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28 "Kyong Hwa Park"
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Original Articles
Machine Learning-Based Prognostic Gene Signature for Early Triple Negative Breast Cancer
Ju Won Kim, Jonghyun Lee, Sung Hak Lee, Sangjeong Ahn, Kyong Hwa Park
Received September 26, 2024  Accepted November 18, 2024  Published online November 19, 2024  
DOI: https://doi.org/10.4143/crt.2024.937    [Accepted]
AbstractAbstract PDF
Purpose
This study aimed to develop a machine learning-based approach to identify prognostic gene signatures for early-stage Triple Negative Breast Cancer (TNBC) using next-generation sequencing data from Asian populations.
Materials and Methods
We utilized next-generation sequencing data to analyze gene expression profiles and identify potential biomarkers. Our methodology involved integrating various machine learning techniques, including feature selection and model optimization. We employed logistic regression, Kaplan-Meier survival analysis, and receiver operating characteristic (ROC) curves to validate the identified gene signatures.
Results
We identified a gene signature significantly associated with relapse in TNBC patients. The predictive model demonstrated robustness and accuracy, with an area under the ROC curve (AUROC) of 0.9087, sensitivity of 0.8750, and specificity of 0.9231. The Kaplan-Meier survival analysis revealed a strong association between the gene signature and patient relapse, further validated by logistic regression analysis.
Conclusion
This study presents a novel machine learning-based prognostic tool for TNBC, offering significant implications for early detection and personalized treatment. The identified gene signature provides a promising approach for improving the management of TNBC, contributing to the advancement of precision oncology.
  • 386 View
  • 29 Download
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Breast cancer
Molecular Classification of Breast Cancer Using Weakly Supervised Learning
Wooyoung Jang, Jonghyun Lee, Kyong Hwa Park, Aeree Kim, Sung Hak Lee, Sangjeong Ahn
Cancer Res Treat. 2025;57(1):116-125.   Published online June 25, 2024
DOI: https://doi.org/10.4143/crt.2024.113
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The molecular classification of breast cancer is crucial for effective treatment. The emergence of digital pathology has ushered in a new era in which weakly supervised learning leveraging whole-slide images has gained prominence in developing deep learning models because this approach alleviates the need for extensive manual annotation. Weakly supervised learning was employed to classify the molecular subtypes of breast cancer.
Materials and Methods
Our approach capitalizes on two whole-slide image datasets: one consisting of breast cancer cases from the Korea University Guro Hospital (KG) and the other originating from The Cancer Genomic Atlas dataset (TCGA). Furthermore, we visualized the inferred results using an attention-based heat map and reviewed the histomorphological features of the most attentive patches.
Results
The KG+TCGA-trained model achieved an area under the receiver operating characteristics value of 0.749. An inherent challenge lies in the imbalance among subtypes. Additionally, discrepancies between the two datasets resulted in different molecular subtype proportions. To mitigate this imbalance, we merged the two datasets, and the resulting model exhibited improved performance. The attentive patches correlated well with widely recognized histomorphologic features. The triple-negative subtype has a high incidence of high-grade nuclei, tumor necrosis, and intratumoral tumor-infiltrating lymphocytes. The luminal A subtype showed a high incidence of collagen fibers.
Conclusion
The artificial intelligence (AI) model based on weakly supervised learning showed promising performance. A review of the most attentive patches provided insights into the predictions of the AI model. AI models can become invaluable screening tools that reduce costs and workloads in practice.
  • 1,529 View
  • 158 Download
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A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer
Chang Min Kim, Kyong Hwa Park, Yun Suk Yu, Ju Won Kim, Jin Young Park, Kyunghee Park, Jong-Han Yu, Jeong Eon Lee, Sung Hoon Sim, Bo Kyoung Seo, Jin Kyeoung Kim, Eun Sook Lee, Yeon Hee Park, Sun-Young Kong
Cancer Res Treat. 2024;56(4):1113-1125.   Published online May 10, 2024
DOI: https://doi.org/10.4143/crt.2024.100
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.

Citations

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  • Significance of Multi-Cancer Genome Profiling Testing for Breast Cancer: A Retrospective Analysis of 3326 Cases from Japan’s National Database
    Kyoka Kawabata, Hinano Nishikubo, Saki Kanei, Rika Aoyama, Yuki Tsukada, Tomoya Sano, Daiki Imanishi, Takashi Sakuma, Koji Maruo, Yurie Yamamoto, Qiang Wang, Zhonglin Zhu, Canfeng Fan, Masakazu Yashiro
    Genes.2024; 15(6): 792.     CrossRef
  • 1,650 View
  • 138 Download
  • 1 Web of Science
  • 1 Crossref
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Eflapegrastim versus Pegfilgrastim for Chemotherapy-Induced Neutropenia in Korean and Asian Patients with Early Breast Cancer: Results from the Two Phase III ADVANCE and RECOVER Studies
Yong Wha Moon, Seung Ki Kim, Keun Seok Lee, Moon Hee Lee, Yeon Hee Park, Kyong Hwa Park, Gun Min Kim, Seungtaek Lim, Seung Ah Lee, Jae Duk Choi, Eunhye Baek, Hyesun Han, Seungjae Baek, Seock-Ah Im
Cancer Res Treat. 2023;55(3):766-777.   Published online January 19, 2023
DOI: https://doi.org/10.4143/crt.2022.987
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials.
Materials and Methods
Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations.
Results
Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations.
Conclusion
This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.

Citations

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  • Comparison of Prophylactic Efficacy of Eflapegrastim and Pegteograstim for Chemotherapy-induced Neutropenia in Pancreatic Cancer Patients Receiving FOLFIRINOX/mFOLFIRINOX
    Eui Seon Lee, Min Jung Geum, Jong Hee Ko, Jae Song Kim, Eun Sun Son, Yun Mi Yu
    Journal of Korean Society of Health-System Pharmacists.2024; 41(3): 253.     CrossRef
  • 4,598 View
  • 270 Download
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PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Res Treat. 2023;55(2):531-541.   Published online September 7, 2022
DOI: https://doi.org/10.4143/crt.2022.221
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Mutations in the PIK3CA gene occur frequently in breast cancer patients. Activating PIK3CA mutations confer resistance to human epidermal growth factor receptor 2 (HER2)-targeted treatments. In this study, we investigated whether PIK3CA mutations were correlated with treatment response or duration in patients with HER2-positive (HER2+) breast cancer.
Materials and Methods
We retrospectively reviewed the clinical information of patients with HER2+ breast cancer who received HER2-targeted therapy for early-stage or metastatic cancers. The pathologic complete response (pCR), progression-free survival (PFS), and overall survival were compared between patients with wild-type PIK3CA (PIK3CAw) and those with mutated PIK3CA (PIK3CAm). Next-generation sequencing was combined with examination of PFS associated with anti-HER2 monoclonal antibody (mAb) treatment.
Results
Data from 90 patients with HER2+ breast cancer were analyzed. Overall, 34 (37.8%) patients had pathogenic PIK3CA mutations. The pCR rate of the PIK3CAm group was lower than that of the PIK3CAw group among patients who received neoadjuvant chemotherapy for early-stage cancer. In the metastatic setting, the PIK3CAm group showed a significantly shorter mean PFS (mPFS) with first-line anti-HER2 mAb. The mPFS of second-line T-DM1 was lower in the PIK3CAm group than that in the PIK3CAw group. Sequencing revealed differences in the mutational landscape between PIK3CAm and PIK3CAw tumors.
Conclusion
Patients with HER2+ breast cancer with activating PIK3CA mutations had lower pCR rates and shorter PFS with palliative HER2-targeted therapy than those with wild-type PIK3CA. Precise targeted-therapy is needed to improve survival of patients with HER2+/PIK3CAm breast cancer.

Citations

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  • Safety and efficacy of pyrotinib for HER‑2‑positive breast cancer in the neoadjuvant setting: A systematic review and meta‑analysis
    Qian Ma, Bai Wei, Bi-Cheng Wang, Ganxin Wang, Xuan Zhou, Yan Wang
    Oncology Letters.2024;[Epub]     CrossRef
  • A novel PIK3CA hot-spot mutation in breast cancer patients detected by HRM-COLD-PCR analysis
    Saoussen Debouki-Joudi, Wala Ben Kridis, Fatma Trifa, Wajdi Ayadi, Abdelmajid Khabir, Tahia Sellami-Boudawara, Jamel Daoud, Afef Khanfir, Raja Mokdad-Gargouri
    Breast Disease.2024; 43(1): 213.     CrossRef
  • Liquid Biopsy in the Clinical Management of Cancers
    Ho-Yin Ho, Kei-See (Kasey) Chung, Chau-Ming Kan, Sze-Chuen (Cesar) Wong
    International Journal of Molecular Sciences.2024; 25(16): 8594.     CrossRef
  • Modeling the management of patients with human epidermal growth factor receptor 2-positive breast cancer with liquid biopsy: the future of precision medicine
    Eleonora Nicolò, Caterina Gianni, Giuseppe Curigliano, Carolina Reduzzi, Massimo Cristofanilli
    Current Opinion in Oncology.2024; 36(6): 503.     CrossRef
  • Current progress in chimeric antigen receptor-modified T cells for the treatment of metastatic breast cancer
    Li Yin, Gui-lai Chen, Zhuo Xiang, Yu-lin Liu, Xing-yu Li, Jing-wang Bi, Qiang Wang
    Biomedicine & Pharmacotherapy.2023; 162: 114648.     CrossRef
  • Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
    Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
    Scientific Reports.2023;[Epub]     CrossRef
  • Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
    Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
    Translational Oncology.2023; 37: 101738.     CrossRef
  • Appraisal of Systemic Treatment Strategies in Early HER2-Positive Breast Cancer—A Literature Review
    Danilo Giffoni de Mello Morais Mata, Rania Chehade, Malek B. Hannouf, Jacques Raphael, Phillip Blanchette, Abdullah Al-Humiqani, Monali Ray
    Cancers.2023; 15(17): 4336.     CrossRef
  • The clinical significance of HER2 expression in DCIS
    Ioanna Akrida, Francesk Mulita
    Medical Oncology.2022;[Epub]     CrossRef
  • 7,230 View
  • 287 Download
  • 8 Web of Science
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Genomic Signatures from Clinical Tumor Sequencing in Patients with Breast Cancer Having Germline BRCA1/2 Mutation
Ju Won Kim, Hyo Eun Kang, Jimi Choi, Seung Gyu Yun, Seung Pil Jung, Soo Yeon Bae, Ji Young You, Yoon-Ji Choi, Yeul Hong Kim, Kyong Hwa Park
Cancer Res Treat. 2023;55(1):155-166.   Published online June 8, 2022
DOI: https://doi.org/10.4143/crt.2021.1567
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants.
Materials and Methods
Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity.
Results
A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w.
Conclusion
We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.

Citations

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  • Clinico-Pathological Factors Determining Recurrence of Phyllodes Tumors of the Breast: The 25-Year Experience at a Tertiary Cancer Centre
    Baijaeek Sain, Arnab Gupta, Aruni Ghose, Sudip Halder, Vishal Mukherjee, Samir Bhattacharya, Radha Raman Mondal, Aditya Narayan Sen, Bijan Saha, Shravasti Roy, Stergios Boussios
    Journal of Personalized Medicine.2023; 13(5): 866.     CrossRef
  • 6,174 View
  • 203 Download
  • 1 Web of Science
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General
Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations
Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Seungtaek Lim, Sung Shim Cho, Jang Ho Cho, Sang Won Shin, Kyong Hwa Park, Yeul Hong Kim
Cancer Res Treat. 2022;54(1):30-39.   Published online May 20, 2021
DOI: https://doi.org/10.4143/crt.2021.218
AbstractAbstract PDFPubReaderePub
Purpose
K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods.
Materials and Methods
Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers).
Results
In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively.
Conclusion
The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Citations

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  • Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer
    Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
    BMC Cancer.2024;[Epub]     CrossRef
  • Supporting Biomarker-Driven Therapies in Oncology: A Genomic Testing Cost Calculator
    Albrecht Stenzinger, Brian Cuffel, Noman Paracha, Eric Vail, Jesus Garcia-Foncillas, Clifford Goodman, Ulrik Lassen, Gilles Vassal, Sean D Sullivan
    The Oncologist.2023; 28(5): e242.     CrossRef
  • Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
    Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
    Scientific Reports.2023;[Epub]     CrossRef
  • Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
    Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
    Cancer Research and Treatment.2022; 54(1): 1.     CrossRef
  • 8,549 View
  • 260 Download
  • 5 Web of Science
  • 4 Crossref
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Gastrointestinal cancer
Clinical Application of Targeted Deep Sequencing in Metastatic Colorectal Cancer Patients: Actionable Genomic Alteration in K-MASTER Project
Youngwoo Lee, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Ah-reum Lim, Ju Won Kim, Yoon Ji Choi, Kyong Hwa Park, Yeul Hong Kim
Cancer Res Treat. 2021;53(1):123-130.   Published online August 18, 2020
DOI: https://doi.org/10.4143/crt.2020.559
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations.
Materials and Methods
As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy.
Results
In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors.
Conclusion
K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

Citations

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    Yonghwa Choi, Jangwoo Lee, Keewon Shin, Ji Won Lee, Ju Won Kim, Soohyeon Lee, Yoon Ji Choi, Kyong Hwa Park, Jwa Hoon Kim
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  • PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
    Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
    Cancer Research and Treatment.2023; 55(2): 531.     CrossRef
  • Genomic analysis of plasma circulating tumor DNA in patients with heavily pretreated HER2 + metastatic breast cancer
    Kyoungmin Lee, Jongwon Lee, Jungmin Choi, Sung Hoon Sim, Jeong Eun Kim, Min Hwan Kim, Yeon Hee Park, Jee Hyun Kim, Su-Jin Koh, Kyong Hwa Park, Myoung Joo Kang, Mi Sun Ahn, Kyoung Eun Lee, Hee-Jun Kim, Hee Kyung Ahn, Han Jo Kim, Keon Uk Park, In Hae Park
    Scientific Reports.2023;[Epub]     CrossRef
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    Yoon Ji Choi, Jung Yoon Choi, Ju Won Kim, Ah Reum Lim, Youngwoo Lee, Won Jin Chang, Soohyeon Lee, Jae Sook Sung, Hee-Joon Chung, Jong Won Lee, Eun Joo Kang, Jung Sun Kim, Taekyu Lim, Hye Sook Kim, Yu Jung Kim, Mi Sun Ahn, Young Saing Kim, Ji Hyun Park, Se
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    Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se
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    Yuanli Wang, Dawu Zheng
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  • Paired analysis of tumor mutation burden calculated by targeted deep sequencing panel and whole exome sequencing in non-small cell lung cancer
    Sehhoon Park, Chung Lee, Bo Mi Ku, Minjae Kim, Woong-Yang Park, Nayoung K. D. Kim, Myung-Ju Ahn
    BMB Reports.2021; 54(7): 386.     CrossRef
  • Evaluation of a Targeted Next-Generation Sequencing Panel for the Non-Invasive Detection of Variants in Circulating DNA of Colorectal Cancer
    Aitor Rodríguez-Casanova, Aida Bao-Caamano, Ramón M. Lago-Lestón, Elena Brozos-Vázquez, Nicolás Costa-Fraga, Isabel Ferreirós-Vidal, Ihab Abdulkader, Yolanda Vidal-Insua, Francisca Vázquez Rivera, Sonia Candamio Folgar, Rafael López-López, Laura Muinelo-R
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  • Implications of Intratumor Heterogeneity on Consensus Molecular Subtype (CMS) in Colorectal Cancer
    Saikat Chowdhury, Matan Hofree, Kangyu Lin, Dipen Maru, Scott Kopetz, John Paul Shen
    Cancers.2021; 13(19): 4923.     CrossRef
  • 10,155 View
  • 360 Download
  • 13 Web of Science
  • 12 Crossref
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Clinical Implication of Concordant or Discordant Genomic Profiling between Primary and Matched Metastatic Tissues in Patients with Colorectal Cancer
Jung Yoon Choi, Sunho Choi, Minhyeok Lee, Young Soo Park, Jae Sook Sung, Won Jin Chang, Ju Won Kim, Yoon Ji Choi, Jin Kim, Dong-Sik Kim, Sung-Ho Lee, Junhee Seok, Kyong Hwa Park, Seon Hahn Kim, Yeul Hong Kim
Cancer Res Treat. 2020;52(3):764-778.   Published online February 16, 2020
DOI: https://doi.org/10.4143/crt.2020.044
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication.
Materials and Methods
Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites.
Results
A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases.
Conclusion
Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.

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Clinical Characteristics of Clear Cell Ovarian Cancer: A Retrospective Multicenter Experience of 308 Patients in South Korea
Hee Yeon Lee, Ji Hyung Hong, Jae Ho Byun, Hee-Jun Kim, Sun Kyung Baek, Jin Young Kim, Ki Hyang Kim, Jina Yun, Jung A Kim, Kwonoh Park, Hyo Jin Lee, Jung Lim Lee, Young-Woong Won, Il Hwan Kim, Woo Kyun Bae, Kyong Hwa Park, Der-Sheng Sun, Suee Lee, Min-Young Lee, Guk Jin Lee, Sook Hee Hong, Yun Hwa Jung, Ho Jung An
Cancer Res Treat. 2020;52(1):277-283.   Published online July 12, 2019
DOI: https://doi.org/10.4143/crt.2019.292
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early stage.
Materials and Methods
Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected.
Results
Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence.
Conclusion
Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.

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Erratum
ERRATUM: Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms
Jinho Kang, Joo Hee Park, Hye Jin Lee, Ukhyun Jo, Jong Kuk Park, Jae Hong Seo, Yeul Hong Kim, Insun Kim, Kyong Hwa Park
Cancer Res Treat. 2019;51(3):1257-1257.   Published online June 5, 2019
DOI: https://doi.org/10.4143/crt.2015.227.2
Corrects: Cancer Res Treat 2016;48(2):715
PDFPubReaderePub
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Original Articles
Phase II Study of Dovitinib in Patients with Castration-Resistant Prostate Cancer (KCSG-GU11-05)
Yoon Ji Choi, Hye Sook Kim, Se Hoon Park, Bong-Seog Kim, Kyoung Ha Kim, Hyo Jin Lee, Hong Suk Song, Dong-Yeop Shin, Ha Young Lee, Hoon-Gu Kim, Kyung Hee Lee, Jae Lyun Lee, Kyong Hwa Park
Cancer Res Treat. 2018;50(4):1252-1259.   Published online January 2, 2018
DOI: https://doi.org/10.4143/crt.2017.438
AbstractAbstract PDFPubReaderePub
Purpose
Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC).
Materials and Methods
This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpointwas 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed.
Results
Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinibwas 2 (range, 0 to 33). Median PFSwas 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common.
Conclusion
Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.

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Gemcitabine and Docetaxel Combination for Advanced Soft Tissue Sarcoma: A Nationwide Retrospective Study
Yunjung Choi, Mi Sun Yun, Sang Hee Lim, Jeeyun Lee, Jin-Hee Ahn, Yu Jung Kim, Kyong Hwa Park, Young Suk Park, Ho Yeong Lim, Hyonggin An, Dong-Churl Suh, Yeul Hong Kim
Cancer Res Treat. 2018;50(1):175-182.   Published online March 30, 2017
DOI: https://doi.org/10.4143/crt.2016.535
AbstractAbstract PDFPubReaderePub
Purpose
This nationwide retrospective study was conducted to evaluate the efficacy and safety of combined gemcitabine and docetaxel (GD) as an off-label therapy for advanced soft tissue sarcoma, which has limited treatment options owing to its rare occurrence.
Materials and Methods
A total of 228 patients received GD therapy for advanced soft tissue sarcoma from 2009 to 2014 in Korea. We retrospectively reviewed the clinical medical records and claims data of these patients.
Results
A total of 218 patients in 20 medical centers were included in the final analysis (median age, 50.0 years). The objective response rate was 15.1% (34/218, in the leiomyosarcoma subgroup; 26.3%). The median overall survival and progression-free survival were 10.3 months (95% confidence interval [CI], 8.4 to 12.2) and 3.3 months (95% CI, 2.8 to 4.7), respectively. The treatment was discontinued in 7.8% of patients owing to adverse events; however, there was no adverse event-related death. Neutropenia (35.7%) and anemia (15.1%) were the most frequent grade 3/4 toxicities. Univariate analysis for identifying the predictors of the progression-free survival period revealed that patients aged ≤ 50 years had a hazard ratio of 1.388 (95% CI, 1.027 to 1.875; p < 0.05) relative to those aged > 50 years, and the group with leiomyosarcoma had a hazard ratio of 0.693 (95% CI, 0.493 to 0.975; p < 0.05) relative to the group with other histopathological subtypes.
Conclusion
GD therapy was tolerable and effective for Korean patients with soft tissue sarcoma. In conclusion, for patients with advanced soft tissue sarcoma, especially leiomyosarcoma, GD therapy could be an important therapeutic option.

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Caveolin-1 Modulates Docetaxel-Induced Cell Death in Breast Cancer Cell Subtypes through Different Mechanisms
Jinho Kang, Joo Hee Park, Hye Jin Lee, Ukhyun Jo, Jong Kuk Park, Jae Hong Seo, Yeul Hong Kim, Insun Kim, Kyong Hwa Park
Cancer Res Treat. 2016;48(2):715-726.   Published online September 21, 2015
DOI: https://doi.org/10.4143/crt.2015.227
Correction in: Cancer Res Treat 2019;51(3):1257
AbstractAbstract PDFPubReaderePub
Purpose
Caveolin-1 (CAV-1) expression is more associated with basal-like cancers than estrogen receptor- or ErbB-2–expressing breast cancers. However, the biological relevance of different levels of CAV-1 expression according to subtype in the epithelial compartment of breast cancer remains unclear.
Materials and Methods
We investigated whether CAV-1 functions as a tumor suppressor and/or modulator of the cytotoxic activity of docetaxel (DTX) in subtypes of breast cancer using in vitro and xenograft models.
Results
The levels of CAV-1 expression were closely associated with DTX sensitivity in triple-negative breast cancer cells. In addition, CAV-1 significantly inhibited cell proliferation and modulated DTX-induced apoptosis through cell cycle arrest in the G2/M phase. The mechanisms underlying DTX-induced apoptosis differed in breast cancers according to the levels of CAV- 1 expression. DTX robustly enhanced Bcl-2 inactivation by CAV-1 in MDA-MB-231 cells, while p53-mediated cell cycle arrest by DTX was more pronounced in CAV-1–low but p53-functional MCF-7 cells. In parallel with the data from breast cancer cell lines, CAV-1–transfected MCF-7 cells showed higher efficacy of DTX treatment in a xenograft model.
Conclusion
We clearly demonstrated cooperative effects between CAV-1 and DTX in mediating apoptosis, suggesting that the levels of CAV-1 expression might be an important indicator for DTX use in breast cancer.

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Case Report
Novel Germline Mutation of BRCA1 Gene in a 56-Year-Old Woman with Breast Cancer, Ovarian Cancer, and Diffuse Large B-Cell Lymphoma
Hye Sook Kim, Soon Wook Lee, Yoon Ji Choi, Sang Won Shin, Yeul Hong Kim, Min Sun Cho, Soon Nam Lee, Kyong Hwa Park
Cancer Res Treat. 2015;47(3):534-538.   Published online October 17, 2014
DOI: https://doi.org/10.4143/crt.2013.151
AbstractAbstract PDFPubReaderePub
We report a case of a 56-year-old woman with breast cancer, ovarian cancer, and diffuse large B-cell lymphoma with a BRCA1 gene mutation. Evidence is mounting that there is a large increase in the risk for hematologic malignancies among patients with genetic changes in the BRCA pathways. The genomic analysis demonstrated a frameshift mutation in the BRCA1 gene: 277_279delinsCC (Phe93fs). It is a novel BRCA1 mutation that has never been reported, and caused malignant lymphoma as well as breast and ovarian cancer.

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Original Articles
Modified MVAC as a Second-Line Treatment for Patients with Metastatic Urothelial Carcinoma after Failure of Gemcitabine and Cisplatin Treatment
Jung Hyun Lee, Sung Gu Kang, Seung Tae Kim, Seok Ho Kang, In Keun Choi, Young Je Park, Sang Chul Oh, Deuk Jae Sung, Jae Hong Seo, Jun Cheon, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Kyong Hwa Park
Cancer Res Treat. 2014;46(2):172-177.   Published online April 15, 2014
DOI: https://doi.org/10.4143/crt.2014.46.2.172
AbstractAbstract PDFPubReaderePub
Purpose

There is no established standard second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who failed gemcitabine and cisplatin (GC) chemotherapy. This study was conducted in order to investigate the efficacy and toxicity of modified methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with metastatic UC previously treated with GC.

Materials and Methods

We retrospectively analyzed 28 patients who received modified MVAC between November 2004 and November 2012. All patients failed prior, first-line GC chemotherapy.

Results

The median age of patients was 64.0 years (range, 33.0 to 77.0 years), and 23 (82.1%) patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The overall response rate and the disease control rate were 36.0% and 64.0%, respectively. After a median follow-up period of 38 weeks (range, 5 to 182 weeks), median progression free survival was 21.0 weeks (95% confidence interval [CI], 6.3 to 35.7 weeks) and median overall survival was 49.0 weeks (95% CI, 18.8 to 79.3 weeks). Grade 3 or 4 hematological toxicities included neutropenia (n=21, 75.0%) and anemia (n=9, 32.1%). Grade 3 or 4 non-hematological toxicities did not occur and there was no treatment-related death.

Conclusion

Modified MVAC appears to be a safe and active chemotherapy regimen in patients with stable physical status and adequate renal function after GC treatment.

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Dose KRAS Mutation Status Affect on the Effect of VEGF Therapy in Metastatic Colon Cancer Patients?
Seung Tae Kim, Kyong Hwa Park, Sang Won Shin, Yeul Hong Kim
Cancer Res Treat. 2014;46(1):48-54.   Published online January 15, 2014
DOI: https://doi.org/10.4143/crt.2014.46.1.48
AbstractAbstract PDFPubReaderePub
PURPOSE
Mutations affecting the KRAS gene are an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, the role of KRAS mutation as a biomarker for anti-vascular endothelial growth factor (VEGF) remains controversial.
MATERIALS AND METHODS
We analyzed retrospective data from 32 CRC patients who were available for KRAS mutation status and received cytotoxic chemotherapy plus bevacizumab as a first-line therapy. Six of 32 patients received anti-EGFR therapies. We used KRAS mutation status as a predictive or prognostic factor in CRC patients receiving bevacizumab.
RESULTS
We observed mutations in KRAS in 59.4% of patients. Bevacizumab was used in combination with oxaliplatin based regimens. There was no significant difference for progression free survival (PFS) and overall survival (OS) in patients with oxaliplatin based cytotoxic chemotherapy plus bevacizumab according to the status of KRAS mutation. After first-line therapy, 28 patients (87.5%) received second-line therapy. In univariate analysis, KRAS mutations did not have a major prognostic value for PFS (hazard ratio, 1.007; 95% confidence interval [CI], 0.469 to 2.162; p>0.05) or OS (hazard ratio, 0.548; 95% CI, 0.226 to 1.328; p>0.05). In addition, anti-EGFR therapies did not affect the impact on OS.
CONCLUSION
KRAS mutation is neither a predictive for bevacizumab nor a prognostic for OS in CRC patients receiving anti-VEGF therapy.

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Impact of KRAS Mutation Status on Outcomes in Metastatic Colon Cancer Patients without Anti-Epidermal Growth Factor Receptor Therapy
Seung Tae Kim, Kyong Hwa Park, Jun Suk Kim, Sang Won Shin, Yeul Hong Kim
Cancer Res Treat. 2013;45(1):55-62.   Published online March 31, 2013
DOI: https://doi.org/10.4143/crt.2013.45.1.55
AbstractAbstract PDFPubReaderePub
PURPOSE
Activating mutation of the KRAS oncogene is an established negative predictor for anti-epidermal growth factor receptor (anti-EGFR) therapies in metastatic colorectal cancer (CRC). However, KRAS mutation as a prognostic factor of survival outcome remains controversial in CRC, independent of anti-EGFR therapies.
MATERIALS AND METHODS
We conducted a retrospective analysis of 103 CRC patients who were available for evaluation of KRAS mutation status. None of the patients analyzed had received anti-EGFR therapies. The role of KRAS mutation status was evaluated as a predictive factor for oxaliplatin or irinotecan and as a prognostic factor in CRC patients who did not receive anti-EGFR therapies.
RESULTS
Mutations in KRAS were observed in 48.5% of patients. The response for oxaliplatin- (p=0.664) and irinotecan-based (p=0.255) cytotoxic chemotherapy did not differ according to the KRAS mutation status. In addition, no significant difference in progression free survival (PFS; oxaliplatin, p=0.583 and irinotecan, p=0.426) and overall survival (OS; p=0.258) was observed between the wild and mutant type of the KRAS gene. In univariate and multivariate analyses, KRAS mutations did not have a major prognostic value regarding PFS (oxaliplatin: hazard ratio, 0.892; 95% confidence interval [CI], 0.590 to 1.347; p=0.586 and irinotecan: hazard ratio, 0.831; 95% CI, 0.524 to 1.319; p=0.433) or OS (hazard ratio, 0.754; 95% CI, 0.460 to 1.236; p=0.263). In addition, anti-vascular endothelial growth factor therapies did not affect PFS to oxaliplatin or irinotecan and OS.
CONCLUSION
KRAS mutation is not a prognostic marker for PFS to oxaliplatin or irinotecan and OS in CRC patients who did not receive anti-EGFR therapies.

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Chemotherapy in Patients Older than or Equal to 75 Years with Advanced Non-small Cell Lung Cancer
Seung Tae Kim, Kyong Hwa Park, Sang Cheul Oh, Jae Hong Seo, Jun Suk Kim, Yeul Hong Kim, Sang Won Shin
Cancer Res Treat. 2012;44(1):37-42.   Published online March 31, 2012
DOI: https://doi.org/10.4143/crt.2012.44.1.37
AbstractAbstract PDFPubReaderePub
PURPOSE
As the number of elderly patients diagnosed with non-small cell lung carcinoma (NSCLC) increases, the number of these patients receiving chemotherapy also increases. However, limited data exists regarding the use of chemotherapy in advanced NSCLC patients who are 75 years of age or older.
MATERIALS AND METHODS
Between May 2002 and October 2008, data for 48 advanced NSCLC patients who were 75 years of age or older who had been treated with chemotherapy were retrospectively analyzed.
RESULTS
The median age of study participants at the time of first line chemotherapy was 76 years (range, 75 to 87 years) and their median Charlson comorbidity index was 2 (range, 1 to 4). Of the total 48 patients, 43 patients (90%) were treated by platinum-based doublet as a first line chemotherapy regimen. Median progression free survival for first line chemotherapy was 5.7 months (95% confidence interval [CI], 4.93 to 6.47 months) with an overall response rate of 33.3%. After first line chemotherapy, only 14 of the 48 patients (29.2%) received second line chemotherapy. The median overall survival (OS) for these patients was 8.2 months (95% CI, 4.44 to 11.96 months). Multivariate analysis results indicated that female gender and having received second-line or more chemotherapy were independent prognostic factors for increased OS for all 48 patients. Charlson Index was not a significant independent prognostic factor for survival. There were 9 treatment related deaths due to infectious causes (18.8%).
CONCLUSION
Patients 75 years of age or older with advanced NSCLC may obtain clinical benefit from the administration of platinum-based doublet or single agent chemotherapy. However, oncologists must consider the aspect of safety in relation to the clinical benefits when managing this patient group.

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  • A phase II trial of Cremorphor EL-free paclitaxel (Genexol-PM) and gemcitabine in patients with advanced non-small cell lung cancer
    Hee Kyung Ahn, Minkyu Jung, Sun Jin Sym, Dong Bok Shin, Shin Myung Kang, Sun Young Kyung, Jeong-Woong Park, Sung Hwan Jeong, Eun Kyung Cho
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An Association Study of Polymorphisms in JAK3 Gene with Lung Cancer in the Korean Population
Wonbeak Yoo, Hae-Yun Jung, Seungjoon Lim, Jae Sook Sung, Kyong Hwa Park, Jeong Seon Ryu, Sang Won Shin, Jun Suk Kim, Jae Hong Seo, Yeul Hong Kim
Cancer Res Treat. 2011;43(2):108-116.   Published online June 30, 2011
DOI: https://doi.org/10.4143/crt.2011.43.2.108
AbstractAbstract PDFPubReaderePub
PURPOSE
The genetic alteration of the janus kinases (JAKs), non-receptor tyrosine kinase, is related to the development of human cancers. However, little is known about how the sequence variation of JAK3 contributes to the development of lung cancer. This study investigated whether polymorphisms at the promoter region of the JAK3 gene are associated with the risk of lung cancer in the Korean population.
MATERIALS AND METHODS
A total of 819 subjects, including 409 lung cancer patients and 410 healthy controls were recruited. The SNaPshot assay and polymerase chain reaction-restriction fragment length polymorphism analysis were used, and logistic regression analyses were performed to characterize the association between polymorphisms of JAK3 and lung cancer risk.
RESULTS
Three polymorphisms (-672 G>A, +64 A>G and +227 G>A) of JAK3 were analyzed for large-scale genotyping (n=819). Statistical analyses revealed that polymorphisms and haplotypes in the JAK3 gene were not significantly associated with lung cancer.
CONCLUSION
JAK3 gene was not significantly associated with the risk of lung cancer in the Korean population.

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  • Association Analysis of Polymorphic Gene Variants in the JAK/STAT Signaling Pathway with Aging and Longevity
    V. V. Erdman, T. R. Nasibullin, I. A. Tuktarova, R. Sh. Somova, O. E. Mustafina
    Russian Journal of Genetics.2019; 55(6): 728.     CrossRef
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No Association between Promoter Polymorphism of STK11 Gene and Lung Cancer Risk in the Korean Population
Jae Sook Sung, Young Mi Whang, Kyong Hwa Park, Jeong-Seon Ryu, Jong Gwon Choi, Jae Hong Seo, Sang Won Shin, Jun Suk Kim, Yeul Hong Kim
Cancer Res Treat. 2009;41(4):211-217.   Published online December 31, 2009
DOI: https://doi.org/10.4143/crt.2009.41.4.211
AbstractAbstract PDFPubReaderePub
Purpose

Serine-threonine kinase11 (STK11) was originally identified in 1997 as the causative mutation that's responsible for Peutz-Jeghers Syndrome (PJS). Several recent studies have reported that the STK11 gene is an important human tumor suppressor gene in lung cancer. We evaluated the associations between the polymorphisms of the STK11 promoter region and the risk of lung cancer in 901 Koreans.

Materials and Methods

By direct sequencing, we first discovered three novel polymorphisms (-1,795 T>C, -981 C>T and -160 G>T) and four known polymorphisms (-1,580 C>T, -1,494 A>C, -881 A>G and -458 G>C) of the STK11 promoter region in 24 blood samples of 24 Korean lung cancer patients. Further genotype analyses were then performed on 443 lung cancer patients and 458 controls.

Results

We discovered three novel polymorphisms and we identified four known polymorphisms of the STK11 promoter region in a Korean population. Statistical analyses revealed that the genotypes and haplotypes in the STK11 gene were not significantly associated with the risk of lung cancer in a Korean population.

Conclusion

This is the first study that's focused on the association of STK11 promoter polymorphisms and the risk of lung cancer in a Korean population. To evaluate the role of the STK11 gene for the risk of lung cancer, the genotypes of the STK11 promoter region (-1,795 T>C, -1,494 A>C and -160 G>T) were determined in 901 Koreans, yet the result revealed no significant difference between the lung cancer patients and the controls. These results suggest that the three promoter polymorphisms we studied are not important risk factors for the susceptibility to lung cancer in Koreans.

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    Jae Sook Sung, Kyong Hwa Park, Seung Tae Kim, Yeul Hong Kim
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Review Article
Immunomodulation of Breast Cancer via Tumor Antigen Specific Th1
Mary L. Disis, Kyong Hwa Park
Cancer Res Treat. 2009;41(3):117-121.   Published online September 28, 2009
DOI: https://doi.org/10.4143/crt.2009.41.3.117
AbstractAbstract PDFPubReaderePub

It has long been assumed that the immune system plays a role in tumor eradication, however, scant clinical evidence exists to support that hypothesis. In recent years, as the immune system and its specific effector cells are better defined, convincing data supporting immune surveillance is emerging. Several studies have shown that an "immune signature" in the tumor microenvironment is associated with a superior outcome in a variety of cancer types. Moreover, studies have suggested that T cells found in high density within the tumor parenchyma are also correlated with a survival benefit. The type of adaptive immune response implicated in improved cancer outcomes is a type 1 response. That is, adaptive immunity associated with T cells that secrete pro-inflammatory cytokines, such as IFN-γ, which can not only support a proliferative antigen specific T cell response but also enhance "cross priming" by activating antigen presenting cells local to the tumor site. There are many methods available that will allow the development of clinical reagents designed to stimulate Th1 immunity; either by in vitro or in vivo manipulation. Clinical trials of a variety of immunotherapeutic strategies indicate that the generation of tumor antigen specific Th1 may be beneficial in inhibiting the growth of common solid tumors.

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    Jan Spacek, Michal Vocka, Eva Zavadova, Bohuslav Konopasek, Lubos Petruzelka
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    ARUN KUMAR
    Asian Journal of Pharmaceutical and Clinical Research.2021; : 20.     CrossRef
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    Alexandre de Nonneville, Pascal Finetti, José Adelaide, Éric Lambaudie, Patrice Viens, Anthony Gonçalves, Daniel Birnbaum, Emilie Mamessier, François Bertucci
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    Palash Kumar Mandal, Subir Biswas, Gunjan Mandal, Suman Purohit, Arnab Gupta, Amita Majumdar (Giri), Sougata Roy Chowdhury, Arindam Bhattacharyya
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    Andrew C. Nelson, Heather L. Machado, Kathryn L. Schwertfeger
    Journal of Mammary Gland Biology and Neoplasia.2018; 23(4): 207.     CrossRef
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    Bonnie A. McGregor, Emily D. Dolan, Karly M. Murphy, Timothy S. Sannes, Krista B. Highland, Denise L. Albano, Alison A. Ward, Anna M. Charbonneau, Mary W. Redman, Rachel M. Ceballos
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    Stefanie J. Mandl, Ryan B. Rountree, Katie Dalpozzo, Lisa Do, John R. Lombardo, Peter L. Schoonmaker, Ulrike Dirmeier, Robin Steigerwald, Thierry Giffon, Reiner Laus, Alain Delcayre
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    Fengyan Xu, Dalin Li, Qiujin Zhang, Zhenkun Fu, Weiguang Yuan, Da Pang, Dianjun Li
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    Tetsuro Sasada, Shigetaka Suekane
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    Anastas Pashov, Bejatolah Monzavi-Karbassi, Gajendra P. S. Raghava, Thomas Kieber-Emmons
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Original Articles
Association of Single Nucleotide Polymorphisms in PIM-1 Gene with the Risk of Korean Lung Cancer
Dae Sik Kim, Jae Sook Sung, Eun Soon Shin, Jeong-Seon Ryu, In Keun Choi, Kyong Hwa Park, Yong Park, Eui Bae Kim, Seh Jong Park, Yeul Hong Kim
Cancer Res Treat. 2008;40(4):190-196.   Published online December 31, 2008
DOI: https://doi.org/10.4143/crt.2008.40.4.190
AbstractAbstract PDFPubReaderePub
Purpose

The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population.

Materials and Methods

To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects.

Results

We found that the T-C-T-C haplotypes of the PIM-1 gene (-1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24~12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32~24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75~34.98, p-value: 0.007).

Conclusions

The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.

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  • A review on structure-function mechanism and signaling pathway of serine/threonine protein PIM kinases as a therapeutic target
    Ajaya Kumar Rout, Budheswar Dehury, Satya Narayan Parida, Sushree Swati Rout, Rajkumar Jena, Neha Kaushik, Nagendra Kumar Kaushik, Sukanta Kumar Pradhan, Chita Ranjan Sahoo, Ashok Kumar Singh, Meenakshi Arya, Bijay Kumar Behera
    International Journal of Biological Macromolecules.2024; 270: 132030.     CrossRef
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    Syed Sultan Beevi, Kavitha Anbrasu, Vinod Kumar Verma, Nagesh Kishan Panchal, Krishna Kiran Kannepalli, Raghu Ram Pillarisetti, Sailaja Madigubba, Jyotsana Dwivedi, Neha Damodar, Radhika Chowdary Darapuneni
    Human Gene.2024; 40: 201295.     CrossRef
  • HCG11 inhibits salivary adenoid cystic carcinoma by upregulating EphA2 via binding to miR-1297
    Shujuan Yan, Meng Wang
    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2023; 135(2): 257.     CrossRef
  • Therapeutic targeting of PIM KINASE signaling in cancer therapy: Structural and clinical prospects
    Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
    Biochimica et Biophysica Acta (BBA) - General Subjects.2021; 1865(11): 129995.     CrossRef
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    Jiajie Xu, Xin Zhu, Qingling Li, Chao Chen, Zhenying Guo, Zhuo Tan, Chuanming Zheng, Minghua Ge
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    Yi Jin, Da-yue Tong, Jian-ning Chen, Zhi-ying Feng, Jian-yong Yang, Chun-kui Shao, Jia-ping Li, Rossella Rota
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  • No Association between PIK3CA Polymorphism and Lung Cancer Risk in the Korean Population
    Jae-Sook Sung, Kyong-Hwa Park, Seung-Tae Kim, Jae-Hong Seo, Sang-Won Shin, Jun-Suk Kim, Yeul-Hong Kim
    Genomics & Informatics.2010; 8(4): 194.     CrossRef
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Clinical Factors Related to Suspected Second Primary Lung Cancer Development in Patients with Head and Neck Cancer
Eui Bae Kim, Yong Park, Seh Jong Park, Dae Sik Kim, Jee Won Kim, Hee Yun Seo, Hwa Jung Sung, In Keun Choi, Kyong Hwa Park, Sang Cheul Oh, Chul Won Choi, Byung Soo Kim, Yeul Hong Kim, Jun Suk Kim, Sang Won Shin, Chul Yong Kim, Kwang-Yoon Jung
Cancer Res Treat. 2008;40(4):178-183.   Published online December 31, 2008
DOI: https://doi.org/10.4143/crt.2008.40.4.178
AbstractAbstract PDFPubReaderePub
Purpose

The rate of second primary lung cancer development for patients with head and neck cancer (HNC) has been noted. The aim of our study was to evaluate the incidence and clinical features of suspected second primary lung cancer that developed in patients with primary HNC.

Materials and Methods

We conducted a retrospective study of 469 patients who were newly diagnosed with HNC at the Korea University Medical Center between January 2000 and December 2006.

Results

A total of 469 patients were included (389 men and 80 women). Eighteen patients (3.8%) had suspected second primary lung cancers. Statistically significant clinical variables for lung cancer development included the origin site for the primary HNC (oro-hypopharynx and larynx) (p=0.048), abnormal chest x-ray findings (p=0.027) and the histological HNC type (squamous cell carcinoma) (p=0.032). When the second primary lung cancers were combined with HNCs, the adjusted overall survival of patients with a second primary lung cancer was 16 months (p<0.001).

Conclusions

Considering the relative risk factors for a second primary lung cancer developing in patients with HNC, advanced diagnostic tools, such as chest CT or PET CT scan, should be applied for the early detection of a second primary lung cancer.

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  • African American race as a risk factor associated with a second primary lung cancer after initial primary head and neck cancer
    Yusra F. Shao, Seongho Kim, John D. Cramer, Dina Farhat, Jeffrey Hotaling, Syed Naweed Raza, George Yoo, Ho‐sheng Lin, Harold Kim, Ammar Sukari, Misako Nagasaka
    Head & Neck.2022; 44(10): 2069.     CrossRef
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    Pablo Rosado, Soledad Fernández, Luis Junquera, Juan Carlos De Vicente
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The Efficacy and Safety of Padexol® (Paclitaxel) and Cisplatin for Treating Advanced Non-small Cell Lung Cancer
Hoon-Kyo Kim, Jun Suk Kim, Hun Mo Ryoo, Dong Gun Shin, Byoung Young Shim, Kyong Hwa Park, Sung Hwa Bae, Chi Hong Kim
Cancer Res Treat. 2006;38(2):66-71.   Published online April 30, 2006
DOI: https://doi.org/10.4143/crt.2006.38.2.66
AbstractAbstract PDFPubReaderePub
Purpose

The authors conducted a multicenter study to evaluate the efficacy and safety of combination chemotherapy with Padexol® and cisplatin for treating patients with advanced non-small cell lung cancer (NSCLC).

Materials and Methods

From November 2003 to April 2005, 42 chemo-naive patients with advanced NSCLC were enrolled into this study from 4 hospitals. The treatment consisted of Padexol® 175 mg/m2 as a 3-hr infusion, and this was followed by cisplatin 75 mg/m2 administered as an intravenous infusion with standard premedication. The treatment was repeated every 3 weeks.

Results

Among the 42 patients (pts), 33 pts were evaluable for response. On the per protocol analysis, 1 patient (pt) (3.0%) achieved complete response (CR), 17 pts (51.5%) achieved partial response (PR), 6 pts (18.2%) achieved stable disease (SD), and 9 pts (27.3%) progressed; therefore, the overall response rate was 54.6% (95% CI: 37.6~71.5%). On the intention-to-treat analysis, 1 pt (2.4%) achieved CR, 18 pts (42.9%) achieved PR, 11 pts (26.2%) achieved SD, and 9 pts (21.4%) progressed; therefore, the overall response rate was 45.2% (95% CI: 30.2~60.3%). The response, as evaluated by the investigators, was independently reviewed by 2 external radiologists and it was as follows; 13 PR (43.3%), 14 SD (46.7%) and 3 progressive disease (10%). The median duration of response was 5.9 months. The median follow-up duration was 10.3 months (range: 1.3 to 22.1 months). The median time to progression was 5.8 months (95% CI: 4.7 to 7.4 months). The median survival time on the intention-to-treat analysis was 10.5 months (95% CI: 8.1 to 18.8 months). The most common grade 3 or 4 hematologic toxicities were neutropenia (26/180 cycles, 14.4%), anemia (7/180 cycles, 3.9%) and febrile neutropenia (2/180 cycles, 1.1%). The most frequent grade 3 or 4 non-hematologic toxicities were nausea (14/42 patients, 14.3%), anorexia (3/42 patients, 7.1%) and myalgia (3/42 patients, 7.1%).

Conclusion

The authors observed that Padexol® was as good as the other paclitaxel (Taxol® or Genexol®) formulations when combined with cisplatin for treating patients with advanced NSCLC.

Citations

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  • The role of weekly nanoparticle albumin bound paclitaxel monotherapy as second line or later treatment for advanced NSCLC in China
    Puyuan Xing, Yixiang Zhu, Ling Shan, Sipeng Chen, Xuezhi Hao, Junling Li
    Oncotarget.2017; 8(50): 87442.     CrossRef
  • Efficacy and Safety of Weekly Low Dose Paclitaxel and Cisplatin as First Line Therapy in Advanced NSCLC of Elderly Patients
    Jung Ho Lee, Mi Hye Kwon, Ji Hyun Jeoung, Go Eun Lee, Eu Gene Choi, Moon Jun Na, Hyun Min Cho, Young Jin Kim, Weon Kuu Chung, Young Jun Cho, Ji Woong Son
    Journal of Lung Cancer.2007; 6(2): 85.     CrossRef
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Oral Etoposide, Ifosfamide and Cisplatin in the Treatment of Extensive Disease Small Cell Lung Cancer
Seok Jin Kim, Hwa Jung Sung, Kyong Hwa Park, So Young Yoon, Sang Cheul Oh, Jae Hong Seo, Chul Won Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Kwang Taek Kim, Young Ho Choi, Jun Suk Kim
Cancer Res Treat. 2002;34(6):421-425.   Published online December 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.6.421
AbstractAbstract PDF
PURPOSE
The combination of cisplatin and etoposide has been a common first line regimen for the treatment of small cell lung cancer (SCLC). The schedule dependence, and equal efficacy, of the oral and intravenous dosing of etoposide has led to prolonged administration of oral etoposide, which is known to produce an encouraging response in SCLC. To improve the efficacy of the cisplatin/etoposide combination, we administered oral etoposide, with added ifosfamide, which had significant single agent activity against SCLC. We conducted this study to evaluate the efficacy and toxicity of the cisplatin, ifosfamide and oral etoposide (PIE) combination in patients with extensive small cell lung cancer.
MATERIALS AND METHODS
Twenty-five patients with histologically confirmed extensive small cell lung cancer were enrolled into this study between January 2000 and May 2002. They were treated with, cisplatin at 20 mg/ m2/day, ifosfamide 1.5 g/m2/day, with mesna (all given intravenously on Days 1~3), and oral etoposide 50 mg/m2 on days 4~17. This cycle was repeated every 4 weeks for up to 6 cycles. We evaluated the corresponding disease responses and toxicities.
RESULTS
The patients' characteristics were as follows: median age 65 years (32~75), 19 males and 6 females. The performance stati were ECOG 0 in 3 patients, ECOG 1 in 12 and ECOG 2 in 10. Sixteen patients had a partial response, 2 had a stable disease and 4 had a progressive disease. Thus, the overall objective response rate was 72.7% (95% CI: 49.6~88.4%), with a median response duration of 7 months (95% CI: 3.5~10.5 months). Myelosuppression was the major observed toxicity. Grades III and IV neutropenia were observed in 42 (46.1%) of the 91 cycles. Significant non-hematological toxicities (>or=Grade III) were uncommon, with the exception of nausea and vomiting.
CONCLUSION
The response rate to the combination of cisplatin, ifosfamide and oral etoposide was similar to that of other combination chemotherapy studies in patients with extensive disease small cell lung cancer. The toxicity of the regimen was considered acceptable.
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Pirarubicin, UFT, Leucovorin Chemotherapy in Non-embolizable and Transcatheter Arterial Chemoembolization-Failed Hepatocellular Carcinoma Patients; A Phase II Clinical Study
Kyong Hwa Park, So Young Yoon, Sang Cheul Oh, Jae Hong Seo, Chul Won Choi, Jong Eun Yeon, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Kwan Soo Byun, Jun Suk Kim, Chang Hong Lee
Cancer Res Treat. 2002;34(4):280-283.   Published online August 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.4.280
AbstractAbstract PDF
Hepatocellular carcinomas are one of the most common malignancies in the world. However, no effective therapeutic modality has been proven to prolong the survival of patients in an inoperable stage. The purpose of this study was to determine the response rate and the toxicities of a combination of pirarubicin, UFT and leucovorin in patients with non-embolizable hepatocellular carcinomas, or who had progressed during their transcatheter arterial chemoembolization treatment.
MATERIALS AND METHODS
Of 23 patients with a hepatocellular carcinoma, 11 had progressed during a transcatheter arterial chemoembolization, with the other 12 being transcatheter arterial chemoembolization-naive. All the patients were treated with pirarubicin (70 mg/m2 i.v., day 1), UFT (350 mg/m2 P.O., day 1~21), and leucovorin (25 mg/m2 P.O., day 1~21).
RESULTS
Twenty patients were able to be evaluated, with a partial response being achieved in four, giving an overall response rate of 20% (95% confidence interval, 7~44%). The median overall survival time was 6 months, and the median survival time of the transcatheter arterial chemoembolization-naive patients was significantly longer than that of those treated by transcatheter arterial chemoembolization (p=0.012). The most significant dose-limiting toxicity was leucopenia and thrombocytopenia.
CONCLUSION
The combination of pirarubicin, UFT and leucovorin therapies showed marginal antitumor activity and significant toxicity in patients with non-embolizable or failed transcatheter arterial chemoembolization hepatocellular carcinomas.
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Phase II Trial of Gemcitabine, UFT-E, Leucovorin Combination Chemotherapy in Advanced Pancreatic Adenocarcinoma
So Young Yoon, Kyong Hwa Park, Sang Chul Oh, Jae Hong Seo, Chul Won Choi, Byung Soo Kim, Jae Seon Kim, Chang Duck Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim
Cancer Res Treat. 2002;34(2):111-116.   Published online April 30, 2002
DOI: https://doi.org/10.4143/crt.2002.34.2.111
AbstractAbstract PDF
PURPOSE
To evaluate the efficacy and toxicity of a Gemcitabine, UFT-E, Leucovorin combination chemotherapy in the treatment of advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients <=70 years, with no prior chemotherapy and with bidimensionally measurable advanced pancreatic adenocarcinoma, ECOG performance status <=2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or a Karnofsky performance status between 50 and 70. Treatment consisted of 1,000 mg/m2 of Gemcitabine on days 1, 8 and 15, repeated every 4 weeks, with UFT-E administered orally 500 mg-700 mg by body surface area (BSA). Leucovorin was administered 45 mg/day orally. Dosages of UFT-E and Leucovorin were divided and administered three times per day from day 1 to day 21. After 7 days of rest, UFT-E and Leucovorin were administered repeatedly.
RESULTS
Twenty-three patients were enrolled between April 1999 to April 2000. Eighty two cycles (median, four cycles) were delivered to all patients. The objective response rate was 15.8% in 19 assessable patients and 13.0% in the intent-to-treat population. Twelve patients (57.9%) displayed stable disease. Grade 3 or 4 neutropenia occurred in 30.4% of patients, nausea/vomiting in 8.3%, diarrhea in 4.3%, and mucositis in 4.3%. The median time to progression was 8 months. The median survival was 8 months in the assessable population and 6 months in the intent-to-treat population Clinical benefit was achieved in 11 (57.9%) of 19 assessable patients.
CONCLUSION
Gemcitabine, UFT-E, Leucovorin combination chemotherapy is a well-tolerated and safe regimen in cases of advanced pancreatic adenocarcinoma. Although the response rate is low, it shows a survival benefit and clinical benefit and deserves further evaluation in a phase III trial.

Citations

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  • Gemcitabine and oxaliplatin combination as first-line treatment for advanced pancreatic cancer: a multicenter phase II study
    Kyung Hee Lee, Min Kyoung Kim, Yeol Hong Kim, Baek Yeol Ryoo, Ho Yeong Lim, Hong Suk Song, Hoon Kyo Kim, Myung Ah Lee, Seock Ah Im, Heung Moon Chang, Jae Yong Cho, Dae Young Zang, Bong Seog Kim, Jun Suk Kim
    Cancer Chemotherapy and Pharmacology.2009; 64(2): 317.     CrossRef
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