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Time-Trend Analysis and Risk Factors for Niraparib-Induced Nausea and Vomiting in Ovarian Cancer: A Prospective Study
Young Wook Jeong, Dongkyu Eugene Kim, Ji Hyun Kim, Se Ik Kim, Hyeong In Ha, Sang-Yoon Park, Myong Cheol Lim
Received September 14, 2024  Accepted November 2, 2024  Published online November 4, 2024  
DOI: https://doi.org/10.4143/crt.2024.899    [Accepted]
AbstractAbstract PDF
Purpose
Nausea and vomiting are major non-hematological adverse events associated with niraparib maintenance therapy. This study aimed to investigate the time-trend patterns of niraparib-induced nausea and vomiting (NINV) and the associated risk factors in patients with ovarian cancer.
Materials and Methods
In this prospective study, we enrolled patients with stage III–IV epithelial ovarian cancer who received niraparib as frontline maintenance therapy. The clinicopathological characteristics and time-trend patterns of patients with NINV were collected through in-person surveys and electronic medical records from the National Cancer Center.
Results
Of 53 patients, 50 (94.3%) were diagnosed with high-grade serous ovarian carcinoma. BRCA mutations and homologous recombination deficiency (HRD) were identified in 23 (43.4%) and 32 (60.4%) patients, respectively. Thirty-one patients (58.5%) had NINV. Time-trend analyses revealed that the first peak intensity of NINV was reached at 3 h post-dose, and the second peak intensity was reached at 11 h post-dose. NINV significantly decreased from week 1 to weeks 8 and 12. In multivariate analyses of risk factors for NINV, HRD-positive tumors (p<0.001) and prior experience of chemotherapy-induced nausea and vomiting (p=0.004) were associated with the occurrence of NINV.
Conclusion
Pre-emptive treatment with antiemetics are required to manage early-phase NINV during niraparib maintenance therapy in patients with risk factors. Additional larger studies are needed to confirm these findings and to develop optimal preventive strategies for NINV.
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Gynecologic cancer
Safety and Tolerability of Weekly Genexol-PM, a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel, with Carboplatin in Gynecologic Cancer: A Phase I Study
So Hyun Nam, Shin-Wha Lee, Young-Jae Lee, Yong Man Kim
Cancer Res Treat. 2023;55(4):1346-1354.   Published online May 15, 2023
DOI: https://doi.org/10.4143/crt.2022.1436
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This phase I study was conducted to determine the maximum tolerated dose and the recommended phase II dose of weekly administered Genexol-PM combined with carboplatin in patients with gynecologic cancer.
Materials and Methods
This open-label, phase I, dose-escalation study of weekly Genexol-PM included 18 patients with gynecologic cancer, who were equally divided into three cohorts of dose levels. Cohort 1 received 100 mg/m2 Genexol-PM and 5 area under the curve (AUC) carboplatin, cohort 2 received 120 mg/m2 Genexol-PM and 5 AUC carboplatin, and cohort 3 received 120 mg/m2 Genexol-PM and 6 AUC carboplatin. The safety and efficacy of each dose were analyzed for each cohort.
Results
Of the 18 patients, 11 patients were newly diagnosed and seven patients were recurrent cases. No dose-limiting toxicity was observed. The maximum tolerated dose was not defined, but a dose up to 120 mg/m2 of Genexol-PM in combination with AUC 5-6 of carboplatin could be recommended for a phase II study. In this intention-to-treat population, five patients dropped out of the study (carboplatin-related hypersensitivity, n=1; refusal of consent, n=4). Most patients (88.9%) with adverse events recovered without sequelae, and no treatment-related death occurred. The overall response rate of weekly Genexol-PM in combination with carboplatin was 72.2%.
Conclusion
Weekly administered Genexol-PM with carboplatin demonstrated an acceptable safety profile in gynecologic cancer pati-ents. The recommended phase II dose of weekly Genexol-PM is up to 120 mg/m2 when combined with carboplatin.

Citations

Citations to this article as recorded by  
  • Multicore, SDS-Based Polyelectrolyte Nanocapsules as Novel Nanocarriers for Paclitaxel to Reduce Cardiotoxicity by Protecting the Mitochondria
    Marzena Szwed, Anastazja Poczta-Krawczyk, Katarzyna D. Kania, Kacper Wiktorowski, Kamila Podsiadło, Agnieszka Marczak, Krzysztof Szczepanowicz
    International Journal of Molecular Sciences.2025; 26(3): 901.     CrossRef
  • Redox-responsive polymer micelles co-encapsulating immune checkpoint inhibitors and chemotherapeutic agents for glioblastoma therapy
    Zhiqi Zhang, Xiaoxuan Xu, Jiawei Du, Xin Chen, Yonger Xue, Jianqiong Zhang, Xue Yang, Xiaoyuan Chen, Jinbing Xie, Shenghong Ju
    Nature Communications.2024;[Epub]     CrossRef
  • Therapeutic impacts of GNE‑477‑loaded H2O2 stimulus‑responsive dodecanoic acid‑phenylborate ester‑dextran polymeric micelles on osteosarcoma
    Songmu Pan, Zhuan Zou, Xiaofeng Zhou, Jiyong Wei, Huijiang Liu, Zhongyi Su, Gui Liao, Guangyu Huang, Zonggui Huang, Yi Xu, Minan Lu, Ronghe Gu
    International Journal of Molecular Medicine.2024;[Epub]     CrossRef
  • Functionalized Polymeric Micelles for Targeted Cancer Therapy: Steps from Conceptualization to Clinical Trials
    Ana Serras, Célia Faustino, Lídia Pinheiro
    Pharmaceutics.2024; 16(8): 1047.     CrossRef
  • Simplified Gambogic Acid Prodrug Nanoparticles to Improve Efficiency and Reduce Toxicity for Clinical Translation Potential
    Ruyi Wang, Yuxiao Xiao, Zhongtao Zhang, Xiaoxian Huang, Wanfang Zhu, Xiao Ma, Feng Feng, Wenyuan Liu, Lingfei Han, Wei Qu
    Advanced Healthcare Materials.2024;[Epub]     CrossRef
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Effect of BRCA1/2 Mutational Status on Survival Outcomes According to Secondary Cytoreductive Surgery and Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer: A Real-World Evidence Study
Se Ik Kim, Hyunji Lim, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song, Maria Lee
Cancer Res Treat. 2023;55(1):245-257.   Published online July 19, 2022
DOI: https://doi.org/10.4143/crt.2022.232
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to investigate the impact of BRCA1/2 mutational status on survival outcomes in patients with platinum-sensitive relapsed (PSR) epithelial ovarian cancer (EOC).
Materials and Methods
We retrospectively identified patients who received secondary treatment for PSR EOC at our institution between January 2007 and June 2021 and who underwent BRCA1/2 gene testing by either germline or somatic methods. The association between BRCA1/2 mutational status and survival outcomes was evaluated. Both secondary cytoreductive surgery (CRS) and maintenance therapy were stratified considering real-world clinical practice.
Results
Of 262 patients, 91 (34.7%) and 171 (65.3%) were assigned to BRCA1/2 mutation and wild-type groups, respectively. The two groups had similar proportions of patients undergoing secondary CRS (26.4% vs. 32.7%, p=0.286) and maintenance therapy (54.9% vs. 46.2%, p=0.178). Overall, no differences in progression-free survival (PFS; median, 19.7 vs. 15.1 months, p=0.120) and overall survival (OS; p=0.400) were observed between the two groups. In multivariate analyses, BRCA1/2 mutational status was not associated with PFS (adjusted hazard ratio, 0.816; 95% confidence interval, 0.596 to 1.119; p=0.207). BRCA1/2 mutational status did not affect PFS among patients who underwent secondary CRS (n=80) and among those who did not (n=182) (p=0.074 and p=0.222, respectively). PFS did not differ in the BRCA1/2 mutational status among the patients who received bevacizumab maintenance (n=90, p=0.992).
Conclusion
In this real-world evidence study, BRCA1/2 mutational status itself was not associated with PFS and OS in PSR EOC, which was consistent with whether secondary CRS or not and with bevacizumab maintenance.
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Gynecologic Cancer
Enhanced Efficacy of Combined Therapy with Checkpoint Kinase 1 Inhibitor and Rucaparib via Regulation of Rad51 Expression in BRCA Wild-Type Epithelial Ovarian Cancer Cells
Hye-yon Cho, Yong-Beom Kim, Wook-ha Park, Jae Hong No
Cancer Res Treat. 2021;53(3):819-828.   Published online December 16, 2020
DOI: https://doi.org/10.4143/crt.2020.1013
AbstractAbstract PDFPubReaderePub
Purpose
This study aimed to evaluate anticancer effects of combination treatment with poly(ADP-ribose) polymerase (PARP) and checkpoint kinase 1 (Chk1) inhibitors in BRCA wild-type ovarian cancer. PARP inhibitors can function as DNA-damaging agents in BRCA wild-type cancer, even if clinical activity is limited. Most epithelial ovarian cancers are characterized by a TP53 mutation causing dysfunction at the G1/S checkpoint, which makes tumor cells highly dependent on Chk1-mediated G/M phase cell-cycle arrest for DNA repair.
Materials and Methods
We investigated the anticancer effects of combination treatment with prexasertib (LY2606368), a selective ATP competitive small molecule inhibitor of Chk1 and Chk2, and rucaparib, a PARP inhibitor, in BRCA wild-type ovarian cancer cell lines (OVCAR3 and SKOV3).
Results
We found that combined treatment significantly decreased cell viability in all cell lines and induced greater DNA damage and apoptosis than in the control and/or using monotherapies. Moreover, we found that prexasertib significantly inhibited homologous recombination–mediated DNA repair and thus showed a marked anticancer effect in combination treatment with rucaparib. The anticancer mechanism of prexasertib and rucaparib was considered to be caused by an impaired G2/M checkpoint due to prexasertib treatment, which forced mitotic catastrophe in the presence of rucaparib.
Conclusion
Our results suggest a novel effective therapeutic strategy for BRCA wild-type epithelial ovarian cancer using a combination of Chk1 and PARP inhibitors.

Citations

Citations to this article as recorded by  
  • ATR, CHK1 and WEE1 inhibitors cause homologous recombination repair deficiency to induce synthetic lethality with PARP inhibitors
    Hannah L. Smith, Elaine Willmore, Lisa Prendergast, Nicola J. Curtin
    British Journal of Cancer.2024; 131(5): 905.     CrossRef
  • Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
    Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Update on Combination Strategies of PARP Inhibitors
    Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
    Cancer Control.2024;[Epub]     CrossRef
  • Molecular Methods for Increasing the Effectiveness of Ovarian Cancer Treatment: A Systematic Review
    Zuzanna Chilimoniuk, Agata Rocka, Martyna Stefaniak, Żaklina Tomczyk, Faustyna Jasielska, Dominika Madras, Agata Filip
    Future Oncology.2022; 18(13): 1627.     CrossRef
  • A Phase 2 study of prexasertib (LY2606368) in platinum resistant or refractory recurrent ovarian cancer
    Panagiotis A. Konstantinopoulos, Jung-min Lee, Bo Gao, Rowan Miller, Jung-Yun Lee, Nicoletta Colombo, Ignace Vergote, Kelly M. Credille, Suzanne R. Young, Samuel McNeely, Xuejing Aimee Wang, Aimee Bence Lin, Ronnie Shapira-Frommer
    Gynecologic Oncology.2022; 167(2): 213.     CrossRef
  • Pharmacological Poly (ADP-Ribose) Polymerase Inhibitors Decrease Mycobacterium tuberculosis Survival in Human Macrophages
    Cassandra L. R. van Doorn, Sanne A. M. Steenbergen, Kimberley V. Walburg, Tom H. M. Ottenhoff
    Frontiers in Immunology.2021;[Epub]     CrossRef
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Gynecologic cancer
Second Primary Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancers after Breast Cancer Diagnosis: Korea Central Cancer Registry
Hyeong In Ha, Eun-Gyeong Lee, Jiwon Lim, So-Youn Jung, Yoon Jung Chang, Young-Joo Won, Myong Cheol Lim
Cancer Res Treat. 2021;53(2):541-548.   Published online November 18, 2020
DOI: https://doi.org/10.4143/crt.2020.1001
AbstractAbstract PDFPubReaderePub
Purpose
A prior history of breast cancer is a risk factor for the subsequent development of primary peritoneal, epithelial ovarian, and fallopian tubal (POFT) cancers. This study aimed to estimate the incidence of secondary POFT malignancy in breast cancer patients and the clinical outcomes of primary and secondary POFT cancer.
Materials and Methods
We searched the Korea Central Cancer Registry to find patients with primary and secondary POFT cancer who had breast cancer in 1999-2017. The incidence rate and standardized incidence ratio were calculated. Additionally, we compared the overall survival of patients with primary and secondary POFT cancer.
Results
Based on the age-standardized rate, the incidence of second primary POFT cancer after breast cancer was 0.0763 per 100,000 women, which increased in Korea between 1999 and 2017. Among the 30,366 POFT cancer patients, 25,721 were primary POFT cancer only, and 493 had secondary POFT cancer after a breast cancer diagnosis. Second primary POFT cancer patients were older at the time of diagnosis (55 vs. 53, p < 0.001) and had a larger proportion of serous histology (68.4% vs. 51.2%, p < 0.001) than patients with primary POFT. There were no differences between the two groups in tumor stage at diagnosis. The 5-year overall survival rates were 60.2% and 56.3% for primary and secondary POFT cancer, respectively (p=0.216).
Conclusion
The incidence of second primary POFT cancer after breast cancer increased in Korea between 1999 and 2017. Besides, second primary POFT cancer patients were diagnosed at older ages and had more serous histology.

Citations

Citations to this article as recorded by  
  • Das Ovarialkarzinom: Score-Werte zur Definition von Risikopatientinnen
    Eberhard Paul, Sebastian M. Jud
    Geburtshilfe und Frauenheilkunde.2024; 84(03): 226.     CrossRef
  • Risk for Second Primary Ovarian Cancer: A Large Population Based on Surveillance, Epidemiology, and End Results Database
    Haiyang Hu, Yangsheng Ren, Huixing Li, Tishuo Zhang, Lin Sun
    Oncology.2024; : 1.     CrossRef
  • High-grade pelvic-type serous carcinoma presenting as a breast rash
    Mark Weingarten, Michael Weingarten, Tamara Kalir, Angela Lamb
    JAAD Case Reports.2022; 20: 20.     CrossRef
  • 6,033 View
  • 141 Download
  • 1 Web of Science
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Germline and Somatic BRCA1/2 Gene Mutational Status and Clinical Outcomes in Epithelial Peritoneal, Ovarian, and Fallopian Tube Cancer: Over a Decade of Experience in a Single Institution in Korea
Se Ik Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Jae-Weon Kim, Noh Hyun Park, Yong-Sang Song
Cancer Res Treat. 2020;52(4):1229-1241.   Published online July 27, 2020
DOI: https://doi.org/10.4143/crt.2020.557
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to present a single institutional experience with BRCA1/2 gene tests and the effects of pathogenic mutations in epithelial peritoneal, ovarian, and fallopian tube cancer (POFTC) on survival outcomes.
Materials and Methods
We identified patients with epithelial POFTCs who underwent BRCA1/2 gene testing by either germline or somatic methods between March 2007 and March 2020. Based on the BRCA1/2 test results, patients were divided into BRCA mutation and wild-type groups, followed by comparisons of clinicopathologic characteristics and survival outcomes after primary treatment.
Results
The annual number of POFTC patients who received BRCA1/2 gene tests increased gradually. In total, 511 patients were included and BRCA1/2 mutations were observed in 143 (28.0%). Among 57 patients who received both germline and somatic tests, three (5.3%) showed discordant results from the two tests. Overall, no differences in progression-free survival (PFS; p=0.467) and overall survival (p=0.641) were observed between the BRCA mutation and wild-type groups; however, multivariate analyses identified BRCA1/2 mutation as an independent favorable prognostic factor for PFS (adjusted hazard ratio [aHR], 0.765; 95% confidence interval [CI], 0.593 to 0.987; p=0.040). In 389 patients with International Federation of Gynecology and Obstetrics stage III-IV, different results were shown depending on primary treatment strategy: while BRCA1/2 mutation significantly improved PFS in the subgroup of neoadjuvant chemotherapy (aHR, 0.619; 95% CI, 0.385 to 0.995; p=0.048), it did not affect patient PFS in the subgroup of primary debulking surgery (aHR, 0.759; 95% CI, 0.530 to 1.089; p=0.135).
Conclusion
BRCA1/2 mutations are frequently observed in patients with epithelial POFTCs, and such patients showed better PFS than did those harboring wild-type BRCA1/2.

Citations

Citations to this article as recorded by  
  • Overview of Molecular Diagnostics in Irish Clinical Oncology
    Tyler Medina, Seán O. Hynes, Maeve Lowery, Paddy Gillespie, Walter Kolch, Cathal Seoighe
    HRB Open Research.2024; 7: 16.     CrossRef
  • Trends in the Incidence and Survival Rates of Primary Ovarian Clear Cell Carcinoma Compared to Ovarian Serous Carcinoma in Korea
    Se Ik Kim, Hyeong In Ha, Kyung Jin Eoh, Jiwon Lim, Young-Joo Won, Myong Cheol Lim
    Frontiers in Oncology.2022;[Epub]     CrossRef
  • Characteristics of homologous recombination repair pathway genes mutation in ovarian cancers
    Zongbi Yi, Min Chen, Shaoxing Sun, Chunxu Yang, Zijie Mei, Hui Yang, Qingming Xiang, Hui Qiu
    Cancer Innovation.2022; 1(3): 220.     CrossRef
  • 7,891 View
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Evaluation of Circulating Tumor DNA in Patients with Ovarian Cancer Harboring Somatic PIK3CA or KRAS Mutations
Aiko Ogasawara, Taro Hihara, Daisuke Shintani, Akira Yabuno, Yuji Ikeda, Kenji Tai, Keiichi Fujiwara, Keisuke Watanabe, Kosei Hasegawa
Cancer Res Treat. 2020;52(4):1219-1228.   Published online May 6, 2020
DOI: https://doi.org/10.4143/crt.2019.688
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Circulating tumor DNA (ctDNA) is an attractive source for liquid biopsy to understand molecular phenotypes of a tumor non-invasively, which is also expected to be both a diagnostic and prognostic marker. PIK3CA and KRAS are among the most frequently mutated genes in epithelial ovarian cancer (EOC). In addition, their hotspot mutations have already been identified and are ready for a highly sensitive analysis. Our aim is to clarify the significance of PIK3CA and KRAS mutations in the plasma of EOC patients as tumor-informed ctDNA.
Methods
We screened 306 patients with ovarian tumors for somatic PIK3CA or KRAS mutations. A total of 85 EOC patients had somatic PIK3CA and/or KRAS mutations, and the corresponding mutations were subsequently analyzed using a droplet digital polymerase chain reaction in their plasma.
Results
The detection rates for ctDNA were 27% in EOC patients. Advanced stage and positive peritoneal cytology were associated with higher frequency of ctDNA detection. Preoperative ctDNA detection was found to be an indicator of outcomes, and multivariate analysis revealed that ctDNA remained an independent risk factor for recurrence (p=0.010). Moreover, we assessed the mutation frequency in matched plasma before surgery and at recurrence from 17 patients, and found six patients had higher mutation rates in cell-free DNA at recurrence compared to that at primary diagnosis.
Conclusion
The presence of ctDNA at diagnosis was an indicator for recurrence, which suggests potential tumor spread even when tumors were localized at the time of diagnosis.

Citations

Citations to this article as recorded by  
  • Circulating tumor DNA as a biomarker for predicting progression-free survival and overall survival in patients with epithelial ovarian cancer: a systematic review and meta-analysis
    Cristina Taliento, Giampaolo Morciano, Camilla Nero, Wouter Froyman, Giuseppe Vizzielli, Matteo Pavone, Stefano Salvioli, Mara Tormen, Francesco Fiorica, Gennaro Scutiero, Giovanni Scambia, Carlotta Giorgi, Pantaleo Greco, Paolo Pinton
    International Journal of Gynecologic Cancer.2024; : ijgc-2024-005313.     CrossRef
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    Takahiro Ebata, Satoshi Yamashita, Hideyuki Takeshima, Hiroshi Yoshida, Yoshiko Kawata, Nao Kino, Toshiharu Yasugi, Yasuhisa Terao, Kan Yonemori, Tomoyasu Kato, Toshikazu Ushijima
    Medical Oncology.2022;[Epub]     CrossRef
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    Dimitra Stergiopoulou, Athina Markou, Lydia Giannopoulou, Paul Buderath, Ioanna Balgkouranidou, Nikolaos Xenidis, Stylianos Kakolyris, Sabine Kasimir-Bauer, Evi Lianidou
    Cancers.2022; 14(15): 3790.     CrossRef
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    Christen A. Khella, Gaurav A. Mehta, Rushabh N. Mehta, Michael L. Gatza
    Journal of Personalized Medicine.2021; 11(2): 149.     CrossRef
  • Tumor-related mutations in cell-free DNA in pre-operative plasma as a prognostic indicator of recurrence in endometrial cancer
    Daisuke Shintani, Taro Hihara, Aiko Ogasawara, Sho Sato, Akira Yabuno, Kenji Tai, Keiichi Fujiwara, Keisuke Watanabe, Kosei Hasegawa
    International Journal of Gynecological Cancer.2020; 30(9): 1340.     CrossRef
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  • 14 Web of Science
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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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 (SUVmax) with PET/CT. Decreases in SUVmax 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.

Citations

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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
  • 8,379 View
  • 135 Download
  • 7 Web of Science
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G Protein–Coupled Receptor 30 Mediates the Anticancer Effects Induced by Eicosapentaenoic Acid in Ovarian Cancer Cells
Yue Zhao, Meng-Fei Zhao, Mei-Lin Yang, Tian-Yu Wu, Cong-Jian Xu, Jing-Mei Wang, Chao-Jun Li, Xi Li
Cancer Res Treat. 2020;52(3):815-829.   Published online March 5, 2020
DOI: https://doi.org/10.4143/crt.2019.380
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
While numerous epidemiological studies have indicated that omega-3 polyunsaturated fatty acids have anticancer properties in various cancers, the effects and mechanisms of eicosapentaenoic acid (EPA) in ovarian cancer cell growth are poorly understood.
Materials and Methods
ES2 ovarian clear cell carcinoma cells and SKOV3 adenocarcinoma cells were treated with palmitic acid or EPA, followed by flow cytometry and cell counting to measure apoptosis and proliferation, respectively. A modified protein lipid overlay assay was used to further verify whether EPA was a ligand of G protein–coupled receptor 30 (GPR30) in ES2 cells. The levels of apoptosis-related genes, phosphorylated AKT, and phosphorylated ERK1/2 were detected to explore the underlying mechanism. Finally, inhibitory effect of EPA on tumor growth via GPR30 was determined in vitro and in vivo.
Results
EPA suppressed ES2 ovarian clear cell carcinoma cells growth via GPR30, a novel EPA receptor, by inducing apoptosis. As a ligand of GPR30, EPA activated the GPR30-cAMP– protein kinase A signaling pathway. When GPR30 was suppressed by siRNA or its inhibitor G15, the antiproliferative action of EPA was impaired. Furthermore, EPA inhibited tumor growth by blocking the activation of AKT and ERK. In the mouse xenograft model, EPA decreased tumor volume and weight through GPR30 by blocking tumor cell proliferation.
Conclusion
These results confirm that EPA is a tumor suppressor in human ovarian clear cell carcinoma cells and functions through a novel fatty acid receptor, GPR30, indicating a mechanistic linkage between omega-3 fatty acids and cancers.

Citations

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    Liliana Torres-López, Miguel Olivas-Aguirre, Oxana Dobrovinskaya
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    Xiuting Xiang, Praneetha Palasuberniam, Rahmawati Pare
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    Susanne Schüler-Toprak, Maciej Skrzypczak, Carsten Gründker, Olaf Ortmann, Oliver Treeck
    Cancers.2023; 15(10): 2845.     CrossRef
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    Mary P. Udumula, Laila M. Poisson, Indrani Dutta, Nivedita Tiwari, Seongho Kim, Jasdeep Chinna-Shankar, Ghassan Allo, Sharif Sakr, Miriana Hijaz, Adnan R. Munkarah, Shailendra Giri, Ramandeep Rattan
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    Xiuyuan Zhang
    Highlights in Science, Engineering and Technology.2022; 19: 89.     CrossRef
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Clinical Implications of Circulating Tumor DNA from Ascites and Serial Plasma in Ovarian Cancer
Mi-Ryung Han, Sug Hyung Lee, Jung Yoon Park, Hyosun Hong, Jung Yoon Ho, Soo Young Hur, Youn Jin Choi
Cancer Res Treat. 2020;52(3):779-788.   Published online February 28, 2020
DOI: https://doi.org/10.4143/crt.2019.700
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients.
Materials and Methods
Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients.
Results
Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC.
Conclusion
Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.

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Impact of Angiotensin Receptor Blockers, Beta Blockers, Calcium Channel Blockers and Thiazide Diuretics on Survival of Ovarian Cancer Patients
Min Ae Cho, Soo Young Jeong, Insuk Sohn, Myeong-Seon Kim, Jun Hyeok Kang, E Sun Paik, Yoo-Young Lee, Chel Hun Choi
Cancer Res Treat. 2020;52(2):645-654.   Published online January 16, 2020
DOI: https://doi.org/10.4143/crt.2019.509
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the impact of four types of antihypertensive medications, angiotensin receptor blockers (ARBs), beta blockers (BBs; both selective and non-selective), calcium channel blockers (CCBs), and thiazide diuretics (TDs) on survival outcomes in epithelial ovarian cancer (EOC).
Materials and Methods
A single-institutional retrospective chart review of 878 patients with EOC was performed. Survival was compared according to use of the four antihypertensive medications during primary treatment. Propensity score matching (ratio 1:3) was performed to control possible associated covariates, such as age, International Federation of Gynecology and Obstetrics stage, residual status after primary debulking surgery, and co-morbidity.
Results
Among 878 patients, 56 patients (6.4%) were ARB users, 62 (7.1%) were BB users, 107 (12.2%) were CCBs users and 32 (3.6%) used TDs. Median progression-free survival (PFS) for ARB, BB, and CCB users was 37.8, 27.2, and 23.6 months compared with 33.6 months for non-users. ARB was associated with 35% decreased risk of disease progression (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.42 to 0.99; p=0.046) in multivariate analysis. After propensity score matching, median PFS for ARB users was 37.8 months and ARB use remained to be associated with lower recurrence rate in univariate (p=0.035) and multivariate analysis (HR, 0.60; 95% CI, 0.39 to 0.93; p=0.022).
Conclusion
In this study, ARBs use during primary treatment is associated with lower recurrence in EOC patients. However, CCBs, BBs, and TDs did not show beneficial impact.

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Development of Web-Based Nomograms to Predict Treatment Response and Prognosis of Epithelial Ovarian Cancer
Se Ik Kim, Minsun Song, Suhyun Hwangbo, Sungyoung Lee, Untack Cho, Ju-Hyun Kim, Maria Lee, Hee Seung Kim, Hyun Hoon Chung, Dae-Shik Suh, Taesung Park, Yong-Sang Song
Cancer Res Treat. 2019;51(3):1144-1155.   Published online November 20, 2018
DOI: https://doi.org/10.4143/crt.2018.508
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Discovery of models predicting the exact prognosis of epithelial ovarian cancer (EOC) is necessary as the first step of implementation of individualized treatment. This study aimed to develop nomograms predicting treatment response and prognosis in EOC.
Materials and Methods
We comprehensively reviewed medical records of 866 patients diagnosed with and treated for EOC at two tertiary institutional hospitals between 2007 and 2016. Patients’ clinico-pathologic characteristics, details of primary treatment, intra-operative surgical findings, and survival outcomes were collected. To construct predictive nomograms for platinum sensitivity, 3-year progression-free survival (PFS), and 5-year overall survival (OS), we performed stepwise variable selection by measuring the area under the receiver operating characteristic curve (AUC) with leave-one-out cross-validation. For model validation, 10-fold cross-validation was applied.
Results
The median length of observation was 42.4 months (interquartile range, 25.7 to 69.9 months), during which 441 patients (50.9%) experienced disease recurrence. The median value of PFS was 32.6 months and 3-year PFS rate was 47.8% while 5-year OS rate was 68.4%. The AUCs of the newly developed nomograms predicting platinum sensitivity, 3-year PFS, and 5-year OS were 0.758, 0.841, and 0.805, respectively. We also developed predictive nomograms confined to the patients who underwent primary debulking surgery. The AUCs for platinum sensitivity, 3-year PFS, and 5-year OS were 0.713, 0.839, and 0.803, respectively.
Conclusion
We successfully developed nomograms predicting treatment response and prognosis of patients with EOC. These nomograms are expected to be useful in clinical practice and designing clinical trials.

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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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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    Sandra Muñoz-Galván, Amancio Carnero
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    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
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    Bernd Nürnberg, Sandra Beer-Hammer
    Biomolecules.2019; 9(9): 427.     CrossRef
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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 Res Treat. 2019;51(3):941-950.   Published online October 8, 2018
DOI: https://doi.org/10.4143/crt.2018.312
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We investigated the clinical relevance and spectrum of BRCA1/2 mutations in Korean ovarian cancer (KoOC) patients.
Materials and Methods
Two hundred seventy-nine KoOC patients were enrolled from three university hospitals between 2012 and 2017. Their peripheral blood samples were obtained for BRCA1/2 mutation analysis by direct sequencing. Clinicopathological characteristics were retrospectively reviewed, and spectrum analyses of BRCA1/2 mutation were assessed by systematic literature review.
Results
Frequency of BRCA1/2 mutations was 16.5% in KoOC patients. BRCA1/2 mutations were significantly associated with family history of breast/ovarian cancer (p<0.001), serous histology (p=0.044), and advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III/IV, p=0.018) but not with early age-of-onset (age < 50, p=0.729). Literature review of BRCA1/2 mutations in KoOC patients found 111 (55 distinct) mutations with high proportion of Korean-specific mutations (24/55, 43.6%). Comparing the spectrum of BRCA1/2 mutation between KoOC and Korean breast cancer (KoBC) patients, the ratio of BRCA1-to-BRCA2 mutations was different, with BRCA1 (78.4%) being predominant in KoOC and BRCA2 in KoBC (59.2%). The most common mutation also differed between the two (c.3627insA of BRCA1 in KoOC and c.7480C>T of BRCA2 in KoBC).
Conclusion
The clinical relevance of BRCA1/2 mutations in KoOC patients was confirmed but that of early age-of-onset was not. Possible inconsistency in the ratio of BRCA1-to-BRCA2 mutations and the most common mutation between KoOC and KoBC may probably suggest presence of mutation sequence-associated penetrance tendency in hereditary Korean breast and ovarian cancer. These data may provide insights for optimal genetic counseling and prophylactic treatment for at-risk relatives of KoOC patients.

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  • Exploring the effect of BRCA1/2 status on chemotherapy-induced hematologic toxicity in patients with ovarian cancer
    In Hee Lee, Soo Jung Lee, Juhyung Kim, Yoon Hee Lee, Gun Oh Chong, Jong Mi Kim, Juhun Lee, Nan Young Lee, Seo Young Park, Dea Gy Hong, Yee Soo Chae
    Cancer Chemotherapy and Pharmacology.2024; 94(1): 103.     CrossRef
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    Jae Hee Lee, Do-Hoon Kim
    Keimyung Medical Journal.2024; 43(1): 44.     CrossRef
  • Basic knowledge for counseling patients undergoing risk-reducing salpingo-oophorectomy
    Jihye Kim, Chel Hun Choi
    Obstetrics & Gynecology Science.2024; 67(4): 343.     CrossRef
  • Prevalence of BRCA1 and BRCA2 mutations in ovarian cancer patients from Yunnan Province in southwest China
    Yongmei Peng, Jiaqian Liao, Xian He, Yongchun Zhou, Lei Zhang, Yue Jia, Hongying Yang
    European Journal of Cancer Prevention.2024;[Epub]     CrossRef
  • Validation of multi-gene panel next-generation sequencing for the detection of BRCA mutation in formalin-fixed, paraffin-embedded epithelial ovarian cancer tissues
    Eun Taeg Kim, Ha Eun Jeong, Hyung Joon Yoon, Ki Hyung Kim, Dong Soo Suh
    Taiwanese Journal of Obstetrics and Gynecology.2023; 62(1): 66.     CrossRef
  • Using species richness calculations to model the global profile of unsampled pathogenic variants: Examples from BRCA1 and BRCA2
    Nandana D. Rao, Brian H. Shirts, Alvaro Galli
    PLOS ONE.2023; 18(2): e0278010.     CrossRef
  • Mutational Analysis of BRCA1 and BRCA2 Genes in Breast Cancer Patients from Eastern Sicily
    Stefania Stella, Silvia Rita Vitale, Federica Martorana, Michele Massimino, Giuliana Pavone, Katia Lanzafame, Sebastiano Bianca, Chiara Barone, Cristina Gorgone, Marco Fichera, Livia Manzella
    Cancer Management and Research.2022; Volume 14: 1341.     CrossRef
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    Sook-Hee Hong
    Journal of Gynecologic Oncology.2021;[Epub]     CrossRef
  • Identification of BRCA1:c.5470_5477del as a Founder Mutation in Chinese Ovarian Cancer Patients
    Jun Li, Sile Han, Cuiyun Zhang, Yanlin Luo, Li Wang, Ping Wang, Yi Wang, Qingxin Xia, Xiaoyan Wang, Bing Wei, Jie Ma, Hongle Li, Yongjun Guo
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Prevalence and clinical characterization of BRCA1 and BRCA2 mutations in Korean patients with epithelial ovarian cancer
    E Sun Paik, Eun Jin Heo, Chel Hun Choi, Jae‐Hoon Kim, Jae‐Weon Kim, Yong‐Man Kim, Sang‐Yoon Park, Jeong‐Won Lee, Jong‐Won Kim, Byoung‐Gie Kim
    Cancer Science.2021; 112(12): 5055.     CrossRef
  • Impact of proactive high-throughput functional assay data on BRCA1 variant interpretation in 3684 patients with breast or ovarian cancer
    Hyun-Ki Kim, Eun Jin Lee, Young-Jae Lee, Jisun Kim, Yongsub Kim, Kyunggon Kim, Shin-Wha Lee, Suhwan Chang, Young Joo Lee, Jong Won Lee, Woochang Lee, Sail Chun, Byung Ho Son, Kyung Hae Jung, Yong-Man Kim, Won-Ki Min, Sei-Hyun Ahn
    Journal of Human Genetics.2020; 65(3): 209.     CrossRef
  • Clinical and histopathologic analysis of gynecological cancer: a single institute experience over 7 years
    Soo-Young Lee, Eunbyeol Kim, Hyo-Shin Kim, Yu-Jin Koo, Dae-Hyung Lee
    Yeungnam University Journal of Medicine.2020; 37(3): 179.     CrossRef
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Different Patterns of Risk Reducing Decisions in Affected or Unaffected BRCA Pathogenic Variant Carriers
Eun-Gyeong Lee, Hyok Jo Kang, Myong Cheol Lim, Boyoung Park, Soo Jin Park, So-Youn Jung, Seeyoun Lee, Han-Sung Kang, Sang-Yoon Park, Boram Park, Jungnam Joo, Jai Hong Han, Sun-Young Kong, Eun Sook Lee
Cancer Res Treat. 2019;51(1):280-288.   Published online May 4, 2018
DOI: https://doi.org/10.4143/crt.2018.079
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers.
Materials and Methods
The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management.
Results
Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001).
Conclusion
RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.

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    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
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    Dabin Kim, Jai Min Ryu, Sang-Ah Han, Zisun Kim, Sung-Won Kim
    Current Oncology.2024; 31(11): 6767.     CrossRef
  • Impact of graphical display on the intention to undergo risk-reducing salpingo-oophorectomy and mastectomy in individuals positive for BRCA pathogenic variant
    Yoon-Jung Choi, Younju Park, Boyoung Park, Heejung Chae, So-Youn Jung, Kum Hei Ryu, Myong Cheol Lim, Soo Jin Park, Yoon Jung Chang, Sun-Young Kong
    Scientific Reports.2024;[Epub]     CrossRef
  • Impact of the coverage of risk-reducing salpingo-oophorectomy by the national insurance system for women with BRCA pathogenic variants in Japan
    Hidetaka Nomura, Akiko Abe, Atsushi Fusegi, Teruyuki Yoshimitsu, Satoki Misaka, Atsushi Murakami, Tsuyoshi Matsumoto, Shiho Tsumura, Motoko Kanno, Yoichi Aoki, Sachiho Netsu, Makiko Omi, Terumi Tanigawa, Sanshiro Okamoto, Kohei Omatsu, Mayu Yunokawa, Hiro
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    Eun-Gyeong Lee, Jiwon Lim, Hyeong In Ha, Myong Cheol Lim, Yoon Jung Chang, Young-Joo Won, So-Youn Jung
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • Differences in Willingness to Undergo BRCA1/2 Testing and Risk Reducing Surgery among the General Public, Cancer Patients, and Healthcare Professionals: A Large Population-Based Survey
    Yoon Jung Chang, Seungyeon Cho, Jungnam Joo, Kum Hei Ryu, Sangwon Lee, Juhee Cho, Myong Cheol Lim, So-Youn Jung, Jai Hong Han, Eun Sook Lee, Sun-Young Kong
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  • Management of patients with BRCA mutation from the point of view of a breast surgeon
    M.L. Riis
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  • Disparities between Uptake of Germline BRCA1/2 Gene Tests and Implementation of Post-test Management Strategies in Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients
    Young Min Hur, Jaehee Mun, Mi-Kyung Kim, Maria Lee, Yun Hwan Kim, Seung-Cheol Kim
    Journal of Korean Medical Science.2021;[Epub]     CrossRef
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    Russian Clinical Laboratory Diagnostics.2021; 66(12): 760.     CrossRef
  • Trends in Risk-Reducing Mastectomy and Risk-Reducing Salpingo-Oophorectomy in Korean Carriers of the BRCA1/2 Mutation
    Sung Mi Jung, Jai Min Ryu, Hyung Seok Park, Ji Soo Park, Eunyoung Kang, Seeyoun Lee, Han-Byoel Lee, Hyun Jo Youn, Tae-Kyung Yoo, Jisun Kim, Jeong Eon Lee, Sang Ah Han, Dongwon Kim, Sung-Won Kim
    Journal of Breast Cancer.2020; 23(6): 647.     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
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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    Isaac T Lynch, Amro M Abdelrahman, Roberto Alva-Ruiz, Alessandro Fogliati, Rondell P Graham, Rory Smoot, Mark J Truty
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Profiling of Serum Metabolites Using MALDI-TOF and Triple-TOF Mass Spectrometry to Develop a Screen for Ovarian Cancer
Jun Hwa Lee, Yun Hwan Kim, Kyung-Hee Kim, Jae Youl Cho, Sang Myung Woo, Byong Chul Yoo, Seung Cheol Kim
Cancer Res Treat. 2018;50(3):883-893.   Published online September 18, 2017
DOI: https://doi.org/10.4143/crt.2017.275
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We sought to develop a matrix assisted laser desorption ionization-time of flight (MALDI-TOF)-based, ovarian cancer (OVC), low-mass-ion discriminant equation (LOME) and to evaluate a possible supportive role for triple-TOF mass analysis in identifying metabolic biomarkers.
Materials and Methods
A total of 114 serum samples from patients with OVC and benign ovarian tumors were subjected to MALDI-TOF analysis and a total of 137 serum samples from healthy female individuals and patients with OVC, colorectal cancer, hepatobiliary cancer, and pancreatic cancer were subjected to triple-TOF analysis. An OVC LOME was constructed by reference to the peak intensity ratios of discriminatory low-mass ion (LMI) pairs. Triple-TOF analysiswas used to select and identify metabolic biomarkers for OVC screening.
Results
Three OVC LOMEs were finally constructed using discriminatory LMI pairs (137.1690 and 84.4119 m/z; 496.5022 and 709.7642 m/z; and 524.5614 and 709.7642 m/z); all afforded accuracies of > 90%. The LMIs at 496.5022 m/z and 524.5614 m/z were those of lysophosphatidylcholine (LPC) 16:0 and LPC 18:0. Triple-TOF analysis selected seven discriminative LMIs; each LMI had a specificity > 90%. Of the seven LMIs, fourwith a 137.0455 m/z ion atretention times of 2.04-3.14 minuteswere upregulated in sera from OVC patients; the ion was identified as that derived from hypoxanthine.
Conclusion
MALDI-TOF–based OVC LOMEs combined with triple-TOF–based OVC metabolic biomarkers allow reliable OVC screening; the techniques are mutually complementary both quantitatively and qualitatively.

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    Andrea Jiménez-Franco, Juan Manuel Jiménez-Aguilar, Marta Canela-Capdevila, Raquel García-Pablo, Helena Castañé, Cristian Martínez-Navidad, Pablo Araguas, Bárbara Malavé, Rocío Benavides-Villarreal, Johana C. Acosta, Alina Iuliana Onoiu, Navita Somaiah, J
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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
AbstractAbstract PDFPubReaderePub
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
AbstractAbstract PDFPubReaderePub
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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Nomograms Predicting Platinum Sensitivity, Progression-Free Survival, and Overall Survival Using Pretreatment Complete Blood Cell Counts in Epithelial Ovarian Cancer
E Sun Paik, Insuk Sohn, Sun-Young Baek, Minhee Shim, Hyun Jin Choi, Tae-Joong Kim, Chel Hun Choi, Jeong-Won Lee, Byoung-Gie Kim, Yoo-Young Lee, Duk-Soo Bae
Cancer Res Treat. 2017;49(3):635-642.   Published online September 27, 2016
DOI: https://doi.org/10.4143/crt.2016.282
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study was conducted to evaluate the prognostic significance of pre-treatment complete blood cell count (CBC), including white blood cell (WBC) differential, in epithelial ovarian cancer (EOC) patients with primary debulking surgery (PDS) and to develop nomograms for platinum sensitivity, progression-free survival (PFS), and overall survival (OS).
Materials and Methods
We retrospectively reviewed the records of 757 patients with EOC whose primary treatment consisted of surgical debulking and chemotherapy at Samsung Medical Center from 2002 to 2012. We subsequently created nomograms for platinum sensitivity, 3-year PFS, and 5-year OS as prediction models for prognostic variables including age, stage, grade, cancer antigen 125 level, residual disease after PDS, and pre-treatment WBC differential counts. The models were then validated by 10-fold cross-validation (CV).
Results
In addition to stage and residual disease after PDS, which are known predictors, lymphocyte and monocyte count were found to be significant prognostic factors for platinum-sensitivity, platelet count for PFS, and neutrophil count for OS on multivariate analysis. The area under the curves of platinum sensitivity, 3-year PFS, and 5-year OS calculated by the 10-fold CV procedure were 0.7405, 0.8159, and 0.815, respectively.
Conclusion
Prognostic factors including pre-treatment CBC were used to develop nomograms for platinum sensitivity, 3-year PFS, and 5-year OS of patients with EOC. These nomograms can be used to better estimate individual outcomes.

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    Jonas Ulevicius, Aldona Jasukaitiene, Arenida Bartkeviciene, Zilvinas Dambrauskas, Antanas Gulbinas, Daiva Urboniene, Saulius Paskauskas
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Adipose Stromal Cells from Visceral and Subcutaneous Fat Facilitate Migration of Ovarian Cancer Cells via IL-6/JAK2/STAT3 Pathway
Boyun Kim, Hee Seung Kim, Soochi Kim, Guy Haegeman, Benjamin K. Tsang, Danny N. Dhanasekaran, Yong Sang Song
Cancer Res Treat. 2017;49(2):338-349.   Published online July 18, 2016
DOI: https://doi.org/10.4143/crt.2016.175
AbstractAbstract PDFPubReaderePub
Purpose
Adipose stromal cells (ASCs) play an important regulatory role in cancer progression and metastasis by regulating systemic inflammation and tissue metabolism. This study examined whether visceral and subcutaneous ASCs (V- and S-ASCs) facilitate the growth and migration of ovarian cancer cells.
Materials and Methods
CD45– and CD31– double-negative ASCs were isolated from the subcutaneous and visceral fat using magnetic-activated cell sorting. Ovarian cancer cells were cultured in conditioned media (CM) obtained from ASCs to determine the cancer-promoting effects of ASCs. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, Boyden chamber assay, and western blotting were performed to determine the proliferative activity, migration ability, and activation of the JAK2/STAT3 pathway, respectively.
Results
CM from ASCs enhanced the migration of the ovarian cancer line, SKOV3, via activation of the JAK2/STAT3 signaling pathway. Interestingly, in response to ASC-CM, the ascites cells derived from an ovarian cancer patient showed an increase in growth and migration. The migration of ovarian cancer cells was suppressed by blocking the activation of JAK2 and STAT3 using a neutralizing antibody against interleukin 6, small molecular inhibitors (e.g., WP1066 and TG101348), and silencing of STAT3 using siRNA. Anatomical differences between S- and V-ASCs did not affect the growth and migration of the ovarian cancer cell line and ascites cells from the ovarian cancer patients.
Conclusion
ASCs may regulate the progression of ovarian cancer, and possibly provide a potential target for anticancer therapy.

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Systemic Inflammatory Response Markers and CA-125 Levels in Ovarian Clear Cell Carcinoma: A Two Center Cohort Study
Hee Seung Kim, Hwa-Young Choi, Maria Lee, Dong Hoon Suh, Kidong Kim, Jae Hong No, Hyun Hoon Chung, Yong Beom Kim, Yong Sang Song
Cancer Res Treat. 2016;48(1):250-258.   Published online March 6, 2015
DOI: https://doi.org/10.4143/crt.2014.324
AbstractAbstract PDFPubReaderePub
Purpose
We compared the predictive and prognostic values of leukocyte differential counts, systemic inflammatory (SIR) markers and cancer antigen 125 (CA-125) levels, and identified the most useful marker in patients with ovarian clear cell carcinoma (OCCC).
Materials and Methods
The study included 109 patients with OCCC who did not have any inflammatory conditions except endometriosis, and underwent primary debulking surgery between 1997 and 2012. Leukocyte differential counts (neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet), SIR markers including neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR), and CA-125 levels were estimated to select potential markers for clinical outcomes.
Results
Among potential markers (neutrophil, monocyte, platelet, NLR, MLR, PLR, and CA-125 levels) selected by stepwise comparison, CA-125 levels were best at predicting advanced stage disease, suboptimal debulking and platinum-resistance (cut-off values, ≥ 46.5, ≥ 11.45, and ≥ 66.4 U/mL; accuracies, 69.4%, 78.7%, and 68.5%) while PLR ≥ 205.4 predicted noncomplete response (CR; accuracy, 71.6%) most accurately. Moreover, PLR < 205.4 was an independent factor for the reduced risk of non-CR (adjusted odds ratio, 0.17; 95% confidence interval [CI], 0.04 to 0.69), and NLR < 2.8 was a favorable factor for improved progression-free survival (PFS; adjusted hazard ratio, 0.49; 95% CI, 0.25 to 0.99) despite lack of a marker for overall survival among the potential markers.
Conclusion
CA-125 levels may be the most useful marker for predicting advanced-stage disease. Suboptimal debulking and platinum-resistance, and PLR and NLR may be most effective to predict non-CR and PFS in patients with OCCC.

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

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Original Article
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
AbstractAbstract PDFPubReaderePub
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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Case Report
Sarcoidosis Mimicking Cancer Metastasis Following Chemotherapy for Ovarian Cancer
Mi Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Dong Soo Suh
Cancer Res Treat. 2013;45(4):354-358.   Published online December 31, 2013
DOI: https://doi.org/10.4143/crt.2013.45.4.354
AbstractAbstract PDFPubReaderePub
We report on a rare case of sarcoidosis that developed after chemotherapy for ovarian cancer, and mimicked a cancer metastasis. A 52-year-old female diagnosed with stage III ovarian cancer underwent curative surgery and postoperative chemotherapy. Four months later, her whole-body positron emission tomography and computed tomography (CT) scan showed high uptake in the mediastinal lymph nodes, and ovarian cancer recurrence was suspected. Biopsy of the mediastinal lymph nodes and subcutaneous nodules revealed noncaseating granulomas. These lesions resolved spontaneously without treatment; however, newly developed perilymphatic and centrilobular nodules were observed on follow-up chest CT. Surgical biopsy of these lesions also showed noncaseating granulomas. She was finally diagnosed with sarcoidosis.

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Original Article
Feasibility of Oxaliplatin, Leucovorin, and 5-Fluorouracil (FOLFOX-4) Chemotherapy in Heavily Pretreated Patients with Recurrent Epithelial Ovarian Cancer
Hee Jun Lee, Hee Seung Kim, Noh Hyun Park, Hyun Hoon Chung, Jae Weon Kim, Yong Sang Song
Cancer Res Treat. 2013;45(1):40-47.   Published online March 31, 2013
DOI: https://doi.org/10.4143/crt.2013.45.1.40
AbstractAbstract PDFPubReaderePub
PURPOSE
The purpose of this study is to evaluate the efficacy and toxicity of oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX-4) chemotherapy in heavily pretreated patients with recurrent epithelial ovarian cancer (EOC).
MATERIALS AND METHODS
Clinical data were reviewed in 28 patients who received FOLFOX-4 as more than the second-line chemotherapy, consisting of 85 mg/m2 of oxaliplatin as a 2-hour infusion, 200 mg/m2 of leucovorin as a 2-hour infusion, and bolus 400 mg/m2 on day 1, followed by a 22-hour infusion of 600 mg/m2 of 5-fluorouracil for two consecutive days every three weeks. In addition, its efficacy and toxicity were compared with those reported in in three previous relevant studies.
RESULTS
A total of 128 cycles of FOLFOX-4 were administered with the median number of five cycles (range, 1 to 10 cycles). In nine patients with measurable disease, complete response (CR) and partial response (PR) were observed in 0 (0%) and two (22.2%) patients, whereas in 19 patients with non-measurable disease, CR and PR were observed in 0 (0%) and five (26.3%) patients. Among all patients, grade 3 anemia, neutropenia, and thrombocytopenia were observed in two (7.1%), three (10.7%), and one (3.6%) patient, and grade 3 fatigue, nausea and vomiting, and peripheral neuropathy were observed in one (3.6%), two (7.1%), and three (10.7%) patients. In addition, median values of time to progressive disease and chemotherapy-specific survival were three months (range, 0 to 10 months) and nine months (range, 4 to 24 months).
CONCLUSION
FOLFOX-4 is feasible as salvage chemotherapy with acceptable toxicity for heavily pretreated patients with recurrent EOC.

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Case Reports
Metastatic Skin Lesions on Lower Extremities in a Patient with Recurrent Serous Papillary Ovarian Carcinoma: A Case Report and Literature Review
Moon-Kyung Kim, Seo-Hee Kim, Yoo-Young Lee, Chel Hun Choi, Tae-Joong Kim, Jeoung-Won Lee, Je-Ho Lee, Duk-Soo Bae, Byoung-Gie Kim
Cancer Res Treat. 2012;44(2):142-145.   Published online June 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.2.142
AbstractAbstract PDFPubReaderePub
Clinical observation of skin metastasis in ovarian cancer cases is relatively uncommon. And distant metastatic skin lesions including the extremities are much rarer still as most metastatic skin lesions are located in the skin in the abdominal wall adjacent to where the primary ovarian tumors exist. We report the case of a 60-year-old woman who presented skin lesions on both lower extremities as a consequence of the metastasis of serous papillary adenocarcinoma of the ovary. She presented with erythematous and painful cutaneous nodules on both upper legs and in the inguinal area 42 months after initial diagnosis of ovarian cancer. Skin biopsy revealed metastasis of adenocarcinoma in the dermis. She was treated with surgical excision and systemic chemotherapy. Literature review has suggested that a combined modality approach including surgical excision and chemotherapy may be useful in the management of skin metastases due to ovarian cancer.

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  • Metastasis of ovarian cancer to nasal skin and skin on the trunk: a rare case report
    Chen Chen, Ouyang Yingyao, Xiang Yan, He Qianru, Wang Hong, Chen Chen, Yang Lei
    Frontiers in Oncology.2023;[Epub]     CrossRef
  • A Rare and Sinister Presentation of Cutaneous Metastasis over Right Lower Limb in a Case of Ovarian Carcinoma
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    Hyeong Mok Kwon, Gyu Yeong Kim, Dong Hoon Shin, Young Kyung Bae
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    Victoria Hastings, Jennifer McEachron, Marguax J. Kanis
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    Isao Otsuka
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    Gina Nam, Young-mee Lim, Min Sun Cho, Junghye Lee, Yun Hwan Kim
    Obstetrics & Gynecology Science.2017; 60(6): 593.     CrossRef
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    Hongyan Cheng, Chunmei Gao, Runtong Zhang, Zhaojie Yang, Guiyu Zhang
    Medicine.2017; 96(49): e9118.     CrossRef
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    Heidi H. McDonald, Milton R. Moore, Jeffrey J. Meffert
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    Ana Marta António, João Vitor Alves, João Goulão, Elvira Bártolo
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Diagnostic Laparoscopy of Patient with Deep Vein Thrombosis before Diagnosis of Ovarian Cancer : A Case Report
Jae Eun Ha, Yong Seok Lee, Hae Nam Lee, Eun Kyung Park
Cancer Res Treat. 2010;42(1):48-52.   Published online March 31, 2010
DOI: https://doi.org/10.4143/crt.2010.42.1.48
AbstractAbstract PDFPubReaderePub

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Epidemiological studies have demonstrated an increased risk of subsequent cancer in the patients who are diagnosed with idiopathic venous thrombosis. Cancers of the breast, lung and ovary in women and adenocarcinomas of an unknown primary cancer are most strongly associated with thrombosis. Mucin-producing cancers are most often associated with VTE and the highest rates of VTE were found for cases of ovarian cancer, but the absolute risk of cancer after thrombosis is relatively low (about 2% over the first year) and so the benefit of screening for cancer in thrombosis patients seems limited. But as this case, the association between thrombosis and occult cancer shows the importance of this association for patients who have thrombosis that is unresponsive to anticoagulant therapy. Especially, we should recognize that such patients can undergo investigation for an underlying malignancy. Diagnostic laparoscopy of an adnexal mass for confirming cancer in the acute setting of deep vein thrombosis (DVT) was performed for our patient. We report here on a case of a patient with DVT in the upper and lower extremities before the diagnosis of ovarian cancer, and we briefly review of the relevant literature.

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    Computational and Mathematical Methods in Medicine.2022; 2022: 1.     CrossRef
  • Increase in Carbohydrate Antigen 19-9 Levels without Tumor Progression after Polaprezinc Administration that Induced Deep Vein Thrombosis in a Colon Cancer Patient
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    HONGWEI SHEN, JIANHONG SHANG, GANG NIU, JUN LIU, ZESHAN YOU, SHANYANG HE
    Oncology Letters.2015; 10(4): 2579.     CrossRef
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