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>

조기에 재발한 미세낭종성 뇌수막종 -증례보고-

하동원 ( Dong Won Ha ),김세혁 ( Se Hyuk Kim ),신용삼 ( Yong Sam Shin ),안영환 ( Young Hwan Ahn ),윤수한 ( Soo Han Yoon ),조기홍 ( Ki Hong Cho ),조경기 ( Kyung Gi Cho ),임현이 ( Hyun Yee Lim ) 대한뇌종양학회·대한신경종양학회·대한소아뇌종양학회 2005 대한뇌종양학회지 Vol.4 No.2

We report a case of microcystic meningioma which showed unusual radiological findings resembling malignant tumor. A 44-year-old woman presented with generalized tonic clonic seizure and right hemiparesis. Computed tomography and magnetic resonance images showed a mass at left frontal, parasagittal area with septa-like enhancement and surrounding edema. 201Tl SPECT showed focal uptake in mass lesion which suggests the malignant tumor. The histopathological findings of this tumor revealed to be a microcystic meningioma and Ki-67 labeling index was 3.8. Although the mass was a subtype of meningioma, it showed a early recurrence 10 months after grossly total resection because of high proliferative index. We suggest that the biological behaviour in addition to morphologic classification should be considered in the management of benign brain tumor, such as meningioma.

A case of atypical Spitz nevi

( Kyoung Geun Lee ),( Won Choi ),( Joon Soo Lim ),( Seung Hyun Cheong ),( Ki Bum Myung ),( Hyung Jin Hahn ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.1

Spitzoid melanocytic lesions may be broadly categorized into Spitz nevi, atypical Spitz tumor (AST), and spitzoid melanomas. Atypical Spitz nevi, also known as AST is rare spitzoid melanocytic proliferations with an uncertain malignant potential and described as conventional Spitz nevi with 1 or more atypical features with indeterminate biological potential. It has clinical features of larger size (>6 mm), irregular borders, irregular topography, or ulceration. Threre are no definite histologic diagnostic criterias among spitzoid melanocytic proliferations, but asymmetry, ulceration, pagetoid melanocytosis, lack of maturation, deep mitoses, and atypia are distinct findings of atypical Spitz nevi. A 2-year-old man presented with several months of pigmented nodule on right knee. Skin biopsy from right knee showed spitzoid melanocytic proliferation from the epidermis to the reticular dermis. Melanocytes arranged in nests were epithelioid with abundant eosinophilic cytoplasm. Each cells showed uniform pleomorphism and mitosis, but there were no atypical mitosis. Few kamino bodies in epidermis and outlier cells in reticular dermis were also detected. Immunohistochemical study revealed positive of HMB-45, S-100, P16 and Ki-67 over 30 percent. We report a case of atypical spitz nevi and distinguishing features of spitzoid melanocytic proliferations through literature review.

Benzyl Isothiocyanate Inhibits Prostate Cancer Development in the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) Model, Which Is Associated with the Induction of Cell Cycle G1 Arrest

Cho, Han Jin,Lim, Do Young,Kwon, Gyoo Taik,Kim, Ji Hee,Huang, Zunnan,Song, Hyerim,Oh, Yoon Sin,Kang, Young-Hee,Lee, Ki Won,Dong, Zigang,Park, Jung Han Yoon MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.2

<P>Benzyl isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has been shown to have anti-tumor properties. In the present study, we investigated whether BITC inhibits the development of prostate cancer in the transgenic adenocarcinoma mouse prostate (TRAMP) mice. Five-week old, male TRAMP mice and their nontransgenic littermates were gavage-fed with 0, 5, or 10 mg/kg of BITC every day for 19 weeks. The weight of the genitourinary tract increased markedly in TRAMP mice and this increase was suppressed significantly by BITC feeding. H and E staining of the dorsolateral lobes of the prostate demonstrated that well-differentiated carcinoma (WDC) was a predominant feature in the TRAMP mice. The number of lobes with WDC was reduced by BITC feeding while that of lobes with prostatic intraepithelial neoplasia was increased. BITC feeding reduced the number of cells expressing Ki67 (a proliferation marker), cyclin A, cyclin D1, and cyclin-dependent kinase (CDK)2 in the prostatic tissue. <I>In vitro</I> cell culture results revealed that BITC decreased DNA synthesis, as well as CDK2 and CDK4 activity in TRAMP-C2 mouse prostate cancer cells. These results indicate that inhibition of cell cycle progression contributes to the inhibition of prostate cancer development in TRAMP mice treated with BITC.</P>

Substance P restores normal skin architecture and reduces epidermal infiltration of sensory nerve fiber in TNCB-induced atopic dermatitis-like lesions in NC/Nga mice

Choi, Hyeongwon,Kim, Dong-jin,Nam, Seungwoo,Lim, Sunki,Hwang, Jae-Sung,Park, Ki Sook,Hong, Hyun Sook,Won, Younsun,Shin, Min Kyung,Chung, Eunkyung,Son, Youngsook Elsevier 2018 JOURNAL OF DERMATOLOGICAL SCIENCE Vol.89 No.3

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense pruritus and eczematous lesion. Substance P (SP) is an 11-amino-acid endogenous neuropeptide that belongs to the tachykinin family and several reports recently have supported the anti-inflammatory and tissue repairing roles of SP.</P> <P><B>Objective</B></P> <P>In this study, we investigated whether SP can improve AD symptoms, especially the impaired skin barrier function, in 2, 4, 6-trinitrochlorobenzene (TNCB)-induced chronic dermatitis of NC/Nga mice or not.</P> <P><B>Method</B></P> <P>AD-like dermatitis was induced in NC/Nga mice by repeated sensitization with TNCB for 5 weeks. The experimental group designations and topical treatments were as follows: vehicle group (AD-VE); SP group (AD-SP); and SP with NK1R antagonist CP99994 (AD-SP-A) group. Histological analysis was performed to evaluate epidermal differentiation, dermal integrity, and epidermal nerve innervation in AD-like lesions. The skin barrier functions and pruritus of NC/Nga mice were evaluated by measuring transepidermal water loss (TEWL) and scratching behavior, respectively.</P> <P><B>Result</B></P> <P>Topical SP treatment resulted in significant down-regulation of Ki67 and the abnormal-type keratins (K) K6, K16, and K17, restoration of filaggrin and claudin-1, marked reduction of TEWL, and restoration of basement membrane and dermal collagen deposition, even under continuous sensitization of low dose TNCB. In addition, SP significantly reduced innervation of itch-evoking nerve fibers, gelatinase activity and nerve growth factor (NGF) expression in the epidermis but upregulated semaphorin-3A (Sema3A) expression in the epidermis, along with reduced scratching behavior in TNCB-treated NC/Nga mice. All of these effects were completely reversed by co-treatment with the NK1R antagonist CP99994. In cultured human keratinocytes, SP treatment reduced expression of TGF-α, but upregulated TGF-β and Sema3A.</P> <P><B>Conclusion</B></P> <P>Topically administered SP can restore normal skin barrier function, reduce epidermal infiltration of itch-evoking nerve fibers in the AD-like skin lesions, and alleviate scratching behavior. Thus, SP may be proposed as a potential medication for chronic dermatitis and AD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Topical Substance P treatment reduced AD-like symptoms in TNCB-induced NC/Nga mice. </LI> <LI> Topical Substance P treatment reduced epidermal acanthosis and expressed normal keratin profiles in AD-like mice. </LI> <LI> Topical Substance P treatment regulated both small nerve attraction and repulsion factors in AD-like skin. </LI> <LI> Topical Substance P treatment recovered skin barrier function and reduced pruritus in AD-like mice. </LI> </UL> </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.

The impact of pathologic differentiation (well/ poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

Kim, Seung Tae,Lee, Su Jin,Lee, Jeeyun,Park, Joon Oh,Park, Young Suk,Lim, Ho Yeong,Kang, Won Ki Grune & Stratton 2017 Journal of clinical oncology Vol.35 No._suppl15

<P> e15686 </P><P> Background: Herein, we investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum-based therapy. Simultaneously, we evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from etoposide plus platinum (EP)-based therapy. Methods: Among patients pathologically diagnosed with metastatic grade 3 GEP-NECs at Samsung Medical Center between June 2013 and March 2016, 31 GEP-NEC patients receiving etoposide and platinum-based therapy were included in this study. Results: Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. Sixteen unclassified GEP-NECs originated from 7 gall-bladder (GB), 6 liver and 3 unknown primary sites. According to pathologic differentiation, 14 patients had well differentiated and 17 had poorly differentiated grade 3 GEP-NECs. Between well differentiated and poorly differentiated grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between well and poorly differentiated grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67≤60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). There was no significant difference in PFS according to pathologic differentiation (well differentiated vs. poorly differentiated) and Ki67 index ( > 60% vs ≤60%). Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs. </P>

필라테스 운동이 여대생의 신체구성과 하지근력 및 척추 형태에 미치는 영향

황윤영(Hwang, Yoon-Young),박기덕(Pack, Gi-Duck),임기원(Lim, Ki-Won) 한국체육과학회 2013 한국체육과학회지 Vol.22 No.5

This study is to provide the preliminary data verifying Pilates effect analyzing the effect of the warm-up, exercise and warm-down were conducted for 50 minutes a day, three time a week and for ten week. Pilates exercises for female university students on their body compositions, changes in the spine and muscular strength. The study is to involve female university students, majoring in general department (non-Physical Education) who take liberal arts classes in K and N university, and it was distinguished between 9(PG: age(20.6±0.9), height (160.9±7.1), weight(53.9±4.5)) female university students who will participate in Pilates Exercise Program and 9(CG: age(22.2±1.4), height(159.9±5.4), weight(52.3±4.7)) female university students who won"t. First, There were insignificant differences in body composition factor. Second, There were significant differences in Peak torque from isokinetic muscular function factor, Total work and Average power. Third, There were insignificant differences in 3-dimension spine body type factor. Through the ten-week Pilates exercises for three times a week, there weren"t significant differences in the body composition and positive effect of isokinetic muscular function factor, and the 3-dimension spine body type was shown.

Experimental Studies On extension of survival time for tumor bearing and immunomodulatory effects of Yukgunjatang,Soshihotang,Houttunynia Herba

Lim, Seong-Woo,Yoon, Sang-Hyub,Ryu, Bong-Ha,Park, Dong-Won,Ryu, KI-Won 경희대학교 동서의학연구소 1991 INTERNATIONAL SYMPOSIUM ON EAST-WEST MEDICINE Vol.1991 No.3

In order to investigate the effects of Yukunjatang. Soshihotang. Houttuynia Herba. on extension of survival title for tumor bearing effect after developing of tumors followed by being grafted with the Sarcoma-180 cells and immunomedulatory effects in mice. the extracts of its herbal medicines were orally administered to mice for 21 days. The experimental studies were performed for observation of extention of survival time for tumor bearing effect, quantitation of T cells and B cells, Interleukin-2 productivity, delayed type hypersensitivity (DTH), lymphocyte transformation for cell mediated immune response, hemagglutinin titer and hemolysin titer far humoral immune response and splenic natural killer cell activity (NKCA) in ICR or C5 7 BI/6mice. The results were summerized as follows: 1.Yukgunjatang and Soshihotang were significantly recognized to extend the survival time of tumor bearing mice (p < 0.05 respectively). 2. For the effect of T cell and B cell quantitation, the only Soshihotang-medicated group showed a significant increase on Interleukin-2 productivity (P < 0.05). 3.Yukgunjatang-medicated group showed a significant increase on Inlerleukin-2 productivity (p < 0.05). 4.Delayed type hypersensivity was not significantly increased in all sample groups as compared with control group. But Houttuynia Herba-medicated group showed a little higher than that of the control group. 5.Natural killer cell activity was not significantly increased in all sample groups as compared with control group. But Houttuynia Herba-medicated group showed a little higher than that of the control group in E/T ratio 50:1 6.Lymphocyte transformation was significantly increased in Soshihotang, Houttuynia Herba, and Soshihotang plus Houttuynia Herba-medicated groups (p < 0.01, p < 0.02. p < 0.02 respectively). 7.Serum antibody titer was not significantly increased in all sample groups as compared with control group. Acoording to tole above results. Yukgunjatang, Soshihotang, and Hottuynia Herba are considered to suggest useful herbal medicines on extension of survival time for tumor beraring and immunomodulatory effect. And then it is expected that medicines are more helpful in treatment of cancer patients.

The immunogenicity and protection effect of an inactivated coxsackievirus A6, A10, and A16 vaccine against hand, foot, and mouth disease

Lim, Heeji,In, Hyun Ju,Lee, Jung-Ah,Sik Yoo, Jung,Lee, Sang-Won,Chung, Gyung Tae,Choi, Young Ki,Chung, Jae Keun,Cho, Sun Ju,Lee, June-Woo Elsevier 2018 Vaccine Vol.36 No.24

<P><B>Abstract</B></P> <P>Coxsackievirus belongs to the <I>Enterovirus</I> genus of the <I>Picornaviridae</I> family and is one of the major pathogens associated with human hand, foot, and mouth disease (HFMD). Historically, outbreaks of HFMD have mainly been caused by enterovirus 71 and coxsackievirus A16. Recently, coxsackieviruses A6 and A10 have been associated with increased occurrences of sporadic HFMD cases and outbreak events globally. In this study, the immunogenicity of coxsackieviruses A6, A10, and A16 (CA6, CA10, and CA16), which were inactivated by formalin or β-propiolactone (BPL) under different conditions, was evaluated as multivalent vaccine candidates. CA6 induced similar immune responses with both inactivation methods, and the immune efficacy of CA10 and CA16 was better following inactivation with BPL than with formalin. There was no sufficient cross-reactivity or cross-protectivity against heterologous strains in groups vaccinated with the BPL-inactivated (BI) monovalent vaccine. Sufficient neutralizing antibody and cell-mediated immune responses were induced in the BI-trivalent vaccinated group. These findings suggest that BI-CA6, CA10, and CA16 are potential multivalent vaccine candidates and that a multivalent vaccine is needed to control HFMD. The coxsackievirus multivalent vaccine could be useful for the development of effective HFMD vaccines.</P>