Cancer Research and Treatment

Original Articles

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.

Citations

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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.

Citations

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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
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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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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

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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.

Citations

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Establishment and characterization of ovarian clear cell carcinoma patient-derived xenografts
Joseph J. Caumanns, Shang Li, Gert J. Meersma, Evelien W. Duiker, Ate G. J. van der Zee, G. Bea A. Wisman, Steven de Jong
Scientific Reports.2025;[Epub] CrossRef
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
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Sum In Tsang, Ayon A. Hassan, Sally K.Y. To, Alice S.T. Wong
Experimental Cell Research.2022; 416(1): 113150. CrossRef
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Alessandra Ciucci, Marianna Buttarelli, Anna Fagotti, Giovanni Scambia, Daniela Gallo
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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
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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
International Journal of Molecular Sciences.2021; 22(17): 9369. CrossRef
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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
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Suad M. Abdirahman, Michael Christie, Adele Preaudet, Marie C. U. Burstroem, Dmitri Mouradov, Belinda Lee, Oliver M. Sieber, Tracy L. Putoczki
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Michael-Antony Lisio, Lili Fu, Alicia Goyeneche, Zu-hua Gao, Carlos Telleria
International Journal of Molecular Sciences.2019; 20(4): 952. CrossRef
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Yoshiaki Maru, Naotake Tanaka, Makiko Itami, Yoshitaka Hippo
Gynecologic Oncology.2019; 154(1): 189. CrossRef
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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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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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Germline mutations of 4567 patients with hereditary breast-ovarian cancer spectrum in Thailand
Chalermkiat Kansuttiviwat, Pongtawat Lertwilaiwittaya, Ekkapong Roothumnong, Panee Nakthong, Peerawat Dungort, Chutima Meesamarnpong, Warisara Tansa-Nga, Khontawan Pongsuktavorn, Supakit Wiboonthanasarn, Warunya Tititumjariya, Nannipa Phuphuripan, Chittap
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Germline Mutational Landscape and Novel Targetable RAD51D Variant in Chinese Patients With Ovarian Cancer
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Siddhartha Yadav, Fergus J. Couch, Susan M. Domchek
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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
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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
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An Open-Label, Randomized, Parallel, Phase II Trial to Evaluate the Efficacy and Safety of a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel as First-Line Treatment for Ovarian Cancer: A Korean Gynecologic Oncology Group Study (KGOG-3021): Shin-Wha Lee, Yong-Man Kim, Chi Heum Cho, Young Tae Kim, Seok Mo Kim, Soo Young Hur, Jae-Hoon Kim, Byoung-Gie Kim, Seung-Cheol Kim, Hee-Sug Ryu, Soon Beom Kang; Cancer Res Treat. 2018;50(1):195-203. Published online March 21, 2017; DOI: https://doi.org/10.4143/crt.2016.376

Abstract PDF PubReader ePub

Purpose
Genexol-PM is a biodegradable cremophor EL–free polymeric micelle formulation of paclitaxel. Here,we compared efficacy and safety of Genexol-PM plus carboplatin versus Genexol plus carboplatin for ovarian cancer treatment.
Materials and Methods
In this multicenter, randomized, phase II study, patients with International Federation of Gynecology and Obstetrics IC-IV epithelial ovarian cancer were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² with 5 area under the curve carboplatin every 3weeks (6 cycles). The primary endpointwas the carbohydrate antigen 125 and Response Evaluation Criteria In Solid Tumor composite overall response rate (ORR).
Results
Of 131 enrolled patients, 98 were included in intention-to-treat analysis. Mean dosages were 260.00±0.00 mg/m² Genexol-PM or 174.24±3.81 mg/m² Genexol. Median followup was 18.0 months (range, 6.1 to 33.8 months). ORR was 88.0% (95% confidence interval [CI], 80.4 to 95.6) with Genexol-PM, and 77.1% (95% CI, 67.1 to 87.1) with Genexol (noninferiority threshold, 16.3%). Median time to progression was 14.8 months (95% CI, 11.3 to 20.2) with Genexol-PM and 15.4 months (95% CI, 13.2 to 29.6) with Genexol (p=0.550). Overall, six patients died. Neutropenia was the most common toxicity (incidences of 86.0% vs. 77.1%, p=0.120). Peripheral neuropathy incidences were 84.0% versus 64.6% (p= 0.148). Peripheral neuropathy of ≥ grade 3 occurred in one patient receiving Genexol. All toxicities were manageable.
Conclusion
Genexol-PM plus carboplatin as first-line treatment in patients with epithelial ovarian cancer demonstrated non-inferior efficacy and well-tolerated toxicities compared with the standard paclitaxel regimen. Further studies are warranted to optimize the dose and schedule, and to investigate long-term outcomes.

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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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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.

Citations

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Impact of molecular testing on the surgical management of advanced epithelial ovarian cancer
Pierre-Emmanuel Colombo, Christophe Taoum, Michel Fabbro, Stanislas Quesada, Philippe Rouanet, Isabelle Ray-Coquard
Critical Reviews in Oncology/Hematology.2024; 202: 104469. CrossRef
The expression and mutation of BRCA1/2 genes in ovarian cancer: a global systematic study
Dinh-Toi Chu, Mai Vu Ngoc Suong, Hue Vu Thi, Thuy-Duong Vu, Manh-Hung Nguyen, Vijai Singh
Expert Review of Molecular Diagnostics.2023; 23(1): 53. CrossRef
Survival outcomes in patients with BRCA mutated, variant of unknown significance, and wild type ovarian cancer treated with PARP inhibitors
Lucia Musacchio, Serena Boccia, Claudia Marchetti, Angelo Minucci, Floriana Camarda, Chiara Cassani, Jole Ventriglia, Vanda Salutari, Viola Ghizzoni, Elena Giudice, Maria resa Te Perri, Maria Vittoria Carbone, Caterina Ricci, Sandro Pignata, Anna Fagotti,
International Journal of Gynecological Cancer.2023; 33(6): 922. CrossRef
Modeling human cancer predisposition syndromes using CRISPR/Cas9 in human cell line models
Garrett M. Draper, Daniel J. Panken, David A. Largaespada
Genes, Chromosomes and Cancer.2023; 62(9): 493. CrossRef
Mutations in Homologous Recombination Genes and Loss of Heterozygosity Status in Advanced-Stage Breast Carcinoma
Brooke B. Bartow, Gene P. Siegal, Ceren Yalniz, Ahmed M. Elkhanany, Lei Huo, Qingqing Ding, Aysegul A. Sahin, Hua Guo, Cristina Magi-Galluzzi, Shuko Harada, Xiao Huang
Cancers.2023; 15(9): 2524. CrossRef
Factors predictingBRCA1/2pathogenic variants in patients with ovarian cancer: a systematic review with meta-analysis
Giovanni Innella, Lea Godino, Giulia Erini, Antonio De Leo, Donatella Santini, Anna Myriam Perrone, Pierandrea De Iaco, Claudio Zamagni, Daniela Turchetti
Journal of Clinical Pathology.2023; 76(8): 510. CrossRef
Association of BRCA1/2 mutations with prognosis and surgical cytoreduction outcomes in ovarian cancer patients: An updated meta‐analysis
Yazhuo Wang, Na Li, Yanan Ren, Jing Zhao
Journal of Obstetrics and Gynaecology Research.2022; 48(9): 2270. CrossRef
Recurrent Ovarian Cancer with BRCAness Phenotype: A Treatment Challenge
Cláudia Caeiro, Inês Leão, Inês Oliveira, Isabel Sousa, Teresa André
Advances in Therapy.2022; 39(11): 5289. CrossRef
Clinical Impact of Next-Generation Sequencing Multi-Gene Panel Highlighting the Landscape of Germline Alterations in Ovarian Cancer Patients
Giorgia Gurioli, Gianluca Tedaldi, Alberto Farolfi, Elisabetta Petracci, Claudia Casanova, Giuseppe Comerci, Rita Danesi, Valentina Arcangeli, Mila Ravegnani, Daniele Calistri, Valentina Zampiga, Ilaria Cangini, Eugenio Fonzi, Alessandra Virga, Davide Tas
International Journal of Molecular Sciences.2022; 23(24): 15789. CrossRef
Implementation of Comprehensive Genomic Profiling in Ovarian Cancer Patients: A Retrospective Analysis
Shira Peleg Hasson, Dov Hershkovitz, Lyri Adar, Miriam Brezis, Eliya Shachar, Rona Aks, Lee Galmor, Yuval Raviv, Shira Ben Neriah, Ofer Merimsky, Edmond Sabo, Ido Wolf, Tamar Safra
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Current update on malignant epithelial ovarian tumors
Sherif B. Elsherif, Priya R. Bhosale, Chandana Lall, Christine O. Menias, Malak Itani, Kristina A. Butler, Dhakshinamoorthy Ganeshan
Abdominal Radiology.2021; 46(6): 2264. CrossRef
Mutation landscape of germline and somatic BRCA1/2 in patients with high-grade serous ovarian cancer
Kyung Jin Eoh, Hye Min Kim, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Young Tae Kim, Eun Ji Nam
BMC Cancer.2020;[Epub] CrossRef
Association of Germline Variants in Human DNA Damage Repair Genes and Response to Adjuvant Chemotherapy in Resected Pancreatic Ductal Adenocarcinoma
Haijie Hu, Yayun Zhu, Ning Pu, Richard A. Burkhart, William Burns, Daniel Laheru, Lei Zheng, Jin He, Michael G. Goggins, Jun Yu
Journal of the American College of Surgeons.2020; 231(5): 527. CrossRef
Reclassification of BRCA1 and BRCA2 variants found in ovarian epithelial, fallopian tube, and primary peritoneal cancers
Hyeong In Ha, Jin-Sun Ryu, Hyoeun Shim, Sun-Young Kong, Myong Cheol Lim
Journal of Gynecologic Oncology.2020;[Epub] CrossRef
Selecting variants of unknown significance through network-based gene-association significantly improves risk prediction for disease-control cohorts
Anastasis Oulas, George Minadakis, Margarita Zachariou, George M. Spyrou
Scientific Reports.2019;[Epub] CrossRef
Effect of BRCA mutational status on survival outcome in advanced-stage high-grade serous ovarian cancer
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
DNA damage response and repair in ovarian cancer: Potential targets for therapeutic strategies
Mohammad Mirza-Aghazadeh-Attari, Caspian Ostadian, Amir Ata Saei, Ainaz Mihanfar, Saber Ghazizadeh Darband, Shirin Sadighparvar, Mojtaba Kaviani, Hossein Samadi Kafil, Bahman Yousefi, Maryam Majidinia
DNA Repair.2019; 80: 59. CrossRef
Clinical and Genetic Characteristics of BRCA1/2 Mutation in Korean Ovarian Cancer Patients: A Multicenter Study and Literature Review
Byung Su Kwon, Jung Mi Byun, Hyun Joo Lee, Dae Hoon Jeong, Tae Hwa Lee, Kyung-Hwa Shin, Dong Soo Suh, Ki Hyung Kim
Cancer Research and Treatment.2019; 51(3): 941. CrossRef
Prevalence and oncologic outcomes of BRCA1/2 mutation and variant of unknown significance in epithelial ovarian carcinoma patients in Korea
Jun Hyeong Seo, Soo Young Jeong, Myeong Seon Kim, Jun Hyeok Kang, E Sun Paik, Yoo-Young Lee, Tae-Joong Kim, Jeong-Won Lee, Byoung-Gie Kim, Duk-Soo Bae, Chel Hun Choi
Obstetrics & Gynecology Science.2019; 62(6): 411. CrossRef
Unclassified Variants of BRCA1 and BRCA2 in Korean Patients With Ovarian Cancer
Min Chul Choi, Ja-Hyun Jang, Sang Geun Jung, Hyun Park, Won Duk Joo, Seung Hun Song, Chan Lee, Je Ho Lee
International Journal of Gynecological Cancer.2018; 28(2): 308. CrossRef
Prevalence of germline BRCA mutations among women with carcinoma of the peritoneum or fallopian tube
Min Chul Choi, Jin-Sik Bae, Sang Geun Jung, Hyun Park, Won Duk Joo, Seung Hun Song, Chan Lee, Ji-Ho Kim, Ki-Chan Lee, Sunghoon Lee, Je Ho Lee
Journal of Gynecologic Oncology.2018;[Epub] CrossRef
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 Research and Treatment.2018; 50(3): 917. CrossRef
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International Journal of Gynecologic Cancer.2018; 28(8): 1514. CrossRef
BRCA1 and BRCA2 mutations in ovarian cancer patients from China: ethnic‐related mutations in BRCA1 associated with an increased risk of ovarian cancer
Tingyan Shi, Pan Wang, Caixia Xie, Sheng Yin, Di Shi, Congchong Wei, Wenbin Tang, Rong Jiang, Xi Cheng, Qingyi Wei, Qing Wang, Rongyu Zang
International Journal of Cancer.2017; 140(9): 2051. CrossRef
Role and clinical application of next-generation sequencing (NGS) for ovarian cancer
Myong Cheol Lim, Leslie M. Randall
Journal of Gynecologic Oncology.2017;[Epub] CrossRef

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26 Crossref

Current Trends of Lung Cancer Surgery and Demographic and Social Factors Related to Changes in the Trends of Lung Cancer Surgery: An Analysis of the National Database from 2010 to 2014: Samina Park, In Kyu Park, Eung Re Kim, Yoohwa Hwang, Hyun Joo Lee, Chang Hyun Kang, Young Tae Kim; Cancer Res Treat. 2017;49(2):330-337. Published online July 18, 2016; DOI: https://doi.org/10.4143/crt.2016.196

Abstract PDF PubReader ePub

Purpose
We investigated current trends in lung cancer surgery and identified demographic and social factors related to changes in these trends.
Materials and Methods
We estimated the incidence of lung cancer surgery using a procedure code-based approach provided by the Health Insurance Review and Assessment Service (http://opendata.hira.or.kr). The population data were obtained every year from 2010 to 2014 from the Korean Statistical Information Service (http://kosis.kr/). The annual percent change (APC) and statistical significance were calculated using the Joinpoint software.
Results
From January 2010 to December 2014, 25,687 patients underwent 25,921 lung cancer surgeries, which increased by 45.1% from 2010 to 2014. The crude incidence rate of lung cancer surgery in each year increased significantly (APC, 9.5; p < 0.05). The male-to-female ratio decreased from 2.1 to 1.6 (APC, −6.3; p < 0.05). The incidence increased in the age group of ≥ 70 years for both sexes (male: APC, 3.7; p < 0.05; female: APC, 5.96; p < 0.05). Furthermore, the proportion of female patients aged ≥ 65 years increased (APC, 7.2; p < 0.05), while that of male patients aged < 65 years decreased (APC, −3.9; p < 0.05). The proportions of segmentectomies (APC, 17.8; p < 0.05) and lobectomies (APC, 7.5; p < 0.05) increased, while the proportion of pneumonectomies decreased (APC, −6.3; p < 0.05). Finally, the proportion of patients undergoing surgery in Seoul increased (APC, 1.1; p < 0.05), while the proportion in other areas decreased (APC, −1.5; p < 0.05).
Conclusion
An increase in the use of lung cancer surgery in elderly patients and female patients, and a decrease in the proportion of patients requiring extensive pulmonary resection were identified. Furthermore, centralization of lung cancer surgery was noted.

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A New Isolated Mediastinal Lymph Node or Small Pulmonary Nodule Arising during Breast Cancer Surveillance Following Curative Surgery: Clinical Factors That Differentiate Malignant from Benign Lesions: Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Wonshik Han, Kyubo Kim, Eui Kyu Chie, In-Ae Park, Young Tae Kim, Dong-Young Noh, Sung Whan Ha, Yung-Jue Bang; Cancer Res Treat. 2014;46(3):280-287. Published online July 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.3.280

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Purpose
A newly isolated mediastinal lymph node (LN) or a small pulmonary nodule, which appears during breast cancer surveillance, may pose a diagnostic dilemma with regard to malignancy. We conducted this study to determine which clinical factors were useful for the differentiation of malignant lesions from benign lesions under these circumstances. Materials and Methods We enrolled breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule that arose during surveillance, and whose lesions were pathologically confirmed. Tissue diagnosis was made by mediastinoscopy, video-assisted thoracic surgery or thoracotomy. Results A total of 43 patients were enrolled (mediastinal LN, 13 patients; pulmonary nodule, 30 patients). Eighteen patients (41.9%) were pathologically confirmed to have a benign lesion (benign group), and 25 patients (58.1%) were confirmed to have malignant lesion (malignant group). Between the two groups, the initial tumor size (p=0.096) and N stage (p=0.749) were similar. Hormone receptor negativity was more prevalent in the malignant group (59.1% vs. 40.9%, p=0.048). The mean lesion size was larger in the malignant group than in the benign group (20.8 mm vs. 14.4 mm, p=0.024). Metastatic lesions had a significantly higher value of maximal standardized uptake (mSUV) than that of benign lesions (6.4 vs. 3.4, p=0.021). Conclusion Hormone receptor status, lesion size, and mSUV on positron emission tomography are helpful in the differentiation of malignant lesions from benign lesions in breast cancer patients who were presented with a new isolated mediastinal LN or small pulmonary nodule during surveillance.

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Unusual metastases of breast cancer: a single-center retrospective study
Pınar ÖZDEMİR AKDUR, Nazan ÇİLEDAĞ
The European Research Journal.2023; 9(6): 1444. CrossRef
18Fluorodeoxyglucose‐positron emission tomography/computed tomography features of suspected solitary pulmonary lesions in breast cancer patients following previous curative treatment
Lei Zhu, Haiman Bian, Lieming Yang, Jianjing Liu, Wei Chen, Xiaofeng Li, Jian Wang, Xiuyu Song, Dong Dai, Zhaoxiang Ye, Wengui Xu, Xiaozhou Yu
Thoracic Cancer.2019; 10(5): 1086. 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

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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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Celecoxib Reverse Invasion and Metastasis of Gastric Cancer through Lnc_AC006548.28-miR-223-LAMC2 Pathway
Guohua Jin, Jianguang Zhang, Tingting Cao, He Zhu, Yang Shi, Kapil Sharma
Computational Intelligence and Neuroscience.2022; 2022: 1. CrossRef
New Visions on Natural Products and Cancer Therapy: Autophagy and Related Regulatory Pathways
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Indian Journal of Surgery.2021; 83(4): 932. CrossRef
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Lin Deng, Ding-qing Feng, Bin Ling
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Zhuyan Shao, Qiang Wen, Tao Zhu, Wei Jiang, Yu Kang, Conjian Xu, Shihua Wang
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Xiaobin Zheng, Neal Andruska, Michael J. Lambrecht, Sisi He, Amadeo Parissenti, Paul J. Hergenrother, Erik R. Nelson, David J. Shapiro
Oncotarget.2018; 9(19): 14741. CrossRef
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Xian Xu, Guo-Qin Zhu, Kai Zhang, Yi-Chan Zhou, Xiao-Lin Li, Wei Xu, Hao Zhang, Yun Shao, Zhen-Yu Zhang, Wei-Hao Sun
Oncotarget.2017; 8(54): 92770. CrossRef
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Hsih-Te Yang, Jiun-Huang Ju, Yue-Ting Wong, Ilya Shmulevich, Jung-Hsien Chiang
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Tülay BAKIREL, Fulya Üstün ALKAN, Oya ÜSTÜNER, Suzan ÇINAR, Funda YILDIRIM, Gaye ERTEN, Utku BAKIREL
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Oncotarget.2015; 6(25): 21353. CrossRef

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Role of Postoperative Radiotherapy for Microscopic Margin Involvement in the Squamous Cell Carcinoma of Esophagus: Sanghyuk Song, Eui Kyu Chie, Hak Jae Kim, Chang-Hyun Kang, Young Tae Kim, Joo Hyun Kim, Charn Il Park; Cancer Res Treat. 2013;45(3):202-209. Published online September 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.3.202

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PURPOSE
The objective of this study was to assess the effect of postoperative radiotherapy on the outcome of esophageal cancer with microscopically positive resection margin by comparing the results with those of patients with negative resection margin.
MATERIALS AND METHODS
Medical records of 88 patients treated with macroscopic resection followed by postoperative radiotherapy for stage II or III squamous cell carcinoma of the esophagus from June 1984 to March 2008 were reviewed. Twelve patients had received chemotherapy. Patients were classified into two groups based on resection margin status: negative resection margin (group A, n=66) and microscopically positive resection margin (group B, n=22). Median follow-up duration of living patients was 68 months (range, 18 to 115 months). Median total radiation dose of group A and group B was 51.5 Gy (range, 45 to 69 Gy) and 52.1 Gy (range, 45 to 64 Gy), respectively.
RESULTS
Median overall survival and disease-free survival were 15 and 10 months, respectively. The five-year overall survival, disease-free survival, and local control rates for group A and group B were 15.9% and 16.4%, 13.5% and 9.1%, and 76.3% and 69.6%, respectively. No statistically significant difference in terms of overall survival, disease-free survival, and local control (p=0.295, p=0.209, and p=0.731, respectively) was observed between group A and group B. Seven patients experienced toxicity of grade 3 or higher.
CONCLUSION
A significant portion of patients with margin involvement reached long term survival after addition of postoperative radiotherapy. These results suggest a potential role of postoperative radiotherapy, especially for patients with margin involvement.

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Efficacy of postoperative radiotherapy in esophageal squamous cell carcinoma patients with positive circumferential resection margin
Reiko Otake, Akihiko Okamura, Kotaro Yamashita, Yu Imamura, Jun Kanamori, Ryotaro Kozuki, Keita Takahashi, Tasuku Toihata, Noriko Yamamoto, Takao Asari, Shinji Mine, Masayuki Watanabe
Esophagus.2021; 18(2): 288. CrossRef
The Impact of Adjuvant Postoperative Radiation Therapy and Chemotherapy on Survival After Esophagectomy for Esophageal Carcinoma
Andrew T. Wong, Meng Shao, Justin Rineer, Anna Lee, David Schwartz, David Schreiber
Annals of Surgery.2017; 265(6): 1146. CrossRef
Alpha linolenic acid and oleic acid additively down-regulate malignant potential and positively cross-regulate AMPK/S6 axis in OE19 and OE33 esophageal cancer cells
Hyun-Seuk Moon, Saime Batirel, Christos S. Mantzoros
Metabolism.2014; 63(11): 1447. CrossRef

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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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Laparoscopic surgery on broken points for uterine sarcoma in the early stage decrease prognosis
Hong Liu, Yi Zhu, Guo-Nan Zhang, Chang Wang, Chao Li, Yu Shi
Scientific Reports.2016;[Epub] CrossRef
Long-term survival of patients with recurrent endometrial stromal sarcoma: a multicenter, observational study
Hiroyuki Yamazaki, Yukiharu Todo, Kenrokuro Mitsube, Hitoshi Hareyama, Chisa Shimada, Hidenori Kato, Katsushige Yamashiro
Journal of Gynecologic Oncology.2015; 26(3): 214. CrossRef
Management of uterine adenosarcomas with and without sarcomatous overgrowth
Edward J. Tanner, Thomas Toussaint, Mario M. Leitao, Martee L. Hensley, Robert A. Soslow, Ginger J. Gardner, Elizabeth L. Jewell
Gynecologic Oncology.2013; 129(1): 140. CrossRef
Uterine Sarcomas: Then and Now
Shaan H. Shah, Jyothi P. Jagannathan, Katherine Krajewski, Kevin N. O???Regan, Suzanne George, Nikhil H. Ramaiya
American Journal of Roentgenology.2012; 199(1): 213. CrossRef
Role of radiotherapy treatment of uterine sarcoma
Sagus Sampath, David K. Gaffney
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Surgical treatment of uterine sarcoma
Joo-Hyun Nam
Best Practice & Research Clinical Obstetrics & Gynaecology.2011; 25(6): 751. CrossRef
The Impact of Tumor Morcellation During Surgery on the Outcomes of Patients with Apparently Early Low-Grade Endometrial Stromal Sarcoma of the Uterus
Jeong-Yeol Park, Dae-Yeon Kim, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam
Annals of Surgical Oncology.2011; 18(12): 3453. CrossRef

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An Analysis of the Risk Factors and Management of Lymphocele after Pelvic Lymphadenectomy in Patients with Gynecologic Malignancies: Hee Yeon Kim, Jae Wook Kim, Sung Hoon Kim, Young Tae Kim, Jae Hoon Kim; Cancer Res Treat. 2004;36(6):377-383. Published online December 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.6.377

Abstract PDF PubReader ePub

Objectives

The incidence and risk factors of lymphocele development after pelvic lymphadenectomy were evaluated and its management investigated.

Materials and Methods

This retrospective study was carried out on 264 patients who received a pelvic lymphadenectomy, between March 1999 and February 2003, due to gynecologic cancer. The patients were classified into two groups; the lymphocele (n=50) and non-lymphocele groups (n=214), as confirmed by ultrasonography, CT scan and MRI. Each group was compared by cancer type and stage, BMI, preoperative Hb, use of pre/postoperative chemotherapy or radiotherapy, number of resected pelvic lymph nodes and the volume of postoperative drainage from a Hemovac® pelvic drain.

Results

Of the 264 patients tested, 15 of 105 cervical cancer (14%), 22 of 115 ovarian cancer (19%) and 11 of 40 endometrial cancer patients (27%), a total of 50 patients (18%), developed lymphoceles. In the lymphocele group (n=50), 13 patients were diagnosed with complicated lymphocele. The BMI and number of resected pelvic lymph nodes were found to be higher in the lymphocele than in the non-lymphocele group (23.94±3.38 vs. 22.52±3.00, p=0.00 and 26.80±14.82 vs. 22.96±10.18, p=0.03, respectively), and showed statistical significance. The occurrence of lymphoceles was lower without postoperative radiotherapy (p=0.01).

Conclusion

Among the 264 patients, a total of 50 patients (18%) developed lymphoceles. The BMI and number of resected lymph nodes were higher in the lymphocele group, and the use of postoperative radiotherapy was associated with a higher risk of lymphoceles. Thirteen of the 50 patients that developed lymphoceles (n=50) required treatment for lymphocele-related complications.

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Oxaliplatin with Biweekly, Low Dose Leucovorin and Bolus and Continuous Infusion 5-fluorouracil (Modified FOLFOX 4) as First-line Therapy for Patients with Metastatic Colorectal Cancer: Hyuk-Chan Kwon, Kyoung Tae Kim, Shin Ae Lee, Jong-Sung Park, Sung-Hyun Kim, Jae-Seok Kim, Hyo Jin Kim; Cancer Res Treat. 2004;36(2):115-120. Published online April 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.2.115

Abstract PDF PubReader ePub

Purpose

To determine the activity and toxicities of low dose leucovorin (LV) plus fluorouracil (5-FU) regimen, combined with oxaliplatin every two weeks (modified FOLFOX 4), as a first-line therapy for patients with metastatic colorectal cancer.

Materials and Methods

Between March 2001 and August 2003, fifty-five patients were enrolled in this study. Patients were treated with oxaliplatin 85 mg/m² as a 2-hour infusion at days 1 plus LV 20 mg/m² over 10 minutes, followed by 5-FU bolusa 400 mg/m² bolus and 22 hour continuous infusion of 600 mg/m² 5-FU at day 1~2. This treatment was repeated in 2 week intervals.

Results

The objective response rate was 40% on an intent-to-treatment analysis. Three patients (6%) demonstrated a complete response and nineteen patients (38%) showeda partial response. Sixteen patients (32%) showed a stable disease and eleven patients (22%) progressed during the course of the treatment. The median time to progression and overall survival time wereas 6.6 months (95% CI: 4.98~8.02 months) and the median overall survival time was 17.0 months (95% CI: 9.15~24.85 months) from the start of the chemotherapy, respectively. A total of 275 cycles were analyzed for toxicity. Major hematologic toxicities included grade 1~2 anemia (23.5%), neutropenia (25.3%) and thrombocytopenia (10.6%). There were only 2 cycles of neutropenic fever. The most common non-hematologic toxicities were grade 1~2 nausea/vomiting (10.9%), diarrhea (9.1%) and grade 1 neuropathy (18.0%). There was no treatment related death.

Conclusion

The modified folfox 4 regimen is safe and effective regimen as a first-line therapy in advanced colorectal cancer patients.

Citations

Citations to this article as recorded by

A Phase II Study of Modified FOLFOX4 for Colorectal Cancer Patients with Peritoneal Carcinomatosis
Dong Hyun Lee, Sung Yong Oh, Yu Rim Lee, Seok Jae Huh, Hyun Hwa Yoon, Sung Hyun Kim, Suee Lee, Ji Hyun Lee, Young Kim, Hyo-Jin Kim, Hyuk-Chan Kwon
Cancer Research and Treatment.2011; 43(4): 225. CrossRef
Outpatient-basis Chemotherapy of Oxaliplatin, 5-fluorouracil, and Leucovorin as First-line Treatment for Patients with Metastatic or Recurrent Colorectal Cancer
Joon Ho Moon, Jong Gwang Kim, Sang Kyun Sohn, Jin Ho Baek, Yoon Young Cho, Yee Soo Chae, Byung Min Ahn, Shi Nae Kim, Soo Jung Lee, In Taek Lee, Gyu Seog Choi, Soo Han Jun
Journal of Korean Medical Science.2007; 22(3): 400. CrossRef
Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer
Byoung Yong Shim, Kang Moon Lee, Hyeon-Min Cho, Hyun Jin Kim, Hong Joo Cho, Jinmo Yang, Jun-Gi Kim, Hoon-Kyo Kim
Cancer Research and Treatment.2005; 37(4): 212. CrossRef
Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil and Low Dose Leucovorin in Patients with Advanced Colorectal Cancer
Yoon Mi Shin, Hae Suk Han, Seong Woo Lim, Byung Chul Kim, Kyung Suck Cheoi, Young Ook Eum, Seung Taek Kim, Ki Hyeong Lee
Cancer Research and Treatment.2005; 37(5): 284. CrossRef
Oxaliplatin with Biweekly Low Dose Leucovorin and Bolus and Continuous Infusion of 5-fluorouracil (Modified FOLFOX 4) as a Salvage Therapy for Patients w ith Advanced G astric Cancer
Sung-Hwan Suh, Hyuk-Chan Kwon, Ji-Hoon Jo, Young-Rak Cho, Bong-Gun Seo, Dong-Mee Lee, Sung-Hyun Kim, Jae-Seok Kim, Hyo-Jin Kim
Cancer Research and Treatment.2005; 37(5): 279. CrossRef
Oxaliplatin: Is It a New Standard Weapon for Colorectal Cancer?
Si-Young Kim
Cancer Research and Treatment.2004; 36(2): 91. CrossRef

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Clinical Significance of Apoptosis and p53 Protein Expression in Stage IIB Squamous Cell Carcinoma of the Cervix Treated with Radiotherapy Alone: Eun Ji Chung, Gwi Eon Kim, Jinsil Seong, Woo Ick Yang, Young Tae Kim, Chang Ok Suh; J Korean Cancer Assoc. 2000;32(3):638-646.

Abstract PDF: PURPOSE
The purpose was to investigate the spontaneous apoptotic index (SAI) and p53 protein expression and to identify the role of SAI and p53 protein positivity.
MATERIALS AND METHODS
Forty six patients with squamous cell carcinoma of the cervix, FIGO stage IIB, treated with curative radiotherapy alone between 1990 and 1993 were included in this study. Definitive radiotherapy including external beam and high-dose-rate brachytherapy was given. Pretreatment paraffin-embedded biopsy specimens of those patients were scored for apoptosis and p53 protein expression using mouse mondegrees Clonal antibody (DO-7) by immuno staining. Clinicopathologic characteristics were also studied in relation to SAI and p53 protein expression, and as prognostic factors for clinical outcome.
RESULTS
SAI and p53 were not related to any clinical characteristics. The range of the SAI was 0.2~4.7% (median 1.1%, mean 1.5%). The rate of p53 protein expression was 65.2% (30/46). Patients whose tumors had high SAI and low p53 protein positivity had better treatment outcome than those with lower SAI. There was also a significant correlation between the SAI and p53 protein expression.
CONCLUSION
The pretreatment SAI and p53 oncoprotein expression are clinically useful in predicting the clinical outcome of FIGO stage IIB squamous cell carcinoma of the uterine cervix patients treated with definitive radiotherapy.

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