Lycorine의 사람 구강 암 세포주에서 survivin 단백질 분해 증진으로 세포자멸사

Joseph H. Jeong,Nam-Pyo Cho,Boonsil Jang 대한구강악안면병리학회 2017 대한구강악안면병리학회지 Vol.41 No.1

Lycorine, a natural alkaloid extracted from the Amaryllidaceae plant family, was reported to various physiological and pharmacological effects including anti-cancer activity. Nevertheless, there is no report of the anticancer effect of lycorine in oral cancer cells. The effects of lycorine on cell proliferation and apoptosis were examined through trypan blue exclusion assay, 4’-6-diamidino-2-phenylindole (DAPI) stain, Live/Dead assay, Western blot analysis and RT-PCR. Lycorine suppressed cell viability and induced apoptosis in MC3 and HSC-3 cell lines. Lycorine decreased survivin protein but did not affect its mRNA. It regulated survivin through accelerating protein degradation in a time-dependent manner although neither proteasome nor lysosome was not associated with lycorine-mediated protein degradation. Collectively, our results suggest that lycorine may be a potential therapeutic anti-cancer drug candidate for the treatment of human oral cancer.

Inducible Mouse Models for Cancer Drug Target Validation

Joseph H. Jeong 대한암예방학회 2016 Journal of cancer prevention Vol.21 No.4

Genetically-engineered mouse (GEM) models have provided significant contributions to our understanding of cancer biology and developing anticancer therapeutic strategies. The development of GEM models that faithfully recapitulate histopathological and clinical features of human cancers is one of the most pressing needs to successfully conquer cancer. In particular, doxycycline-inducible transgenic mouse models allow us to regulate (induce or suppress) the expression of a specific gene of interest within a specific tissue in a temporal manner. Leveraging this mouse model system, we can determine whether the transgene expression is required for tumor maintenance, thereby validating the transgene product as a target for anticancer drug development (target validation study). In addition, there is always a risk of tumor recurrence with cancer therapy. By analyzing recurrent tumors derived from fully regressed tumors after turning off transgene expression in tumor-bearing mice, we can gain an insight into the molecular basis of how tumor cells escape from their dependence on the transgene (tumor recurrence study). Results from such studies will ultimately allow us to predict therapeutic responses in clinical settings and develop new therapeutic strategies against recurrent tumors. The aim of this review is to highlight the significance of doxycycline-inducible transgenic mouse models in studying target validation and tumor recurrence.

Low-cost electrospun WC/C composite nanofiber as a powerful platinum-free counter electrode for dye sensitized solar cell

Jeong, I.,Lee, J.,Vincent Joseph, K.L.,Lee, H.I.,Kim, J.K.,Yoon, S.,Lee, J. Elsevier 2014 Nano energy Vol.9 No.-

Tungsten carbide/carbon (WC/C) composite nanofibers were successfully prepared through electrospinning followed by a one-step heat treatment using in-situ carburization. The WC/C nanofibers were applied to low-cost and platinum-free counter electrodes for dye sensitized solar cells (DSSCs), and their catalytic activities were investigated and compared to platinum (Pt) CEs for triiodide/iodide (I<SUB>3</SUB><SUP>-</SUP>/I<SUP>-</SUP>) as well as organic disulfide/thiolate (T<SUB>2</SUB>/T<SUP>-</SUP>) electrolytes. When WC/C nanofibers are used as the CE catalyst in iodine electrolytes, the DSSCs exhibited a power conversion efficiency (PCE) of 7.77%, corresponding to 96% of that of Pt CEs. In the case of T<SUB>2</SUB>/T<SUP>-</SUP> redox couples, the DSSCs based on WC/C nanofibers achieved PCE of 5.85%, which is almost twice that of Pt (3.07%). The high catalytic activities of WC/C nanofibers are attributed to synergetic effects from the combination of catalytically active WC and one-dimensional (1D) conductive carbon acting as an efficient charge transport pathway. In addition, spray-coated WC/C nanofiber CE films have a three-dimensional porous network, enhancing the permeation of the electrolyte into the CE film and the diffusion of redox couples. The electrospinning process used for the synthesis of the WC/C nanofibers is facile and scalable and is therefore promising for the commercialization of DSSCs.

Loss of Rab25 promotes the development of skin squamous cell carcinoma through the dysregulation of integrin trafficking

Jeong, Haengdueng,Lim, Kyung‐,Min,Kim, Kwang H,Cho, Yejin,Lee, Buhyun,Knowles, Byron C,Roland, Joseph T,Zwerner, Jeffrey P,Goldenring, James R,Nam, Ki Taek Longman 2019 The Journal of pathology Vol.249 No.2

<P><B>Abstract</B></P><P>Rab25 can function as both a tumor suppressor and a tumor promoter across different tissues. This study sought to clarify the role of Rab25 as a tumor suppressor in skin squamous cell carcinoma (SCC). Rab25 loss was closely associated with neoplastic transition in both humans and mice. Rab25 loss was well correlated with increased cell proliferation and poor differentiation in human SCC. While Rab25 knockout (KO) in mice did not induce spontaneous tumor formation, it did significantly accelerate tumor generation and promote malignant transformation in a mouse two‐stage skin carcinogenesis model. Xenografting of a Rab25‐deficient human keratinocyte cell line, HaCaT, also elicited neoplastic transformation. Notably, Rab25 deficiency led to dysregulation of integrins β1, β4, and α6, which matched well with increased epidermal proliferation and impaired desmosome–tight junction formation. Rab25 deficiency induced impairment of integrin recycling, leading to the improper expression of integrins. In line with this, significant attenuation of integrin β1, β4, and α6 expression was identified in human SCCs where Rab25 was deficient. Collectively, these results suggest that loss of Rab25 promotes the development and neoplastic transition of SCC through dysregulation of integrin trafficking. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>

Buddhist Psychology : Some Implications for Education

Joseph H . pearl,Jeong Hwa Moon 한국교육심리학회 1993 敎育心理硏究 Vol.7 No.2

Mandibular Growth after Distraction in Patients under 48 Months age

Holier, Larry H.,Kim, Jeong-Hwan,Grayson, Barry,McCarthy, Joseph G. THE CATHOLIC UNIVERSITY OF KOREA 2000 Bulletin of The Catholic Research Institutes of Me Vol.28 No.-

Distraction osteogenesis is an effective technique for reconstruction of the congenitally deficient mandible. However, the age at which it is best performed remains under discussion Distraction performed at an early age, while possible allowing the face to develop with a more normal functional matrix, may entail a higher rate of complications. Additionally, it is possible that subsequent asymmetric growth of the mandible may necessitate serial distraction. To address this issue, the clinical records and cephalometric radiographs of all patients less than 48 months of age undergoing mandibular distraction at NYU Medical Center between August of 1989 and August of 1997 were examined. There was a total of 14 patients ranging in age from 19 months to 43 months. Nine patients had a diagnosis of unilateral craniofacial microsomia, three had Treacher Collins syndrome, one had Nager syndrome, and one had bilateral developmental micrognathia. The average amount of distraction was 27mm(range, 23 to 39 mm) in unilateral cases and 24 mm in bilateral cases (range, 15 to 31 mm). The period of clinical follow-up averaged 32.6 months (range, 12 to 92 months). All patients showed significant improvement in craniofacial appereance, and in 4 patients, long-term tracheostomy tubes removed. There were two major complications. In one patient with craniofacial microsomia, there was a relapse in the early postretention phase related to the presence of a dentigerous cyst. This required removal of the cyst and repeat distraction. In the patient with Nager syndrome, a coronoid ankylosis developed requiring surgical release. There were no other major complications. The scars required revision in only two of the patients. Cephalometric analysis of the patients in the study revealed a differential in the rate of growth between the affected and the unaffected side in all cases of craniofacial microsomia. The affected side always grew at a slower rate that the contralateral side after the distraction process was complete. This led to a progressive asymmetry of the rami and an occlusal cant. For this reason, secondary distraction was required in one patient and is planned in a second. Initial overcorrection of the patient would seem to minimize the likelihood that secondary distraction will be necessary. Distraction osteogenesis for reconstruction of the mandible in this subset of young patients was a safe and effective technique for improving the craniofacial skeletal from and appearance, with minimal associated morbidity. Longer follow-up is necessary to assess the full impact of growth in these cases. (Plastic and Reconstructive Surgery 103:1361-70 1999)

Glutamine Triggers Acetylation-Dependent Degradation of Glutamine Synthetase via the Thalidomide Receptor Cereblon

Van Nguyen, T.,Lee, J.,Sweredoski, Michael J.,Yang, S.J.,Jeon, S.J.,Harrison, Joseph S.,Yim, J.H.,Lee, S.,Handa, H.,Kuhlman, B.,Jeong, J.S.,Reitsma, Justin M.,Park, C.S.,Hess, S.,Deshaies, Raymond J. Cell Press 2016 Molecular cell Vol.61 No.6

<P>Cereblon (CRBN), a substrate receptor for the cullin-RING ubiquitin ligase 4 (CRL4) complex, is a direct protein target for thalidomide teratogenicity and antitumor activity of immunomodulatory drugs (IMiDs). Here we report that glutamine synthetase (GS) is an endogenous substrate of CRL4(CRBN). Upon exposing cells to high glutamine concentration, GS is acetylated at lysines 11 and 14, yielding a degron that is necessary and sufficient for binding and ubiquitylation by CRL4 CRBN and degradation by the proteasome. Binding of acetylated degron peptides to CRBN depends on an intact thalidomide-binding pocket but is not competitive with IMiDs. These findings reveal a feedback loop involving CRL4 CRBN that adjusts GS protein levels in response to glutamine and uncover a new function for lysine acetylation.</P>

AHNAK Loss in Mice Promotes Type II Pneumocyte Hyperplasia and Lung Tumor Development

Park, Jun Won,Kim, Il Yong,Choi, Ji Won,Lim, Hee Jung,Shin, Jae Hoon,Kim, Yo Na,Lee, Seo Hyun,Son, Yeri,Sohn, Mira,Woo, Jong Kyu,Jeong, Joseph H.,Lee, Cheolju,Bae, Yun Soo,Seong, Je Kyung American Association for Cancer Research 2018 Molecular Cancer Research Vol.16 No.8

<P>AHNAK is known to be a tumor suppressor in breast cancer due to its ability to activate the TGFβ signaling pathway. However, the role of AHNAK in lung tumor development and progression remains unknown. Here, the Ahnak gene was disrupted to determine its effect on lung tumorigenesis and the mechanism by which it triggers lung tumor development was investigated. First, AHNAK protein expression was determined to be decreased in human lung adenocarcinomas compared with matched nonneoplastic lung tissues. Then, Ahnak<I><SUP>−/−</SUP></I> mice were used to investigate the role of AHNAK in pulmonary tumorigenesis. Ahnak<I><SUP>−/−</SUP></I> mice showed increased lung volume and thicker alveolar walls with type II pneumocyte hyperplasia. Most importantly, approximately 20% of aged Ahnak<I><SUP>−/−</SUP></I> mice developed lung tumors, and Ahnak<I><SUP>−/−</SUP></I> mice were more susceptible to urethane-induced pulmonary carcinogenesis than wild-type mice. Mechanistically, Ahnak deficiency promotes the cell growth of lung epithelial cells by suppressing the TGFβ signaling pathway. In addition, increased numbers of M2-like alveolar macrophages (AM) were observed in Ahnak<I><SUP>−/−</SUP></I> lungs, and the depletion of AMs in Ahnak<I><SUP>−/−</SUP></I> lungs alleviated lung hyperplastic lesions, suggesting that M2-like AMs promoted the progression of lung hyperplastic lesions in Ahnak-null mice. Collectively, AHNAK suppresses type II pneumocyte proliferation and inhibits tumor-promoting M2 alternative activation of macrophages in mouse lung tissue. These results suggest that AHNAK functions as a novel tumor suppressor in lung cancer.</P><P><B>Implications:</B> The tumor suppressor function of AHNAK, in murine lungs, occurs by suppressing alveolar epithelial cell proliferation and modulating lung microenvironment. <I>Mol Cancer Res; 16(8); 1287–98. ©2018 AACR</I>.</P>

Inducible TPL2 Transgenic Mouse Models to Study Human Cancers

Jun-Han Lee,Joo-Hyung Lee,Sang Hyuk Lee,Sung-Im Do,Sung-Dae Cho,Kazuhito Sakamoto,Kay-Uwe Wagner,Fang-Ming Deng,Jonathan Melamed,Ola Forslund,Jae U. Jung,Joseph H. Jeong 한국실험동물학회 2015 한국실험동물학회 학술발표대회 논문집 Vol.2015 No.8

Ahnak gene deficiency promotes type II pneumocyte hyperplasia and lung tumor development in mice

Jun Won Park,Il Yong Kim,Dong Su Kyeong,Ji Won Choi,Hee Jung Lim,Jae Hoon Shin,Yo Na Kim,Seo Hyun Lee,Yeri Son,Mira Sohn,Jong Kyu Woo,Joseph H. Jeong,Cheolju Lee,Yun Soo Bae,Je Kyung Seong 한국실험동물학회 2018 한국실험동물학회 학술발표대회 논문집 Vol.2018 No.7