Cancer Research and Treatment

Eun Ji Nam

11 Articles

Breast cancer

Implication and Influence of Multigene Panel Testing with Genetic Counseling in Korean Patients with BRCA1/2 Mutation-Negative Breast Cancer: Ji Soo Park, Saeam Shin, Yoon Jung Lee, Seung-Tae Lee, Eun Ji Nam, Jung Woo Han, Sun Hwa Lee, Tae Il Kim, Hyung Seok Park; Cancer Res Treat. 2022;54(4):1099-1110. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.978

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Purpose
The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer.
Materials and Methods
Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed.
Results
At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee.
Conclusion
Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.

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Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer
Yoo-Na Kim, Yun Soo Chung, Eunhyang Park, Seung Tae Lee, Jung-Yun Lee
Scientific Reports.2024;[Epub] CrossRef
Implementation of BRCA Test among Young Breast Cancer Patients in South Korea: A Nationwide Cohort Study
Yung-Huyn Hwang, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Beom Seok Ko, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, Il Yong Chung
Cancer Research and Treatment.2024; 56(3): 802. CrossRef
Germline RAD51C and RAD51D Mutations in High-Risk Chinese Breast and/or Ovarian Cancer Patients and Families
Ava Kwong, Cecilia Yuen Sze Ho, Chun Hang Au, Sze Keong Tey, Edmond Shiu Kwan Ma
Journal of Personalized Medicine.2024; 14(8): 866. CrossRef
Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis
Jong Eun Park, Min-Chae Kang, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Chang-Seok Ki, Sun-Young Kong
Cancers.2024; 16(19): 3318. CrossRef
Clinical Significance of PALB2 Pathogenic Germline Variant
Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
Laboratory Medicine Online.2024; 14(4): 311. CrossRef
Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
Antonella Turchiano, Marilidia Piglionica, Stefania Martino, Rosanna Bagnulo, Antonella Garganese, Annunziata De Luisi, Stefania Chirulli, Matteo Iacoviello, Michele Stasi, Ornella Tabaku, Eleonora Meneleo, Martina Capurso, Silvia Crocetta, Simone Lattaru
Genes.2023; 14(8): 1530. CrossRef

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Gynecologic cancer

Impact of the Learning Curve on the Survival of Abdominal or Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer: Lan Ying Li, Lan Ying Wen, Sun Hee Park, Eun Ji Nam, Jung Yun Lee, Sunghoon Kim, Young Tae Kim, Sang Wun Kim; Cancer Res Treat. 2021;53(1):243-251. Published online October 12, 2020; DOI: https://doi.org/10.4143/crt.2020.063

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Purpose
The objective of this study was to define the learning curve required to attain satisfactory oncologic outcomes of cervical cancer patients who were undergoing open or minimally invasive surgery for radical hysterectomy, and to analyze the correlation between the learning curve and tumor size.
Materials and Methods
Cervical cancer patients (stage IA-IIA) who underwent open radical hysterectomy (n=280) or minimal invasive radical hysterectomy (n=282) were retrospectively reviewed. The learning curve was evaluated using cumulative sum of 5-year recurrence rates. Survival outcomes were analyzed based on the operation period (“learning period,” P1 vs. “skilled period,” P2), operation mode, and tumor size.
Results
The 5-year disease-free and overall survival rates between open and minimally invasive groups were 91.8% and 89.0% (p=0.098) and 96.1% and 97.2% (p=0.944), respectively. The number of surgeries for learning period was 30 and 60 in open and minimally invasive group, respectively. P2 had better 5-year disease-free survival than P1 after adjusting for risk factors (hazard ratio, 0.392; 95% confidence interval, 0.210 to 0.734; p=0.003). All patients with tumors < 2 cm had similar 5-year disease-free survival regardless of operation mode or learning curve. Minimally invasive group presented lower survival rates than open group when tumors ≥ 2 cm in P2. Preoperative conization improved disease-free survival in patients with tumors ≥ 2 cm, especially in minimally invasive group.
Conclusion
Minimally invasive radical hysterectomy required more cases than open group to achieve acceptable 5-year disease-free survival. When tumors ≥ 2 cm, the surgeon’s proficiency affected survival outcomes in both groups.

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Radical Hysterectomy With Preoperative Conization in Early-Stage Cervical Cancer: A Systematic Review and Pairwise and Network Meta-Analysis
Xinbin Zhu, Lele Ye, Yunfeng Fu, Bingbing You, Weiguo Lu
Journal of Minimally Invasive Gynecology.2024; 31(3): 193. CrossRef
Minimally invasive radical hysterectomy and the importance of avoiding cancer cell spillage for early-stage cervical cancer: a narrative review
Atsushi Fusegi, Hiroyuki Kanao, Shiho Tsumura, Atsushi Murakami, Akiko Abe, Yoichi Aoki, Hidetaka Nomura
Journal of Gynecologic Oncology.2023;[Epub] CrossRef
Association of Hospital Surgical Volume With Survival in Early-Stage Cervical Cancer Treated With Radical Hysterectomy
Nicolò Bizzarri, Lukáš Dostálek, Luc R. C. W. van Lonkhuijzen, Diana Giannarelli, Aldo Lopez, Henrik Falconer, Denis Querleu, Ali Ayhan, Sarah H. Kim, David Isla Ortiz, Jaroslav Klat, Fabio Landoni, Juliana Rodriguez, Ranjit Manchanda, Jan Kosťun, Pedro T
Obstetrics & Gynecology.2023; 141(1): 207. CrossRef
Learning Laparoscopic Radical Hysterectomy: Are We Facing an Emerging Situation?
Graziella Moufawad, Antonio Simone Laganà, Nassir Habib, Vito Chiantera, Andrea Giannini, Federico Ferrari, Amerigo Vitagliano, Luigi Della Corte, Giuseppe Bifulco, Zaki Sleiman
International Journal of Environmental Research and Public Health.2023; 20(3): 2053. CrossRef
Breast Reconstruction with DIEP Flap: The Learning Curve at a Breast Reconstruction Center and a Single-Surgeon Study
Charalampos Varnava, Philipp Wiebringhaus, Tobias Hirsch, Alexander Dermietzel, Maximilian Kueckelhaus
Journal of Clinical Medicine.2023; 12(8): 2894. CrossRef
A meta-analysis of survival after minimally invasive radical hysterectomy versus abdominal radical hysterectomy in cervical cancer: center-associated factors matter
Si Sun, Jing Cai, Ruixie Li, Yujia Wang, Jing Zhao, Yuhui Huang, Linjuan Xu, Qiang Yang, Zehua Wang
Archives of Gynecology and Obstetrics.2022; 306(3): 623. CrossRef
Comparison of Minimally Invasive Versus Abdominal Radical Hysterectomy for Early-Stage Cervical Cancer: An Updated Meta-Analysis
Mengting Zhang, Wei Dai, Yuexiu Si, Yetan Shi, Xiangyuan Li, Ke Jiang, Jingyi Shen, Liying Ying
Frontiers in Oncology.2022;[Epub] CrossRef
Assessment of ESGO Quality Indicators in Cervical Cancer Surgery: A Real-World Study in a High-Volume Chinese Hospital
Yan Ding, Xuyin Zhang, Junjun Qiu, Jianfeng Zhang, Keqin Hua
Frontiers in Oncology.2022;[Epub] CrossRef
Trends in Surgical Morbidity and Survival Outcomes for Radical Hysterectomy in West China: An 11-Year Retrospective Cohort Study
Huining Jing, Ying Yang, Yinxia Liu, Peijun Zou, Zhengyu Li
Frontiers in Oncology.2022;[Epub] CrossRef
Comparison of Prognosis between Minimally Invasive and Abdominal Radical Hysterectomy for Patients with Early-Stage Cervical Cancer
Tomohito Tanaka, Shoko Ueda, Shunsuke Miyamoto, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
Current Oncology.2022; 29(4): 2272. CrossRef
Open versus minimally invasive radical hysterectomy for early cervical cancer: A two-center retrospective cohort study with pathologic review of usual-type adenocarcinoma and adenosquamous carcinoma
Yeorae Kim, Se Ik Kim, Hyojin Kim, Maria Lee, Hee Seung Kim, Kidong Kim, Hyun Hoon Chung, Jae Hong No, Yong Beom Kim, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song, Cheol Lee, Dong Hoon Suh
Gynecologic Oncology.2022; 167(1): 28. CrossRef
Laparoscopic Versus Abdominal Radical Hysterectomy for Cervical Cancer
Fuyun Zhang, Xiaomei Song
American Journal of Clinical Oncology.2022; 45(11): 465. CrossRef
Surgical Approach and Use of Uterine Manipulator Are Not Associated with LVSI in Surgery for Early-stage Cervical Cancer
Yinxia Liu, Shuying Huang, Xiu Ming, Huining Jing, Zhengyu Li
Journal of Minimally Invasive Gynecology.2021; 28(9): 1573. CrossRef
Minimally Invasive Radical Hysterectomy for Cervical Cancer: A Systematic Review and Meta-analysis
Anna Jo Bodurtha Smith, Tiffany Nicole Jones, Diana Miao, Amanda Nickles Fader
Journal of Minimally Invasive Gynecology.2021; 28(3): 544. CrossRef
The Surgeon’s Proficiency Affected Survival Outcomes of Minimally Invasive Surgery for Early-Stage Cervical Cancer: A Retrospective Study of 851 Patients
Ying Yang, Yue Huang, Zhengyu Li
Frontiers in Oncology.2021;[Epub] CrossRef
MicroRNA-300 Inhibits the Proliferation and Metastasis of Cervical Cancer Cells via Posttranscriptional Suppression of G Protein-Coupled Receptor 34 (GPR34)
Mei Wang, Ying Tian, Lin Miao, Wenxia Zhao, Antonio Raffone
Journal of Oncology.2021; 2021: 1. CrossRef

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Early Assessment of Response to Neoadjuvant Chemotherapy with ¹⁸F-FDG-PET/CT in Patients with Advanced-Stage Ovarian Cancer: Young Shin Chung, Hyun-Soo Kim, Jung-Yun Lee, Won Jun Kang, Eun Ji Nam, Sunghoon Kim, Sang Wun Kim, Young Tae Kim; Cancer Res Treat. 2020;52(4):1211-1218. Published online April 28, 2020; DOI: https://doi.org/10.4143/crt.2019.506

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Purpose
The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients.
Materials and Methods
Forty consecutive patients underwent ¹⁸F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUV_max) with PET/CT. Decreases in SUV_max were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and I chemotherapy response score (CRS) at IDS.
Results
A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335).
Conclusion
Early assessment with ¹⁸F-FDG-PET/CT after one cycle of NAC can be useful to predic response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.

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The Evaluation Value of CT in the Efficacy of Neoadjuvant Chemotherapy in Ovarian Cancer Patients
Daying Mou, Shengyan Xie, Pingyuan Li, Mohammad Farukh Hashmi
Contrast Media & Molecular Imaging.2022;[Epub] CrossRef
Radiomics Analysis of PET and CT Components of 18F-FDG PET/CT Imaging for Prediction of Progression-Free Survival in Advanced High-Grade Serous Ovarian Cancer
Xihai Wang, Zaiming Lu
Frontiers in Oncology.2021;[Epub] CrossRef

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Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer: Lan Ying Li, Hee Jung Kim, Sun Ae Park, So Hyun Lee, Lee Kyung Kim, Jung Yun Lee, Sunghoon Kim, Young Tae Kim, Sang Wun Kim, Eun Ji Nam; Cancer Res Treat. 2019;51(3):1117-1127. Published online November 6, 2018; DOI: https://doi.org/10.4143/crt.2018.405

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Purpose
Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing.
Materials and Methods
To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA).
Results
Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25, HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845).
Conclusion
We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

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Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
Journal of Clinical Medicine.2024; 13(9): 2718. CrossRef
Uncovering miRNA–mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors
Łukasz Biegała, Damian Kołat, Arkadiusz Gajek, Elżbieta Płuciennik, Agnieszka Marczak, Agnieszka Śliwińska, Michał Mikula, Aneta Rogalska
Cells.2024; 13(10): 867. CrossRef
Patient-derived xenograft models in cancer therapy: technologies and applications
Yihan Liu, Wantao Wu, Changjing Cai, Hao Zhang, Hong Shen, Ying Han
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef
Deregulations of RNA Pol II Subunits in Cancer
Martina Muste Sadurni, Marco Saponaro
Applied Biosciences.2023; 2(3): 459. CrossRef
Transcriptome and Metabolome Analyses Reveal the Mechanism of Corpus Luteum Cyst Formation in Pigs
Jiage Dai, Jiabao Cai, Taipeng Zhang, Mingyue Pang, Xiaoling Xu, Jiahua Bai, Yan Liu, Yusheng Qin
Genes.2023; 14(10): 1848. CrossRef
Prediction of Chemoresistance—How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer
Jacek Wilczyński, Edyta Paradowska, Justyna Wilczyńska, Miłosz Wilczyński
Current Oncology.2023; 31(1): 229. CrossRef
Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?
Jacek Wilczyński, Edyta Paradowska, Miłosz Wilczyński
Journal of Personalized Medicine.2023; 14(1): 49. CrossRef
PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Julia C. F. Quintanilha, Alessandro Racioppi, Jin Wang, Amy S. Etheridge, Stefanie Denning, Carol E. Peña, Andrew D. Skol, Daniel J. Crona, Danyu Lin, Federico Innocenti
The Pharmacogenomics Journal.2022; 22(1): 82. CrossRef
AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization
Eros Azzalini, Domenico Tierno, Michele Bartoletti, Renzo Barbazza, Giorgio Giorda, Fabio Puglisi, Sabrina Chiara Cecere, Nunzia Simona Losito, Daniela Russo, Giorgio Stanta, Vincenzo Canzonieri, Serena Bonin
Cancers.2022; 14(2): 304. CrossRef
Comparative analysis of cancer gene mutations using targeted sequencing in matched primary and recurrent gastric cancers after chemotherapy
Yeon-Ju Huh, Sung-Yup Cho, Min-Sun Cho, Kyoung-Eun Lee, Joo-Ho Lee
Genes & Genomics.2022; 44(11): 1425. CrossRef
Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization
Shunsuke Miyamoto, Tomohito Tanaka, Kensuke Hirosuna, Ruri Nishie, Shoko Ueda, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
Cancers.2022; 14(12): 2969. CrossRef
HCP5, as the sponge of miR-1291, facilitates AML cell proliferation and restrains apoptosis via increasing PIK3R5 expression
Yan Liu, Xue-Bing Jing, Zhen-Cheng Wang, Qing-Kun Han
Human Genomics.2021;[Epub] CrossRef
Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer
Sandra Muñoz-Galván, Amancio Carnero
Cancers.2021; 13(16): 4029. CrossRef
CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate
Aalia Batool, Hao Liu, Yi-Xun Liu, Su-Ren Chen
Cancers.2020; 12(8): 2269. CrossRef
A recombinant platform to characterize the role of transmembrane protein hTMEM205 in Pt(ii)-drug resistance and extrusion
Marc J Gallenito, Tahir S Qasim, Jasmine N Tutol, Ved Prakash, Sheel C Dodani, Gabriele Meloni
Metallomics.2020; 12(10): 1542. CrossRef
Function, Regulation and Biological Roles of PI3Kγ Variants
Bernd Nürnberg, Sandra Beer-Hammer
Biomolecules.2019; 9(9): 427. CrossRef

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Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2: Kyung Jin Eoh, Ji Eun Kim, Hyung Seok Park, Seung-Tae Lee, Ji Soo Park, Jung Woo Han, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Jae Hoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2018;50(3):917-925. Published online September 27, 2017; DOI: https://doi.org/10.4143/crt.2017.220

Abstract PDF Supplementary Material PubReader ePub

Purpose
Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS.
Materials and Methods
Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing.
Results
Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance.
Conclusion
Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

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International Journal of Molecular Sciences.2023; 24(23): 17020. CrossRef
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Scientific Reports.2021;[Epub] CrossRef
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Lesa M. Dawson, Kerri N. Smith, Salem Werdyani, Robyn Ndikumana, Cindy Penney, Louisa L. Wiede, Kendra L. Smith, Justin A. Pater, Andrée MacMillan, Jane Green, Sheila Drover, Terry‐Lynn Young, Darren D. O’Rielly
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Germline and Somatic BRCA1/2 Mutations in 172 Chinese Women With Epithelial Ovarian Cancer
Yan You, Lei Li, Junliang Lu, Huanwen Wu, Jing Wang, Jie Gao, Ming Wu, Zhiyong Liang
Frontiers in Oncology.2020;[Epub] CrossRef
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Journal of Ovarian Research.2020;[Epub] CrossRef
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Malwina Suszynska, Piotr Kozlowski
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Ana Isabel Sánchez Bermúdez, M.ª Desamparados Sarabia Meseguer, Verónica Guardiola Castillo, Francisco Ruiz Espejo, José Antonio Noguera Velasco
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Magdalena Koczkowska, Natalia Krawczynska, Maciej Stukan, Alina Kuzniacka, Izabela Brozek, Marcin Sniadecki, Jaroslaw Debniak, Dariusz Wydra, Wojciech Biernat, Piotr Kozlowski, Janusz Limon, Bartosz Wasag, Magdalena Ratajska
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Journal of Medical Genetics.2018; 55(9): 571. CrossRef

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Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models: Kyung Jin Eoh, Young Shin Chung, So Hyun Lee, Sun-Ae Park, Hee Jung Kim, Wookyeom Yang, In Ok Lee, Jung-Yun Lee, Hanbyoul Cho, Doo Byung Chay, Sunghoon Kim, Sang Wun Kim, Jae-Hoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2018;50(3):956-963. Published online October 17, 2017; DOI: https://doi.org/10.4143/crt.2017.181

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients.
Materials and Methods
Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity.
Results
Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers.
Conclusions
Tumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

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TOWARDS Study: Patient-Derived Xenograft Engraftment Predicts Poor Survival in Patients With Newly Diagnosed Triple-Negative Breast Cancer
Christos Vaklavas, Cindy B. Matsen, Zhengtao Chu, Kenneth M. Boucher, Sandra D. Scherer, Satya Pathi, Anna Beck, Kirstyn E. Brownson, Saundra S. Buys, Namita Chittoria, Elyse D'Astous, H. Evin Gulbahce, N. Lynn Henry, Stephen Kimani, Jane Porretta, Regina
JCO Precision Oncology.2024;[Epub] CrossRef
Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice
Mingtang Zeng, Zijing Ruan, Jiaxi Tang, Maozhu Liu, Chengji Hu, Ping Fan, Xinhua Dai
Cancer Cell International.2023;[Epub] CrossRef
Cancer “Avatars”: Patient-Derived Xenograft Growth Correlation with Postoperative Recurrence and Survival in Pancreaticobiliary Cancer
Isaac T Lynch, Amro M Abdelrahman, Roberto Alva-Ruiz, Alessandro Fogliati, Rondell P Graham, Rory Smoot, Mark J Truty
Journal of the American College of Surgeons.2023; 237(3): 483. CrossRef
Identification of Prognostic Markers of Gynecologic Cancers Utilizing Patient-Derived Xenograft Mouse Models
Ha-Yeon Shin, Eun-ju Lee, Wookyeom Yang, Hyo Sun Kim, Dawn Chung, Hanbyoul Cho, Jae-Hoon Kim
Cancers.2022; 14(3): 829. CrossRef
Experimental models for ovarian cancer research
Sum In Tsang, Ayon A. Hassan, Sally K.Y. To, Alice S.T. Wong
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Alessandra Ciucci, Marianna Buttarelli, Anna Fagotti, Giovanni Scambia, Daniela Gallo
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Harnessing preclinical models for the interrogation of ovarian cancer
Tianyu Qin, Junpeng Fan, Funian Lu, Li Zhang, Chen Liu, Qiyue Xiong, Yang Zhao, Gang Chen, Chaoyang Sun
Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef
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Helena Castillo‐Ecija, Guillem Pascual‐Pasto, Sara Perez‐Jaume, Claudia Resa‐Pares, Monica Vila‐Ubach, Carles Monterrubio, Ana Jimenez‐Cabaco, Merce Baulenas‐Farres, Oscar Muñoz‐Aznar, Noelia Salvador, Maria Cuadrado‐Vilanova, Nagore G Olaciregui, Leire B
The Journal of Pathology: Clinical Research.2021; 7(4): 338. CrossRef
Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review
Tomohito Tanaka, Ruri Nishie, Shoko Ueda, Shunsuke Miyamoto, Sousuke Hashida, Hiromi Konishi, Shinichi Terada, Yuhei Kogata, Hiroshi Sasaki, Satoshi Tsunetoh, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
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Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine
Jennifer L. Leiting, Stephen J. Murphy, John R. Bergquist, Matthew C. Hernandez, Tommy Ivanics, Amro M. Abdelrahman, Lin Yang, Isaac Lynch, James B. Smadbeck, Sean P. Cleary, David M. Nagorney, Michael S. Torbenson, Rondell P. Graham, Lewis R. Roberts, Gr
JHEP Reports.2020; 2(2): 100068. CrossRef
Patient-derived xenograft model engraftment predicts poor prognosis after surgery in patients with pancreatic cancer
Qi Chen, Tao Wei, Jianxin Wang, Qi Zhang, Jin Li, Jingying Zhang, Lei Ni, Yi Wang, Xueli Bai, Tingbo Liang
Pancreatology.2020; 20(3): 485. CrossRef
A Biobank of Colorectal Cancer Patient-Derived Xenografts
Suad M. Abdirahman, Michael Christie, Adele Preaudet, Marie C. U. Burstroem, Dmitri Mouradov, Belinda Lee, Oliver M. Sieber, Tracy L. Putoczki
Cancers.2020; 12(9): 2340. CrossRef
High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints
Michael-Antony Lisio, Lili Fu, Alicia Goyeneche, Zu-hua Gao, Carlos Telleria
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Efficient use of patient-derived organoids as a preclinical model for gynecologic tumors
Yoshiaki Maru, Naotake Tanaka, Makiko Itami, Yoshitaka Hippo
Gynecologic Oncology.2019; 154(1): 189. CrossRef
Current Status of Patient-Derived Ovarian Cancer Models
Yoshiaki Maru, Yoshitaka Hippo
Cells.2019; 8(5): 505. CrossRef
Establishment of patient‐derived xenograft model in ovarian cancer and its influence factors analysis
Jianfa Wu, Yunxi Zheng, Qi Tian, Ming Yao, Xiaofang Yi
Journal of Obstetrics and Gynaecology Research.2019; 45(10): 2062. CrossRef
Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells
Ugo Testa, Eleonora Petrucci, Luca Pasquini, Germana Castelli, Elvira Pelosi
Medicines.2018; 5(1): 16. CrossRef

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Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls: Ji Soo Park, Eun Ji Nam, Hyung Seok Park, Jung Woo Han, Jung-Yun Lee, Jieun Kim, Tae Il Kim, Seung-Tae Lee; Cancer Res Treat. 2017;49(4):1012-1021. Published online January 17, 2017; DOI: https://doi.org/10.4143/crt.2016.433

Abstract PDF Supplementary Material PubReader ePub

Purpose
Comparison of variant frequencies in the general population has become an essential part of the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for interpreting sequence variants. We determined the optimal number of relevant ethnic controls that should be used to accurately calculate the odds ratio (OR) of genetic variants.
Materials and Methods
Using the ACMG guidelines, we reclassified BRCA1 and BRCA2 mutations and variants of unknown significance in 745 Korean patients susceptible to hereditary breast and ovarian cancer compared with 1,314 Korean population controls.
Results
We observed that the ORs were falsely inflated when we analyzed several variants using non-Korean population data. Our simulation indicated that the number of controls needed for the lower limit of a 95% confidence interval to exceed 1.0 varied according to the frequency of the variant in each patient group, with more than 820 controls needed for a variant existing in 1% of cases. Using a sufficient number of relevant population data, we could efficiently classify variants and identified the BRCA1 p.Leu1780Pro mutation as a possible pathogenic founder mutation in Korean patients.
Conclusion
Our study suggests that BRCA1 p.Leu1780Pro is a novel pathogenic mutation found in Korean patients. We also determined the optimal number of relevant ethnic controls needed for accurate variant classification according to the ACMG guidelines.

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Genomic disparity impacts variant classification of cancer susceptibility genes in Turkish breast cancer patients
Nihat B. Agaoglu, Busra Unal, Connor P. Hayes, McKenzie Walker, Ozden Hatirnaz Ng, Levent Doganay, Nisan D. Can, Huma Q. Rana, Arezou A. Ghazani
Cancer Medicine.2024;[Epub] CrossRef
Variant reclassification and clinical implications
Nicola Walsh, Aislinn Cooper, Adrian Dockery, James J O'Byrne
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Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain)
Ana S. Pitiot, Pilar Blay, Ander Díaz‐Navarro, Sara Fernández‐Arrojo, Rosa Romero, Ángel Álvarez‐Eguiluz, Marta G. Alvarado, Nieves Álvarez, Paula García‐Teijido, Yolanda Fernández, Isabel Palacio, Xose S. Puente, Milagros Balbín
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Reversion of pathogenic BRCA1 L1780P mutation confers resistance to PARP and ATM inhibitor in breast cancer
Se-Young Jo, Jeong Dong Lee, Jeongsoo Won, Jiho Park, Taeyong Kweon, Seongyeon Jo, Joohyuk Sohn, Seung-Il Kim, Sangwoo Kim, Hyung Seok Park
iScience.2024; 27(8): 110469. CrossRef
Mutations of TP53 and genes related to homologous recombination repair in breast cancer with germline BRCA1/2 mutations
Jinyong Kim, Kyeonghun Jeong, Hyeji Jun, Kwangsoo Kim, Jeong Mo Bae, Myung Geun Song, Hanbaek Yi, Songyi Park, Go-un Woo, Dae-Won Lee, Tae-Yong Kim, Kyung-Hun Lee, Seock-Ah Im
Human Genomics.2023;[Epub] CrossRef
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Sihan Liu, Mingjun Zhong, Yu Huang, Qian Zhang, Ting Chen, Xiaofei Xu, Wan Peng, Xiaolu Wang, Xiaoshu Feng, Lu Kang, Yu Lu, Jing Cheng, Fengxiao Bu, Huijun Yuan
Genome Medicine.2023;[Epub] CrossRef
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Kelly A. Hirko, Gabrielle Rocque, Erica Reasor, Ammanuel Taye, Alex Daly, Ramsey I. Cutress, Ellen R. Copson, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im, Yeon Hee Park
BMC Medicine.2022;[Epub] CrossRef
Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer
Jeong Dong Lee, Won-Ji Ryu, Hyun Ju Han, Tae Yeong Kim, Min Hwan Kim, Joohyuk Sohn
Cancers.2022; 14(10): 2405. CrossRef
Discovery of BRCA1/BRCA2 founder variants by haplotype analysis
Won Kyung Kwon, Hyeok-Jae Jang, Jeong Eon Lee, Yeon Hee Park, Jai Min Ryu, Jonghan Yu, Ja-Hyun Jang, Jong-Won Kim
Cancer Genetics.2022; 266-267: 19. CrossRef
Hereditary variants of unknown significance in African American women with breast cancer
J. Tyson McDonald, Luisel J. Ricks-Santi, Alvaro Galli
PLOS ONE.2022; 17(10): e0273835. CrossRef
Clinical phenotypes combined with saturation genome editing identifying the pathogenicity of BRCA1 variants of uncertain significance in breast cancer
Qiting Wan, Li Hu, Tao Ouyang, Jinfeng Li, Tianfeng Wang, Zhaoqing Fan, Tie Fan, Benyao Lin, Ye Xu, Yuntao Xie
Familial Cancer.2021; 20(2): 85. CrossRef
Analysis of BRCA1/2 variants of unknown significance in the prospective Korean Hereditary Breast Cancer study
Joo Heung Kim, Sunggyun Park, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Sung-Won Kim, Jong Won Lee, Min Hyuk Lee, Sue K. Park, Woo-Chul Noh, Doo Ho Choi, Wonshik Han, Sung Hoo Jung
Scientific Reports.2021;[Epub] CrossRef
A Population-Based Analysis of BRCA1/2 Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study
Kyung-Sun Park, Woochang Lee, Moon-Woo Seong, Sun-Young Kong, Kyung-A Lee, Jung-Sook Ha, Eun-Hae Cho, Sung-Hee Han, Inho Park, Jong-Won Kim
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Colin M. E. Halverson, Laurie M. Connors, Bronson C. Wessinger, Ellen W. Clayton, Georgia L. Wiesner
Molecular Genetics & Genomic Medicine.2020;[Epub] CrossRef
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Dan Li, Yujian Shi, Ang Li, Dandan Cao, Huijun Su, Haiqi Yang, Qihuan Zhi, Yuchen Yang, Zhaoji Lan, Tianliangwen Zhou, Xiaobin You, Guifang Hu
Breast Cancer.2020; 27(6): 1158. CrossRef
Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant
Hyung Seok Park, Jai Min Ryu, Ji Soo Park, Seock-Ah Im, So-Youn Jung, Eun-Kyu Kim, Woo-Chan Park, Jun Won Min, Jeeyeon Lee, Ji Young You, Jeong Eon Lee, Sung-Won Kim
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Hyeong In Ha, Jin-Sun Ryu, Hyoeun Shim, Sun-Young Kong, Myong Cheol Lim
Journal of Gynecologic Oncology.2020;[Epub] CrossRef
Prevalence and oncologic outcomes of BRCA 1/2 mutations in unselected triple-negative breast cancer patients in Korea
Jai Min Ryu, Hee Jun Choi, Isaac Kim, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Se Kyung Lee, Doo Ho Choi, Yeon Hee Park, Jong-Won Kim, Jeong-sun Seo, Jung-Hoon Park, Jeong Eon Lee, Sung-Won Kim
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Min-Kyung So, Tae-Dong Jeong, Woosung Lim, Byung-In Moon, Nam Sun Paik, Seung Cheol Kim, Jungwon Huh
Breast Cancer.2019; 26(4): 510. CrossRef
Challenges and Considerations in Sequence Variant Interpretation for Mendelian Disorders
Young-Eun Kim, Chang-Seok Ki, Mi-Ae Jang
Annals of Laboratory Medicine.2019; 39(5): 421. CrossRef
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Se Ik Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song
Journal of Ovarian Research.2019;[Epub] CrossRef
Clinical significance of variants of unknown significances in BRCA genes
Min Chul Choi
Journal of Gynecologic Oncology.2019;[Epub] CrossRef
Establishment of chemosensitivity tests in triple-negative and BRCA-mutated breast cancer patient-derived xenograft models
Hyung Seok Park, Jeong Dong Lee, Jee Ye Kim, Seho Park, Joo Heung Kim, Hyun Ju Han, Yeon A. Choi, Ae Ran Choi, Joo Hyuk Sohn, Seung Il Kim, Harriet Wikman
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Difference in Risk of Breast and Ovarian Cancer According to Putative Functional Domain Regions in Korean BRCA1/2 Mutation Carriers
Ji Soo Park, Seung-Tae Lee, Jung Woo Han, Tae Il Kim, Eun Ji Nam, Hyung Seok Park
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Kyungju Lee, Ja-Hyun Jang, Seung-Tae Lee, Kyong-Ah Yoon, Eun Sook Lee, Jong-Won Kim, Sun-Young Kong
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Jee-Soo Lee, Sohee Oh, Sue Kyung Park, Min-Hyuk Lee, Jong Won Lee, Sung-Won Kim, Byung Ho Son, Dong-Young Noh, Jeong Eon Lee, Hai-Lin Park, Man Jin Kim, Sung Im Cho, Young Kyung Lee, Sung Sup Park, Moon-Woo Seong
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Jai Min Ryu, Goeun Kang, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Se Kyung Lee, Soo Youn Bae, Sungmin Park, Hyun-June Paik, Jong-Won Kim, Sung-Shin Park, Jeong Eon Lee, Sung-Won Kim
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14,523 View
646 Download
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28 Crossref

Long Non-coding RNA HOXA11 Antisense Promotes Cell Proliferation and Invasion and Predicts Patient Prognosis in Serous Ovarian Cancer: Ga Won Yim, Hee Jung Kim, Lee Kyung Kim, Sang Wun Kim, Sunghoon Kim, Eun Ji Nam, Young Tae Kim; Cancer Res Treat. 2017;49(3):656-668. Published online October 11, 2016; DOI: https://doi.org/10.4143/crt.2016.263

Abstract PDF PubReader ePub

Purpose
The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novel HOXA11 antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC).
Materials and Methods
HOXA11as expression was examined in 129 SOC tissue samples by real time reverse transcription polymerase chain reaction. Clinicopathological factors and patient survival were compared between the high (n=27) and low HOXA11as expression group (n=102). To investigate the role of HOXA11as in cell proliferation, invasion, and migration, HOXA11as expression in ovarian cancer cells was knocked down using RNA interference.
Results
HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue (p < 0.05). Higher HOXA11as expression was significantly correlated with histological grade (p=0.017) and preoperative cancer antigen 125 (p=0.048). HOXA11as overexpression in SOC cells led to increased cell proliferation, invasion, and migration. Moreover, HOXA11as was associated with the expression of genes involved in cell invasion, migration, and epithelial-mesenchymal transition (EMT), including vascular endothelial growth factor, matrix metalloproteinase 9 (MMP-9), B-catenin, E-cadherin, Snail, Twist, and vimentin. Multivariate analysis revealed that HOXA11as was a prognostic factor of progressive disease and mortality (hazard ratio [HR], 1.730; p=0.043 and HR, 2.170; p=0.033, respectively). Progression-free and overall survival were significantly shorter in patients with high HOXA11as expression.
Conclusion
These findings highlight the clinical significance of HOXA11as to predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness via regulation of vascular endothelial growth factor (VEGF), MMP-9, and EMT-related mechanisms.

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Puxiang Chen, Xiaolin Fang, Bing Xia, Yan Zhao, Qiaoyan Li, Xiaoying Wu
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RETRACTED ARTICLE: Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer
Haihai Liang, Xiaoguang Zhao, Chengyu Wang, Jian Sun, Yingzhun Chen, Guoyuan Wang, Lei Fang, Rui Yang, Mengxue Yu, Yunyan Gu, Hongli Shan
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Huijian Li, Mi Gong, Min Zhao, Xinru Wang, Wenjun Cheng, Yankai Xia
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Mei S Ong, Wanpei Cai, Yi Yuan, Hin C Leong, Tuan Z Tan, Asad Mohammad, Ming L You, Frank Arfuso, Boon C Goh, Sudha Warrier, Gautam Sethi, Nicholas S Tolwinski, Peter E Lobie, Celestial T Yap, Shing C Hooi, Ruby Y Huang, Alan P Kumar
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Na Li, Meilan Yang, Ke Shi, Wei Li
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Oncotarget.2017; 8(41): 70579. CrossRef

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Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients: Kyung Jin Eoh, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Jeongwoo Han, Jung-Yun Lee, Sang Wun Kim, Sunghoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2017;49(2):408-415. Published online July 27, 2016; DOI: https://doi.org/10.4143/crt.2016.135

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type).
Materials and Methods
We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status.
Results
Thirty-seven (37/116, 31.9%) BRCA1/2 mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively).
Conclusion
Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

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Journal of Ovarian Research.2019;[Epub] CrossRef
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Synergistic Effect of COX-2 Inhibitor on Paclitaxel-Induced Apoptosis in the Human Ovarian Cancer Cell Line OVCAR-3: Hee Jung Kim, Ga Won Yim, Eun Ji Nam, Young Tae Kim; Cancer Res Treat. 2014;46(1):81-92. Published online January 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.1.81

Abstract PDF PubReader ePub

PURPOSE
Celecoxib, a highly selective cyclooxygenase-2 inhibitor, regulates apoptosis of several types of human cancer cells. The purpose of this study was to investigate whether celecoxib in combination with paclitaxel modulates apoptosis of ovarian cancer cells, and to identify the signal pathway by which celecoxib mediates apoptosis.
MATERIALS AND METHODS
OVCAR-3 cells were exposed to paclitaxel (20 microM) in the absence or presence of celecoxib (10 microM). Cell viability was evaluated using a Cell Counting Kit-8 assay. Apoptosis was evaluated using Annexin-V/7-aminoactinomycin D staining and a cellular DNA fragmentation enzyme-linked immunosorbent assay. Caspase-3, -9, and cleavage of poly ADP-ribose polymerase (PARP) were determined by western blotting. Expression of nuclear factor-kappaB (NF-kappaB) and vascular endothelial growth factor (VEGF) and Akt activation were assessed using reverse transcriptase-polymerase chain reaction and western blotting.
RESULTS
Celecoxib enhanced paclitaxel-induced growth inhibition of OVCAR-3 cells. Celecoxib significantly increased paclitaxel-induced apoptosis of OVCAR-3 cells. Pretreatment with celecoxib also increased activation of caspase-9, -3 and cleaved PARP following paclitaxel-treatment. Exposure of OVCAR-3 cells to celecoxib in combination with paclitaxel resulted in downregulation of NF-kappaB activation and VEGF expression. Furthermore, combining celecoxib and paclitaxel inhibited phosphorylation of Akt.
CONCLUSION
OVCAR-3 cells were sensitized to paclitaxel-induced apoptosis by celecoxib through downregulation of NF-kappaB and Akt activation, suggesting that celecoxib may work synergistically with paclitaxel to inhibit different targets and ultimately produce anticancer effects. Combining celecoxib with paclitaxel may prove beneficial in the clinical treatment of ovarian cancer.

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Endometrial Stromal Sarcomas: A Retrospective Analysis of 28 Patients, Single Center Experience for 20 Years: Eun Ji Nam, Jae Wook Kim, Dae Woo Lee, Si Young Jang, Jong Wook Hong, Young Tae Kim, Jae Hoon Kim, Sunghoon Kim, Sang Wun Kim; Cancer Res Treat. 2008;40(1):6-10. Published online March 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.1.6

Abstract PDF PubReader ePub

Purpose

The aim of this study was to evaluate the behavior of endometrial stromal sarcomas (ESSs) in relation to their clinical and pathogenic features, and to determine the optimal treatment strategy.

Materials and Methods

A retrospective analysis was performed involving 28 patients with histologic-proven ESSs treated at our institution between 1987 and 2006.

Results

The median follow-up was 54.7±63.1 months and the 5-year survival rate was 82.0%. Twenty-two (81.5%) and 5 patients (18.5%) had low- and high-grade disease, respectively. Univariate analysis revealed that the histologic grades, based on mitotic count, were associated with longer survival (p=0.004). However, among those patients with low-grade tumors, 5/20 patients (25%) had a recurrence and 2/21 patients (9.5%) had distant metastasis during the follow-up period. With the exception of 2 patients, 26 patients with ESSs underwent hysterectomy as primary treatment. Adjuvant treatment after surgery was administered to 14/26 patients (53.8%). Hormone therapy with progesterone, chemotherapy, and/or radiotherapy did not influence overall survival. However, the postoperative adjuvant therapy group, regardless of the treatment modality, was associated with relatively increased overall survival when compared to the surgery only group (p=0.054).

Conclusions

The preoperative differential diagnosis of ESSs from other benign gynecologic diseases is often difficult. We recommend adjuvant therapy be administered after hysterectomy in patients with ESS to prevent recurrence or distant metastasis.

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