile neutropenic patients with lowrisk for complications. Methods : We conducted a prospective clinical trial of oral antibiotic therapy in the patients with neutropenia and fever during chemotherapy for cancer. Underlying malignancies were solid tumor or lymphoma with short duration of neurtropenia and the patients had no evidence of clinically or microbiologically documented infections. Oral ciprofloxacin was given to the patients who lacked signs of sepsis on admission, had a rising tendency of neutrophil count (ANC >100 /㎕ ) at 72 hours, and were afebrile at 72 hours. All patients were hospitalized until neutropenia and fever resolved. Results : A total of 40 episodes of 38 patients were enrolled from February 1998 to September 1999. The mean neutrophil counts on admission were 156/㎕ and the mean duration of neutropenia was 2.4 days. The episodes which had neutrophil count below 100 /㎕ were 26 (65%). Treatment was successful in 39 of 40 episodes (97.5% : 95 % confidence interval, 86.8% to 99.9%). Adverse reactions of oral ciprofloxacin were skin rash and epigastric soreness in two cases, respectively. There were no deaths during the study. Conclusions : For low-risk febrile patients with neutropenia during cancer chemotherapy, switch therapy to oral ciprofloxacin at 72 hours following intravenous broad-spectrum antibiotics is effective and safe,

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>

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>