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.

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,

Clinical Outcome of Modified Cervical Lateral Mass Screw Fixation Technique

Kim, Seong-Hwan,Seo, Won-Deog,Kim, Ki-Hong,Yeo, Hyung-Tae,Choi, Gi-Hwan,Kim, Dae-Hyun The Korean Neurosurgical Society 2012 Journal of Korean neurosurgical society Vol.52 No.2

Objective : The purpose of this study was 1) to analyze clinically-executed cervical lateral mass screw fixation by the Kim's technique as suggested in the previous morphometric and cadaveric study and 2) to examine various complications and bicortical purchase that are important for b-one fusion. Methods : A retrospective study was done on the charts, operative records, radiographs, and clinical follow up of thirty-nine patients. One hundred and seventy-eight lateral mass screws were analyzed. The spinal nerve injury, violation of the facet joint, vertebral artery injury, and the bicortical purchases were examined at each lateral mass. Results : All thirty-nine patients received instrumentations with poly axial screws and rod systems, in which one hundred and seventy-eight screws in total. No vertebral artery injury or nerve root injury were observed. Sixteen facet joint violations were observed (9.0%). Bicortical purchases were achieved on one hundred and fifty-six (87.6%). Bone fusion was achieved in all patients. Conclusion : The advantages of the Kim's technique are that it is performed by using given anatomical structures and that the complication rate is as low as those of other known techniques. The Kim's technique can be performed easily and safely without fluoroscopic assistance for the treatment of many cervical diseases.

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>

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.

Effects of Cu,Zn-superoxide dismutase on cell proliferation and neuroblast differentiation in the mouse dentate gyrus.

Yoo, Dae Young,Shin, Bich Na,Kim, In Hye,Kim, Woosuk,Kim, Dae Won,Yoo, Ki-Yeon,Choi, Jung Hoon,Lee, Choong Hyun,Yoon, Yeo Sung,Choi, Soo Young,Won, Moo-Ho,Hwang, In Koo Kluwer Academic/Plenum Publishers 2012 Neurochem Res Vol.37 No.2

<P>Oxidative stress is one of the most important factors in reducing adult hippocampal neurogenesis in the adult brain. In this study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) on lipid peroxidation, cell proliferation, and neuroblast differentiation in the mouse dentate gyrus using malondialdehyde (MDA), Ki67, and doublecortin (DCX), respectively. We constructed an expression vector, PEP-1, fused PEP-1 with SOD1, and generated PEP-1-SOD1 fusion protein. We administered PEP-1 and 100 or 500 관g PEP-1-SOD1 intraperitoneally once a day for 3 weeks and sacrificed at 30 min after the last administrations. PEP-1 administration did not change the MDA levels compared to those in the vehicle-treated group, while PEP-1-SOD1 treatment significantly reduced MDA levels compared to the vehicle-treated group. In the PEP-1-treated group, the number of Ki67-positive nuclei was similar to that in the vehicle-treated group. In the 100 관g PEP-1-SOD1-treated group, the number of Ki67-positive nuclei was slightly decreased; however, in the 500 관g PEP-1-SOD1-treated group, Ki67-positive nuclei were decreased to 78.5% of the vehicle-treated group. The number of DCX-positive neuroblasts in the PEP-1-treated group was similar to that in the vehicle-treated group. However, the arborization of DCX-positive neuroblasts was significantly decreased in both the 100 and 500 관g PEP-1-SOD1-treated groups compared to that in the vehicle-treated group. The number of DCX-positive neuroblasts with tertiary dendrites was markedly decreased in the 500 관g PEP-1-SOD1-treated group. These results suggest that a SOD1 supplement to healthy mice may not be necessary to modulate cell proliferation and neuroblast differentiation in the dentate gyrus.</P>

Focal adhesion kinase and src expression in premalignant and malignant skin lesions

( Ju Yeon Choi ),( Jae Yun Lim ),( Han Saem Kim ),( Jung Min ),( Jung In Kim ),( Hyun Min Seo ),( Sang Hyeon Hwang ),( Chong Won Choi ),( Yoon Hwan Kim ),( Jin Hee Sohn ),( Hyunjoo Lee ),( Won Serk Ki 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Focal adhesion kinase (FAK) and Src are non-receptor tyrosine kinases. FAK and Src play a critical role in inducing malignant transformation in tumor cells. Objectives: We performed immunohistochemical staining for total and phosphorylated forms of FAK and Src, to evaluate the role of FAK and Src in the development of premalignant and malignant skin lesions. Methods: A total of 59 facial skin samples (30 actinic keratoses, 10 Bowen``s diseases, 13 squamous cell carcinomas and six perilesional skins) were immunohistochemically stained for Ki-67, total (t) and phosphorylated (p) form of FAK and Src. Methods: A total of 59 facial skin samples (30 actinic keratoses, 10 Bowen``s diseases, 13 squamous cell carcinomas and six perilesional skins) were immunohistochemically stained for Ki-67, total (t) and phosphorylated (p) form of FAK and Src. Results: Cells positive for t-Src, p-Src-y530, t-FAK and pFAK-s722 were detected in premalignant intra-epithelial lesions (PELs) and squamous cell carcinomas (SCCs), but not in the perilesional skin. There was a tendency towards high correlation between Ki-67 and t-FAK or pFAK-s722, suggestive of the active role of FAK in cell proliferation. Conclusion: Our findings of higher t-Src and p-Src-y530 positive cells in PELs, as compared to SCCs (with higher Ki-67 level), are suggestive of the other role of Src in tumor formation and progression, which requires further investigation.

비혈연간 동종골수이식에 의해 치료된 중증 재생불량성빈혈 1예

김현중,이홍기,이방훈,이창근,이종태,정현식,김원석,윤성수,강원기,박근칠,김대식,고영혜,박찬형 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

비혈연간 동종골수이식은 혈연간 동종골수이식이 불가능한 환자에서 기존의 면역역제요법으로 효과가 없었던 경우나 재발한 경우에 적응증이 될수 있다. 이식 거부와 이식편대숙주병의 발생이 골수 이식의 성공률을 감소시키므로, 보다 강력한 conditioning regimen의 사용과 T cell이 제거된 골수를 사용하는 것이 필요하다. 기존의 high dose corticosteroid나 cyclosporine에 대하여 불응성인 이식편대숙주병의 치료를 위해서 ATG와 Mycophenolate mofetil (Cellcept®) 의 사용이나 Tacrolimus, Methotrexate와 같은 다른 면역억제제치료를 고려해 볼 수 있다. It is known that allogenic bone marrow transplantation is the most effective treatment for aplastic anemia. However, this treatment is only applicable to a minority of patients because the proportion of patients who have HLA-matched siblings about 25% to 30% of all the aplastic anemia patients. In the case of the absence of HLA-matched donor, unrelated allogenic bone marrow transplantation is considered. However, (because of severe acute and chronic GVHD and graft failure) the success rate of this approach is only 20~30%. Recently, it was reported that increased immunosuppressive condition combined with T cell depletion of the marrow graft would result in greater success. There was no case of successfully treated aplastic anemia patient by unrelated allogenic bone marrow transplantation in Korea. Here, we report a case of severe aplastic anemia successfully treated with unrelated allogenic bone marrow transplantation.