Cancer Research and Treatment

Seock-Ah Im

45 Articles

Breast cancer

Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Cancer Res Treat. 2025;57(2):443-456. Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296

Abstract PDF Supplementary Material PubReader ePub: Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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General

The Survival and Financial Benefit of Investigator-Initiated Trials Conducted by Korean Cancer Study Group: Bum Jun Kim, Chi Hoon Maeng, Bhumsuk Keam, Young-Hyuck Im, Jungsil Ro, Kyung Hae Jung, Seock-Ah Im, Tae Won Kim, Jae Lyun Lee, Dae Seog Heo, Sang-We Kim, Keunchil Park, Myung-Ju Ahn, Byoung Chul Cho, Hoon-Kyo Kim, Yoon-Koo Kang, Jae Yong Cho, Hwan Jung Yun, Byung-Ho Nam, Dae Young Zang; Cancer Res Treat. 2025;57(1):39-46. Published online July 10, 2024; DOI: https://doi.org/10.4143/crt.2024.421

Abstract PDF PubReader ePub: Purpose
The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients.
Materials and Methods
We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided.
Results
From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient.
Conclusion
Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

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Recent Developments in the Therapeutic Landscape of Advanced or Metastatic Hormone Receptor–Positive Breast Cancer: Eunice Yoojin Lee, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im; Cancer Res Treat. 2023;55(4):1065-1076. Published online October 5, 2023; DOI: https://doi.org/10.4143/crt.2023.846

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Hormone receptor–positive (HR+) disease is the most frequently diagnosed subtype of breast cancer. Among tumor subtypes, natural course of HR+ breast cancer is indolent with favorable prognosis compared to other subtypes such as human epidermal growth factor protein 2–positive disease and triple-negative disease. HR+ tumors are dependent on steroid hormone signaling and endocrine therapy is the main treatment option. Recently, the discovery of cyclin-dependent kinase 4/6 inhibitors and their synergistic effects with endocrine therapy has dramatically improved treatment outcome of advanced HR+ breast cancer. The demonstrated efficacy of additional nonhormonal agents, such as targeted therapy against mammalian target of rapamycin and phosphatidylinositol 3-kinase signaling, poly(ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapeutic agents have further expanded the available therapeutic options. This article reviews the latest advancements in the treatment of HR+ breast cancer, and in doing so discusses not only the development of currently available treatment regimens but also emerging therapies that invite future research opportunities in the field.

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Breast Cancer and Tumor Microenvironment: The Crucial Role of Immune Cells
Tânia Moura, Paula Laranjeira, Olga Caramelo, Ana M. Gil, Artur Paiva
Current Oncology.2025; 32(3): 143. CrossRef
Metastasiertes hormonrezeptorpositives Mammakarzinom – die Qual der Wahl
Marion T. van Mackelenbergh, Michael Friedrich, Nicolai Maass
Die Gynäkologie.2025; 58(5): 306. CrossRef
Therapies for the Treatment of Advanced/Metastatic Estrogen Receptor-Positive Breast Cancer: Current Situation and Future Directions
Rohan Kalyan Rej, Joyeeta Roy, Srinivasa Rao Allu
Cancers.2024; 16(3): 552. CrossRef

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Breast cancer

Eflapegrastim versus Pegfilgrastim for Chemotherapy-Induced Neutropenia in Korean and Asian Patients with Early Breast Cancer: Results from the Two Phase III ADVANCE and RECOVER Studies: Yong Wha Moon, Seung Ki Kim, Keun Seok Lee, Moon Hee Lee, Yeon Hee Park, Kyong Hwa Park, Gun Min Kim, Seungtaek Lim, Seung Ah Lee, Jae Duk Choi, Eunhye Baek, Hyesun Han, Seungjae Baek, Seock-Ah Im; Cancer Res Treat. 2023;55(3):766-777. Published online January 19, 2023; DOI: https://doi.org/10.4143/crt.2022.987

Abstract PDF Supplementary Material PubReader ePub

Purpose
We investigated the consistent efficacy and safety of eflapegrastim, a novel long-acting granulocyte-colony stimulating factor (G-CSF), in Koreans and Asians compared with the pooled population of two global phase 3 trials.
Materials and Methods
Two phase 3 trials (ADVANCE and RECOVER) evaluated the efficacy and safety of fixed-dose eflapegrastim (13.2 mg/0.6 mL [3.6 mg G-CSF equivalent]) compared to pegfilgrastim (6 mg based on G-CSF) in breast cancer patients who received neoadjuvant or adjuvant docetaxel/cyclophosphamide. The primary objective was to demonstrate non-inferiority of eflapegrastim compared to pegfilgrastim in mean duration of severe neutropenia (DSN) in cycle 1, in Korean and Asian subpopulations.
Results
Among a total of 643 patients randomized to eflapegrastim (n=314) or pegfilgrastim (n=329), 54 Asians (29 to eflapegrastim and 25 to pegfilgrastim) including 28 Koreans (14 to both eflapegrastim and pegfilgrastim) were enrolled. The primary endpoint, DSN in cycle 1 in the eflapegrastim arm was non-inferior to the pegfilgrastim arm in Koreans and Asians. The DSN difference between the eflapegrastim and pegfilgrastim arms was consistent across populations: –0.120 days (95% confidence interval [CI], –0.227 to –0.016), –0.288 (95% CI, –0.714 to 0.143), and –0.267 (95% CI, –0.697 to 0.110) for pooled population, Koreans and Asians, respectively. There were few treatment-related adverse events that caused discontinuation of eflapegrastim (1.9%) or pegfilgrastim (1.5%) in total and no notable trends or differences across patient populations.
Conclusion
This study may suggest that eflapegrastim showed non-inferior efficacy and similar safety compared to pegfilgrastim in Koreans and Asians, consistently with those of pooled population.

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Comparison of Prophylactic Efficacy of Eflapegrastim and Pegteograstim for Chemotherapy-induced Neutropenia in Pancreatic Cancer Patients Receiving FOLFIRINOX/mFOLFIRINOX
Eui Seon Lee, Min Jung Geum, Jong Hee Ko, Jae Song Kim, Eun Sun Son, Yun Mi Yu
Journal of Korean Society of Health-System Pharmacists.2024; 41(3): 253. CrossRef

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A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03): Dae-Won Lee, Bhumsuk Keam, Keun Seok Lee, Jin-Hee Ahn, Joohyuk Sohn, Jin Seok Ahn, Moon Hee Lee, Jee Hyun Kim, Kyung Eun Lee, Hyo Jung Kim, Si-Young Kim, Yeon Hee Park, Chan-Young Ock, Kyung-Hun Lee, Sae-Won Han, Sung-Bae Kim, Young Hyuck Im, Hyun Cheol Chung, Do-Youn Oh, Seock-Ah Im; Cancer Res Treat. 2023;55(2):523-530. Published online November 8, 2022; DOI: https://doi.org/10.4143/crt.2022.1360

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Purpose
This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer.
Materials and Methods
Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events.
Results
A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%).
Conclusion
This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

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Unraveling the immune landscape and therapeutic biomarker PMEPA1 for oxaliplatin resistance in colorectal cancer: A comprehensive approach
Zhengguang Zhang, Tianming Lu, Zhe Zhang, Zixian Liu, Ruoning Qian, Ruogu Qi, Fuqiong Zhou, Min Li
Biochemical Pharmacology.2024; 222: 116117. CrossRef
Efficacy and safety of utidelone plus capecitabine in advanced first-line therapy for metastatic breast cancer: A multicenter real-world study
Pingping Bi, Xi Wang, Rui Liu, Xiuqin Li, Shanrong Wei, Jiawen Zhao, Xin Tan, Fan Zhang, Qing Mao, Ying Zhang, Baoyan Tang, Xueqiong Xun, Rong Guo, Kai Zheng, Shaoqiang Zhou, Shicong Tang
Surgery Open Science.2023; 16: 171. CrossRef

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The Pattern of Care for Brain Metastasis from Breast Cancer over the Past 10 Years in Korea: A Multicenter Retrospective Study (KROG 16-12): Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Hee-Jun Kim, Yong Bae Kim, Jee Suk Chang, Jee Hyun Kim, Doo Ho Choi, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Byung Ock Choi, Sea-Won Lee, Suzy Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki Chung, Kyung Su Kim, Ji Ho Nam, Won Sup Yoon, Jin Hee Kim, Jihye Cha, Yoon Kyeong Oh, In Ah Kim; Cancer Res Treat. 2022;54(4):1121-1129. Published online December 31, 2021; DOI: https://doi.org/10.4143/crt.2021.1083

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea.
Materials and Methods
We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients).
Results
Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance.
Conclusion
The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

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Comparison of initial and sequential salvage brain-directed treatment in patients with 1–4 vs. 5–10 brain metastases from breast cancer (KROG 16–12)
Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Hee-Jun Kim, Yong Bae Kim, Jee Suk Chang, Jee Hyun Kim, Doo Ho Choi, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Byung Ock Choi, Sea-Won Lee, Suzy Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki C
Breast Cancer Research and Treatment.2023; 200(1): 37. CrossRef

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A Real-world Efficacy of Nab-paclitaxel Monotherapy in Metastatic Breast Cancer: Jung Sun Kim, Koung Jin Suh, Dae-Won Lee, Go-un Woo, Miso Kim, Se Hyun Kim, Han Suk Ryu, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, So Yeon Park, In Ae Park, Jee Hyun Kim, Seock-Ah Im; Cancer Res Treat. 2022;54(2):488-496. Published online August 13, 2021; DOI: https://doi.org/10.4143/crt.2021.394

Abstract PDF PubReader ePub

Purpose
We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients.
Materials and Methods
This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled.
Results
A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m² on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m² every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction.
Conclusion
This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

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Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE)
P. Meyer-Wilmes, J. Huober, M. Untch, J.-U. Blohmer, W. Janni, C. Denkert, P. Klare, T. Link, K. Rhiem, C. Bayer, M. Reinisch, V. Bjelic-Radisic, D.M. Zahm, C. Hanusch, C. Solbach, G. Heinrich, A.D. Hartkopf, A. Schneeweiss, P. Fasching, N. Filmann, V. Ne
ESMO Open.2024; 9(5): 103009. CrossRef
Real-world study on the effect of nab-paclitaxel treatment on clinical outcomes and laboratory parameters in patients across metastatic tumor sites
Vikas Talreja, Sangeeta Khetwani, Ethirajan Nanadagopal, Nilesh Eknath Borkar, Kunal Khobragade
International Journal of Molecular and Immuno Oncology.2024; 9: 46. CrossRef
Safety and efficacy of generic nab-paclitaxel-based therapy in Chinese patients with malignant tumors in a real-world setting: a multicenter prospective observational study
Fei He, Yancai Sun, Wenzhou Zhang, Qiongshi Wu, Donghang Xu, Zaixian Bai, Zhiying Hao, Weiyi Feng, Kanghuai Zhang, Jiang Liu, Mei Dong, Guangxuan Liu, Guohui Li
Discover Oncology.2024;[Epub] CrossRef
Nanoparticle albumin-bound paclitaxel and PD-1 inhibitor (sintilimab) combination therapy for soft tissue sarcoma: a retrospective study
Zhichao Tian, Shuping Dong, Yang Yang, Shilei Gao, Yonghao Yang, Jinpo Yang, Peng Zhang, Xin Wang, Weitao Yao
BMC Cancer.2022;[Epub] CrossRef
Paclitaxel

Reactions Weekly.2022; 1926(1): 383. CrossRef
Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity
Ľuboš Nižnanský, Denisa Osinová, Roman Kuruc, Alexandra Hengerics Szabó, Andrea Szórádová, Marián Masár, Žofia Nižnanská
International Journal of Molecular Sciences.2022; 23(24): 15619. CrossRef
A Novel Microcrystalline BAY-876 Formulation Achieves Long-Acting Antitumor Activity Against Aerobic Glycolysis and Proliferation of Hepatocellular Carcinoma
Hua Yang, Mu-Zi-he Zhang, Hui-wei Sun, Yan-tao Chai, Xiaojuan Li, Qiyu Jiang, Jun Hou
Frontiers in Oncology.2021;[Epub] CrossRef

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General

Radiation Response Prediction Model Based on Integrated Clinical and Genomic Data Analysis: Bum-Sup Jang, Ji-Hyun Chang, Seung Hyuck Jeon, Myung Geun Song, Kyung-Hun Lee, Seock-Ah Im, Jong-Il Kim, Tae-You Kim, Eui Kyu Chie; Cancer Res Treat. 2022;54(2):383-395. Published online August 24, 2021; DOI: https://doi.org/10.4143/crt.2021.759

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Purpose
The value of the genomic profiling by targeted gene-sequencing on radiation therapy response prediction was evaluated through integrated analysis including clinical information. Radiation response prediction model was constructed based on the analyzed findings.
Materials and Methods
Patients who had the tumor sequenced using institutional cancer panel after informed consent and received radiotherapy for the measurable disease served as the target cohort. Patients with irradiated tumor locally controlled for more than 6 months after radiotherapy were defined as the durable local control (DLC) group, otherwise, non-durable local control (NDLC) group. Significant genomic factors and domain knowledge were used to develop the Bayesian Network model to predict radiotherapy response.
Results
Altogether, 88 patients were collected for analysis. Of those, 41 (43.6%) and 47 (54.4%) patients were classified as the NDLC and DLC group, respectively. Somatic mutations of NOTCH2 and BCL were enriched in the NDLC group, whereas, mutations of CHEK2, MSH2, and NOTCH1 were more frequently found in the DLC group. Altered DNA repair pathway was associated with better local failure–free survival (hazard ratio, 0.40; 95% confidence interval, 0.19 to 0.86; p=0.014). Smoking somatic signature was found more frequently in the DLC group. Area under the receiver operating characteristic curve of the Bayesian network model predicting probability of 6-month local control was 0.83.
Conclusion
Durable radiation response was associated with alterations of DNA repair pathway and smoking somatic signature. Bayesian network model could provide helpful insights for high precision radiotherapy. However, these findings should be verified in prospective cohort for further individualization.

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Estimating the risk and benefit of radiation therapy in (y)pN1 stage breast cancer patients: A Bayesian network model incorporating expert knowledge (KROG 22–13)
Bum-Sup Jang, Seok-Joo Chun, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
Computer Methods and Programs in Biomedicine.2024; 245: 108049. CrossRef
Prediction of Overall Disease Burden in (y)pN1 Breast Cancer Using Knowledge-Based Machine Learning Model
Seok-Joo Chun, Bum-Sup Jang, Hyeon Seok Choi, Ji Hyun Chang, Kyung Hwan Shin
Cancers.2024; 16(8): 1494. CrossRef
Selection of patients with pancreatic adenocarcinoma who may benefit from radiotherapy
I-Shiow Jan, Hui Ju Ch’ang
Radiation Oncology.2023;[Epub] CrossRef
Characterization of the gene signature correlated with favorable response to chemoradiotherapy in rectal cancer: A hypothesis‐generating study
Seung Hyuck Jeon, Eui Kyu Chie
Cancer Medicine.2023; 12(7): 8981. CrossRef
Krüppel-like Factor 10 as a Prognostic and Predictive Biomarker of Radiotherapy in Pancreatic Adenocarcinoma
Yi-Chih Tsai, Min-Chieh Hsin, Rui-Jun Liu, Ting-Wei Li, Hui-Ju Ch’ang
Cancers.2023; 15(21): 5212. CrossRef

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Gastrointestinal Cancer

Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer: Kyung-Hun Lee, Eui Kyu Chie, Seock-Ah Im, Jee Hyun Kim, Jihyun Kwon, Sae-Won Han, Do-Youn Oh, Jin-Young Jang, Jae-Sung Kim, Tae-You Kim, Yung-Jue Bang, Sun Whe Kim, Sung W. Ha; Cancer Res Treat. 2021;53(4):1096-1103. Published online December 30, 2020; DOI: https://doi.org/10.4143/crt.2020.928

Abstract PDF PubReader ePub

Purpose
Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.
Materials and Methods
Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m² on days 1 and 8 and cisplatin 60 mg/m² on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m²/wk), and then gemcitabine 1,000 mg/m² on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.
Results
Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.
Conclusion
Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

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NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis
Xiao-Dong Huang, Yong-Wei Chen, Lv Tian, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Dong-Dong Lin, Feng-Jun Xiao
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Efficacy of Cisplatin-Containing Chemotherapy Regimens in Patients of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
Obaid Ur Rehman, Eeshal Fatima, Zain Ali Nadeem, Arish Azeem, Jatin Motwani, Habiba Imran, Hadia Mehboob, Alishba Khan, Omer Usman
Journal of Gastrointestinal Cancer.2024; 55(2): 559. CrossRef
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Xiao-Dong Huang, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Qiao-Wei Liu, Yi-Wu Wang, Ya-Jin Liao, Dong-Dong Lin, Feng-Jun Xiao
Cell Death Discovery.2024;[Epub] CrossRef
Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center
Johannes Felix Englisch, Alexander Englisch, Dominik Dannehl, Kenneth Eissler, Christian Martin Tegeler, Sabine Matovina, Léa Louise Volmer, Diethelm Wallwiener, Sara Y. Brucker, Andreas Hartkopf, Tobias Engler
Archives of Gynecology and Obstetrics.2024; 311(2): 437. CrossRef
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Chunhong Sui, Yijia Luo, Xiao Xiao, Jiaxue Liu, Xiaotong Shao, Yingxue Xue, Cheng Wang, Wenliang Li
ChemistrySelect.2023;[Epub] CrossRef
Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
Da Eun Lee, Hyeon Woong Kang, So Yi Kim, Myeong Jin Kim, Jae Woong Jeong, Woosol Chris Hong, Sungsoon Fang, Hyung Sun Kim, Yun Sun Lee, Hyo Jung Kim, Joon Seong Park
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Yeting Lu, Shuping Zhou, Gong Cheng, Yi Ruan, Yuan Tian, Kaiji Lv, Shuo Han, Xinhua Zhou, Xiangya Ding
Journal of Oncology.2022; 2022: 1. CrossRef
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Advances in Clinical Medicine.2022; 12(10): 9540. CrossRef
Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients
Alice Usai, Gregorio Di Franco, Margherita Piccardi, Perla Cateni, Luca Emanuele Pollina, Caterina Vivaldi, Enrico Vasile, Niccola Funel, Matteo Palmeri, Luciana Dente, Alfredo Falcone, Dimitri Giunchi, Alessandro Massolo, Vittoria Raffa, Luca Morelli
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Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef

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153 Download
10 Crossref

Breast Cancer

Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial: Kyung-Hun Lee, Joohyuk Sohn, Annabel Goodwin, Tiziana Usari, Silvana Lanzalone, Seock-Ah Im, Sung-Bae Kim; Cancer Res Treat. 2021;53(4):1084-1095. Published online March 24, 2021; DOI: https://doi.org/10.4143/crt.2020.1381

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy.
Materials and Methods
Patients with human epidermal growth factor receptor 2–negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician’s choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions.
Results
Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4, 84.8] vs. 25.0% [95% CI, 3.2, 65.1]). Median overall survival was 20.7 months (95% CI, 9.4, 40.1) versus 21.2 months (95% CI, 2.7, 35.0) months (HR, 1.41 [95% CI, 0.49, 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population.
Conclusion
In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 TEAEs, SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.

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Detection and analysis of the safety profile of talazoparib based on FAERS database
Mufei Tang, Peiyan Liu, Linzhe Du, Yuanyuan Li, Jinjin Chen, Yang Li
Expert Opinion on Drug Safety.2025; 24(5): 577. CrossRef
HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis
Pu-Chun Li, Yi-Fan Zhu, Jia-Ni Pan, Qiao-Yan Zhu, Yu-Yang Liao, Xiao-Wen Ding, Lin-Feng Zheng, Wen-Ming Cao
Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment
Haixia Liu, Xiaohui Chen, Yimin Jia, Hengyi Chen, Xiaohui Wang, Guoxiang Liu, Yang Luo
Interdisciplinary Medicine.2023;[Epub] CrossRef
Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer
Shicheng Yang, Allen Green, Needa Brown, Alexis Robinson, Merline Senat, Bryanna Testino, Daniela M. Dinulescu, Srinivas Sridhar
Frontiers in Oncology.2023;[Epub] CrossRef
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer
S.-A. Im, A. Gennari, Y.H. Park, J.H. Kim, Z.-F. Jiang, S. Gupta, T.H. Fadjari, K. Tamura, M.Y. Mastura, M.L.T. Abesamis-Tiambeng, E.H. Lim, C.-H. Lin, A. Sookprasert, N. Parinyanitikul, L.-M. Tseng, S.-C. Lee, P. Caguioa, M. Singh, Y. Naito, R.A. Hukom,
ESMO Open.2023; 8(3): 101541. CrossRef
Molecular Biology Mechanisms and Emerging Therapeutics of Triple-Negative Breast Cancer
Zhiying Zhang, Rui Zhang, Donghai Li
Biologics: Targets and Therapy.2023; Volume 17: 113. CrossRef
Development of the PARP inhibitor talazoparib for the treatment of advanced BRCA1 and BRCA2 mutated breast cancer
Evthokia A. Hobbs, Jennifer K. Litton, Timothy A. Yap
Expert Opinion on Pharmacotherapy.2021; : 1. CrossRef

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Implications of Tamoxifen Resistance in Palbociclib Efficacy for Patients with Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Subgroup Analyses of KCSG-BR15-10 (YoungPEARL): Jiyun Lee, Seock-Ah Im, Gun Min Kim, Kyung Hae Jung, Seok Yun Kang, In Hae Park, Jee Hyun Kim, Hee Kyung Ahn, Yeon Hee Park; Cancer Res Treat. 2021;53(3):695-702. Published online December 17, 2020; DOI: https://doi.org/10.4143/crt.2020.1246

Abstract PDF PubReader ePub

Purpose
YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC.
Results
In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

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Palbociclib plus endocrine therapy in hormone receptor-positive and HER2 negative metastatic breast cancer: a multicenter real-world study in the northwest of China
Jiao Yang, Bing Zhao, Xiaoling Ling, Donghui Li, Jiuda Zhao, Yonggang Lv, Guangxi Wang, Xinlan Liu, Nanlin Li, Jin Yang
BMC Cancer.2023;[Epub] CrossRef

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Breast cancer

Association of Insulin, Metformin, and Statin with Mortality in Breast Cancer Patients: Mihong Choi, Jiyeon Han, Bo Ram Yang, Myoung-jin Jang, Miso Kim, Dae-Won Lee, Tae-Yong Kim, Seock-Ah Im, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee; Cancer Res Treat. 2021;53(1):65-76. Published online September 23, 2020; DOI: https://doi.org/10.4143/crt.2020.430

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study investigated the association of insulin, metformin, and statin use with survival and whether the association was modified by the hormone receptor status of the tumor in patients with breast cancer.
Materials and Methods
We studied 7,452 patients who had undergone surgery for breast cancer at Seoul National University Hospital from 2008 to 2015 using the nationwide claims database. Exposure was defined as a recorded prescription of each drug within 12 months before the diagnosis of breast cancer.
Results
Patients with prior insulin or statin use were more likely to be older than 50 years at diagnosis and had a higher comorbidity index than those without it (p < 0.01 for both). The hazard ratio (HR) for death with insulin use was 5.7 (p < 0.01), and the effect was attenuated with both insulin and metformin exposure with an HR of 1.2 (p=0.60). In the subgroup analyses, a heightened risk of death with insulin was further prominent with an HR of 17.9 (p < 0.01) and was offset by co-administration of metformin with an HR of 1.3 (p=0.67) in patients with estrogen receptor (ER)–negative breast cancer. Statin use was associated with increased overall mortality only in patients with ER-positive breast cancer with HR for death of 1.5 (p=0.05).
Conclusion
Insulin or statin use before the diagnosis of breast cancer was associated with an increase in all-cause mortality. Subsequent analyses suggested that metformin or statin use may have been protective in patients with ER-negative disease, which warrants further studies.

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Repurposing of Metabolic Drugs Metformin and Simvastatin as an Emerging Class of Cancer Therapeutics
Santosh Kumar Maurya, Smriti Chaudhri, Shashank Kumar, Sanjay Gupta
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Statins and prognosis of female breast cancer: a meta-analysis
Francisco Cezar Aquino de Moraes, Pedro Henrique de Souza Wagner, Isabella Christina Amaral de Lara, Barbara Lins Silva, Ana Laura Soares Silva, Artur de Oliveira Macena Lôbo, Luana Izabela Azevedo de Carvalho, Michele Kreuz, Maria Cristina Figueroa Magal
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Are statins onco- suppressive agents for every type of tumor? A systematic review of literature
Luca Filaferro, Fabiana Zaccarelli, Giovanni Francesco Niccolini, Andrea Colizza, Federica Zoccali, Michele Grasso, Massimo Fusconi
Expert Review of Anticancer Therapy.2024; 24(6): 435. CrossRef
Investigating the relationship between insulin use and all-cause mortality, breast cancer mortality, and recurrence risk in diabetic patients with breast cancer: A comprehensive systematic review and meta-analysis
Marina V. Loktionova, Mahdi Mohammadian, Roya Choopani, Soleiman Kheiri, Abdollah Mohammadian-Hafshejani, Kathleen Bennett
PLOS ONE.2024; 19(12): e0314565. CrossRef
Impact of statin use on breast cancer recurrence and mortality before and after diagnosis: a systematic review and meta-analysis
Xiaolin Jia, Ye Lu, Zili Xu, Qingqing Mu
Frontiers in Oncology.2023;[Epub] CrossRef
Effect of statins use on risk and prognosis of breast cancer: a meta-analysis
Guodong Zhao, Yanjun Ji, Qing Ye, Xin Ye, Guanqun Wo, Xi Chen, Xinyi Shao, Jinhai Tang
Anti-Cancer Drugs.2022; 33(1): e507. CrossRef
Studying the Cytotoxic Activity of Newly Designed and Synthesized HDAC Inhibitors Derivatives of Pentanoyl Anilide‐5‐Biguanide
Othman Makki Sagheer, Mohammed Hassan Mohammed, Jaafar S. Wadi, Zaid O. Ibraheem
Macromolecular Symposia.2022;[Epub] CrossRef
RETRACTED: Metformin and Breast Cancer: Where Are We Now?
Mónica Cejuela, Begoña Martin-Castillo, Javier Menendez, Sonia Pernas
International Journal of Molecular Sciences.2022; 23(5): 2705. CrossRef
Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression
Giorgia Centonze, Dora Natalini, Alessio Piccolantonio, Vincenzo Salemme, Alessandro Morellato, Pietro Arina, Chiara Riganti, Paola Defilippi
Frontiers in Oncology.2022;[Epub] CrossRef
Synthesis of gamma biguanides butyric acid analogues as HDAC inhibitors and studying their cytotoxic activity
Othman Makki Sagheer, Mohammed Hassan Mohammed, Zaid O. Ibraheem, Jaafar S. Wadi, Mustafa F. Tawfeeq
Materials Today: Proceedings.2021; 47: 5983. CrossRef
Statins: a repurposed drug to fight cancer
Wen Jiang, Jin-Wei Hu, Xu-Ran He, Wei-Lin Jin, Xin-Yang He
Journal of Experimental & Clinical Cancer Research.2021;[Epub] CrossRef
Potential intrinsic subtype dependence on the association between metformin use and survival in surgically resected breast cancer: a Korean national population-based study
Byoung Hyuck Kim, Moon-June Cho, Jeanny Kwon
International Journal of Clinical Oncology.2021; 26(11): 2004. CrossRef

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Gastrointestinal cancer

Adjuvant Chemotherapy in Microsatellite Instability–High Gastric Cancer: Jin Won Kim, Sung-Yup Cho, Jeesoo Chae, Ji-Won Kim, Tae-Yong Kim, Keun-Wook Lee, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2020;52(4):1178-1187. Published online June 11, 2020; DOI: https://doi.org/10.4143/crt.2020.313

Abstract PDF Supplementary Material PubReader ePub

Purpose
Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated. Material and Methods This study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers.
Results
Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040).
Conclusion
MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.

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Perioperative chemotherapy for gastric cancer patients with microsatellite instability or deficient mismatch repair: A systematic review and meta‐analysis
Baike Liu, Chaoyong Shen, Xiaonan Yin, Tianxiang Jiang, Yihui Han, Ruiwan Yuan, Yuan Yin, Zhaolun Cai, Bo Zhang
Cancer.2025;[Epub] CrossRef
Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma
Katherine I. Zhou, Brent A. Hanks, John H. Strickler
Journal of Gastrointestinal Cancer.2024; 55(2): 483. CrossRef
The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023
Feng‐Hua Wang, Xiao‐Tian Zhang, Lei Tang, Qi Wu, Mu‐Yan Cai, Yuan‐Fang Li, Xiu‐Juan Qu, Hong Qiu, Yu‐Jing Zhang, Jie‐Er Ying, Jun Zhang, Ling‐Yu Sun, Rong‐Bo Lin, Chang Wang, Hao Liu, Miao‐Zhen Qiu, Wen‐Long Guan, Sheng‐Xiang Rao, Jia‐Fu Ji, Yan Xin, Wei‐
Cancer Communications.2024; 44(1): 127. CrossRef
Clinical Significance of Fibrinogen and Platelet to Pre-Albumin Ratio in Predicting the Prognosis of Advanced Gastric Cancer
Huakai Tian, Zitao Liu, Zuo Zhang, Lipeng Zhang, Zhen Zong, Jiang Liu, Houqun Ying, Hui Li
Journal of Inflammation Research.2023; Volume 16: 4373. CrossRef
Fatty acid metabolism is related to the immune microenvironment changes of gastric cancer and RGS2 is a new tumor biomarker
Shifeng Yang, Boshi Sun, Wenjing Li, Hao Yang, Nana Li, Xinyu Zhang
Frontiers in Immunology.2022;[Epub] CrossRef
Chemotherapy in Neuroendocrine Tumors
Satya Das, Taymeyah Al-Toubah, Jonathan Strosberg
Cancers.2021; 13(19): 4872. CrossRef

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Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant: Hyung Seok Park, Jai Min Ryu, Ji Soo Park, Seock-Ah Im, So-Youn Jung, Eun-Kyu Kim, Woo-Chan Park, Jun Won Min, Jeeyeon Lee, Ji Young You, Jeong Eon Lee, Sung-Won Kim; Cancer Res Treat. 2020;52(3):680-688. Published online January 28, 2020; DOI: https://doi.org/10.4143/crt.2019.351

Abstract PDF Supplementary Material PubReader ePub

Purpose
Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data.
Materials and Methods
The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study.
Results
The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations.
Conclusion
L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

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Whole Exome-Wide Association Identifies Rare Variants in GALNT9 Associated with Middle Eastern Papillary Thyroid Carcinoma Risk
Rong Bu, Abdul K. Siraj, Saud Azam, Kaleem Iqbal, Zeeshan Qadri, Maha Al-Rasheed, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya
Cancers.2023; 15(17): 4235. CrossRef
Feasibility of targeted cascade genetic testing in the family members of BRCA1/2 gene pathogenic variant/likely pathogenic variant carriers
Jeeyeon Lee, Ji Yeon Ham, Ho Yong Park, Jin Hyang Jung, Wan Wook Kim, Byeongju Kang, Yee Soo Chae, Soo Jung Lee, In Hee Lee, Nan Young Lee
Scientific Reports.2022;[Epub] CrossRef
Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer
Jeong Dong Lee, Won-Ji Ryu, Hyun Ju Han, Tae Yeong Kim, Min Hwan Kim, Joohyuk Sohn
Cancers.2022; 14(10): 2405. CrossRef
Discovery of BRCA1/BRCA2 founder variants by haplotype analysis
Won Kyung Kwon, Hyeok-Jae Jang, Jeong Eon Lee, Yeon Hee Park, Jai Min Ryu, Jonghan Yu, Ja-Hyun Jang, Jong-Won Kim
Cancer Genetics.2022; 266-267: 19. CrossRef
Local Laboratory Testing of Germline BRCA Mutations vs. Myriad: A Single-Institution Experience in Korea
Joohyun Hong, Jiyun Lee, Minsuk Kwon, Ji-Yeon Kim, Jong-Won Kim, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
Diagnostics.2021; 11(2): 370. CrossRef
Analysis of BRCA1/2 variants of unknown significance in the prospective Korean Hereditary Breast Cancer study
Joo Heung Kim, Sunggyun Park, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Sung-Won Kim, Jong Won Lee, Min Hyuk Lee, Sue K. Park, Woo-Chul Noh, Doo Ho Choi, Wonshik Han, Sung Hoo Jung
Scientific Reports.2021;[Epub] CrossRef
A Population-Based Analysis of BRCA1/2 Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study
Kyung-Sun Park, Woochang Lee, Moon-Woo Seong, Sun-Young Kong, Kyung-A Lee, Jung-Sook Ha, Eun-Hae Cho, Sung-Hee Han, Inho Park, Jong-Won Kim
Cancers.2021; 13(9): 2192. CrossRef

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Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells: Miso Lee, Kyung-Hun Lee, Ahrum Min, Jeongeun Kim, Seongyeong Kim, Hyemin Jang, Jee Min Lim, So Hyeon Kim, Dong-Hyeon Ha, Won Jae Jeong, Koung Jin Suh, Yae-Won Yang, Tae Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2019;51(2):451-463. Published online June 6, 2018; DOI: https://doi.org/10.4143/crt.2017.341

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pim kinases are highly conserved serine/threonine kinases, and different expression patterns of each isoform (Pim-1, Pim-2, and Pim-3) have been observed in various types of human cancers, including gastric cancer. AZD1208 is a potent and selective inhibitor that affects all three isoforms of Pim. We investigated the effects of AZD1208 as a single agent and in combination with an Akt inhibitor in gastric cancer cells.
Materials and Methods
The antitumor activity of AZD1208 with/without an Akt inhibitor was evaluated in a large panel of gastric cancer cell lines through growth inhibition assays. The underlying mechanism was also examined by western blotting, immunofluorescence assay, and cell cycle analysis.
Results
AZD1208 treatment decreased gastric cancer cell proliferation rates and induced autophagy only in long-term culture systems. Light chain 3B (LC3B), a marker of autophagy, was increased in sensitive cells in a dose-dependent manner with AZD1208 treatment, which suggested that the growth inhibition effect of AZD1208 was achieved through autophagy, not apoptosis. Moreover, we found that cells damaged by Pim inhibition were repaired by activation of the DNA damage repair pathway, which promoted cell survival and led the cells to become resistant to AZD1208. We also confirmed that the combination of an Akt inhibitor with AZD1208 produced a highly synergistic effect in gastric cancer cell lines.
Conclusion
Treatment with AZD1208 alone induced considerable cell death through autophagy in gastric cancer cells. Moreover, the combination of AZD1208 with an Akt inhibitor showed synergistic antitumor effects through regulation of the DNA damage repair pathway.

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Reza Panahizadeh, Padideh Panahi, Vahid Asghariazar, Shima Makaremi, Ghasem Noorkhajavi, Elham Safarzadeh
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Yuzhen Li, Lang Shi, Fan Zhao, Yanwen Luo, Mingjiao Zhang, Xiongfei Wu, Jiefu Zhu
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Rituparna Choudhury, Chandan Kumar Bahadi, Ipsa Pratibimbita Ray, Pragyanshree Dash, Isha Pattanaik, Suman Mishra, Soumya R. Mohapatra, Srinivas Patnaik, Kumar Nikhil
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Ping Lin, Lingyan He, Nan Tian, Xuchen Qi
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Feng‐Ze Yan, Ying‐Chun Ouyang, Tie‐Gang Meng, Hong‐Yong Zhang, Wei Yue, Xin‐Ran Zhang, Yue Xue, Zhen‐Bo Wang, Qing‐Yuan Sun
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Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
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TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy
Jin Won Kim, Ahrum Min, Seock-Ah Im, Hyemin Jang, Yu Jin Kim, Hee-Jun Kim, Kyung-Hun Lee, Tae-Yong Kim, Keun Wook Lee, Do-Youn Oh, Jee-Hyun Kim, Yung-Jue Bang
Cancers.2020; 12(2): 334. CrossRef
PIM1 (Moloney Murine Leukemia Provirus Integration Site) Inhibition Decreases the Nonhomologous End-Joining DNA Damage Repair Signaling Pathway in Pulmonary Hypertension
Marie-Claude Lampron, Géraldine Vitry, Valérie Nadeau, Yann Grobs, Renée Paradis, Nolwenn Samson, Ève Tremblay, Olivier Boucherat, Jolyane Meloche, Sébastien Bonnet, Steeve Provencher, François Potus, Roxane Paulin
Arteriosclerosis, Thrombosis, and Vascular Biology.2020; 40(3): 783. CrossRef
Inhibition of PIM1 attenuates the stem cell–like traits of breast cancer cells by promoting RUNX3 nuclear retention
Hui Liu, Cheng Chen, Dongshen Ma, Yubing Li, Qianqian Yin, Qing Li, Chenxi Xiang
Journal of Cellular and Molecular Medicine.2020; 24(11): 6308. CrossRef
Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer
Dong-Hyeon Ha, Ahrum Min, Seongyeong Kim, Hyemin Jang, So Hyeon Kim, Hee-Jun Kim, Han Suk Ryu, Ja-Lok Ku, Kyung-Hun Lee, Seock-Ah Im
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Soraya Alnabulsi, Enas A. Al-Hurani
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Maiara Bernardes Marques, Michael González-Durruthy, Bruna Félix da Silva Nornberg, Bruno Rodrigues Oliveira, Daniela Volcan Almeida, Ana Paula de Souza Votto, Luis Fernando Marins
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Francesca Musumeci, Chiara Greco, Giancarlo Grossi, Alessio Molinari, Silvia Schenone
Cancers.2018; 10(11): 430. CrossRef

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Randomized Open Label Phase III Trial of Irinotecan Plus Capecitabine versus Capecitabine Monotherapy in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane: PROCEED Trial (KCSG BR 11-01): In Hae Park, Seock-Ah Im, Kyung Hae Jung, Joo Hyuk Sohn, Yeon Hee Park, Keun Seok Lee, Sung Hoon Sim, Kyong-Hwa Park, Jee Hyun Kim, Byung Ho Nam, Hee-Jun Kim, Tae-Yong Kim, Kyung-Hun Lee, Sung-Bae Kim, Jin-Hee Ahn, Suee Lee, Jungsil Ro; Cancer Res Treat. 2019;51(1):43-52. Published online February 14, 2018; DOI: https://doi.org/10.4143/crt.2017.562

Abstract PDF PubReader ePub

Purpose
We investigated whether irinotecan plus capecitabine improved progression-free survival (PFS) compared with capecitabine alone in patients with human epidermal growth factor 2 (HER2) negative and anthracycline and taxane pretreated metastatic breast cancer (MBC).
Materials and Methods
A total of 221 patients were randomly assigned to irinotecan (80 mg/m2, days 1 and 8) and capecitabine (1,000 mg/m2 twice a day, days 1-14) or capecitabine alone (1,250 mg/m2 twice a day, days 1-14) every 3 weeks. The primary endpoint was PFS.
Results
There was no significant difference in PFS between the combination and monotherapy arm (median, 6.4 months vs. 4.7 months; hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63 to 1.11; p=0.84). In patients with triple-negative breast cancer (TNBC, n=90), the combination significantly improved PFS (median, 4.7 months vs. 2.5 months; HR, 0.58; 95% CI, 0.37 to 0.91; p=0.02). Objective response rate was numerically higher in the combination arm, though it failed to reach statistical significance (44.4% vs. 33.3%, p=0.30). Overall survival did not differ between arms (median, 20.4 months vs. 24.0 months; p=0.63). While grade 3 or 4 neutropenia was more common in the combination arm (39.6% vs 9.0%), hand-foot syndrome was more often observed in capecitabine arm. Quality of life measurements in global health status was similar. However, patients in the combination arm showed significantly worse symptom scales especially in nausea/vomiting and diarrhea.
Conclusion
Irinotecan plus capecitabine did not prove clinically superior to single-agent capecitabine in anthracycline- and taxane-pretreated HER2 negative MBC patients. Toxicity profiles of the two groups differed but were manageable. The role of added irinotecan in patients with TNBC remains to be elucidated.

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Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients: Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park; Cancer Res Treat. 2019;51(1):211-222. Published online April 23, 2018; DOI: https://doi.org/10.4143/crt.2018.132

Abstract PDF Supplementary Material PubReader ePub

Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors: Tae Min Kim, Keun-Wook Lee, Do-Youn Oh, Jong-Seok Lee, Seock-Ah Im, Dong-Wan Kim, Sae-Won Han, Yu Jung Kim, Tae-You Kim, Jee Hyun Kim, Hyesun Han, Woo Ho Kim, Yung-Jue Bang; Cancer Res Treat. 2018;50(3):835-842. Published online August 29, 2017; DOI: https://doi.org/10.4143/crt.2017.303

Abstract PDF Supplementary Material PubReader ePub

Purpose
Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors.
Materials and Methods
Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort.
Results
A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Doselimiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer).
Conclusion
Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.

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Bilateral Salpingo-oophorectomy Compared to Gonadotropin-Releasing Hormone Agonists in Premenopausal Hormone Receptor–Positive Metastatic Breast Cancer Patients Treated with Aromatase Inhibitors: Koung Jin Suh, Se Hyun Kim, Kyung-Hun Lee, Tae-Yong Kim, Yu Jung Kim, Sae-Won Han, Eunyoung Kang, Eun-Kyu Kim, Kidong Kim, Jae Hong No, Wonshik Han, Dong-Young Noh, Maria Lee, Hee Seung Kim, Seock-Ah Im, Jee Hyun Kim; Cancer Res Treat. 2017;49(4):1153-1163. Published online February 27, 2017; DOI: https://doi.org/10.4143/crt.2016.463

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although combining aromatase inhibitors (AI) with gonadotropin-releasing hormone agonists (GnRHa) is becoming more common, it is still not clear if GnRHa is as effective as bilateral salpingo-oophorectomy (BSO).
Materials and Methods
We retrospectively analyzed data of 66 premenopausal patients with hormone receptor– positive, human epidermal growth factor receptor 2–negative recurrent and metastatic breast cancer who had been treated with AIs in combination with GnRHa or BSO between 2002 and 2015.
Results
The median patient age was 44 years. Overall, 24 (36%) received BSO and 42 (64%) received GnRHa. The clinical benefit rate was higher in the BSO group than in the GnRHa group (88% vs. 69%, p=0.092). Median progression-free survival (PFS) was longer in the BSO group, although statistical significance was not reached (17.2 months vs. 13.3 months, p=0.245). When propensity score matching was performed, the median PFS was 17.2 months for the BSO group and 8.2 months for the GnRHa group (p=0.137). Multivariate analyses revealed that the luminal B subtype (hazard ratio, 1.67; 95% confidence interval [CI], 1.08 to 2.60; p=0.022) and later-line treatment (≥ third line vs. first line; hazard ratio, 3.24; 95% CI, 1.59 to 6.59; p=0.001) were independent predictive factors for a shorter PFS. Incomplete ovarian suppression was observed in a subset of GnRHa-treated patients whose disease showed progression, with E2 levels higher than 21 pg/mL.
Conclusion
Both BSO and GnRHa were found to be effective in our AI-treated premenopausal metastatic breast cancer patient cohort. However, further studies in larger populations are needed to determine if BSO is superior to GnRHa.

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Incomplete ovarian function suppression in premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonists
Jinna Lin, Shuqi Zheng, Qiang Liu
Cancer Treatment Reviews.2025; 133: 102879. CrossRef
Ovarian escape in premenopausal breast cancer: Challenges and strategies for optimizing hormone suppression
Lan Luo, Yonglin Zhang, Li Zhang, Senguo Yang, Tian Zhou, Ke Luo, Shu Liu
Cancer Treatment Reviews.2025; : 102970. CrossRef
Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study
Yifei Chen, Ruyan Zhang, Ying Yan, Huiping Li, Guohong Song
Breast Cancer Research and Treatment.2024; 206(3): 543. CrossRef
Oophorectomy in Premenopausal Patients with Estrogen Receptor-Positive Breast Cancer: New Insights into Long-Term Effects
Fatima Khan, Kristin Rojas, Matthew Schlumbrecht, Patricia Jeudin
Current Oncology.2023; 30(2): 1794. CrossRef
Comparison of outcomes in patients with luminal type breast cancer treated with a gonadotropin-releasing hormone analog or bilateral salpingo-oophorectomy: A cohort retrospective study
Dwi Ris Andriyanto, Prihantono, Salman Ardi Syamsu, Muhammad Ihwan Kusuma, Joko Hendarto, Indra, Nilam Smaradania, Elridho Sampepajung, Asrul Mappiwali, Muhammad Faruk
Annals of Medicine & Surgery.2022;[Epub] CrossRef
Awareness of the Causes Leading to Surgical Ablation of Ovarian Function in Premenopausal Breast Cancer—A Single-Center Analysis
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Brändli SP, Palm J, Kowalewski MP, Reichler IM
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Gebra Cuyún Carter, Maitreyee Mohanty, Keri Stenger, Claudia Morato Guimaraes, Shivaprasad Singuru, Pradeep Basa, Sheena Singh, Vanita Tongbram, Sherko Kuemmel, Valentina Guarneri, Sara M Tolaney
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Oophorectomy as a Hormonal Ablation Therapy in Metastatic and Recurrent Breast Cancer: Current Indications and Results
Islam H. Metwally, Omar Hamdy, Saleh S. Elbalka, Mohamed Elbadrawy, Dina M. Elsaid
Indian Journal of Surgical Oncology.2019; 10(3): 542. CrossRef
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Aditya Bardia, Sara Hurvitz
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Korean Cancer Patients’ Awareness of Clinical Trials, Perceptions on the Benefit and Willingness to Participate: Yoojoo Lim, Jee Min Lim, Won Jae Jeong, Kyung-Hun Lee, Bhumsuk Keam, Tae-Yong Kim, Tae Min Kim, Sae-Won Han, Do Youn Oh, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2017;49(4):1033-1043. Published online April 7, 2017; DOI: https://doi.org/10.4143/crt.2016.413

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to assess current levels of awareness of clinical trials (CTs), perceptions regarding their benefits and willingness to participate to CTs among Korean cancer patients.
Materials and Methods
From December 2012 to August 2015, we distributed questionnaires to cancer patients receiving systemic anti-cancer therapy at Seoul National University Hospital, Seoul, Korea.
Results
A total of 397 out of 520 requested patients (76.3%) responded to the survey. Among the 397 patients, 62.5% were female and the median age was 52 years. Overall, 97.4% (387/397) answered that they have at least heard of CTs. When asked about their level of awareness, 23.8% (92/387) answered that they could more than roughly explain about CTs. The average visual analogue scale score of CT benefit in all patients was 6.43 (standard deviation, 2.20). Patients who were only familiar with the term without detailed knowledge of the contents had the least expectation of benefit from CTs (p=0.015). When asked about their willingness to participate in CTs, 56.7% (225/397) answered positively. Patients with higher levels of awareness of CTs showed higher willingness to participate (p < 0.001). Heavily treated patients and patients with previous experience regarding CTs also showed a higher willingness to participate (p < 0.001). The perceived benefit of CTs was higher in the group willing to participate (p=0.026).
Conclusion
The patient’s level of awareness regarding CTs was positively related to the positive perception and willingness to participate. Although the general awareness of CTs was high, a relatively large proportion of patients did not have accurate knowledge; therefore, proper and accurate patient education is necessary.

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Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis: Seongyeong Kim, Ahrum Min, Kyung-Hun Lee, Yaewon Yang, Tae-Yong Kim, Jee Min Lim, So Jung Park, Hyun-Jin Nam, Jung Eun Kim, Sang-Hyun Song, Sae-Won Han, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, David Hangauer, Johnson Yiu-Nam Lau, Kyongok Im, Dong Soon Lee, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2017;49(3):643-655. Published online October 6, 2016; DOI: https://doi.org/10.4143/crt.2016.168

Abstract PDF Supplementary Material PubReader ePub

Purpose
KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo.
Materials and Methods
The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects.
Results
KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho- Src and proliferative-signaling molecules were down-regulated in KX-01–sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01– induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01–sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model.
Conclusion
KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.

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Efficacy and tolerability of tirbanibulin 1% ointment in the treatment of cancerization field: a real‐life Italian multicenter observational study of 250 patients
Gianluca Nazzaro, Andrea Carugno, Paolo Bortoluzzi, Stefano Buffon, Chiara Astrua, Elena Zappia, Emanuele Trovato, Stefano Caccavale, Vincenzo Pellegrino, Giovanni Paolino, Riccardo Balestri, Rossella Lacava, Giulia Ciccarese, Alice Verdelli, Stefania Bar
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Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer
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Anti-tumor effects of tirbanibulin in squamous cell carcinoma cells are mediated via disruption of tubulin-polymerization
Viola K. DeTemple, Antje Walter, Sabine Bredemeier, Ralf Gutzmer, Katrin Schaper-Gerhardt
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SAR Probing of KX2-391 Provided Analogues With Juxtaposed Activity Profile Against Major Oncogenic Kinases
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Wen Shuai, Guan Wang, Yiwen Zhang, Faqian Bu, Sicheng Zhang, Duane D. Miller, Wei Li, Liang Ouyang, Yuxi Wang
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Tirbanibulin: review of its novel mechanism of action and how it fits into the treatment of actinic keratosis
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CA19-9 or CEA Decline after the First Cycle of Treatment Predicts Survival in Advanced Biliary Tract Cancer Patients Treated with S-1 and Cisplatin Chemotherapy: Dae-Won Lee, Seock-Ah Im, Yu Jung Kim, Yaewon Yang, Jiyoung Rhee, Im Il Na, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, In Sil Choi, Do-Youn Oh, Jee Hyun Kim, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2017;49(3):807-815. Published online January 18, 2017; DOI: https://doi.org/10.4143/crt.2016.326

Abstract PDF PubReader ePub

Purpose
While tumor markers (carbohydrate antigen 19-9 [CA 19-9] and carcinoembryonic antigen [CEA]) can aid in the diagnosis of biliary tract cancer, their prognostic role has not been clearly elucidated. Therefore, this study was conducted to evaluate the prognostic role of tumor markers and tumor marker change in patients with advanced biliary tract cancer.
Materials and Methods
Patients with pathologically proven metastatic or relapsed biliary tract cancer who were treated in a phase II trial of first-line S-1 and cisplatin chemotherapy were enrolled. Serum tumor markers were measured at baseline and after the first cycle of chemotherapy.
Results
Among a total of 104 patients, 80 (77%) had elevated baseline tumor markers (69 with CA 19-9 elevation and 40 with CEA). A decline ≥ 30% of the elevated tumor marker level after the first cycle of chemotherapy conferred an improved time to progression (TTP), overall survival (OS), and better chemotherapy response. Multivariate analysis revealed tumor marker decline as an independent positive prognostic factor of TTP (adjusted hazard ratio [HR], 0.44; p=0.003) and OS (adjusted HR, 0.37; p < 0.001). Subgroup analysis revealed similar results in each group of patients with CA 19-9 elevation and CEA elevation. In addition, elevated baseline CEA was associated with poor survival in both univariate and multivariate analysis.
Conclusion
Tumor marker decline was associated with improved survival in biliary tract cancer. Measuring tumor marker after the first cycle of chemotherapy can be used as an early assessment of treatment outcome.

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Clinical epidemiology of gallbladder cancer in North-Central India and association of immunological markers, NLR, MLR and PLR in the diagnostic/prognostic prediction of GBC
Jyotsna Singh, Durgesh Shukla, Sanjiv Gupta, Braj Raj Shrivastav, Pramod Kumar Tiwari
Cancer Treatment and Research Communications.2021; 28: 100431. CrossRef
Neoadjuvant Intraperitoneal Chemotherapy in Patients with Pseudomyxoma Peritonei—A Novel Treatment Approach
Aruna Prabhu, Andreas Brandl, Satoshi Wakama, Shouzou Sako, Haruaki Ishibashi, Akiyoshi Mizumoto, Nobuyuki Takao, Kousuke Noguchi, Shunsuke Motoi, Masumi Ichinose, Yang Liu, Yutaka Yonemura
Cancers.2020; 12(8): 2212. CrossRef
Clinical and Translational Research Challenges in Biliary Tract Cancers
Angela Lamarca, Melissa Frizziero, Mairéad G. McNamara, Juan W. Valle
Current Medicinal Chemistry.2020; 27(29): 4756. CrossRef
Therapeutic outcomes and prognostic factors in unresectable gallbladder cancer treated with gemcitabine plus cisplatin
Min su You, Ji Kon Ryu, Young Hoon Choi, Jin Ho Choi, Gunn Huh, Woo Hyun Paik, Sang Hyub Lee, Yong-Tae Kim
BMC Cancer.2019;[Epub] CrossRef
Efficacy of interventional therapy and effect on inflammatory factors in patients with gastric cancer after chemotherapy
Puzhao Wu, Jing Wang
Oncology Letters.2019;[Epub] CrossRef
CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer
Naminatsu Takahara, Yousuke Nakai, Hiroyuki Isayama, Takashi Sasaki, Kei Saito, Kensaku Noguchi, Tatsunori Suzuki, Tomoka Nakamura, Tatsuya Sato, Kazunaga Ishigaki, Ryunosuke Hakuta, Tsuyoshi Takeda, Rie Uchino, Suguru Mizuno, Hirofumi Kogure, Minoru Tada
Cancer Chemotherapy and Pharmacology.2017; 80(6): 1105. CrossRef

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Efficacy and Safety of Regorafenib in Korean Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib: A Multicenter Study Based on the Management Access Program: Myoung Kyun Son, Min-Hee Ryu, Joon Oh Park, Seock-Ah Im, Tae-Yong Kim, Su Jin Lee, Baek-Yeol Ryoo, Sook Ryun Park, Yoon-Koo Kang; Cancer Res Treat. 2017;49(2):350-357. Published online July 19, 2016; DOI: https://doi.org/10.4143/crt.2016.067

Abstract PDF PubReader ePub

Purpose
The aim of this study was to confirm the efficacy and safety of regorafenib for advanced gastrointestinal stromal tumors (GISTs) reported in the GRID phase III trial in Korean patients.
Materials and Methods
Fifty-seven Korean patientswith advanced GISTwho experienced both imatinib and sunitinib failure were enrolled in the management access program between December 2012 and November 2013 and treated with regorafenib (160 mg orally once daily in a 3 weeks on /1 week off).
Results
None of the patients achieved a complete or partial response while 25 patients (44%) showed stable disease for ≥ 12 weeks. With a median follow-up of 12.7 months (range, 0.2 to 27.6 months), the median progression-free survival and overall survival were 4.5 months (95% confidence interval [CI], 3.8 to 5.3) and 12.9 months (95% CI, 8.1 to 17.7), respectively. Interestingly, 15 patients (26%) experienced an exacerbation of their cancer-related symptoms (abdominal pain in eight and abdominal distension in five) during the rest period for regorafenib, but all were ameliorated upon the resumption of regorafenib. The most common grade 3 or 4 adverse event was a hand-foot skin reaction (25%). The regorafenib dose was reduced in 44 patients (77%) due to toxicity, which manifested mainly as a handfoot skin reaction (n=31).
Conclusion
This study confirmed the efficacy and safety of regorafenib for advanced GIST after imatinib and sunitinib failure in Korean patients. Considering the exacerbation of the cancer-related symptoms observed during the rest periods, further exploration of the continuous dosing schedule of regorafenib is warranted in future clinical trials.

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English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology
Seiichi Hirota, Ukihide Tateishi, Yuji Nakamoto, Hidetaka Yamamoto, Shinji Sakurai, Hirotoshi Kikuchi, Tatsuo Kanda, Yukinori Kurokawa, Haruhiko Cho, Toshirou Nishida, Akira Sawaki, Masato Ozaka, Yoshito Komatsu, Yoichi Naito, Yoshitaka Honma, Fumiaki Tak
International Journal of Clinical Oncology.2024; 29(6): 647. CrossRef
A randomised phase 2 study of continuous or intermittent dosing schedule of imatinib re-challenge in patients with tyrosine kinase inhibitor-refractory gastrointestinal stromal tumours
Hyung-Don Kim, Changhoon Yoo, Min-Hee Ryu, Yoon-Koo Kang
British Journal of Cancer.2023; 129(2): 275. CrossRef
Case Report: Should Regorafenib be prescribed as a continuous schedule in gastrointestinal stromal tumors? Three case reports on Regorafenib personalized schedule
Maria Susanna Grimaudo, Alice Laffi, Nicolò Gennaro, Roberta Fazio, Federico D’Orazio, Laura Samà, Licia Vanessa Siracusano, Federico Sicoli, Salvatore Lorenzo Renne, Armando Santoro, Alexia Francesca Bertuzzi
Frontiers in Oncology.2023;[Epub] CrossRef
Evaluation of Systemic Treatment Options for Gastrointestinal Stromal Tumours
Marin Golčić, Robin L. Jones, Paul Huang, Andrea Napolitano
Cancers.2023; 15(16): 4081. CrossRef
Medical oncological treatment for patients with Gastrointestinal Stromal Tumor (GIST) – A systematic review
Charlotte Margareta Brinch, Ninna Aggerholm-Pedersen, Estrid Hogdall, Anders Krarup-Hansen
Critical Reviews in Oncology/Hematology.2022; 172: 103650. CrossRef
Health-Related Quality of Life and Side Effects in Gastrointestinal Stromal Tumor (GIST) Patients Treated with Tyrosine Kinase Inhibitors: A Systematic Review of the Literature
Deborah van de Wal, Mai Elie, Axel Le Cesne, Elena Fumagalli, Dide den Hollander, Robin L. Jones, Gloria Marquina, Neeltje Steeghs, Winette T. A. van der Graaf, Olga Husson
Cancers.2022; 14(7): 1832. CrossRef
Efficacy and safety of regorafenib in Japanese patients with advanced gastrointestinal stromal tumors
Ryugo Teranishi, Tsuyoshi Takahashi, Toshirou Nishida, Seiichi Hirota, Yukinori Kurokawa, Takuro Saito, Kazuyoshi Yamamoto, Kotaro Yamashita, Koji Tanaka, Tomoki Makino, Masaaki Motoori, Takeshi Omori, Kiyokazu Nakajima, Hidetoshi Eguchi, Yuichiro Doki
International Journal of Clinical Oncology.2022; 27(7): 1164. CrossRef
The Role of Regorafenib in the Management of Advanced Gastrointestinal Stromal Tumors: A Systematic Review
Vahe Khachatryan, Asmaa Muazzam, Chandani Hamal, Lakshmi Sai Deepak Reddy Velugoti, Godfrey Tabowei, Greeshma N Gaddipati, Maria Mukhtar, Mohammed J Alzubaidee, Raga Sruthi Dwarampudi, Sheena Mathew, Sumahitha Bichenapally, Lubna Mohammed
Cureus.2022;[Epub] CrossRef
CT Image Examination Based on Virtual Reality Analysis in Clinical Diagnosis of Gastrointestinal Stromal Tumors
Zhiying Wang, Qiaoyan Qu, Ke Cai, Ting Xu, Zhihan Lv
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Agnieszka Kaczmarska, Patrycja Śliwa, Monika Lejman, Joanna Zawitkowska
International Journal of Molecular Sciences.2021; 22(21): 12089. CrossRef
Molecular Modeling Study of c-KIT/PDGFRα Dual Inhibitors for the Treatment of Gastrointestinal Stromal Tumors
Seketoulie Keretsu, Suparna Ghosh, Seung Joo Cho
International Journal of Molecular Sciences.2020; 21(21): 8232. CrossRef
Regorafenib treatment outcome for Taiwanese patients with metastatic gastrointestinal stromal tumors after failure of imatinib and sunitinib: A prospective, non‑randomized, single‑center study
Chia‑Hsiang Hu, Chun‑Nan Yeh, Jen‑Shi Chen, Chun‑Yi Tsai, Shang‑Yu Wang, Chi‑Tung Cheng, Ta‑Sen Yeh
Oncology Letters.2020; 20(3): 2131. CrossRef
Meta-Analysis of Regorafenib-Associated Adverse Events and Their Management in Colorectal and Gastrointestinal Stromal Cancers
Ganfeng Xie, Yuzhu Gong, Shuang Wu, Chong Li, Songtao Yu, Zhe Wang, Jianfang Chen, Quanfeng Zhao, Jianjun Li, Houjie Liang
Advances in Therapy.2019; 36(8): 1986. CrossRef
Phase II Trial of Continuous Regorafenib Dosing in Patients with Gastrointestinal Stromal Tumors After Failure of Imatinib and Sunitinib
Jae-Joon Kim, Min-Hee Ryu, Changhoon Yoo, Mo Youl Beck, Jung Eun Ma, Yoon-Koo Kang
The Oncologist.2019; 24(11): e1212. CrossRef
Growing Role of Regorafenib in the Treatment of Patients with Sarcoma
Mark Agulnik, Steven Attia
Targeted Oncology.2018; 13(4): 417. CrossRef
Treatment patterns, efficacy and toxicity of regorafenib in gastrointestinal stromal tumour patients
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Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib
Bin Zhao, Hong Zhao
Oncotarget.2017; 8(55): 93813. CrossRef

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Feasibility and Efficacy of Eribulin Mesilate in Korean Patients with Metastatic Breast Cancer: Korean Multi-center Phase IV Clinical Study Results: Yeon Hee Park, Tae Yong Kim, Young-Hyuck Im, Keun-Seok Lee, In Hae Park, Joohyuk Sohn, Soo-Hyeon Lee, Seock-Ah Im, Jee Hyun Kim, Se Hyun Kim, Soo Jung Lee, Su-Jin Koh, Ki Hyeong Lee, Yoon Ji Choi, Eun Kyung Cho, Suee Lee, Seok Yun Kang, Jae Hong Seo, Sung-Bae Kim, Kyung Hae Jung; Cancer Res Treat. 2017;49(2):423-429. Published online August 3, 2016; DOI: https://doi.org/10.4143/crt.2016.191

Abstract PDF PubReader ePub

Purpose
Eribulin mesilate was approved for the treatment of patients with locally advanced or metastatic breast cancer (MBC),who had received at least two chemotherapeutic regimens, including anthracycline and taxane. On the other hand, the efficacy and safety information of eribulin in Korean patients is limited by the lack of clinical trials.
Materials and Methods
In this multicenter, open-label, single-arm, phase IV study, locally advanced or MBC patients were enrolled between June 2013 and April 2014 from 14 centers in Korea. One point four mg/m2 dose of eribulin was administered on days 1 and 8 of every 21 days. The primary endpoint was the frequency and intensity of the treatment emergent adverse event. The secondary endpoint was the disease control rate, which included the rate of complete responses, partial responses, and stable disease.
Results
A total of 101 patients received at least one dose of eribulin and were included in the safety set. The patients received a total of 543 treatment cycles, with a median of three cycles (range, 1 to 31 cycles). The most common adverse event was neutropenia (91.1% of patients, 48.3% of cycles). The frequent non-hematological adverse events included alopecia, decrease in appetite, fatigue/asthenia, and myalgia/arthralgia. The peripheral neuropathy of any grade occurred in 27 patients (26.7%), including grade 3 in two patients. Disease control rate was 52.7% and 51.3% of patients in the full analysis set and per-protocol set, respectively.
Conclusion
This study demonstrated the feasible safety profile and activity of eribulin in Korean patients with MBC.

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Effectiveness and healthcare costs of eribulin versus capecitabine among metastatic breast cancer patients in Taiwan
Yu-Ju Lin, Chun-Nan Kuo, Yu Ko
The Breast.2021; 57: 18. CrossRef
Prognostic and predictive factors of eribulin in patients with heavily pre-treated metastatic breast cancer
Pei-Hsin Chen, Dah-Cherng Yeh, Heng-Hsin Tung, Chin-Yao Lin
Medicine.2021; 100(47): e27859. CrossRef
Multifarious targets beyond microtubules—role of eribulin in cancer therapy
Priya Seshadri, Barnali Deb, Prashant Kumar
Frontiers in Bioscience-Scholar.2021;[Epub] CrossRef
A nationwide, multicenter retrospective study on the effectiveness and safety of eribulin in Korean breast cancer patients (REMARK)
Min Ho Park, Soo Jung Lee, Woo Chul Noh, Chang Wan Jeon, Seok Won Lee, Gil Soo Son, Byung-In Moon, Jin Sun Lee, Sung Soo Kang, Young Jin Suh, Geumhee Gwak, Tae Hyun Kim, Young Bum Yoo, Hyun-Ah Kim, Min Young Kim, Ju Yeon Kim, Joon Jeong
The Breast.2020; 54: 121. CrossRef
Effect of eribulin on patients with metastatic breast cancer: multicenter retrospective observational study in Taiwan
Kun-Ming Rau, Fu Ou-Yang, Ta-Chung Chao, Yao-Lung Kuo, Tsui-Fen Cheng, Tsu-Yi Chao, Dar-Ren Chen, Yen-Dun Tzeng, Being-Whey Wang, Chun-Yu Liu, Ming-Hung Hu, Yin-Che Lu, Wei-Jen Ou, Chin-Ho Kuo, Chieh-Han Chuang, Jung-Yu Kan, Fang-Ming Chen, Ming-Feng Hou
Breast Cancer Research and Treatment.2018; 170(3): 583. CrossRef
Incidence and clinical parameters associated with eribulin mesylate-induced peripheral neuropathy
Bin Zhao, Hong Zhao, Jiaxin Zhao
Critical Reviews in Oncology/Hematology.2018; 128: 110. CrossRef
Angiomodulators in cancer therapy: New perspectives
Lenka Varinska, Peter Kubatka, Jan Mojzis, Anthony Zulli, Katarina Gazdikova, Pavol Zubor, Dietrich Büsselberg, Martin Caprnda, Radka Opatrilova, Iveta Gasparova, Martin Klabusay, Martin Pec, Eitan Fibach, Mariusz Adamek, Peter Kruzliak
Biomedicine & Pharmacotherapy.2017; 89: 578. CrossRef
Eribulin in Advanced Breast Cancer: Safety, Efficacy and New Perspectives
Ornella Garrone, Emanuela Miraglio, Anna Maria Vandone, Paola Vanella, Daniele Lingua, Marco C Merlano
Future Oncology.2017; 13(30): 2759. CrossRef
Incidence and relative risk of peripheral neuropathy in cancer patients treated with eribulin: a meta-analysis
Ling Peng, Yun Hong, Xianghua Ye, Peng Shi, Junyan Zhang, Yina Wang, Qiong Zhao
Oncotarget.2017; 8(67): 112076. CrossRef

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Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor–Positive Metastatic Breast Cancer in Korea: Seung Hoon Beom, Jisu Oh, Tae-Yong Kim, Kyung-Hun Lee, Yaewon Yang, Koung Jin Suh, Hyeong-Gon Moon, Sae-Won Han, Do-Youn Oh, Wonshik Han, Tae-You Kim, Dong-Young Noh, Seock-Ah Im; Cancer Res Treat. 2017;49(2):454-463. Published online August 23, 2016; DOI: https://doi.org/10.4143/crt.2016.259

Abstract PDF PubReader ePub

Purpose
Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)–positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients.
Materials and Methods
This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment historywere extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity.
Results
The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated.
Conclusion
Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

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Is hormonal therapy effective in advanced endometrial cancer? A systematic review and meta-analysis
Josee-Lyne Ethier, Danielle N. Desautels, Eitan Amir, Helen MacKay
Gynecologic Oncology.2017; 147(1): 158. CrossRef

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Prognostic Value of Axillary Nodal Ratio after Neoadjuvant Chemotherapy of Doxorubicin/Cyclophosphamide Followed by Docetaxel in Breast Cancer: A Multicenter Retrospective Cohort Study: Se Hyun Kim, Kyung Hae Jung, Tae-Yong Kim, Seock-Ah Im, In Sil Choi, Yee Soo Chae, Sun Kyung Baek, Seok Yun Kang, Sarah Park, In Hae Park, Keun Seok Lee, Yoon Ji Choi, Soohyeon Lee, Joo Hyuk Sohn, Yeon-Hee Park, Young-Hyuck Im, Jin-Hee Ahn, Sung-Bae Kim, Jee Hyun Kim; Cancer Res Treat. 2016;48(4):1373-1381. Published online March 23, 2016; DOI: https://doi.org/10.4143/crt.2015.475

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy.
Materials and Methods
This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model.
Results
A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] –, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]; intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2– subtype.
Conclusion
LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2– patients is notable and worthy of further investigation.

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Breast Cancer Patients With Positive Apical or Infraclavicular/Ipsilateral Supraclavicular Lymph Nodes Should Be Excluded in the Application of the Lymph Node Ratio System
Zhe Wang, Wei Chong, Huikun Zhang, Xiaoli Liu, Yawen Zhao, Zhifang Guo, Li Fu, Yongjie Ma, Feng Gu
Frontiers in Cell and Developmental Biology.2022;[Epub] CrossRef
The prognostic role of lymph node ratio in breast cancer patients received neoadjuvant chemotherapy: A dose-response meta-analysis
Jinzhao Liu, Yifei Li, Weifang Zhang, Chenhui Yang, Chao Yang, Liang Chen, Mingjian Ding, Liang Zhang, Xiaojun Liu, Guozhong Cui, Yunjiang Liu
Frontiers in Surgery.2022;[Epub] CrossRef
Prognostic implications of regression of metastatic axillary lymph nodes after neoadjuvant chemotherapy in patients with breast cancer
Yul Ri Chung, Ji Won Woo, Soomin Ahn, Eunyoung Kang, Eun-Kyu Kim, Mijung Jang, Sun Mi Kim, Se Hyun Kim, Jee Hyun Kim, So Yeon Park
Scientific Reports.2021;[Epub] CrossRef
Using a novel T-lymph node ratio model to evaluate the prognosis of nonmetastatic breast cancer patients who received preoperative radiotherapy followed by mastectomy
Yang Wang, Yuanyuan Zhao, Song Liu, Weifang Tang, Hong Gao, Xucai Zheng, Shikai Hong, Shengying Wang
Medicine.2017; 96(42): e8203. CrossRef
The genetic variants in the PTEN/PI3K/AKT pathway predict susceptibility and CE(A)F chemotherapy response to breast cancer and clinical outcomes
Xiang Li, Ruishan Zhang, Zhuangkai Liu, Shuang Li, Hong Xu
Oncotarget.2017; 8(12): 20252. CrossRef
Prognostic Significance of Inner Quadrant Involvement in Breast Cancer Treated with Neoadjuvant Chemotherapy
Ji Hyun Chang, Wan Jeon, Kyubo Kim, Kyung Hwan Shin, Wonshik Han, Dong-Young Noh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Journal of Breast Cancer.2016; 19(4): 394. CrossRef

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Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study: Younak Choi, Do-Youn Oh, Kyubo Kim, Eui Kyu Chie, Tae-Yong Kim, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Sung Whan Ha, Yung-Jue Bang; Cancer Res Treat. 2016;48(3):1045-1055. Published online October 16, 2015; DOI: https://doi.org/10.4143/crt.2015.226

Abstract PDF PubReader ePub

Purpose
The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC. Materials and Methods Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively.
Results
Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group. Conclusion In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone.

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Dose-Escalated SBRT for Borderline and Locally Advanced Pancreatic Cancer: Resectability Rate and Pathological Results of a Multicenter Prospective Study
Barbara Salas-Salas, Laura Ferrera-Alayon, Alberto Espinosa-Lopez, Maria Luisa Perez-Rodriguez, Antonio Alayón Afonso, Andres Vera-Rosas, Gabriel Garcia-Plaza, Rodolfo Chicas-Sett, Maria Soledad Martinez-Martin, Elisa Salcedo, Andrea Kannemann, Marta Llor
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B. Salas, L. Ferrera-Alayón, A. Espinosa-López, A. Vera-Rosas, E. Salcedo, A. Kannemann, A. Alayon, R. Chicas-Sett, M. LLoret, P.C. Lara
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Bi-Yang Cao, Le-Tian Zhang, Chen-Chen Wu, Jing Wang, Lin Yang
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Comparing concurrent chemoradiotherapy, 125I seed implantation combined with chemotherapy, and chemotherapy alone efficacy in treating unresectable locally advanced pancreatic cancer
Yanfen Zheng, Rui Huang, Wenxue Zou, Chao Liu, Hongxin Niu, Jinbo Yue
Precision Radiation Oncology.2022; 6(2): 144. CrossRef
Concurrent Nab-paclitaxel and Radiotherapy
William T. Arscott, Kevin T. Nead, Adham Bear, Sriram Venigalla, Jacob Shabason, John N. Lukens, John P. Plastaras, Andrzej Wojcieszynski, James Metz, Mark O’Hara, Kim A. Reiss, Ursina Teitelbaum, Arturo Loaiza-Bonilla, Jeffrey Drebin, Major K. Lee, Stuti
American Journal of Clinical Oncology.2021; 44(9): 469. CrossRef
Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Cancer Research and Treatment.2020; 52(1): 149. CrossRef
Current trends and issues of conversion surgery for patients with locally advanced unresectable pancreatic cancer
Toshimichi ASANO, Satoshi HIRANO, Toru NAKAMURA, Takehiro NOJI, Keisuke OKAMURA, Takahiro TSUCHIKAWA, Yuma EBIHARA, Toshiaki SHICHINOHE
Suizo.2018; 33(1): 48. CrossRef
Survival benefit of conversion surgery for patients with initially unresectable pancreatic cancer who responded favorably to nonsurgical treatment
Toshimichi Asano, Satoshi Hirano, Toru Nakamura, Keisuke Okamura, Takahiro Tsuchikawa, Takehiro Noji, Yoshitsugu Nakanishi, Kimitaka Tanaka, Toshiaki Shichinohe
Journal of Hepato-Biliary-Pancreatic Sciences.2018; 25(7): 342. CrossRef
Which patients with locally advanced pancreatic cancer treated with induction chemotherapy are most likely to benefit from post-induction chemoradiotherapy?
Sophie Otter, Irene Chong, Ria Kalaitzaki, Diana Tait
International Journal of Hepatobiliary and Pancreatic Diseases.2018; 8(1): 1. CrossRef
Change in carbohydrate antigen 19-9 level as a prognostic marker of overall survival in locally advanced pancreatic cancer treated with concurrent chemoradiotherapy
Yi-Jun Kim, Hyeon Kang Koh, Eui Kyu Chie, Do-Youn Oh, Yung-Jue Bang, Eun Mi Nam, Kyubo Kim
International Journal of Clinical Oncology.2017; 22(6): 1069. CrossRef
Risk factors of liver metastasis from advanced pancreatic adenocarcinoma: a large multicenter cohort study
Dong S., Wang L., Guo Y. B., Ying H. F., Shen X. H., Meng Z. Q., Chen Hao, Chen Q. W., Li Z. S.
World Journal of Surgical Oncology.2017;[Epub] CrossRef
Risk factors for latent distant organ metastasis detected by staging laparoscopy in patients with radiologically defined locally advanced pancreatic ductal adenocarcinoma
Ilhan Karabicak, Sohei Satoi, Hiroaki Yanagimoto, Tomohisa Yamamoto, Satoshi Hirooka, So Yamaki, Hisashi Kosaka, Kentaro Inoue, Yoichi Matsui, Masanori Kon
Journal of Hepato-Biliary-Pancreatic Sciences.2016; 23(12): 750. CrossRef

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Splenomegaly and Its Associations with Genetic Polymorphisms and Treatment Outcome in Colorectal Cancer Patients Treated with Adjuvant FOLFOX: Mi-Jung Kim, Sae-Won Han, Dae-Won Lee, Yongjun Cha, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Se Hyung Kim, Seock-Ah Im, Yung-Jue Bang, Tae-You Kim; Cancer Res Treat. 2016;48(3):990-997. Published online January 14, 2016; DOI: https://doi.org/10.4143/crt.2015.296

Abstract PDF Supplementary Material PubReader ePub

Purpose
Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients.
Materials and Methods
Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells.
Results
Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, –42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly.
Conclusion
Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.

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Deepanshi Mahajan, Vasudha Sambyal, Kamlesh Guleria
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Deepanshi Mahajan, Vasudha Sambyal, Meena Sudan, Manjit Singh Uppal, Kamlesh Guleria
DNA and Cell Biology Reports.2025; 6(1): 22. CrossRef
Oxaliplatin‑induced changes in splenic volume and liver fibrosis indices: retrospective analyses of colon cancer patients receiving adjuvant chemotherapy
Kadriye Bir Yücel, Atiye Cenay Karabörk Kilic, Osman Sütcüoglu, Ozan Yazıcı, Koray Kilic, Gözde Savaş, Aytug Uner, Nazan Günel, Ahmet Özet, Nuriye Özdemir
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Effects of methanolic leaf extract and fractions of Irvingia gabonensis on hematological parameters in Wistar rats with splenomegaly
Fidelia Okoben, InnocentMary Ejiofor, Ikechukwu Mbagwu, Daniel Ajaghaku, Fredrick Anowi
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Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure
A. Puente, J.I. Fortea, C. Del Pozo, M. Serrano, M. Alonso-Peña, A. Giráldez, L. Tellez, J. Martinez, M. Magaz, L. Ibañez, J. Garcia, E. Llop, C. Alvarez-Navascues, M. Romero, E. Rodriguez, M.T. Arias Loste, A. Antón, V. Echavarria, C. López, A. Albillos,
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The “appearing” and “disappearing” ascites in the treatment of colorectal cancer: a case report
Hong-Ming Cui, Xin-Peng Shu, Zheng-Qiang Wei, Xing-Ye Wu
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A contrast-enhanced CT-based whole-spleen radiomics signature for early prediction of oxaliplatin-related thrombocytopenia in patients with gastrointestinal malignancies: a retrospective study
Yuhong Dai, Yiqi Cheng, Ziling Zhou, Zhen Li, Yan Luo, Hong Qiu
PeerJ.2023; 11: e16230. CrossRef
Natural Language Processing of Large-Scale Structured Radiology Reports to Identify Oncologic Patients With or Without Splenomegaly Over a 10-Year Period
Simon Sun, Kaelan Lupton, Karen Batch, Huy Nguyen, Lior Gazit, Natalie Gangai, Jessica Cho, Kevin Nicholas, Farhana Zulkernine, Varadan Sevilimedu, Amber Simpson, Richard K. G. Do
JCO Clinical Cancer Informatics.2022;[Epub] CrossRef
Model establishment and microarray analysis of mice with oxaliplatin‑induced hepatic sinusoidal obstruction syndrome
Chen Zhu, Xinwei Cheng, Ping Gao, Qianyan Gao, Ximin Wang, Dong Liu, Xiuhua Ren, Chengliang Zhang
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Chen Zhu, Xiuhua Ren, Dong Liu, Chengliang Zhang
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Dominika Jedlińska-Pijanowska, Beata Kasztelewicz, Justyna Czech-Kowalska, Maciej Jaworski, Klaudia Charusta-Sienkiewicz, Anna Dobrzańska, Michael Nevels
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Ryo Ohta, Takeshi Yamada, Keisuke Hara, Takuma Iwai, Kohji Tanakaya, Keiichiro Ishibashi, Kazuhiko Yoshimatsu, Chihiro Kosugi, Masahiro Tsubaki, Hideo Nakajima, Masatoshi Oya, Hiroshi Yoshida, Keiji Koda, Hideyuki Ishida
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Justin G. Lees, Daniel White, Brooke A. Keating, Mallory E. Barkl-Luke, Preet G. S. Makker, David Goldstein, Gila Moalem-Taylor, Senthilnathan Palaniyandi
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N. Sanoj Rejinold, Kondareddy Cherukula, Jong Hoon Ha, In‐Kyu Park, Yeu‐Chun Kim
Advanced Therapeutics.2019;[Epub] CrossRef
Protective effect of Korean red ginseng on oxaliplatin-mediated splenomegaly in colon cancer
Jeonghyun Kang, Joon Seong Park, Sung Gwe Ahn, Jin Hong Lim, Seung Hyuk Baik, Dong Sup Yoon, Kang Young Lee, Joon Jeong
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Chunlei Xu, Xushan Tang, Yanli Qu, Saifuding Keyoumu, Ning Zhou, Yong Tang
Cancer Chemotherapy and Pharmacology.2016; 78(1): 119. CrossRef

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Effect of Time Interval between Breast-Conserving Surgery and Radiation Therapy on Outcomes of Node-Positive Breast Cancer Patients Treated with Adjuvant Doxorubicin/Cyclophosphamide Followed by Taxane: Hyeon Kang Koh, Kyung Hwan Shin, Kyubo Kim, Eun Sook Lee, In Hae Park, Keun Seok Lee, Jungsil Ro, So-Youn Jung, Seeyoun Lee, Seok Won Kim, Han-Sung Kang, Eui Kyu Chie, Wonshik Han, Dong-Young Noh, Kyung-Hun Lee, Seock-Ah Im, Sung Whan Ha; Cancer Res Treat. 2016;48(2):483-490. Published online June 5, 2015; DOI: https://doi.org/10.4143/crt.2015.111

Abstract PDF PubReader ePub

Purpose
This study evaluated the effect of surgery-radiotherapy interval (SRI) on outcomes in patients treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) and adjuvant four cycles of doxorubicin/cyclophosphamide (AC) followed by four cycles of taxane. Materials and Methods From 1999 to 2007, 397 eligible patients were diagnosed. The effect of SRI on outcomes was analyzed using a Cox proportional hazards model, and a maximal chi-square method was used to identify optimal cut-off value of SRI for each outcome.
Results
The median SRI was 6.7 months (range, 5.6 to 10.3 months). A SRI of 7 months was the significant cut-off value for distant metastasis-free survival (DMFS) and disease-free survival (DFS) using a maximal chi-square method. For overall survival, a significant cut-off value was not found. The patients with SRI > 7 months had worse 6-year DMFS and DFS than those with SRI ≤ 7 months on univariate analysis (DMFS, 81% vs. 91%, p=0.003; DFS, 78% vs. 89%, p=0.002). On multivariate analysis, SRI > 7 months did not affect DMFS and DFS. Conclusion RT delayed for more than 7 months after BCS and adjuvant four cycles of AC followed by four cycles of taxane did not compromise clinical outcomes.

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MiR-210 regulates lung adenocarcinoma by targeting HIF-1α
Guolei Cao, Peiwen Fan, Ronghui Ma, Qinghe Wang, Lili He, Haiwen Niu, Qin Luo
Heliyon.2023; 9(5): e16079. CrossRef
Timing of postmastectomy radiotherapy following adjuvant chemotherapy for high-risk breast cancer: A post hoc analysis of a randomised controlled clinical trial
Si-Ye Chen, Guang-Yi Sun, Yu Tang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Xu-Ran Zhao, Yu-Chun Song, Bo Chen, Shu-Nan Qi, Yuan Tang, Ning-Ning Lu, Ning Li, Hui Fang, Ye-Xiong Li, Shu-Lian Wang
European Journal of Cancer.2022; 174: 153. CrossRef
Timing of Postmastectomy Radiotherapy Following Adjuvant Chemotherapy for High-Risk Breast Cancer: A Post-Hoc Analysis of a Randomised Controlled Clinical Trial
Si-Ye Chen, Guang-Yi Sun, Yu Tang, Hao Jing, Yong-Wen Song, Jing Jin, Yue-Ping Liu, Xu-Ran Zhao, Yu-Chun Song, Bo Chen, Shu-Nan Qi, Yuan Tang, Ning-Ning Lu, Ning Li, Hui Fang, Ye-Xiong Li, Shu-Lian Wang
SSRN Electronic Journal .2022;[Epub] CrossRef
Social Determinants of Racial Disparities in Breast Cancer Mortality Among Black and White Women
Oluwole Adeyemi Babatunde, Jan M. Eberth, Tisha Felder, Robert Moran, Samantha Truman, James R. Hebert, Jiajia Zhang, Swann Arp Adams
Journal of Racial and Ethnic Health Disparities.2021; 8(1): 147. CrossRef
How Does the Interval Between Completion of Adjuvant Chemotherapy and Initiation of Radiotherapy Impact Clinical Outcomes in Operable Breast Cancer Patients?
Lu Cao, Cheng Xu, Gang Cai, Wei-Xiang Qi, Rong Cai, Shu-Bei Wang, Dan Ou, Min Li, Kun-Wei Shen, Jia-Yi Chen
Annals of Surgical Oncology.2021; 28(4): 2155. CrossRef
Saving the Breast Saves the Lives of Breast Cancer Patients
Mohammad Esmaeil Akbari, Maryam Khayamzadeh, Hamid Reza Mirzaei, Afshin Moradi, Atieh Akbari, Farid Moradian, Neda Khalili
International Journal of Surgical Oncology.2020; 2020: 1. CrossRef
Timing of Chemotherapy and Radiotherapy Following Breast-Conserving Surgery for Early-Stage Breast Cancer: A Retrospective Analysis
Si-Ye Chen, Yu Tang, Shu-Lian Wang, Yong-Wen Song, Hui Fang, Jian-Yang Wang, Hao Jing, Jiang-Hu Zhang, Guang-Yi Sun, Xu-Ran Zhao, Jing Jin, Yue-Ping Liu, Bo Chen, Shu-Nan Qi, Ning Li, Yuan Tang, Ning-Ning Lu, Hua Ren, Zi-Hao Yu, Ye-Xiong Li
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Evaluation of tissue computed tomography number changes and dosimetric shifts after conventional whole-breast irradiation in patients undergoing breast-conserving surgery
Joo Hwan Lee, Dong Soo Lee, So Hyun Park, Young Kyu Lee, Jeong Soo Kim, Yong Seok Kim
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The influence of timing of radiation therapy following breast-conserving surgery on 10-year disease-free survival
Marissa C van Maaren, Reini W Bretveld, Jan J Jobsen, Renske K Veenstra, Catharina GM Groothuis-Oudshoorn, Hendrik Struikmans, John H Maduro, Luc JA Strobbe, Philip MP Poortmans, Sabine Siesling
British Journal of Cancer.2017; 117(2): 179. CrossRef

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Circulating Plasma Biomarkers for TSU-68, an Oral Antiangiogenic Agent, in Patients with Metastatic Breast Cancer: Changhoon Yoo, Sung-Bae Kim, Jungsil Ro, Seock-Ah Im, Young-Hyuck Im, Jee Hyun Kim, Jin-Hee Ahn, Kyung Hae Jung, Hong Suk Song, Seok Yun Kang, Hee Sook Park, Hyun-Cheol Chung; Cancer Res Treat. 2016;48(2):499-507. Published online July 14, 2015; DOI: https://doi.org/10.4143/crt.2015.089

Abstract PDF PubReader ePub: Purpose
This study analyzed the role of plasma biomarkers for TSU-68 in a previous phase II trial comparing TSU-68 plus docetaxel and docetaxel alone in patients with metastatic breast cancer.
Materials and Methods
A total of 77 patients were eligible for this study (38 in the TSU-68 plus docetaxel arm and 39 in the docetaxel alone arm). Blood samples were collected prior to the start of each cycle, and vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)- AA, -AB, -BB, fibroblast growth factor, M30, C-reactive protein (CRP), and interleukin 6 (IL-6) levels were measured using enzyme linked immunosorbent assay. The primary endpoint was progression-free survival (PFS).
Results
In patients with baseline PDGF-AA ≥ median, median PFS was significantly worse in the TSU-68 plus docetaxel group than in the docetaxel alone group (5.4 months vs. 13.7 months, p=0.049), while a trend toward a PFS benefit was observed in those with baseline PDGF-AA < median (9.7 months vs. 4.0 months, p=0.18; p for interaction=0.03). In the TSU-68 plus docetaxel group, PFS showed significant association with fold changes in CRP (p=0.001), IL-6 (p < .001), PDGF-BB (p=0.02), and VEGF (p=0.047) following the first treatment cycle.
Conclusion
Baseline PDGF-AA levels and dynamics of VEGF, PDGF-BB, CRP, and IL-6 levels were predictive for the efficacy of TSU-68.

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The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy: Younak Choi, Tae-Yong Kim, Do-Youn Oh, Kyung-Hun Lee, Sae-Won Han, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2016;48(1):171-179. Published online March 13, 2015; DOI: https://doi.org/10.4143/crt.2014.292

Abstract PDF Supplementary Material PubReader ePub

Purpose
A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well established. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear. Materials and Methods We retrospectively enrolled APC patients who received palliative chemotherapy between 2003 and 2010. The patients were stratified according to the status of DM, in accordance with 2010 DM criteria (American Heart Association/American Diabetes Association). DM at least 2 years’ duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent-onset).
Results
Of the 349 APC patients, 183 (52.4%) had DM. Among the patients with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87; recent-onset, 73) and the remaining 23 patients developed DM during treatment of APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%), and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed association with decreased overall survival (OS), whereas a diagnosis of DM (HR, 0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS. Metformin treatment itself conferred better OS in comparison within DM patients (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044). Conclusion For APC patients receiving palliative chemotherapy, metformin treatment is associated with longer OS. Patients with DM tend to survive longer than those without DM.

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Nomogram for Predicting Breast Conservation after Neoadjuvant Chemotherapy: Min Kyoon Kim, Wonshik Han, Hyeong-Gon Moon, Soo Kyung Ahn, Jisun Kim, Jun Woo Lee, Ju-Yeon Kim, Taeryung Kim, Kyung-Hun Lee, Tae-Yong Kim, Sae-Won Han, Seock-Ah Im, Tae-You Kim, In Ae Park, Dong-Young Noh; Cancer Res Treat. 2015;47(2):197-207. Published online September 4, 2014; DOI: https://doi.org/10.4143/crt.2013.247

Abstract PDF PubReader ePub

Purpose
The ability to accurately predict the likelihood of achieving breast conservation surgery (BCS) after neoadjuvant chemotherapy (NCT) is important in deciding whether NCT or surgery should be the first-line treatment in patients with operable breast cancers. Materials and Methods We reviewed the data of 513 women, who had stage II or III breast cancer and received NCT and surgery from a single institution. The ability of various clinicopathologic factors to predict the achievement of BCS and tumor size reduction to ≤ 3 cm was assessed. Nomograms were built and validated in an independent cohort. Results BCS was performed in 50.1% of patients, with 42.2% of tumors reduced to ≤ 3 cm after NCT. A multivariate logistic regression analysis showed that smaller initial tumor size, longer distance between the lesion and the nipple, absence of suspicious calcifications on mammography, and a single tumor were associated with BCS rather than mastectomy (p < 0.05). Negative estrogen receptor, smaller initial tumor size, higher Ki-67 level, and absence of in situ component were associated with residual tumor size ≤ 3 cm (p < 0.05). Two nomograms were developed using these factors. The areas under the receiver operating characteristic curves for nomograms predicting BCS and residual tumor ≤ 3 cm were 0.800 and 0.777, respectively. The calibration plots showed good agreement between the predicted and actual probabilities. Conclusion We have established a model with novel factors that predicts BCS and residual tumor size after NCT. This model can help in making treatment decisions for patients who are candidates for NCT.

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Risk scoring system for predicting breast conservation after neoadjuvant chemotherapy
Lobna Ouldamer, Sofiane Bendifallah, Joseph Pilloy, Flavie Arbion, Gilles Body, Caroline Brisson, Vincent Lavoué, Jean Lévêque, Emile Daraï
The Breast Journal.2019; 25(4): 696. CrossRef
Score for the Survival Probability in Metastasis Breast Cancer: A Nomogram-Based Risk Assessment Model
Zhenchong Xiong, Guangzheng Deng, Xinjian Huang, Xing Li, Xinhua Xie, Jin Wang, Zeyu Shuang, Xi Wang
Cancer Research and Treatment.2018; 50(4): 1260. CrossRef
Development of Nomogram to Predict the Best Military Category Using Physical Fitness Variables: A Model Development in Navy Trainees
Milad Nazarzadeh, Ali Reza Khoshdel, Abolfazl Goodarzi, Alireza Mosavi Jarrahi
Journal of Archives in Military Medicine.2018;[Epub] CrossRef
Predicting Successful Conservative Surgery after Neoadjuvant Chemotherapy in Hormone Receptor-Positive, HER2-Negative Breast Cancer
Chang Seok Ko, Kyu Min Kim, Jong Won Lee, Han Shin Lee, Sae Byul Lee, Guiyun Sohn, Jisun Kim, Hee Jeong Kim, Il Yong Chung, Beom Seok Ko, Byung Ho Son, Seung Do Ahn, Sung-Bae Kim, Hak Hee Kim, Sei Hyun Ahn
Journal of Breast Disease.2018; 6(2): 52. CrossRef
External validation of a published nomogram for prediction of brain metastasis in patients with extra-cerebral metastatic breast cancer and risk regression analysis
Ludivine Genre, Henri Roché, Léonel Varela, Dorra Kanoun, Monia Ouali, Thomas Filleron, Florence Dalenc
European Journal of Cancer.2017; 72: 200. CrossRef
Facteurs prédictifs de traitement conservateur après chimiothérapie néo-adjuvante dans le cancer du sein
J. Pilloy, C. Fleurier, M. Chas, L. Bédouet, M.L. Jourdan, F. Arbion, G. Body, L. Ouldamer
Gynécologie Obstétrique Fertilité & Sénologie .2017; 45(9): 466. CrossRef
Actual Conversion Rate from Total Mastectomy to Breast Conservation after Neoadjuvant Chemotherapy for Stages II–III Breast Cancer Patients
Hyejin Mo, Yumi Kim, Jiyoung Rhu, Kyung-Hun Lee, Tae-Yong Kim, Seock-Ah Im, Eun-Shin Lee, Han-Byoel Lee, Hyeong-Gon Moon, Dong-Young Noh, Wonshik Han
Journal of Breast Disease.2017; 5(2): 51. CrossRef

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Prognostic Value of Splenic Artery Invasion in Patients Undergoing Adjuvant Chemoradiotherapy after Distal Pancreatectomy for Pancreatic Adenocarcinoma: Byoung Hyuck Kim, Kyubo Kim, Eui Kyu Chie, Jin-Young Jang, Sun Whe Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Ijin Joo, Sung W. Ha; Cancer Res Treat. 2015;47(2):274-281. Published online September 12, 2014; DOI: https://doi.org/10.4143/crt.2014.025

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate the outcome of adjuvant chemoradiotherapy (CRT) after distal pancreatectomy (DP) in patients with pancreatic adenocarcinoma, and to identify the prognostic factors for these patients.
Materials and Methods
We performed a retrospective review of 62 consecutive patients who underwent curative DP followed by adjuvant CRT between 2000 and 2011. There were 31 men and 31 women, and the median age was 64 years (range, 38 to 80 years). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes with a median dose of 50.4 Gy (range, 40 to 55.8 Gy). All patients received concomitant chemotherapy, and 53 patients (85.5%) also received maintenance chemotherapy. The median follow-up period was 24 months.
Results
Forty patients (64.5%) experienced relapse. Isolated locoregional recurrence developed in 5 patients (8.1%) and distant metastasis in 35 patients (56.5%), of whom 13 had both locoregional recurrence and distant metastasis. The median overall survival (OS) and disease-free survival (DFS) were 37.5 months and 15.4 months, respectively. On multivariate analysis, splenic artery (SA) invasion (p=0.0186) and resection margin (RM) involvement (p=0.0004) were identified as significant adverse prognosticators for DFS. Also, male gender (p=0.0325) and RM involvement (p=0.0007) were associated with a significantly poor OS. Grade 3 or higher hematologic and gastrointestinal toxicities occurred in 22.6% and 4.8% of patients, respectively.
Conclusion
Adjuvant CRT may improve survival after DP for pancreatic body or tail adenocarcinoma. Our results indicated that SA invasion was a significant factor predicting inferior DFS, as was RM involvement. When SA invasion is identified preoperatively, neoadjuvant treatment may be considered.

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Prognostic impact of splenic vessel involvement and tumor size in distal pancreatectomy for adenocarcinoma: a retrospective multicentric cohort study
Dominique Gantois, Théophile Guilbaud, Ugo Scemama, Edouard Girard, Olivier Picaud, Marine Lefevre, Myriam Elgani, Zeinab Hamidou, Vincent Moutardier, Paul Balandraud, Mircea Chirica, Louise Barbier, David Fuks, David Jérémie Birnbaum
Langenbeck's Archives of Surgery.2022; 407(1): 153. CrossRef
Splenic-vasculature involvement is associated with poor prognosis in resected distal pancreatic cancer
Feng Yin, Mohammed Saad, Jingmei Lin, Christopher R Jackson, Bing Ren, Cynthia Lawson, Dipti M Karamchandani, Belen Quereda Bernabeu, Wei Jiang, Teena Dhir, Richard Zheng, Christopher W Schultz, Dongwei Zhang, Courtney L Thomas, Xuchen Zhang, Jinping Lai,
Gastroenterology Report.2021; 9(2): 139. CrossRef
Meta-analysis of recurrence pattern after resection for pancreatic cancer
M Tanaka, A L Mihaljevic, P Probst, M Heckler, U Klaiber, U Heger, M W Büchler, T Hackert
British Journal of Surgery.2019; 106(12): 1590. CrossRef
Improved Survival in Patients with Resected Pancreatic Carcinoma Using Postoperative Intensity-Modulated Radiotherapy and Regional Intra-Arterial Infusion Chemotherapy
Ningyi Ma, Zheng Wang, Jiandong Zhao, Jiang Long, Jin Xu, Zhigang Ren, Guoliang Jiang
Medical Science Monitor.2017; 23: 2315. CrossRef
Role of Adjuvant Radiotherapy in Left-Sided Pancreatic Cancer—Population-Based Analysis with Propensity Score Matching
Yu Jin Lim, Kyubo Kim, Eui Kyu Chie, BoKyong Kim, Sung W. Ha
Journal of Gastrointestinal Surgery.2015; 19(12): 2183. CrossRef

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TGF-β Suppresses COX-2 Expression by Tristetraprolin-Mediated RNA Destabilization in A549 Human Lung Cancer Cells: Soyeong Kang, Ahrum Min, Seock-Ah Im, Sang-Hyun Song, Sang Gyun Kim, Hyun-Ah Kim, Hee-Jun Kim, Do-Youn Oh, Hyun-Soon Jong, Tae-You Kim, Yung-Jue Bang; Cancer Res Treat. 2015;47(1):101-109. Published online October 22, 2014; DOI: https://doi.org/10.4143/crt.2013.192

Abstract PDF PubReader ePub

Purpose
Overexpression of cyclooxygenase 2 (COX-2) is thought to promote survival of transformed cells. Transforming growth factor β (TGF-β) exerts anti-proliferative effects on a broad range of epithelial cells. In the current study, we investigated whether TGF-β can regulate COX-2 expression in A549 human lung adenocarcinoma cells, which are TGF-β-responsive and overexpress COX-2.
Materials and Methods
Western blotting, Northern blotting, and mRNA stability assays were performed to demonstrate that COX-2 protein and mRNA expression were suppressed by TGF-β. We also evaluated the effects of tristetraprolin (TTP) on COX-2 mRNA using RNA interference.
Results
We demonstrated that COX-2 mRNA and protein expression were both significantly suppressed by TGF-β. An actinomycin D chase experiment demonstrated that COX-2 mRNA was more rapidly degraded in the presence of TGF-β, suggesting that TGF-β–induced inhibition of COX-2 expression is achieved via decreased mRNA stability. We also found that TGF-β rapidly and transiently induced the expression of TTP, a well-known mRNA destabilizing factor, before suppression of COX-2 mRNA expression was observed. Using RNA interference, we confirmed that increased TTP levels play a pivotal role in the destabilization of COX-2 mRNA by TGF-β. Furthermore, we showed that Smad3 is essential to TTP-dependent down-regulation of COX-2 expression in response to TGF-β.
Conclusion
The results of this study show that TGF-β down-regulated COX-2 expression via mRNA destabilization mediated by Smad3/TTP in A549 cells.

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A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer: Hyun Jung Lee, Dae-Seog Heo, Joo-Youn Cho, Sae-Won Han, Hye-Jung Chang, Hyeon-Gyu Yi, Tae-Eun Kim, Se-Hoon Lee, Do-Youn Oh, Seock-Ah Im, In-Jin Jang, Yung-Jue Bang; Cancer Res Treat. 2014;46(3):234-242. Published online July 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.3.234

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Purpose
The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. Materials and Methods Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m², and the dose of HM30181A was escalated from 30-210 mg/m². Results A total of twenty-four patients were enrolled. Only one patient experienced a doselimiting toxicity—a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m² of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m² and the area under the curve of plasma concentration- time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m². The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m². The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m². Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. Conclusion The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m².

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Ming-Shen Dai, Ta-Chung Chao, Chang-Fang Chiu, Yen-Shen Lu, Her-Shyong Shiah, Christopher G. C. A. Jackson, Noelyn Hung, Jianguo Zhi, David L. Cutler, Rudolf Kwan, Douglas Kramer, Wing-Kai Chan, Albert Qin, Kuan-Chiao Tseng, Cheung Tak Hung, Tsu-Yi Chao
Therapeutic Advances in Medical Oncology.2023;[Epub] CrossRef
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Jimmy He, Christopher G. C. A. Jackson, Sanjeev Deva, Tak Hung, Katriona Clarke, Eva Segelov, Tsu‐Yi Chao, Ming‐Shen Dai, Hsien‐Tang Yeh, Wen Wee Ma, Douglas Kramer, Wing‐Kai Chan, Rudolf Kwan, David Cutler, Jay Zhi
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Itraconazole synergistically increases therapeutic effect of paclitaxel and 99mTc-MIBI accumulation, as a probe of P-gp activity, in HT-29 tumor-bearing nude mice
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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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Adenoid Cystic Carcinoma of the Breast: A Case Series of Six Patients and Literature Review: Miso Kim, Dae-Won Lee, Jin Im, Koung Jin Suh, Bhumsuk Keam, Hyeong-Gon Moon, Seock-Ah Im, Wonshik Han, In Ae Park, Dong-Young Noh; Cancer Res Treat. 2014;46(1):93-97. Published online January 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.1.93

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Adenoid cystic carcinoma (ACC) of the breast is a very rare and indolent tumor with a favorable prognosis, despite its triple-negative status. Due to its rarity, there has been no consensus regarding treatments, and treatment guidelines have not been established. Here, we report on six patients with ACC of the breast. All of the patients initially presented with localized disease and no axillary lymph node metastases. Although some of our patients developed local recurrence or distant metastases, all patients had a favorable clinical course, and to date, none of the patients has died from complications of her disease. Here, we described the clinicopathologic features of ACC of the breast and review the current literature.

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Locoregional Recurrence in Adenoid Cystic Carcinoma of the Breast: A Retrospective, Multicenter Study (KROG 22-14)
Sang Min Lee, Bum-Sup Jang, Won Park, Yong Bae Kim, Jin Ho Song, Jin Hee Kim, Tae Hyun Kim, In Ah Kim, Jong Hoon Lee, Sung-Ja Ahn, Kyubo Kim, Ah Ram Chang, Jeanny Kwon, Hae Jin Park, Kyung Hwan Shin
Cancer Research and Treatment.2025; 57(1): 150. CrossRef
Unexpected presentation: metastatic adenoid cystic carcinoma (AdCC) of the breast masquerading as a large cystic-solid renal mass
Benjamin Ngie Xiong Wong, David Chun Chen, Justin Duplessis, Dixon Woon
BMJ Case Reports.2025; 18(1): e262550. CrossRef
Breast acinic cell carcinoma with weak progesterone receptor expression: a case report and literature review
Caiyun Bai, Xiaodong Xin, Yisen Yang, Fengjiang Qu, Zhimin Fan
Frontiers in Oncology.2025;[Epub] CrossRef
MYB expression by immunohistochemistry is highly specific and sensitive for detection of solid variant of adenoid cystic carcinoma of the breast among all triple‐negative breast cancers
Harsh Batra, Priya S C Bose, Yang Ding, Alan Dai, Hui Chen, Constance T Albarracin, Hongxia Sun, Aysegul A Sahin, Fei Yang, Ignacio I Wistuba, Maria G Raso
Histopathology.2024; 85(3): 503. CrossRef
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Sung Ui Jung
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Adenoid Cystic Carcinoma of the Breast: Multimodality Imaging Findings and Review of the Literature
Nilgun Guldogan, Gul Esen, Yasemin Kayadibi, Fusun Taskin, Aysenur Oktay Alfatli, Fatma Nur Soylu Boy, Pinar Balci, Onur Bugdayci, Fatma Tokat, Tulin Ozturk, Mehtap Tunaci, Akif Enes Arikan
Academic Radiology.2023; 30(6): 1107. CrossRef
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Tao Huang, Qigen Fang, Lianjie Niu, Lina Wang, Xianfu Sun
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Locally Advanced Adenoid Cystic Carcinoma of the Breast—A Case Report with a Review of the Literature
Joanna Rypel, Paulina Kubacka, Joanna Mykała-Cieśla, Jacek Pająk, Weronika Bulska-Będkowska, Jerzy Chudek
Medicina.2023; 59(11): 2005. CrossRef
Adenoid Cystic Carcinoma of the Breast and Intraoperative Electron Radiotherapy: Single Case Report and Review of Literature
Giuseppe Accardo, Alba ML Capobianco, Giuseppe La Torre, Alexios Thodas, Graziella Marino, Leuconoe Grazia Sisti, Giulia Vita
Future Oncology.2022; 18(7): 871. CrossRef
Breast adenoid cystic carcinoma: a report of seven cases and literature review
Meilin Zhang, Yanbiao Liu, Hongguang Yang, Feng Jin, Ang Zheng
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Adenoid cystic carcinoma and basaloid carcinoma of the breast: A clinicopathological study
Vicente Marco, Felip Garcia, Isabel T. Rubio, Teresa Soler, Laura Ferrazza, Ignasi Roig, Inmaculada Mendez, Xavier Andreu, Clarisa González Mínguez, Francesc Tresserra
Revista Española de Patología.2021; 54(4): 242. CrossRef
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Wenxiang Zhang, Yi Fang, Zhihui Zhang, Jing Wang
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Yun-Chung Cheung, Shir-Hwa Ueng, Shu-Hang Ng, Wen-Lin Kuo
Current Medical Imaging Formerly Current Medical Imaging Reviews.2021; 17(4): 539. CrossRef
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Gábor Cserni, Cecily M. Quinn, Maria Pia Foschini, Simonetta Bianchi, Grace Callagy, Ewa Chmielik, Thomas Decker, Falko Fend, Anikó Kovács, Paul J. van Diest, Ian O. Ellis, Emad Rakha, Tibor Tot
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Adenoid Cystic Carcinoma Breast: a Rare Entity
Santosh Tummidi, Shubhra Prasad, Deepti Joshi, Ashwani Tandon, Anjaly Mohan, Pradeep Saxena, Neelkamal Kapoor
Indian Journal of Surgical Oncology.2020; 11(S2): 226. CrossRef
Adenoid cystic carcinoma of the breast
Devon N Thomas, Armand Asarian, Philip Xiao
Journal of Surgical Case Reports.2019;[Epub] CrossRef
Adenoid cystic carcinoma of the breast in a male
Wenyang Pang, Zhengyi Wang, Xiaoyan Jin, Qiang Zhang
Medicine.2019; 98(32): e16760. CrossRef
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Thomas Edward Glover, Ryan Butel, Cara Manmeet Bhuller, Emma Louise Senior
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Hasnae Alaoui Mhamdi, Hampig Raphael Kourie, Christiane Jungels, Philippe Aftimos, Rhizlane Belbaraka, Martine Piccart-Gebhart
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Patrick M. Dillon, Samhita Chakraborty, Christopher A. Moskaluk, Prashant J. Joshi, Christopher Y. Thomas
Head & Neck.2016; 38(4): 620. CrossRef
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Emad A Rakha, Mohammed A Aleskandarany, Rehab M Samaka, Zsolt Hodi, Andrew H S Lee, Ian O Ellis
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Breast lesions of uncertain malignant nature and limited metastatic potential: proposals to improve their recognition and clinical management
Emad A Rakha, Sunil Badve, Vincenzo Eusebi, Jorge S Reis‐Filho, Stephen B Fox, David J Dabbs, Thomas Decker, Zsolt Hodi, Shu Ichihara, Andrew HS Lee, José Palacios, Andrea L Richardson, Anne Vincent‐Salomon, Fernando C Schmitt, Puay‐Hoon Tan, Gary M Tse,
Histopathology.2016; 68(1): 45. CrossRef
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G. Treglia, F. Bertagna, L. Ceriani, L. Giovanella
Revista Española de Medicina Nuclear e Imagen Molecular.2015; 34(3): 205. CrossRef
A rare case of adenoid cystic carcinoma of the breast detected by 18F-FDG PET/CT
G. Treglia, F. Bertagna, L. Ceriani, L. Giovanella
Revista Española de Medicina Nuclear e Imagen Molecular (English Edition).2015; 34(3): 205. CrossRef
Radiologic and Pathological Correlation of Adenoid Cystic Carcinoma of the Breast: A Case Report
Jung Gyu Kim, Shin Young Kim, Hae Yoen Jung, Sung Yong Kim, Deuk Young Lee, Sang Hyun Park
Journal of the Korean Society of Radiology.2015; 72(6): 411. CrossRef
Imaging Manifestation of Adenoid Cystic Carcinoma of the Breast
Wei Tang, Wei Jun Peng, Ya Jia Gu, Hui Zhu, Ting Ting Jiang, Can Li
Journal of Computer Assisted Tomography.2015; 39(4): 523. CrossRef
Adenoid cystic carcinoma of the breast from a single-center cohort
Elizabeth Kander, Sania Raza, Sagar Dhamne, Mariana Solari, Sarika Jain
Cancer Treatment Communications.2015; 4: 182. CrossRef
Breast Neoplasms with Dermal Analogue Differentiation (Mammary Cylindroma): Report of 3 Cases and a Proposal for a New Terminology
Emad A. Rakha, Andrew H.S. Lee, Rachael Sheeran, Chris Abbosh, Zsolt Hodi, Will Merchant, Ian O. Ellis, Abeer M. Shaaban
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Influence of Ribosomal Protein L39-L in the Drug Resistance Mechanisms of Lacrimal Gland Adenoid Cystic Carcinoma Cells
Qing Ye, Shao-Feng Ding, Zhi-An Wang, Jie Feng, Wen-Bin Tan
Asian Pacific Journal of Cancer Prevention.2014; 15(12): 4995. CrossRef
Adenoid cystic carcinoma of breast: Recent advances
Kosuke Miyai
World Journal of Clinical Cases.2014; 2(12): 732. CrossRef

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Clinical Implications of VEGF, TGF-beta1, and IL-1beta in Patients with Advanced Non-small Cell Lung Cancer: Ji-Won Kim, Youngil Koh, Dong-Wan Kim, Yong-Oon Ahn, Tae Min Kim, Sae-Won Han, Do-Youn Oh, Se-Hoon Lee, Seock-Ah Im, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang; Cancer Res Treat. 2013;45(4):325-333. Published online December 31, 2013; DOI: https://doi.org/10.4143/crt.2013.45.4.325

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PURPOSE
Vascular endothelial growth factor (VEGF)-A, VEGF165b, interleukin (IL)-1beta, and transforming growth factor (TGF)-beta1 are known to influence tumor angiogenesis. Clinical implications of these cytokines need to be elucidated.
MATERIALS AND METHODS
Using clinical data and baseline serum samples of 140 consecutive patients with advanced non-small cell lung cancer who received platinum-based combination chemotherapy, we investigated the association among serum cytokine levels, treatment outcomes, as well as leukocyte and platelet counts.
RESULTS
The median age of patients was 64 years (range, 26 to 86 years). The male to female ratio was 104:36. High TGF-beta1 and IL-1beta levels were associated with shorter progression-free survival, and high VEGF-A and IL-1beta levels were associated with shorter overall survival in the univariate analysis. VEGF165b was not related to the treatment outcomes. Leukocytosis and thrombocytosis were associated with shorter overall survival. The multivariate analysis demonstrated that VEGF-A, IL-1beta, and leukocytosis were significant prognostic factors (p=0.0497, p=0.047, and p<0.001, respectively). Leukocytosis was not associated with recent pneumonia (p=0.937) and correlated with VEGF-A (p<0.001) and TGF-beta1 (p=0.020) levels.
CONCLUSION
Serum VEGF-A, TGF-1beta, and IL-1beta levels, in addition to leukocyte and platelet counts, are shown to be associated with clinical outcomes. Leukocyte and platelet counts are correlated with serum VEGF-A and TGF-beta1 levels.

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IL‐1β promotes the nuclear translocaiton of S100A4 protein in gastric cancer cells MGC803 and the cell's stem‐like properties through PI3K pathway
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Camille Emprou, Pauline Le Van Quyen, Jérémie Jégu, Nathalie Prim, Noëlle Weingertner, Eric Guérin, Erwan Pencreach, Michèle Legrain, Anne‐Claire Voegeli, Charlotte Leduc, Bertrand Mennecier, Pierre‐Emmanuel Falcoz, Anne Olland, Nicolas Santelmo, Elisabet
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Cordycepin inhibits LPS-induced inflammatory responses by modulating NOD-Like Receptor Protein 3 inflammasome activation
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Syndrome of Inappropriate Antidiuretic Hormone Secretion: A Poor Prognosis in Small-cell Lung Cancer
Xu Wang, Min Liu, Lei Zhang, Kewei Ma
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Alexander Kaltenborn, Svenja Matzke, Moritz Kleine, Till Krech, Wolf Ramackers, Florian W. R. Vondran, Jürgen Klempnauer, Hüseyin Bektas, Harald Schrem
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Association of CT perfusion imaging with plasma levels of TGF-β1 and VEGF in patients with NSCLC
Da-Wei Li, Bao-Zhong Wu, Yu-Sen Shi, Zhi-Qun Li, Xu-Dong Liu, Xiao-Hua Li
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Anne-Marie Baird, Steven G. Gray, Derek J. Richard, Kenneth J. O’Byrne
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Dysregulation of TGFβ1 Activity in Cancer and Its Influence on the Quality of Anti-Tumor Immunity
Kristian Hargadon
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Associations of Circulating Cytokines and Chemokines With Cancer Mortality in Men With Rheumatoid Arthritis
Bryant R. England, Jeremy Sokolove, William H. Robinson, Geoffrey M. Thiele, Apar K. Ganti, Harlan Sayles, Kaleb Michaud, Liron Caplan, Lisa A. Davis, Grant W. Cannon, Brian Sauer, Namrata Singh, E. Blair Solow, Andreas M. Reimold, Gail S. Kerr, Pascale S
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The inflammasome: an emerging therapeutic oncotarget for cancer prevention
Wang Zhiyu, Neng Wang, Qi Wang, Cheng Peng, Jin Zhang, Pengxi Liu, Aihua Ou, Shaowen Zhong, Mario D. Cordero, Yi Lin
Oncotarget.2016; 7(31): 50766. CrossRef
Elevated chronic inflammatory factors and myeloid‐derived suppressor cells indicate poor prognosis in advanced melanoma patients
Huanhuan Jiang, Christoffer Gebhardt, Ludmila Umansky, Philipp Beckhove, Torsten J. Schulze, Jochen Utikal, Viktor Umansky
International Journal of Cancer.2015; 136(10): 2352. CrossRef
The Clinical Research of Serum VEGF, TGF-β1, and Endostatin in Non-small Cell Lung Cancer
Shu-Guang Liu, Shuang-Hu Yuan, Hui-Yong Wu, Jie Liu, Cheng-Suo Huang
Cell Biochemistry and Biophysics.2015; 72(1): 165. CrossRef
Platelet VEGF and serum TGF-β1 levels predict chemotherapy response in non-small cell lung cancer patients
Bao-Hong Fu, Zhan-Zhao Fu, Wei Meng, Tao Gu, Xiao-Dong Sun, Zhi Zhang
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Pulmonary Large-Cell Neuroendocrine Carcinoma: From Epidemiology to Therapy
Morena Fasano, Carminia Maria Della Corte, Federica Papaccio, Fortunato Ciardiello, Floriana Morgillo
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The angiogenic responses induced by release of angiogenic proteins from tumor cell‐activated platelets are regulated by distinct molecular pathways
Hongyan Wu, Fangtian Fan, Zhaoguo Liu, Feng Zhang, Yuping Liu, Zhonghong Wei, Cunsi Shen, Yuzhu Cao, Aiyun Wang, Yin Lu
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Serum Calprotectin, CD26 and EGF to Establish a Panel for the Diagnosis of Lung Cancer
Sonia Blanco-Prieto, Lorena Vázquez-Iglesias, Mar Rodríguez-Girondo, Leticia Barcia-Castro, Alberto Fernández-Villar, María Isabel Botana-Rial, Francisco Javier Rodríguez-Berrocal, María Páez de la Cadena, Rossella Rota
PLOS ONE.2015; 10(5): e0127318. CrossRef

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A Case of Desmoplastic Small Round Cell Tumor Diagnosed in a Young Female Patient: Ji-Won Kim, Jin Hyun Park, Hyeon Jin Cho, Ji-Hyun Kwon, Youngil Koh, Su-Jung Kim, Se Hyung Kim, Se-Hoon Lee, Seock-Ah Im, Yong-Tae Kim, Woo Ho Kim; Cancer Res Treat. 2009;41(4):233-236. Published online December 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.4.233

Abstract PDF PubReader ePub

Desmoplastic small round cell tumor is a very rare malignancy. We report the case of a 26-year-old woman who suffered from dyspepsia and abdominal pain for 2 months. We performed an endoscopic biopsy of the duodenal mass and diagnosed her disease as desmoplastic small round cell tumor using immunohistochemical staining, fluorescence in situ hybridization, and reverse transcriptase polymerase chain reaction. Because the mass invaded the pancreas and superior mesenteric vein as well as duodenum and the disease was disseminated to liver and peritoneum, she received palliative chemotherapy using vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide. The maximal response to chemotherapy was stable disease. The patient expired 9 months after diagnosis.

Citations

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Intra-Abdominal Desmoplastic Small Round Cell Tumor: Current Treatment Options and Perspectives
Guixia Wei, Xinyao Shu, Yuwen Zhou, Xia Liu, Xiaorong Chen, Meng Qiu
Frontiers in Oncology.2021;[Epub] CrossRef
A Case Report of Abdominal Desmoplastic Small Round Cell Tumor in a Young Tunisian Woman
Karim Nacef, Mohamed Ali Chaouch, Rym Bouriga, Mohamed Ben Khalifa, Asma Chaouch, Mossab Ghannouchi, Moez Boudokhane
Journal of Gastrointestinal Cancer.2019; 50(3): 568. CrossRef
Primary desmoplastic small-round-cell tumor of the ovary
Ahmed Atef, Khaled Gaballa, Mohammad Zuhdy, Khalid Atallah, Wagdi Elkashef, Shadi Awny, Basma Gadelhak, Basel Refky
Journal of the Egyptian National Cancer Institute.2019;[Epub] CrossRef
Tumor intraabdominal desmoplásico de células pequeñas y redondas
Andrés Alejandro Briseño-Hernández, Deissy Roxana Quezada-López, Lilia Edith Corona-Cobián, Agar Castañeda-Chávez, Alfonso Tonatiuh Duarte-Ojeda, Michel Dassaejv Macías-Amezcua
Cirugía y Cirujanos.2015; 83(3): 243. CrossRef
Intra-abdominal desmoplastic small round cell tumour
Andrés Alejandro Briseño-Hernández, Deissy Roxana Quezada-López, Lilia Edith Corona-Cobián, Agar Castañeda-Chávez, Alfonso Tonatiuh Duarte-Ojeda, Michel Dassaejv Macías-Amezcua
Cirugía y Cirujanos (English Edition).2015; 83(3): 243. CrossRef
Primary desmoplastic small round cell tumor of the duodenum
Qi Liu, Nan Liu, DeXing Chen
European Journal of Medical Research.2014;[Epub] CrossRef
Tumor desmoplásico de células pequeñas y redondas. Diagnóstico y tratamiento
Izaskun Markinez Gordobil, Inmaculada Ruiz, Raúl Jiménez, Eloisa Villarreal, Aintzane Lizarazu, Nerea Borda, Xabier Arteaga, Miguel Ángel Medrano, Esther Guisasola, Adolfo Beguiristain, José María E. Navascués
Gaceta Médica de Bilbao.2012; 109(3): 101. CrossRef
Desmoplastic small round cell tumor of the abdomen: A case report and literature review of therapeutic options
Hafida Benhammane, Leila Chbani, Abdelmalek Ousadden, Ouadii Mouquit, Siham Tizniti, Afaf Riffi Amarti, Nouafal Mellas, Omar El Mesbahi
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Analysis of Prognostic Factors of Pediatric-Type Sarcomas in Adult Patients
Hee Kyung Ahn, Ji Eun Uhm, Jeeyun Lee, Do Hoon Lim, Sung Wook Seo, Ki-Sun Sung, Su Jin Lee, Duk Joo Lee, Kyung Kee Baek, Won-Seog Kim, Joon Oh Park
Oncology.2011; 80(1-2): 21. CrossRef

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Gemcitabine and Vinorelbine Combination Chemotherapy in Anthracycline- and Taxane-pretreated Advanced Breast Cancer: Hye Jin Kim, Jin-Soo Kim, Myung-Deok Seo, So-Yeon Oh, Do-Youn Oh, Jee Hyun Kim, Se-Hoon Lee, Dong-Wan Kim, Seock-Ah Im, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang; Cancer Res Treat. 2008;40(2):81-86. Published online June 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.2.81

Abstract PDF PubReader ePub

Purpose

Anthracycline and taxanes are effective agents in advanced breast cancer and prolong survival times. Some patients achieve prolongation of life with capecitabine, gemcitabine, or vinorelbine, even after failure of both anthracycline and taxanes. We analyzed the efficacy and toxicity of gemcitabine and vinorelbine combination chemotherapy in anthracycline- and taxane-pretreated advanced breast cancer.

Materials and Methods

The medical records of anthracycline- and taxane-pretreated metastatic breast cancer patients who received gemcitabine and vinorelbine combination chemotherapy at the Seoul National University Hospital were reviewed. Gemcitabine (1,000 mg/m²) and vinorelbine (25 mg/m²) were administered intravenously on days 1 and 8 every 3 weeks.

Results

Between 2000 and 2006, 57 patients were eligible (median age, 45 years), and the median number of previous chemotherapy regimens was 3 (range, 1~5). The overall response rate was 30% (95% CI, 18.1~41.9), and the disease control rate was 46% (PR, 30%; SD, 16%). The median duration of follow-up was 33.4 months, the median time-to-progression (TTP) was 3.9 months, and the median overall survival was 10.8 months. None of thepatients with patients with anthracycline and taxane primary resistance showed a response and the median TTP for these patients was significantly shorter than that of other patients (1.9 vs. 4.4 months; p=0.018). Although the efficacy was unsatisfactory in patients with both anthracycline and taxane primary resistance, gemcitabine and vinorelbine combination chemotherapy showed comparable efficacy in anthracycline- and/or taxane-sensitive patients and the patients with secondary resistance, even after failure of second-line therapy. Grade 3/4 hematologic toxicities included neutropenia (18.1%) and febrile neutropenia (0.3%), and non-hematologic toxicities were tolerable.

Conclusion

Gemcitabine and vinorelbine combination chemotherapy in anthracycline- and taxane-pretreated advanced breast cancer was effective and tolerable.

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Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015
Jun Yamamura, Norikazu Masuda, Daigo Yamamoto, Shigeru Tsuyuki, Masahide Yamaguchi, Satoru Tanaka, Junji Tsurutani, Shinya Tokunaga, Katsuhide Yoshidome, Makiko Mizutani, Toyokazu Aono, Asako Ooe, Hirokazu Tanino, Nobuki Matsunami, Hiroyuki Yasojima, Taka
Chemotherapy.2017; 62(5): 307. CrossRef
Phase II study of gemcitabine and vinorelbine as second- or third-line therapy in patients with primary refractory or platinum-resistant recurrent ovarian and primary peritoneal cancer by the Korean Cancer Study Group (KCSG)_KCSG GY10-10
Sook Hee Hong, Soohyeon Lee, Hoon-Gu Kim, Hyo Jin Lee, Kyung Hae Jung, Sang-Cheol Lee, Na-Ri Lee, Jina Yun, In Sook Woo, Kyong Hwa Park, Kyoung-ha Kim, Ho Young Kim, Sun Young Rha, Jae Ho Byun
Gynecologic Oncology.2015; 136(2): 212. CrossRef
‘Who’, ‘when’ and ‘how’ in re-irradiation of recurrent painful bone metastases
Florence Mok, Kenneth Li, Rebecca Yeung, Kam-Hung Wong, Brian Yu, Erin Wong, Gillian Bedard, Edward Chow
Journal of Bone Oncology.2013; 2(1): 33. CrossRef
Gemcitabine in combination with vinorelbine in elderly patients with anthracycline- and taxane-pretreated metastatic breast cancer
Ningning Dong, Mingyu Wang, Huiqing Li, Yongchun Cui, Qisen Guo
Cancer Chemotherapy and Pharmacology.2012; 69(5): 1315. CrossRef
Safety and efficacy of gemcitabine plus cisplatin combination in pretreated metastatic breast cancer patients
Luiz Gustavo Oliveira Brito, Jurandyr Moreira de Andrade, Thiago Lins-Almeida, Fábio Eduardo Zola, Mariana Novaes Pinheiro, Heitor Ricardo Cosiski Marana, Daniel Guimarães Tiezzi, Fernanda Maris Peria
Medical Oncology.2012; 29(1): 33. CrossRef

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The Synergism between Belotecan and Cisplatin in Gastric Cancer: Joo Young Jung, Sang Hyun Song, Tae-Young Kim, Jung Hyun Park, Hyun-Soon Jong, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Noe Kyoung Kim; Cancer Res Treat. 2006;38(3):159-167. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.159

Abstract PDF PubReader ePub

Purpose

We wanted to demonstrate the anti-cancer effect and interaction between belotecan and cisplatin on gastric cancer cell line and we evaluated the mechanisms of this synergistic effect in vitro.

Materials and Methods

The growth inhibitory effect of belotocan and cisplatin against several gastric cancer cell lines (SNU-5, SNU-16 and SNU-601) was estimated by tetrazolium dye assay. The effect of a combination treatment was evaluated by the isobologram method. The biochemical mechanisms for the interaction between the drugs were analyzed by measuring the formation of DNA interstrand cross-links (ICLs) and DNA topo-I activity.

Results

Belotecan showed synergism with cisplatin for growth inhibitory effect on the gastric cancer cell lines SNU-5, and SNU-16, but this was subadditive on the SNU-601 cell line. The formation of DNA ICLs in SNU-16 cells by cisplatin was increased by combination with belotecan, but this was not affected in SNU-601 cells. The topo-I inhibition by belotecan was enhanced at high concentrations of cisplatin in SNU-16, but not in SNU-601 cells.

Conclusion

Belotecan and cisplatin show various combination effect against gastric cancer cells. The synergism between cisplatin and belotecan could be the result of one of the following mechanisms: the modulating effect of belotecan on the repair of cisplatin-induced DNA adducts and the enhancing effect of cisplatin on the belotecan-induced topo-I inhibitory effect.

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Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef
The Advancement of Biodegradable Polyesters as Delivery Systems for Camptothecin and Its Analogues—A Status Report
Katarzyna Strzelecka, Urszula Piotrowska, Marcin Sobczak, Ewa Oledzka
International Journal of Molecular Sciences.2023; 24(2): 1053. CrossRef
Safe approaches for camptothecin delivery: Structural analogues and nanomedicines
Pablo Botella, Eva Rivero-Buceta
Journal of Controlled Release.2017; 247: 28. CrossRef
Sageone, a diterpene from Rosmarinus officinalis, synergizes with cisplatin cytotoxicity in SNU-1 human gastric cancer cells
Sabina Shrestha, Yeon Woo Song, Hyeonji Kim, Dong Sun Lee, Somi Kim Cho
Phytomedicine.2016; 23(13): 1671. CrossRef
Synthesis, characterisation, in vitro DNA binding properties and antioxidant activities of Ln(III) complexes with chromone-3-carbaldehyde-(2′-hydroxy) benzoyl hydrazone
Yong Li, Zheng-yin Yang, Tian-rong Li
Progress in Reaction Kinetics and Mechanism.2015; 40(4): 313. CrossRef
Combination therapy of cilengitide with belotecan against experimental glioblastoma
Young‐Hoon Kim, Jin Kyung Lee, Bokyong Kim, Judy Park DeWitt, Jung Eun Lee, Jung Ho Han, Seung‐Ki Kim, Chang Wan Oh, Chae‐Yong Kim
International Journal of Cancer.2013; 133(3): 749. CrossRef
Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model
Chae-Yong Kim, Su-Jung Lee, Seung-Ki Kim, Chul-Kee Park, Kyu-Chang Wang, Byung-Kyu Cho
Journal of Clinical Neuroscience.2012; 19(2): 301. CrossRef
Phase II study of combined belotecan and cisplatin as first-line chemotherapy in patients with extensive disease of small cell lung cancer
Junshik Hong, Minkyu Jung, Yu Jin Kim, Sun Jin Sym, Sun Young Kyung, Jinny Park, Sang Pyo Lee, Jeong Woong Park, Eun Kyung Cho, Sung Hwan Jeong, Dong Bok Shin, Jae Hoon Lee
Cancer Chemotherapy and Pharmacology.2012; 69(1): 215. CrossRef

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Gefitinib Trial in a Fanconi's Anemia Patient with Multiple Squamous Cell Carcinomas and Hepatocellular Carcinoma: Hae Sun Jung, Gun-Woo Byun, Kyoung-Eun Lee, Yeung Chul Mun, Seung Hyun Nam, Jung Mi Kwon, Shi Nae Lee, Seock-Ah Im, Chu-Myong Seong, Soon Nam Lee; Cancer Res Treat. 2005;37(6):370-373. Published online December 31, 2005; DOI: https://doi.org/10.4143/crt.2005.37.6.370

Abstract PDF PubReader ePub

FA (Fanconi's Anemia) is an autosomal recessive disorder that is characterized by pancytopenia with bone marrow hypoplasia, diverse congenital abnormalities and an increased predisposition towards malignancy. The mainstay of the treatment for these cancers has been surgery, because of the hypersensitive reactions of FA patients to DNA cross- linking agents or radiation. Therefore, there has been no effective therapy for advanced squa mous cell carcinoma. We report here on a patient suffering from advanced multiple squamous cell carcinoma and hepatocellular carcinoma along with an FA, and this patient was treated with gefitinib.

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Oral Tongue Cancer in a Patient with Fanconi Anemia: A Case Report and Literature Review
Siyao Deng, Wenjing Ye, Shichuan Zhang, Guiquan Zhu, Peng Zhang, Yanqiong Song, Fanglei Duan, Jinyi Lang, Shun Lu
Cancer Management and Research.2021; Volume 13: 3145. CrossRef
Treatment of Fanconi Anemia–Associated Head and Neck Cancer: Opportunities to Improve Outcomes
Rex H. Lee, Hyunseok Kang, Sue S. Yom, Agata Smogorzewska, Daniel E. Johnson, Jennifer R. Grandis
Clinical Cancer Research.2021; 27(19): 5168. CrossRef
Gefitinib and Afatinib Show Potential Efficacy for Fanconi Anemia–Related Head and Neck Cancer
Helena Montanuy, Águeda Martínez-Barriocanal, José Antonio Casado, Llorenç Rovirosa, Maria José Ramírez, Rocío Nieto, Carlos Carrascoso-Rubio, Pau Riera, Alan González, Enrique Lerma, Adriana Lasa, Jordi Carreras-Puigvert, Thomas Helleday, Juan A. Bueren,
Clinical Cancer Research.2020; 26(12): 3044. CrossRef
Angiogenesis in chronic liver disease and its complications
Stephanie Coulon, Femke Heindryckx, Anja Geerts, Christophe Van Steenkiste, Isabelle Colle, Hans Van Vlierberghe
Liver International.2011; 31(2): 146. CrossRef

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Expression of Cyclooxygenase-2 in Human Breast Cancer: Relationship with HER-2/neu and other Clinicopathological Prognostic Factors: Eunmi Nam, Soon Nam Lee, Seock-Ah Im, Do-Yeun Kim, Kyoung Eun Lee, Sun Hee Sung; Cancer Res Treat. 2005;37(3):165-170. Published online June 30, 2005; DOI: https://doi.org/10.4143/crt.2005.37.3.165

Abstract PDF PubReader ePub

Purpose

Previous epidemiologic studies have demonstrated that nonsteroidal anti-inflammatory drugs can reduce the risk of breast cancer, and this possibly happens via cyclooxygenase (COX) inhibition. Moreover, growth factor-inducible COX-2, which is overexpressed in neoplastic tissue, is an attractive therapeutic target. Thus, we evaluated the expression of COX-2 in breast cancer tissues, and we assessed the association between COX-2 expression and HER-2/neu expression and also with several clinicopathological features.

Materials and Methods

We analyzed the surgical specimens from 112 women with breast cancer who had undergone lumpectomy or mastectomy. The expressions of COX-2, HER-2/neu, MMP-2 and TIMP-2 were determined immunohistochemically. The correlations between COX-2 expression and several variables, including clinicopathological factors, HER-2/neu expression, MMP-2 expression and TIMP-2 expression were analyzed. Survival analysis was also performed with respect to COX-2 overexpression.

Results

The overexpression of COX-2 protein was observed in 28.6% of the breast cancer tissues. Tumors with lymph node metastasis more frequently showed COX-2 overexpression than did those tumors without metastasis (p=0.039), and the increased COX-2 expression correlated positively with HER-2/neu overexpression (p=0.000). No significant differences were found for the MMP-2 or TIMP-2 expression rates in the COX-2 positive and negative groups. The survival analysis revealed no significant differences according to the COX-2 expression.

Conclusion

This study results suggest that increased COX-2 expression is related with the progression of breast cancer, e.g., with lymph node invasion. COX-2 overexpression found to be related with HER-2/neu overexpression, but not with MMP-2 or TIMP-2 expression. These results support the potential use of selective agents that inhibit COX-2 or HER-2/neu for the management of breast cancer.

Citations

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Postoperative administration of ketorolac averts morphine-induced angiogenesis and metastasis in triple-negative breast cancer
Zhongqi Liu, Shi Cheng, Ganglan Fu, Fengtao Ji, Chengli Wang, Minghui Cao
Life Sciences.2020; 251: 117604. CrossRef
Functional analysis of polymorphisms in the COX-2 gene and risk of lung cancer
Joyce L. Moraes, Amanda B. Moraes, Veronica Aran, Marcelo R. Alves, Luciene Schluckbier, Mariana Duarte, Edson Toscano, Mauro Zamboni, Cinthya Sternberg, Emanuela de Moraes, José R. Lapa E Silva, Carlos Gil Ferreira
Molecular and Clinical Oncology.2017; 6(4): 494. CrossRef
Cyclooxygenase-2 Expression in Invasive Breast Carcinomas of No Special Type and Correlation with Pathological Profiles Suggest a Role in Tumorigenesis Rather than Cancer Progression
Nurul Akmar Misron, Lai-Meng Looi, Nik Raihan Nik Mustapha
Asian Pacific Journal of Cancer Prevention.2015; 16(4): 1553. CrossRef
Stromal, rather than epithelial cyclooxygenase-2 (COX-2) expression is associated with overall survival of breast cancer patients
Justyna Urban, Łukasz Kuźbicki, Grzegorz Szatkowski, Agata Stanek-Widera, Dariusz Lange, Barbara W Chwirot
BMC Cancer.2014;[Epub] CrossRef
Prognostic influence of cyclooxygenase-2 protein and mRNA expression in node-negative breast cancer patients
Isabel Sicking, Karlien Rommens, Marco J Battista, Daniel Böhm, Susanne Gebhard, Antje Lebrecht, Cristina Cotarelo, Gerald Hoffmann, Jan G Hengstler, Marcus Schmidt
BMC Cancer.2014;[Epub] CrossRef

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Open-label, Randomized Comparison of the Efficacy of Intravenous Dolasetron Mesylate and Ondansetron in the Prevention of Acute and Delayed Cisplatin-induced Emesis in Cancer Patients: Jin-Soo Kim, Ji Yeon Baek, Sook Ryun Park, In Sil Choi, Sang-Il Kim, Dong-Wan Kim, Seock-Ah Im, Tae-You Kim, Dae Seog Heo, Yung-Jue Bang, Noe Kyeong Kim; Cancer Res Treat. 2004;36(6):372-376. Published online December 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.6.372

Abstract PDF PubReader ePub

Purpose

The aim of this study is to compare the antiemetic efficacy and tolerability of intravenous dolasetron mesylate and ondansetron in the prevention of acute and delayed emesis.

Material and Methods

From April 2002 through October 2002, a total of 112 patients receiving cisplatin- based combination chemotherapy were randomized to receive a single i.v. dose of dolasetron 100 mg or ondansetron 8 mg, 30 minutes before the initiation of chemotherapy. In the ondansetron group, two additional doses of ondansetron 8 mg were given at intervals of 2 to 4 hours. To prevent delayed emesis, dolasetron 200 mg p.o. daily or ondansetron 8 mg p.o. bid was administered from the 2^nd days to a maximum of 5 days. The primary end point was the proportion of patients that experienced no emetic episodes and required no rescue medication (complete response, CR) during the 24 hours (acute period) and during Day 2 to Day 5±2 days (delayed period), after chemotherapy. The secondary end points included the incidence and severity of emesis.

Results

105 patients were evaluable for efficacy. CR rates during the acute period were 36.0% for a single dose of dolasetron 100 mg, and 43.6% for three doses of ondansetron 8 mg. CR rates during the delayed period were 8.0% and 10.9%, respectively. There was no significant difference in the efficacy between the two groups. Adverse effects were mostly mild to moderate and not related to study medication.

Conclusions

A single i.v. dose of dolasetron 100 mg is as effective as three i.v. doses of ondansetron 8 mg in preventing acute and delayed emesis after cisplatin-based chemotherapy, with a comparable safety profile.

Citations

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Efficacy, safety and effectiveness of ondansetron compared to other serotonin-3 receptor antagonists (5-HT3RAs) used to control chemotherapy-induced nausea and vomiting: systematic review and meta-analysis
Giovana Paula Rezende Simino, Lays Pires Marra, Eli Iola Gurgel de Andrade, Francisco de Assis Acúrcio, Ilka Afonso Reis, Vânia Eloisa De Araújo, Mariângela Leal Cherchiglia
Expert Review of Clinical Pharmacology.2016; 9(9): 1183. CrossRef
Interventions to decrease the risk of adverse cardiac events for patients receiving chemotherapy and serotonin (5-HT3) receptor antagonists: a systematic review
Andrea C Tricco, Charlene Soobiah, Wing Hui, Jesmin Antony, Vladi Struchkov, Brian Hutton, Brenda Hemmelgarn, David Moher, Sharon E Straus
BMC Pharmacology and Toxicology.2015;[Epub] CrossRef

9,652 View
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Elimusertib, a Novel ATR Inhibitor, Induces Anti-Tumor Effects through Replication Catastrophe in Breast Cancers: Mudong Kim, Ahrum Min, Sohyeon Kim, Seongyeong Kim, Yu-jin Kim, Sujin Ham, Miso Lee, Eunice Yoojin Lee, Jinyong Kim, Dae-Won Lee, Kyung-Hun Lee, Seock-Ah Im; Received November 19, 2024 Accepted March 31, 2025 Published online April 7, 2025; DOI: https://doi.org/10.4143/crt.2024.1105 [Accepted]

Abstract PDF: Purpose
Sustained cell proliferation and cell cycle acceleration in cancer cells inherently increase DNA damage, which interferes with homeostatic replication and transcription. Ataxia telangiectasia and Rad3-related (ATR) is crucial for initiation of the DNA damage response, and ATR inhibitors, such as elimusertib, induce increased replication stress and DNA damage. We investigated the anti-tumor effects of elimusertib and its mechanism of action in relation to replication stress.
Materials and Methods
Anti-tumor effects were evaluated by MTT assay and colony formation assay in breast cancer cell lines in vitro, in breast cancer cell xenografts in vivo, and in patient-derived xenograft models. Cell cycle was assessed by flow cytometry and BrdU assay was used to measure replicating cells and S-phase progression. Alkaline and neutral comet assay was used to measure single and double stranded DNA damages, respectively.
Results
Elimusertib delayed S-phase progression in MDA-MB-453 and MDA-MB-231 cells and induced caspase-7-dependent apoptosis. Furthermore, the increase in sub-G1 population in the FACS analysis and Annexin V assay also confirmed apoptotic cell death. In the BrdU assay, single stranded DNA (ssDNA) increased in sensitive cells and aberrant ssDNA induced DNA damage in S-phase and eventually caused replication catastrophe. Finally, these anti-tumor effects were proven in in vivo xenograft and patient-derived xenograft models.
Conclusion
Elimusertib had anti-tumor effects and induced replication catastrophe in breast cancer cells with a high replication rate. Moreover, cells under high DNA replication stress were sensitive to elimusertib. Further studies and treatment strategies with elimusertib are warranted for cancers with a high replication rate.

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