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4 "Ji Young Kim"
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Original Articles
Unraveling the Genetic Landscape of Langerhans Cell Histiocytosis in Korean Patients: Comprehensive Insights from Mutational Profiles and Clinical Correlations
Kyung-Nam Koh, Ha Ra Jun, Ji-Young Lee, Ji Young Kim, Su Hyun Yoon, Young Kwon Koh, Sung Han Kang, Hyery Kim, Ho Joon Im, Sung-Min Chun
Received August 14, 2024  Accepted December 22, 2024  Published online December 24, 2024  
DOI: https://doi.org/10.4143/crt.2024.782    [Accepted]
AbstractAbstract PDF
Purpose
This study aimed to conduct a comprehensive genetic analysis of patients with Langerhans cell histiocytosis (LCH), focusing on the frequency of MAPK pathway mutations, detailed mutation profiles of MAPK pathway genes, and their correlation with clinical features and prognosis in Korean LCH patients.
Materials and Methods
We performed targeted next-generation sequencing, capable of capturing exons from 382 cancer-related genes, on genomic DNA extracted from formaldehyde-fixed and paraffin-embedded samples of 45 pathologically confirmed LCH patients.
Results
The majority of patients (91.1%) exhibited single-system disease, with bone being the most common location (84.4%). Initial treatments varied, and no patients died during a median follow-up of 6.8 years. Our genetic assays revealed that all patients had MAPK pathway alterations, including BRAF mutations in 51.2%, MAP2K1 mutations in 42.2%, RAF1 mutations in 4.4%, and a KRAS mutation in 2.2%. These mutations were mutually exclusive. Detailed mutation profiles indicated that among the BRAF mutations, there were 18 point mutations and 5 in-frame deletions, while most MAP2K1 mutations were in-frame deletions, with only one missense mutation. We detected previously unreported variations of point mutations in BRAF, MAP2K1, KRAS, and the first instance of a RAF1-KLC1 fusion in LCH. MAP2K1 mutations occurred more frequently in older patients, whereas BRAF V600 mutations were commonly associated with unifocal bone disease. Genetic mutations did not correlate with high-risk features or event-free survival.
Conclusion
This study identified mutually exclusive MAPK pathway mutations in every LCH patient through comprehensive genetic analysis, highlighting the importance of inclusive testing in understanding the disease's genetics.
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Underexpression of HOXA11 Is Associated with Treatment Resistance and Poor Prognosis in Glioblastoma
Young-Bem Se, Seung Hyun Kim, Ji Young Kim, Ja Eun Kim, Yun-Sik Dho, Jin Wook Kim, Yong Hwy Kim, Hyun Goo Woo, Se-Hyuk Kim, Shin-Hyuk Kang, Hak Jae Kim, Tae Min Kim, Soon-Tae Lee, Seung Hong Choi, Sung-Hye Park, Il Han Kim, Dong Gyu Kim, Chul-Kee Park
Cancer Res Treat. 2017;49(2):387-398.   Published online July 19, 2016
DOI: https://doi.org/10.4143/crt.2016.106
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Homeobox (HOX) genes are essential developmental regulators that should normally be in the silenced state in an adult brain. The aberrant expression of HOX genes has been associated with the prognosis of many cancer types, including glioblastoma (GBM). This study examined the identity and role of HOX genes affecting GBM prognosis and treatment resistance.
Materials and Methods
The full series of HOX genes of five pairs of initial and recurrent human GBM samples were screened by microarray analysis to determine the most plausible candidate responsible for GBM prognosis. Another 20 newly diagnosed GBM samples were used for prognostic validation. In vitro experiments were performed to confirm the role of HOX in treatment resistance. Mediators involved in HOX gene regulation were searched using differentially expressed gene analysis, gene set enrichment tests, and network analysis.
Results
The underexpression of HOXA11 was identified as a consistent signature for a poor prognosis among the HOX genes. The overall survival of the GBM patients indicated a significantly favorable prognosis in patients with high HOXA11 expression (31±15.3 months) compared to the prognoses in thosewith lowHOXA11 expression (18±7.3 months, p=0.03). When HOXA11 was suppressed in the GBM cell lines, the anticancer effect of radiotherapy and/or temozolomide declined. In addition, five candidate mediators (TGFBR2, CRIM1, TXNIP, DPYSL2, and CRMP1) that may confer an oncologic effect after HOXA11 suppression were identified.
Conclusion
The treatment resistance induced by the underexpression of HOXA11 can contribute to a poor prognosis in GBM. Further investigation will be needed to confirm the value of HOXA11 as a potential target for overcoming the treatment resistance by developing chemo- or radiosensitizers.

Citations

Citations to this article as recorded by  
  • Intratumoral IL-12 delivery via mesenchymal stem cells combined with PD-1 blockade leads to long-term antitumor immunity in a mouse glioblastoma model
    Junseong Park, Soon A. Park, Yoon-Seob Kim, Dokyeong Kim, Sun Shin, Sug Hyung Lee, Sin-Soo Jeun, Yeun-Jun Chung, Stephen Ahn
    Biomedicine & Pharmacotherapy.2024; 173: 115790.     CrossRef
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    Zong-Qing Zheng, Gui-Qiang Yuan, Guo-Guo Zhang, Qian-Qian Nie, Zhong Wang
    Discover Oncology.2023;[Epub]     CrossRef
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    Xiang-Long Li, Bin Wang, Fu-Bing Yang, Li-Gang Chen, Jian You
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    U Sangeetha Shenoy, Divya Adiga, Shama Prasada Kabekkodu, Keith D Hunter, Raghu Radhakrishnan
    Cell Biology and Toxicology.2022; 38(1): 1.     CrossRef
  • High expression ofHOXA4in patients with glioma indicates unfavorable clinical outcomes
    Zhenghong Yu, Zhendong Liu, Xiaoyu Lian, Xingbo Cheng, Binfeng Liu, Bo Zhang, Hongbo Wang, Jialin Wang, Ang Li, Zhishuai Ren, Bo Pang, Rongjun Qian, Yanzheng Gao
    Cell Cycle.2022; 21(22): 2387.     CrossRef
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    C. Kong, Z. Zhu, Y. Li, P. Xue, L. Chen
    Clinical and Translational Oncology.2021; 23(7): 1334.     CrossRef
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    Sara Momtazmanesh, Nima Rezaei
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Srikumar Chakravarthi, Barani Karikalan
    Current Cancer Therapy Reviews.2021; 17(2): 97.     CrossRef
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    Céline S. Gonçalves, Elisa Le Boiteux, Philippe Arnaud, Bruno M. Costa
    Cellular and Molecular Life Sciences.2020; 77(19): 3797.     CrossRef
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    Jinyun Li, Meng Ye, Chongchang Zhou
    Frontiers in Oncology.2020;[Epub]     CrossRef
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    Ana Paço, Simone Aparecida de Bessa Garcia, Renata Freitas
    Cells.2020; 9(7): 1613.     CrossRef
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    Zewei Tu, Lei Wu, Peng Wang, Qing Hu, Chuming Tao, Kuangxun Li, Kai Huang, Xingen Zhu
    Frontiers in Cell and Developmental Biology.2020;[Epub]     CrossRef
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    World Journal of Gastroenterology.2019; 25(22): 2763.     CrossRef
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    Basic & Clinical Pharmacology & Toxicology.2019; 125(6): 499.     CrossRef
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    Rui Zhang, Tong-tong Zhang, Gao-qiang Zhai, Xian-yu Guo, Yuan Qin, Ting-qing Gan, Yu Zhang, Gang Chen, Wei-jia Mo, Zhen-bo Feng
    World Journal of Surgical Oncology.2018;[Epub]     CrossRef
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    Ricardo Bonfim-Silva, Fernanda Ursoli Ferreira Melo, Carolina Hassibe Thomé, Kuruvilla Joseph Abraham, Fábio Augusto Labre De Souza, Fernando Silva Ramalho, Hélio Rubens Machado, Ricardo Santos De Oliveira, Angelo A. Cardoso, Dimas Tadeu Covas, Aparecida
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    Jian-Chun Su, Xue-Feng Hu
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    Xiao-Jie Sun, Qiang Wang, Baofeng Guo, Xian-Ying Liu, Bing Wang
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    Hongmei Luo, Yu Qin, Frederic Reu, Sujuan Ye, Yang Dai, Jingcao Huang, Fangfang Wang, Dan Zhang, Ling Pan, Huanling Zhu, Yu Wu, Ting Niu, Zhijian Xiao, Yuhuan Zheng, Ting Liu
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Case Report
Pazopanib for Non-small Cell Lung Cancer: The First Case Report in Korea
Jaemin Jo, Jung Ho Kim, Ji Young Kim, Changlim Hyun, Jiyoung Rhee, Jungmi Kwon, Sanghoon Han, Wookun Kim
Cancer Res Treat. 2016;48(1):393-397.   Published online February 17, 2015
DOI: https://doi.org/10.4143/crt.2014.209
AbstractAbstract PDFPubReaderePub
Pazopanib is a potent multitargeted tyrosine kinase inhibitor that has been shown to have good efficacy in patients with renal cell carcinoma. A previous phase II trial demonstrated that short-term pazopanib administration was generally well tolerated and showed antitumor activity in patients with early-stage non-small cell lung cancer. Herein, we report on the case of a 66-year-old man with simultaneous metastatic squamous cell carcinoma of the lung and renal cell carcinoma who was treated with pazopanib. The patient showed an unexpected partial response and experienced a 10-month progression-free survival without significant toxicity. To the best of the authors’ knowledge, this is the first report of pazopanib treatment in a non-small cell lung cancer patient in Korea. The results in this patient suggest that pazopanib may be a valid treatment option for advanced non-small cell lung cancer.
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Original Article
Effects of Polyamines on TNFalpha- or Tamoxifen-induced Apoptosis in Human Breast Cancer Cells
Ji Young Kim, Ki Young Kim, Kyeong Hee Lee, Ki Whan Hong, Byeong Gee Kim
Cancer Res Treat. 2001;33(5):385-391.   Published online October 31, 2001
DOI: https://doi.org/10.4143/crt.2001.33.5.385
AbstractAbstract PDF
PURPOSE
To investigate the effects of polyamines on tumor necrosis factor alpha (TNFalpha)-or tamoxifen (TAM)-induced apoptosis in estrogen receptor (ER)-positive MCF- 7 and ER-negative MDA-MB-231 human breast cancer cells.
MATERIALS AND METHODS
Cell viability was assessed by using MTT assay. Reactive oxygen species (ROS) generation was measured using 2', 7'-dichlorofluorescin diacetste (DCFDA) by fluorescence plate reader. DNA fragmentation was assessed by 1.5% agarose gel electrophoresis.
RESULTS
TNFalpah and TAM showed significant dose- and time- dependent inhibitory effects on the growth of MCF-7 human cells. However, the growth of MDA-MB-231 cells were not inhibited by TNFalpha or TAM treatment. The generation of ROS was increased in dose-and time-dependent manner by TNFalpha treatment in MCF-7 cells. Polyamines, especially spermine suppressed TNFalpha-induced ROS generation in MCF-7 cells. Antioxidant effects of polyamines were also demonstrated by DNA fragmentation, cell morphology as well as ROS generation assay. Polyamines also blocked TAM-induced cell death in MCF-7 cell. However, MDA-MB-231 cells showed resistance to the cytotoxic effects of TNFalpha or TAM.
CONCLUSION
These results suggest that polyamines may prevent TNFalpha or TAM-induced apoptosis in MCF-7 human breast cancer cells.

Citations

Citations to this article as recorded by  
  • Influence of Estrogen and Polyamines on Mifepristone-induced Apoptosis in Prostate Cancer Cells
    Eun Kyung Choi, Hwi-June Song, Min S. Park, Byeong Gee Kim
    Cancer Research and Treatment.2004; 36(1): 85.     CrossRef
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