Cancer Research and Treatment

Original 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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Lung and Thoracic cancer

Analytical and Clinical Validation of a Highly Sensitive NGS-Based ctDNA Assay with Real-World Concordance in Non–Small Cell Lung Cancer: Hanbaek Yi, Jeonghwan Youk, Yoojoo Lim, Hanseong Roh, Dongsoo Kyung, Hwang-Phill Kim, Duhee Bang, Bhumsuk Keam, Tae-Min Kim, Miso Kim, Dong-Wan Kim, Tae-You Kim; Cancer Res Treat. 2024;56(3):765-773. Published online January 8, 2024; DOI: https://doi.org/10.4143/crt.2023.1294

Abstract PDF Supplementary Material PubReader ePub

Purpose
There have been needs to improve the sensitivity of liquid biopsy. This report aims to report the analytical and clinical validation of a next-generation sequencing (NGS)–based circulating tumor DNA (ctDNA) assay.
Materials and Methods
Analytical validation was conducted in vitro by evaluating the limit of detection (LOD), precision, and specificity for various genomic aberrations. The real-world performance in non–small cell lung cancer (NSCLC) was assessed by comparing the results of AlphaLiquid100 to the tissue-based results.
Results
The LODs with 30 ng input DNA were 0.11%, 0.11%, 0.06%, 0.21%, and 2.13 copies for detecting single nucleotide variants, insertions, deletions, fusions, and copy number alterations (CNA), respectively. Quantitatively, single nucleotide variants/insertions and deletions, fusions, and CNAs showed a good correlation (R²=0.91, 0.40, and 0.65; y=0.95, 1.06, and 1.19) to the manufacturer’s values, and per-base specificities for all types of variants were near 100%. In real-world NSCLC (n=122), key actionable mutations in NSCLC were detected in 60.7% (74/122) with the ctDNA assay. Comparative analysis against the NGS-based tissue results for all key mutations showed positive percent agreement (PPA) of 85.3%. For individual genes, the PPA was as high as 95.7% for epidermal growth factor receptor (EGFR) mutations and 83.3% for ALK translocations. AlphaLiquid100 detected drug-sensitive EGFR mutation at a variant allele frequency as low as 0.02% and also identified an EGFR mutation in a case where tissue sample missed. Blood samples collected post-targeted therapies revealed additional acquired mutations.
Conclusion
The AlphaLiquid100 ctDNA assay demonstrates robust analytical validity, offering clinically important information for NSCLC patients.

Citations

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Reporting of molecular test results from cell-free DNA analyses: expert consensus recommendations from the 2023 European Liquid Biopsy Society ctDNA Workshop
Vincent D. de Jager, Patrizio Giacomini, Jennifer A. Fairley, Rodrigo A. Toledo, Simon J. Patton, Simon A. Joosse, Claudia Koch, Zandra C. Deans, Sofia Agelaki, Claus Lindbjerg Andersen, Daniel Andersson, Beatriz Bellosillo, Inger Riise Bergheim, Daan van
eBioMedicine.2025; 114: 105636. CrossRef
Next-generation sequencing impact on cancer care: applications, challenges, and future directions
Mariano Zalis, Gilson Gabriel Viana Veloso, Pedro Nazareth Aguiar Jr., Nathalia Gimenes, Marina Xavier Reis, Silvio Matsas, Carlos Gil Ferreira
Frontiers in Genetics.2024;[Epub] CrossRef
Profiling Cell-Free DNA from Malignant Pleural Effusion for Oncogenic Driver Mutations in Patients with Treatment-Naive Stage IV Adenocarcinoma: A Multicenter Prospective Study
Shih-Chieh Chang, Yu-Feng Wei, Chung-Yu Chen, Yi-Chun Lai, Po-Wei Hu, Jui-Chi Hung, Cheng-Yu Chang
Molecular Diagnosis & Therapy.2024; 28(6): 803. CrossRef
Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer
Sohyun Hwang, Seonjeong Woo, Beodeul Kang, Haeyoun Kang, Jung Sun Kim, Sung Hwan Lee, Chang Il Kwon, Dong Soo Kyung, Hwang-Phill Kim, Gwangil Kim, Chan Kim, Hong Jae Chon
Journal of Hepatology.2024;[Epub] CrossRef

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Gastrointestinal cancer

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer: Keun-Wook Lee, Sae-Won Han, Tae Won Kim, Joong Bae Ahn, Ji Yeon Baek, Sang Hee Cho, Howard Lee, Jin Won Kim, Ji-Won Kim, Tae-You Kim, Yong Sang Hong, Seung-Hoon Beom, Yongjun Cha, Yoonjung Choi, Seonhui Kim, Yung-Jue Bang; Cancer Res Treat. 2024;56(2):590-601. Published online December 7, 2023; DOI: https://doi.org/10.4143/crt.2023.1117

Abstract PDF Supplementary Material PubReader ePub

Purpose
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
Materials and Methods
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m²; leucovorin 400 mg/m²; 5-fluorouracil 400 mg/m² bolus and 2,400 mg/m² infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
Results
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
Conclusion
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Citations

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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

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Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer: Dae-Won Lee, Yoojoo Lim, Hwang-Phill Kim, Su Yeon Kim, Hanseong Roh, Jun-Kyu Kang, Kyung‑Hun Lee, Min Jung Kim, Seung-Bum Ryoo, Ji Won Park, Seung-Yong Jeong, Kyu Joo Park, Gyeong Hoon Kang, Sae-Won Han, Tae-You Kim; Cancer Res Treat. 2023;55(3):927-938. Published online March 7, 2023; DOI: https://doi.org/10.4143/crt.2023.268

Abstract PDF Supplementary Material PubReader ePub

Purpose
Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib.
Materials and Methods
In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes.
Results
A total of 285 blood samples from 110 patients were analyzed. Higher baseline cfDNA concentration was associated with worse progression-free survival (PFS) and overall survival (OS). After 2 cycles of treatment, variant allele frequency (VAF) in the majority of ctDNA mutations decreased with a mean relative change of –31.6%. Decreases in the VAF of TP53, APC, TCF7L2, and ROS1 after 2 cycles of regorafenib were associated with longer PFS. We used the sum of VAF at each time point as a surrogate for the overall ctDNA burden. A reduction in sum (VAF) of ≥ 50% after 2 cycles was associated with longer PFS (6.1 vs. 2.7 months, p=0.002), OS (11.3 vs. 5.9 months, p=0.001), and higher disease control rate (86.3% vs. 51.1%, p < 0.001). VAF of the majority of the ctDNA mutations increased at the time of disease progression, and VAF of BRAF increased markedly.
Conclusion
Reduction in ctDNA burden as estimated by sum (VAF) could be used to predict treatment outcome of regorafenib.

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A Systematic Review and Meta-Analysis of the Efficacy and Safety of Regorafenib in the Treatment of Metastatic Colorectal Cancer
Bingjun Liang, Ming Tang, Chao Huang, Yidian Yang, Yue He, Shengrong Liao, Weizeng Shen
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
Pairwise analysis of plasma cell-free DNA before and after palliative second-line paclitaxel plus ramucirumab treatment in patients with metastatic gastric cancer
Ji-Won Kim, Dong Soo Kyung, Won Yeong Ko, Hwang-Phill Kim, Sung-Hyun Hwang, Kui-Jin Kim, Ju Hyun Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Koung Jin Suh, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Keun-Wook Lee
Gastric Cancer.2025;[Epub] CrossRef
Adjuvant therapy for stage IIB + IIC melanoma
Parisa Malekzadeh, Mary S. Brady
Journal of Surgical Oncology.2024; 129(1): 91. CrossRef
Variant allele frequency in circulating tumor DNA correlated with tumor disease burden and predicted outcomes in patients with advanced breast cancer
Jianxin Zhong, Hanfang Jiang, Xiaoran Liu, Hao Liao, Feng Xie, Bin Shao, Shidong Jia, Huiping Li
Breast Cancer Research and Treatment.2024; 204(3): 617. CrossRef
Stage-Specific Plasma Metabolomic Profiles in Colorectal Cancer
Tetsuo Ishizaki, Masahiro Sugimoto, Yu Kuboyama, Junichi Mazaki, Kenta Kasahara, Tomoya Tago, Ryutaro Udo, Kenichi Iwasaki, Yutaka Hayashi, Yuichi Nagakawa
Journal of Clinical Medicine.2024; 13(17): 5202. CrossRef
Nivolumab plus anlotinib hydrochloride in advanced gastric adenocarcinoma and esophageal squamous cell carcinoma: the phase II OASIS trial
Jing Wu, Shilong Zhang, Shan Yu, Guo An, Yi Wang, Yiyi Yu, Li Liang, Yan Wang, Xiaojing Xu, YanShi Xiong, Di Shao, Zhun Shi, Nannan Li, Jingyuan Wang, Dawei Jin, Tianshu Liu, Yuehong Cui
Nature Communications.2024;[Epub] CrossRef
The Diagnostic Utility of cfDNA and ctDNA in Liquid Biopsies for Gastrointestinal Cancers over the Last Decade
Nur Rahadiani, Marini Stephanie, Amelia Fossetta Manatar, Ening Krisnuhoni
Oncology Research and Treatment.2024; 48(3): 125. CrossRef
Mutational evolution after chemotherapy‐progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis
Sheehyun Kim, Yongjun Cha, Yoojoo Lim, Hanseong Roh, Jun‐Kyu Kang, Kyung‐Hun Lee, Min Jung Kim, Ji Won Park, Seung‐Bum Ryoo, Hwang‐Phill Kim, Seung‐Yong Jeong, Kyu Joo Park, Sae‐Won Han, Tae‐You Kim
International Journal of Cancer.2023; 153(3): 571. CrossRef
A Phase II Exploratory Study to Identify Biomarkers Predictive of Clinical Response to Regorafenib in Patients with Metastatic Colorectal Cancer Who Have Failed First-Line Therapy
Karen Gambaro, Maud Marques, Suzan McNamara, Mathilde Couetoux du Tertre, Cyrla Hoffert, Archana Srivastava, Anna Schab, Thierry Alcindor, Adrian Langleben, Lucas Sideris, Mahmoud Abdelsalam, Mustapha Tehfe, Felix Couture, Gerald Batist, Petr Kavan
International Journal of Molecular Sciences.2023; 25(1): 43. CrossRef

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Case Report

Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA: Jung-Ki Yoon, Jongseong Ahn, Sheehyun Kim, Hwang-Phil Kim, Jun-kyu Kang, Duhee Bang, Yoojoo Lim, Tae-You Kim; Cancer Res Treat. 2023;55(3):1048-1052. Published online January 31, 2023; DOI: https://doi.org/10.4143/crt.2022.1529

Abstract PDF Supplementary Material PubReader ePub

Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. However, clinical studies have been limited to breast cancer patients with germline mutations. Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446*)) detected by cell-free DNA analysis after failing standard therapies. This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cell-free DNA. Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446*) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy.

Citations

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Circulating tumor DNA validity and potential uses in metastatic breast cancer
Ottavia Amato, Nefeli Giannopoulou, Michail Ignatiadis
npj Breast Cancer.2024;[Epub] CrossRef
DNA damage targeted therapy for advanced breast cancer
Vanessa Patel, Sandra Casimiro, Catarina Abreu, Tiago Barroso, Rita Teixeira de Sousa, Sofia Torres, Leonor Abreu Ribeiro, Gonçalo Nogueira-Costa, Helena Luna Pais, Conceição Pinto, Leila Costa, Luís Costa
Exploration of Targeted Anti-tumor Therapy.2024; 5(3): 678. CrossRef
Practical Utility of Liquid Biopsies for Evaluating Genomic Alterations in Castration-Resistant Prostate Cancer
Seung-Hwan Jeong, Dongsoo Kyung, Hyeong Dong Yuk, Chang Wook Jeong, Wookjae Lee, Jung-Ki Yoon, Hwang-Phill Kim, Duhee Bang, Tae-You Kim, Yoojoo Lim, Cheol Kwak
Cancers.2023; 15(10): 2847. CrossRef

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Original Articles

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

Abstract PDF Supplementary Material PubReader ePub

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.

Citations

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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
OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death
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
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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
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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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Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef

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Gastrointestinal cancer

A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer: Jwa Hoon Kim, Sun Young Kim, Ji Yeon Baek, Yong Jun Cha, Joong Bae Ahn, Han Sang Kim, Keun-Wook Lee, Ji-Won Kim, Tae-You Kim, Won Jin Chang, Joon Oh Park, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Yeul Hong Kim, Tae Won Kim; Cancer Res Treat. 2020;52(4):1135-1144. Published online April 24, 2020; DOI: https://doi.org/10.4143/crt.2020.218

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations.
Materials and Methods
In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1.
Results
The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths.
Conclusion
Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

Citations

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Current efficacy of immune checkpoint inhibitors in microsatellite unstable colorectal cancer and potential biomarkers
Mariam Rojas, Clara Rodrigo, Reinaldo Moreno, Marta Cascante, Joan Maurel
Exploration of Digestive Diseases.2025;[Epub] CrossRef
Optimal early endpoint for second-line or subsequent immune checkpoint inhibitors in previously treated advanced solid cancers: a systematic review
Jingqiu Li, Xiaoding Zhou, Lei Wu, Jiabao Ma, Yan Tan, Songke Wu, Jie Zhu, Qifeng Wang, Qiuling Shi
BMC Cancer.2025;[Epub] CrossRef
Molecular subtypes of endometrial cancer: Implications for adjuvant treatment strategies
Ye Yang, Su Fang Wu, Wei Bao
International Journal of Gynecology & Obstetrics.2024; 164(2): 436. CrossRef
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Suying Yan, Wanting Wang, Zhiqiang Feng, Jun Xue, Weizheng Liang, Xueliang Wu, Zhiquan Tan, Xipeng Zhang, Shuai Zhang, Xichuan Li, Chunze Zhang
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Inken Salewski, Steffen Kuntoff, Andreas Kuemmel, Rico Feldtmann, Stephan B. Felix, Larissa Henze, Christian Junghanss, Claudia Maletzki
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BioPATH: A Biomarker Study in Asian Patients with HER2+ Advanced Breast Cancer Treated with Lapatinib and Other Anti-HER2 Therapy: Sung-Bae Kim, In-Gu Do, Janice Tsang, Tae-You Kim, Yoon-Sim Yap, Gerardo Cornelio, Gyungyub Gong, Soonmyung Paik, Suee Lee, Ting-Ying Ng, Sarah Park, Ho-Suk Oh, Joanne Chiu, Joohyuk Sohn, Moonhee Lee, Young-Jin Choi, Eun Mi Lee, Kyong-Hwa Park, Christos Nathaniel, Jungsil Ro; Cancer Res Treat. 2019;51(4):1527-1539. Published online June 4, 2019; DOI: https://doi.org/10.4143/crt.2018.598

Abstract PDF PubReader ePub

Purpose
BioPATH is a non-interventional study evaluating the relationship of molecular biomarkers (PTEN deletion/downregulation, PIK3CA mutation, truncated HER2 receptor [p95HER2], and tumor HER2 mRNA levels) to treatment responses in Asian patients with HER2+ advanced breast cancer treated with lapatinib and other HER2-targeted agents. Materials and Methods Female Asian HER2+ breast cancer patients (n=154) who were candidates for lapatinib-based treatment following metastasis and having an available primary tumor biopsy specimen were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, overall survival on lapatinib, correlation between biomarker status and PFS for any previous trastuzumab-based treatment, and conversion/conservation rates of the biomarker status between tissue samples collected at primary diagnosis and at recurrence/metastasis. Potential relationships between tumor mRNA levels of HER2 and response to lapatinib-based therapy were also explored.
Results
p95HER2, PTEN deletion/downregulation, and PIK3CA mutation did not demonstrate any significant co-occurrence pattern and were not predictive of clinical outcomes on either lapatinib-based treatment or any previous trastuzumab-based therapy in the metastatic setting. Proportions of tumors positive for p95HER2 expression, PIK3CA mutation, and PTEN deletion/down-regulation at primary diagnosis were 32%, 31.2%, and 56.2%, respectively. Despite limited availability of paired samples, biomarker status patterns were conserved in most samples. HER2 mRNA levels were not predictive of PFS on lapatinib.
Conclusion
The prevalence of p95HER2 expression, PIK3CA mutation, and PTEN deletion/downregulation at primary diagnosis were similar to previous reports. Importantly, no difference was observed in clinical outcome based on the status of these biomarkers, consistent with reports from other studies.

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PIK3CA Mutation is Associated with Poor Response to HER2-Targeted Therapy in Breast Cancer Patients
Ju Won Kim, Ah Reum Lim, Ji Young You, Jung Hyun Lee, Sung Eun Song, Nam Kwon Lee, Seung Pil Jung, Kyu Ran Cho, Cheol Yong Kim, Kyong Hwa Park
Cancer Research and Treatment.2023; 55(2): 531. CrossRef
Discordance of PIK3CA mutational status between primary and metastatic breast cancer: a systematic review and meta-analysis
Justus Rosin, Ella Svegrup, Antonios Valachis, Ioannis Zerdes
Breast Cancer Research and Treatment.2023; 201(2): 161. CrossRef
Association of PIK3CA mutation with outcomes in HER2-positive breast cancer treated with anti-HER2 therapy: A meta-analysis and bioinformatic analysis of TCGA‑BRCA data
Haizhu Chen, Xingbin Hu, Daquan Wang, Ying Wang, Yunfang Yu, Herui Yao
Translational Oncology.2023; 37: 101738. CrossRef
Comparison of PIK3CA Mutation Prevalence in Breast Cancer Across Predicted Ancestry Populations
Jessica W. Chen, Karthikeyan Murugesan, Justin Y. Newberg, Ethan S. Sokol, Heidi M. Savage, Thomas J. Stout, Sophia L. Maund, Katherine E. Hutchinson
JCO Precision Oncology.2022;[Epub] CrossRef
Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments
Ugo Testa, Germana Castelli, Elvira Pelosi
Medical Sciences.2020; 8(1): 18. CrossRef

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Impact of Mucin Proportion in the Pretreatment MRI on the Outcomes of Rectal Cancer Patients Undergoing Neoadjuvant Chemoradiotherapy: Eunji Kim, Kyubo Kim, Se Hyung Kim, Sae-Won Han, Tae-You Kim, Seung-Yong Jeong, Kyu Joo Park, Jaemoon Koh, Gyeong Hoon Kang, Eui Kyu Chie; Cancer Res Treat. 2019;51(3):1188-1197. Published online December 20, 2018; DOI: https://doi.org/10.4143/crt.2018.434

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate treatment response to neoadjuvant chemoradiotherapy (CRT) with regard to mucin status in pathology and pretreatment magnetic resonance imaging (MRI) in locally advanced rectal cancer.
Materials and Methods
Between 2003 and 2011, 306 patients with locally advanced rectal cancer received neoadjuvant CRT followed by surgery, and mucinous adenocarcinoma (MAC) was found in 27 (8.8%). All MAC patients had MRI before and after CRT and mucin proportion at MRI was measured. Therapeutic response was assessed by pathology after total mesorectal excision. To determine the optimal cut-off for mucin proportion in predicting good CRT response (near total or total regression) and negative circumferential resection margin (CRM), the receiver-operating characteristic analysis was performed.
Results
After neoadjuvant CRT, overall downstaging occurred in 44.4% of MAC and 72.4% of non-MAC (p=0.001), and positive CRM (≤1 mm) was observed more frequently in MAC (p<0.001). The optimal threshold for treatment response was 30% for mucin proportion, and there are nine with low mucin proportion (<30%) and 18 with high mucin proportion (≥30%) in pretreatment MRI. Negative CRM and tumor downstaging occurred more common in patients with mucin <30%, although statistically insignificant (p=0.071 and p=0.072, respectively). Regarding oncologic outcomes, lower mucin proportion in pretreatment MRI was associated with better disease-free and overall survival in MAC group (p=0.092 and 0.056, respectively), but the difference did not reach statistical significance.
Conclusion
Poor treatment outcome with neoadjuvant CRT was observed in patients with MAC, especially those with high mucin proportion at pretreatment MRI.

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Mucinous histology is a negative predictor of neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma
Xiangwen Tan, Yiwei Zhang, Xiaofeng Wu, Qing Fang, Yunhua Xu, Shuxiang Li, Jinyi Yuan, Xiuda Peng, Kai Fu, Shuai Xiao
BMC Gastroenterology.2024;[Epub] CrossRef
Incomplete Resection Is Twice as Likely in Locally Advanced Mucinous Compared to Nonmucinous Rectal Adenocarcinoma: A National Propensity‐Matched Analysis
Leah E. Hendrick, Samer Naffouje, Iman Imanirad, Allan Lima Pereira, Tiago Biachi, Julian Sanchez, Sophie Dessureault, Amalia Stefanou, Sean P. Dineen, Seth Felder
Journal of Surgical Oncology.2024;[Epub] CrossRef
Accelerated T2W Imaging with Deep Learning Reconstruction in Staging Rectal Cancer: A Preliminary Study
Lan Zhu, Bowen Shi, Bei Ding, Yihan Xia, Kangning Wang, Weiming Feng, Jiankun Dai, Tianyong Xu, Baisong Wang, Fei Yuan, Hailin Shen, Haipeng Dong, Huan Zhang
Journal of Imaging Informatics in Medicine.2024;[Epub] CrossRef
Mucinous rectal cancers: clinical features and prognosis in a population-based cohort
Malin Enblad, Klara Hammarström, Joakim Folkesson, Israa Imam, Milan Golubovik, Bengt Glimelius
BJS Open.2022;[Epub] CrossRef
Mucin-Containing Rectal Cancer: A Review of Unique Imaging, Pathology, and Therapeutic Response Features
David D. Childs, Caio Max Sao Pedro Rocha Lima, Yi Zhou
Seminars in Roentgenology.2021; 56(2): 186. CrossRef
Advances in radiological staging of colorectal cancer
R.J. Goiffon, A. O'Shea, M.G. Harisinghani
Clinical Radiology.2021; 76(12): 879. CrossRef
A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer
Klara Hammarström, Israa Imam, Artur Mezheyeuski, Joakim Ekström, Tobias Sjöblom, Bengt Glimelius
Cancers.2020; 13(1): 16. CrossRef

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Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer: Jin Won Kim, Jong Gwang Kim, Byung Woog Kang, Ik-Joo Chung, Young Seon Hong, Tae-You Kim, Hong Suk Song, Kyung Hee Lee, Dae Young Zang, Yoon Ho Ko, Eun-Kee Song, Jin Ho Baek, Dong‐Hoe Koo, So Yeon Oh, Hana Cho, Keun-Wook Lee; Cancer Res Treat. 2019;51(1):223-239. Published online October 19, 2018; DOI: https://doi.org/10.4143/crt.2018.073

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC).
Materials and Methods
Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians.
Results
Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients’ QOL was maintained to a similar degree, regardless of their actual response to chemotherapy.
Conclusion
This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

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Health-related quality of life with bemarituzumab plus mFOLFOX6 in patients with FGFR2b-overexpressing, advanced gastric or gastroesophageal junction cancer
Z.A. Wainberg, P.C. Enzinger, S. Qin, K. Yamaguchi, J. Wang, X. Zhou, A. Gnanasakthy, K. Taylor, A. Yusuf, I. Majer, A. Jamotte, Y.-K. Kang
ESMO Gastrointestinal Oncology.2024; 6: 100095. CrossRef
Impact of systemic cancer treatment on quality of life and mental well-being: a comparative analysis of patients with localized and advanced cancer
Adán Rodríguez-Gonzalez, Alberto Carmona-Bayonas, Raquel Hernandez San Gil, Patricia Cruz-Castellanos, Mónica Antoñanzas-Basa, David Lorente-Estelles, María Jose Corral, Manuel González-Moya, Oscar Alfredo Castillo-Trujillo, Emilio Esteban, Paula Jiménez-
Clinical and Translational Oncology.2023; 25(12): 3492. CrossRef
Reminiscence therapy-based care program alleviates anxiety and depression, as well as improves the quality of life in recurrent gastric cancer patients
Xing Wu, Weiwei Zhang
Frontiers in Psychology.2023;[Epub] CrossRef
Toxicities and Quality of Life during Cancer Treatment in Advanced Solid Tumors
Eun Mi Lee, Paula Jiménez-Fonseca, Rocio Galán-Moral, Sara Coca-Membribes, Ana Fernández-Montes, Elena Sorribes, Esmeralda García-Torralba, Laura Puntí-Brun, Mireia Gil-Raga, Juana Cano-Cano, Caterina Calderon
Current Oncology.2023; 30(10): 9205. CrossRef
Psychosocial functioning in individuals with advanced oesophago-gastric cancer: a mixed methods systematic review
Cara Ghiglieri, Martin Dempster, Sam Wright, Lisa Graham-Wisener
BMC Palliative Care.2023;[Epub] CrossRef
Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial)
Keun-Wook Lee, Ik-Joo Chung, Min-Hee Ryu, Young Iee Park, Byung-Ho Nam, Ho-Suk Oh, Kyung Hee Lee, Hye Sook Han, Bong-Gun Seo, Jae-Cheol Jo, Hyo Rak Lee, Jin Won Kim, Sook Ryun Park, Sang Hee Cho, Yoon-Koo Kang
Gastric Cancer.2021; 24(1): 156. CrossRef
Effect of early tumor response on the health-related quality of life among patients on second-line chemotherapy for advanced gastric cancer in the ABSOLUTE trial
Kazumasa Fujitani, Kohei Shitara, Atsuo Takashima, Keisuke Koeda, Hiroki Hara, Norisuke Nakayama, Shuichi Hironaka, Kazuhiro Nishikawa, Yutaka Kimura, Kenji Amagai, Hisashi Hosaka, Yoshito Komatsu, Ken Shimada, Ryohei Kawabata, Hideki Ohdan, Yasuhiro Kode
Gastric Cancer.2021; 24(2): 467. CrossRef
Quality-of-Life Assessment in Patients Receiving Palliative Chemotherapy: Call for Action
Maheswari Senthil
Annals of Surgical Oncology.2021; 28(1): 7. CrossRef
Impact of gastric cancer treatment on quality of life of patients
Kerstin Schütte, Christian Schulz, Kristina Middelberg-Bisping
Best Practice & Research Clinical Gastroenterology.2021; 50-51: 101727. CrossRef
Influencing Factors and Effects of Treatment on Quality of Life in Patients With Gastric Cancer—A Systematic Review
Sophia Kristina Rupp, Andreas Stengel
Frontiers in Psychiatry.2021;[Epub] CrossRef
Chronological changes in quality of life and body composition after gastrectomy for locally advanced gastric cancer
Ki Bum Park, Ji Yeon Park, Seung Soo Lee, Ho Young Chung, Oh Kyoung Kwon
Annals of Surgical Treatment and Research.2020; 98(5): 262. CrossRef
Viennese risk prediction score for Advanced Gastroesophageal carcinoma based on Alarm Symptoms (VAGAS score): characterisation of alarm symptoms in advanced gastro-oesophageal cancer and its correlation with outcome
Hannah Christina Puhr, Eleonore Pablik, Anna Sophie Berghoff, Gerd Jomrich, Sebastian Friedrich Schoppmann, Matthias Preusser, Aysegül Ilhan-Mutlu
ESMO Open.2020; 5(2): e000623. CrossRef

11,855 View
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NFATC3–PLA2G15 Fusion Transcript Identified by RNA Sequencing Promotes Tumor Invasion and Proliferation in Colorectal Cancer Cell Lines: Jee-Eun Jang, Hwang-Phill Kim, Sae-Won Han, Hoon Jang, Si-Hyun Lee, Sang-Hyun Song, Duhee Bang, Tae-You Kim; Cancer Res Treat. 2019;51(1):391-401. Published online June 14, 2018; DOI: https://doi.org/10.4143/crt.2018.103

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was designed to identify novel fusion transcripts (FTs) and their functional significance in colorectal cancer (CRC) lines.
Materials and Methods
We performed paired-end RNA sequencing of 28 CRC cell lines. FT candidates were identified using TopHat-fusion, ChimeraScan, and FusionMap tools and further experimental validation was conducted through reverse transcription-polymerase chain reaction and Sanger sequencing. FT was depleted in human CRC line and the effects on cell proliferation, cell migration, and cell invasion were analyzed.
Results
One thousand three hundred eighty FT candidates were detected through bioinformatics filtering. We selected six candidate FTs, including four inter-chromosomal and two intrachromosomal FTs and each FT was found in at least one of the 28 cell lines. Moreover, when we tested 19 pairs of CRC tumor and adjacent normal tissue samples, NFATC3–PLA2G15 FT was found in two. Knockdown of NFATC3–PLA2G15 using siRNA reduced mRNA expression of epithelial–mesenchymal transition (EMT) markers such as vimentin, twist, and fibronectin and increased mesenchymal–epithelial transition markers of E-cadherin, claudin-1, and FOXC2 in colo-320 cell line harboring NFATC3–PLA2G15 FT. The NFATC3–PLA2G15 knockdown also inhibited invasion, colony formation capacity, and cell proliferation.
Conclusion
These results suggest that that NFATC3–PLA2G15 FTs may contribute to tumor progression by enhancing invasion by EMT and proliferation.

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Nishu Dalal, Rekha Jalandra, Minakshi Sharma, Hridayesh Prakash, Govind K. Makharia, Pratima R. Solanki, Rajeev Singh, Anil Kumar
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Filippo Pagani, Giovanni Randon, Vincenzo Guarini, Alessandra Raimondi, Michele Prisciandaro, Riccardo Lobefaro, Maria Di Bartolomeo, Gabriella Sozzi, Filippo de Braud, Patrizia Gasparini, Filippo Pietrantonio
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Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma: Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo; Cancer Res Treat. 2019;51(2):510-518. Published online June 13, 2018; DOI: https://doi.org/10.4143/crt.2018.226

Abstract PDF Supplementary Material PubReader ePub

Purpose
The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC).
Materials and Methods
This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints.
Results
A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8).
Conclusion
OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

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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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Jin Won Kim, Hee Young Na, Sejoon Lee, Ji-Won Kim, Koung Jin Suh, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jong Seok Lee, Jaihwan Kim, Jin-Hyeok Hwang, Kihwan Hwang, Chae-Yong Kim, Yong Beom Kim, Soomin Ahn, Kyu Sang Lee, Hyojin Kim, Hye Seung Lee, So Yeo
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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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Redefining the Positive Circumferential Resection Margin by Incorporating Preoperative Chemoradiotherapy Treatment Response in Locally Advanced Rectal Cancer: A Multicenter Validation Study: Joo Ho Lee, Eui Kyu Chie, Seung-Yong Jeong, Tae-You Kim, Dae Yong Kim, Tae Hyun Kim, Sun Young Kim, Ji Yeon Baek, Hee Jin Chang, Min Ju Kim, Sung Chan Park, Jae Hwan Oh, Sung Hwan Kim, Jong Hoon Lee, Doo Ho Choi, Hee Chul Park, Sung-Bum Kang, Jae-Sung Kim; Cancer Res Treat. 2018;50(2):506-517. Published online May 24, 2017; DOI: https://doi.org/10.4143/crt.2016.607

Abstract PDF PubReader ePub

Purpose
This study was conducted to validate the prognostic influence of treatment response among patients with positive circumferential resection margin for locally advanced rectal cancer.
Materials and Methods
Clinical data of 197 patientswith positive circumferentialresection margin defined as ≤ 2 mm after preoperative chemoradiotherapy followed by total mesorectal excision between 2004 and 2009were collected forthis multicenter validation study. All patients underwent median 50.4Gy radiationwith concurrentfluoropyrimidine based chemotherapy. Treatmentresponse was dichotomized to good response, including treatmentresponse of grade 2 or 3, and poor response, including grade 0 or 1.
Results
After 52 months median follow-up, 5-year overall survival (OS) for good responders and poor responders was 79.1% and 48.4%, respectively (p < 0.001). In multivariate analysis, circumferential resection margin involvement and treatment response were a prognosticator for OS and locoregional recurrence-free survival. In subgroup analysis, good responders with close margin showed significantly better survival outcomes for survival. Good responders with involved margin and poor responders with close margin shared similar results, whereas poorresponderswith involved margin hadworst survival (5-year OS, 81.2%, 57.0%, 50.0%, and 32.4%, respectively; p < 0.001).
Conclusion
Among patients with positive circumferential resection margin after preoperative chemoradiotherapy, survival of the good responders was significantly better than poor responders. Subgroup analysis revealed that definition of positive circumferential resection margin may be individualized as involvement for good responders, whereas ≤ 2 mm for poor responders.

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Tailored Strategy for Locally Advanced Rectal Carcinoma (GRECCAR 4): Long-term Results From a Multicenter, Randomized, Open-Label, Phase II Trial
Philippe Rouanet, Eric Rullier, Bernard Lelong, Philippe Maingon, Jean-Jacques Tuech, Denis Pezet, Florence Castan, Stephanie Nougaret
Diseases of the Colon & Rectum.2022; 65(8): 986. CrossRef
Colorectal Cancer Surgery Quality in Manitoba: A Population-Based Descriptive Analysis
Iresha Ratnayake, Jason Park, Natalie Biswanger, Allison Feely, Grace Musto, Kathleen Decker
Current Oncology.2021; 28(3): 2239. CrossRef

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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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Survey of willingness to participate in clinical trials and influencing factors among cancer and non-cancer patients
Teck Long King, Shirin Hui Tan, Shirley Siang Ning Tan, Wei Hong Lai, Mohamad Adam Bujang, Pei Jye Voon
Scientific Reports.2025;[Epub] CrossRef
Exploring clinical trials awareness, information access and participation amongst Australians with ovarian cancer: a qualitative study
Natalie Williams, Hayley Russell, Bridget Bradhurst
Supportive Care in Cancer.2025;[Epub] CrossRef
Depression and anxiety among hemophilia patients enrolled in clinical trials: a multi-center cohort study
Zhen Peng, Xiaoyu Zhu, Chongwei Wang, Mingfeng Zhou, Xiaoling Xu, Yin Chen
Annals of Hematology.2023; 102(7): 1927. CrossRef
Depression and anxiety in cancer patient enrolled in clinical trials with serious adverse events
Zhen Peng, Chongwei Wang, Yubei Sun, Yan Ma, Jumei Wang, Fei Xu, Xiaoling Xu, Yin Chen
Cancer Medicine.2023; 12(19): 20015. CrossRef
Acceptance Factors and Psychological Investigation of Clinical Trials in Cancer Patients
Jiangjie Sun, Jingyi Fang, Chenchen Zhang, Nannan Jia, Weiming Zhao, Jinjian Gao, Yingying Huang, Jiqing Hao, Liping Zhang, Carmen M Galvez-Sánchez
Behavioural Neurology.2023; 2023: 1. CrossRef
Understanding and attitudes of the Jordanian public about clinical research ethics
Mera A Ababneh, Sayer I Al-Azzam, Karem Alzoubi, Abeer Rababa’h, Saddam Al Demour
Research Ethics.2021; 17(2): 228. CrossRef
A patient-focused, theory-guided approach to survey design identified barriers to and drivers of clinical trial participation
Jamie C. Brehaut, Kelly Carroll, Justin Presseau, Dawn P. Richards, Jenn Gordon, Angèle Bénard, Natasha Hudek, Ian D. Graham, Dean A. Fergusson, Susan Marlin
Journal of Clinical Epidemiology.2021; 132: 106. CrossRef
Awareness of breast cancer patients in Poland about clinical trials as available treatment options
Mikołaj Bartoszkiewicz, Joanna Kufel-Grabowska, Maria Litwiniuk
Breast Disease.2021; 40(1): 33. CrossRef
Results from a Theory-Guided Survey to Support Breast Cancer Trial Participation: Barriers, Enablers, and What to Do about them
Jamie C. Brehaut, Kelly Carroll, Jenn Gordon, Justin Presseau, Dawn P. Richards, Dean A. Fergusson, Ian D. Graham, Susan Marlin
Current Oncology.2021; 28(3): 2014. CrossRef
Regional Differences in Access to Clinical Trials for Cancer in Korea
Woorim Kim, Seongkyeong Jang, Yoon Jung Chang
Quality Improvement in Health Care.2021; 27(1): 20. CrossRef
How Cancer Patients Perceive Clinical Trials (CTs) in the Era of CTs: Current Perception and Its Differences Between Common and Rare Cancers
Ji Hyun Park, Ji Sung Lee, HaYeong Koo, Jeong Eun Kim, Jin-Hee Ahn, Min-Hee Ryu, Sook-ryun Park, Shin-kyo Yoon, Jae Cheol Lee, Yong-Sang Hong, Sun Young Kim, Kyo-Pyo Kim, Chang-Hoon Yoo, Jung Yong Hong, Jae Lyun Lee, Kyung Hae Jung, Baek-Yeol Rhyoo, Tae W
Journal of Cancer Education.2020; 35(3): 545. CrossRef
Colorectal cancer survivors’ willingness to participate in a hypothetical clinical trial of Korean medicine: A cross-sectional study
Yown Hwangbo, Gyung Mo Son, Kyung Hee Kim, Myeong Sook Kwon, Kun Hyung Kim
European Journal of Integrative Medicine.2020; 33: 101033. CrossRef
Perception and Satisfaction of Anticancer Drug Clinical Trials in Cancer Patients
Ju Kyung Jeon, Jeong Hye Kim
Asian Oncology Nursing.2019; 19(1): 18. CrossRef
Challenges in informed consent decision-making in Korean clinical research: A participant perspective
Im-Soon Choi, Eun Young Choi, Iyn-Hyang Lee, Dermot Cox
PLOS ONE.2019; 14(5): e0216889. CrossRef
Clinical Trials: What, Where, When?
Olga S. Kobyakova, Ivan A. Deev, Evgeny S. Kulikov, Roman I. Shtykh, Igor D. Pimenov, Olga I. Zvonareva, Igor V. Mareev
Annals of the Russian academy of medical sciences.2018; 73(5): 314. CrossRef

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Identification of Diverse Adenosine-to-Inosine RNA Editing Subtypes in Colorectal Cancer: Si-Hyun Lee, Hwang-Phill Kim, Jun-Kyu Kang, Sang-Hyun Song, Sae-Won Han, Tae-You Kim; Cancer Res Treat. 2017;49(4):1077-1087. Published online January 25, 2017; DOI: https://doi.org/10.4143/crt.2016.301

Abstract PDF Supplementary Material PubReader ePub

Purpose
RNA editing generates protein diversity by altering RNA sequences in coding regions without changing the overall DNA sequence. Adenosine-to-inosine (A-to-I) RNA editing events have recently been reported in some types of cancer, but they are rare in human colorectal cancer (CRC). Therefore, this study was conducted to identify diverse RNA editing in CRC.
Materials and Methods
We compared transcriptome data of 39 CRC samples and paired adjacent tissues from The Cancer Genome Atlas database to identify RNA editing patterns in CRC, focusing on canonical A-to-I RNA edits in coding sequence regions. We investigated nonsynonymous RNA editing patterns by comparing tumor and normal tissue transcriptome data.
Results
The number of RNA edits varied from 12 to 42 per sample. We also observed that hypoand hyper-RNA editing patterns were distinguishable within the samples. We found 10 recurrent nonsynonymous RNA editing candidates in nine genes (PDLIM, NEIL1, SRP9, GLI1, APMAP, IGFBP7, ZNF358, COPA, and ZNF587B) and validated some by Sanger sequencing and the inosine chemical erasing assay. We further showed that editing at these positions was performed by the adenosine deaminase acting on RNA 1 enzyme. Most of these genes are hypoedited in CRC, but editing of GLI1 was increased in cancer tissues compared with normal tissues.
Conclusion
Our results show that nonsynonymous RNA editing patterns can be used to identify CRC patients and could serve as novel biomarkers for CRC.

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Frontiers in Genetics.2020;[Epub] CrossRef
The Novel Zinc Finger Protein 587B Gene, ZNF587B, Regulates Cell Proliferation and Metastasis in Ovarian Cancer Cells in vivo and in vitro

Yujie Liu, Qianying Ouyang, Zeen Sun, Jieqiong Tan, Weihua Huang, Jie Liu, Zhaoqian Liu, Honghao Zhou, Feiyue Zeng, Yingzi Liu
Cancer Management and Research.2020; Volume 12: 5119. CrossRef
Non-Coding RNA Editing in Cancer Pathogenesis
Giulia Romano, Michela Saviana, Patricia Le, Howard Li, Lavender Micalo, Giovanni Nigita, Mario Acunzo, Patrick Nana-Sinkam
Cancers.2020; 12(7): 1845. CrossRef
Automated Isoform Diversity Detector (AIDD): a pipeline for investigating transcriptome diversity of RNA-seq data
Noel-Marie Plonski, Emily Johnson, Madeline Frederick, Heather Mercer, Gail Fraizer, Richard Meindl, Gemma Casadesus, Helen Piontkivska
BMC Bioinformatics.2020;[Epub] CrossRef
RNA editing alterations define manifestation of prion diseases
Eirini Kanata, Franc Llorens, Dimitra Dafou, Athanasios Dimitriadis, Katrin Thüne, Konstantinos Xanthopoulos, Nikolaos Bekas, Juan Carlos Espinosa, Matthias Schmitz, Alba Marín-Moreno, Vincenzo Capece, Orr Shormoni, Olivier Andréoletti, Stefan Bonn, Juan
Proceedings of the National Academy of Sciences.2019; 116(39): 19727. CrossRef
Epigenetic and epitranscriptomic changes in colorectal cancer: diagnostic, prognostic, and treatment implications
Elisa Porcellini, Noemi Laprovitera, Mattia Riefolo, Matteo Ravaioli, Ingrid Garajova, Manuela Ferracin
Cancer Letters.2018;[Epub] CrossRef
Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis
Phaik Ju Teoh, Omer An, Tae-Hoon Chung, Jing Yuan Chooi, Sabrina H. M. Toh, Shuangyi Fan, Wilson Wang, Bryan T. H. Koh, Melissa J. Fullwood, Melissa G. Ooi, Sanjay de Mel, Cinnie Y. Soekojo, Leilei Chen, Siok Bian Ng, Henry Yang, Wee Joo Chng
Blood.2018; 132(12): 1304. CrossRef
ADAR1 prevents small intestinal injury from inflammation in a murine model of sepsis
Shanshou Liu, Jiangang Xie, Bin Zhao, Xiaomin Hu, Xiao Li, Bin Zhang, Xianqi Wang, Yanjun Wang, Jinquan Jiang, Wen Yin, Junjie Li
Cytokine.2018; 104: 30. CrossRef

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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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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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Annabel Shen, Rebecca A. Simonette, Peter L. Rady, Stephen K. Tyring
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Yingjie Cui, Jing Zhang, Guifang Zhang
Current Medicinal Chemistry.2024; 31(14): 1874. CrossRef
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
International Journal of Dermatology.2024; 63(11): 1566. CrossRef
Dickkopf-1 (DKK1) drives growth and metastases in castration-resistant prostate cancer
Letizia Rinella, Gloria Fiorentino, Mara Compagno, Cristina Grange, Massimo Cedrino, Francesca Marano, Ornella Bosco, Elena Vissio, Luisa Delsedime, Patrizia D’Amelio, Benedetta Bussolati, Emanuela Arvat, Maria Graziella Catalano
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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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Tirbanibulin decreases cell proliferation and downregulates protein expression of oncogenic pathways in human papillomavirus containing HeLa cells
Stephen Moore, Veda Kulkarni, Angela Moore, Jennifer R. Landes, Rebecca Simonette, Qin He, Peter L. Rady, Stephen K. Tyring
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Topical Pharmacological Treatment of Actinic Keratoses: Focus on Tirbanibulin 1% Ointment
Mario Valenti, Matteo Bianco, Alessandra Narcisi, Antonio Costanzo, Riccardo Borroni, Marco Ardigò
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Rajibul Islam, Khor Poh Yen, Nur Najihah ’Izzati Mat Rani, Md. Selim Hossain
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Angela Moore, Kara Hurley, Stephen A. Moore, Luke Moore
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Synthesis and evaluation of tirbanibulin derivatives: a detailed exploration of the structure–activity relationship for anticancer activity
Jaebeom Park, Minji Kang, Ahyoung Lim, Kyung-Jin Cho, Chong Hak Chae, Byumseok Koh, Hongjun Jeon
RSC Advances.2023; 13(50): 35583. CrossRef
Tirbanibulina: revisión de su mecanismo de acción novedoso y de cómo encaja en el tratamiento de la queratosis actínica
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Maan T. Khayat, Abdelsattar M. Omar, Farid Ahmed, Mohammad I. Khan, Sara M. Ibrahim, Yosra A. Muhammad, Azizah M. Malebari, Thikryat Neamatallah, Moustafa E. El-Araby
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Minru Liao, Rui Qin, Wei Huang, Hong-Ping Zhu, Fu Peng, Bo Han, Bo Liu
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SAR Probing of KX2-391 Provided Analogues With Juxtaposed Activity Profile Against Major Oncogenic Kinases
Abdelsattar M. Omar, Maan T. Khayat, Farid Ahmed, Yosra A. Muhammad, Azizah M. Malebari, Sara M. Ibrahim, Mohammad I. Khan, Dhaval K. Shah, Wayne E. Childers, Moustafa E. El-Araby
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Todd Schlesinger, Eggert Stockfleth, Ayman Grada, Brian Berman
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Recent Progress on Tubulin Inhibitors with Dual Targeting Capabilities for Cancer Therapy
Wen Shuai, Guan Wang, Yiwen Zhang, Faqian Bu, Sicheng Zhang, Duane D. Miller, Wei Li, Liang Ouyang, Yuxi Wang
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Y. Gilaberte, M.T. Fernández-Figueras
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Rajibul Islam, Kok Wai Lam
European Journal of Medicinal Chemistry.2020; 207: 112812. CrossRef
Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy
Kinsie E Arnst, Souvik Banerjee, Hao Chen, Shanshan Deng, Dong‐Jin Hwang, Wei Li, Duane D Miller
Medicinal Research Reviews.2019; 39(4): 1398. CrossRef
Reversible binding of the anticancer drug KXO1 (tirbanibulin) to the colchicine-binding site of β-tubulin explains KXO1's low clinical toxicity
Lu Niu, Jianhong Yang, Wei Yan, Yamei Yu, Yunhua Zheng, Haoyu Ye, Qiang Chen, Lijuan Chen
Journal of Biological Chemistry.2019; 294(48): 18099. CrossRef
Discovery of Novel Dual Mechanism of Action Src Signaling and Tubulin Polymerization Inhibitors (KX2-391 and KX2-361)
Michael P. Smolinski, Yahao Bu, James Clements, Irwin H. Gelman, Taher Hegab, David L. Cutler, Jane W. S. Fang, Gerald Fetterly, Rudolf Kwan, Allen Barnett, Johnson Y. N. Lau, David G. Hangauer
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Michael J. Ciesielski, Yahao Bu, Stephan A. Munich, Paola Teegarden, Michael P. Smolinski, James L. Clements, Johnson Y. N. Lau, David G. Hangauer, Robert A. Fenstermaker
Journal of Neuro-Oncology.2018; 140(3): 519. 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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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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Association of VEGF promoter polymorphisms with gastrointestinal tract cancer risk and therapy response: a systematic review
Deepanshi Mahajan, Vasudha Sambyal, Kamlesh Guleria
Egyptian Journal of Medical Human Genetics.2025;[Epub] CrossRef
Association of Vascular Endothelial Growth Factor Gene Polymorphisms with Esophageal Squamous Cell Cancer Risk in North-West Indians: A Case–Control Study
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
Journal of Chemotherapy.2024; 36(3): 249. CrossRef
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
Sciences of Pharmacy.2024; 3(1): 11. CrossRef
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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,
Digestive and Liver Disease.2024; 56(10): 1721. CrossRef
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
Frontiers in Oncology.2024;[Epub] CrossRef
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
Molecular Medicine Reports.2022;[Epub] CrossRef
Oxaliplatin-induced hepatic sinusoidal obstruction syndrome
Chen Zhu, Xiuhua Ren, Dong Liu, Chengliang Zhang
Toxicology.2021; 460: 152882. CrossRef
Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection
Dominika Jedlińska-Pijanowska, Beata Kasztelewicz, Justyna Czech-Kowalska, Maciej Jaworski, Klaudia Charusta-Sienkiewicz, Anna Dobrzańska, Michael Nevels
PLOS ONE.2020; 15(5): e0233096. CrossRef
Oxaliplatin-induced increase in splenic volume: experiences from multicenter study in Japan
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
International Journal of Clinical Oncology.2020; 25(12): 2075. CrossRef
Oxaliplatin-induced haematological toxicity and splenomegaly in mice
Justin G. Lees, Daniel White, Brooke A. Keating, Mallory E. Barkl-Luke, Preet G. S. Makker, David Goldstein, Gila Moalem-Taylor, Senthilnathan Palaniyandi
PLOS ONE.2020; 15(9): e0238164. CrossRef
Olive Oil‐Based Ultrafine Theranostic Photo Nanoemulsions: A Versatile Tumor Maneuvering Nanoplatform for Precise Controlled Drug Release in Tumor and Complete Tumor Eradication Mediated by Photo‐Chemotherapy
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
Annals of Surgical Treatment and Research.2018; 95(3): 161. CrossRef
Automatized spleen segmentation in non-contrast-enhanced MR volume data using subject-specific shape priors
Oliver Gloger, Klaus Tönnies, Robin Bülow, Henry Völzke
Physics in Medicine & Biology.2017; 62(14): 5861. CrossRef
UGT1A1 gene polymorphism is associated with toxicity and clinical efficacy of irinotecan-based chemotherapy in patients with advanced colorectal cancer
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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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
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Aberrant Epigenetic Modifications of LPHN2 Function as a Potential Cisplatin-Specific Biomarker for Human Gastrointestinal Cancer: Mi-Seong Jeon, Sang-Hyun Song, Jiyeon Yun, Jee-Youn Kang, Hwang-Phill Kim, Sae-Won Han, Tae-You Kim; Cancer Res Treat. 2016;48(2):676-686. Published online September 22, 2015; DOI: https://doi.org/10.4143/crt.2015.153

Abstract PDF PubReader ePub

Purpose
Epigenetic alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. However, there are currently no standardized epigenetic biomarkers for drug sensitivity in human gastrointestinal cancer. Therefore, the aim of this study is to identify a novel epigenetic biomarker in gastrointestinal cancer.
Materials and Methods
Using bisulfite sequencing and pyrosequencing analysis, DNA methylation patterns of gastric, colon primary tissues and their cancer cells were analyzed, and histone modifications were analyzed using chromatin immunoprecipitation assay. In addition, cancer cells were exposed to cisplatin and treated with a DNA methyltransferase inhibitor.
Results
We report that in human gastric and colon cancers, latrophilin 2 (LPHN2) is silenced by epigenetic modifications, including CpG island methylation and aberrant histone modifications. We also confirmed that LPHN2 was silenced by DNA hypermethylation in primary gastric and colon tumor tissues compared to their normal counterparts. Interestingly, we found that cancer cells with methylated LPHN2 showed higher sensitivity to cisplatin. Also, 5-aza- 2′-deoxycytidine combined with cisplatin decreased the cytotoxicity of cisplatin in cancer cells with methylated LPHN2. In addition, LPHN2 knockdown in cancer cells with high LPHN2 expression sensitized these cells to the anti-proliferative effects of cisplatin.
Conclusion
In human gastrointestinal cancer, we found that LPHN2 is regulated by epigenetic modifications, and that cancer cells with lower LPHN2 expression show higher sensitivity to cisplatin. Therefore, the methylation status of LPHN2 is a potential novel epigenetic biomarker for cisplatin treatment in human gastric and colon cancers.

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Histone modification: Biomarkers and potential therapies in colorectal cancer
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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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Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors: Do-Youn Oh, Se-Hoon Lee, Sae-Won Han, Mi-Jung Kim, Tae-Min Kim, Tae-You Kim, Dae Seog Heo, Miyuki Yuasa, Yasuo Yanagihara, Yung-Jue Bang; Cancer Res Treat. 2015;47(4):607-615. Published online February 26, 2015; DOI: https://doi.org/10.4143/crt.2014.249

Abstract PDF PubReader ePub

Purpose
OPB-31121 is an oral STAT3 inhibitor with a good preclinical antitumor activity. This phase I dose-escalation study of OPB-31121 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. Materials and Methods Patients received OPB-31121 once daily for 28 days of each cycle followed by 2 weeks rest. A standard 3+3 design was used for dose-escalation. Safety and response were evaluated by the National Cancer Institute–Common Terminology Criteria for Adverse Events (NCICTCAE) ver. 3.0 and Response Evaluation Criteria in Solid Tumor (RECIST) ver. 1.0, respectively.
Results
Twenty-five patients were treated with OPB-31121 at five dose levels: 100 mg (n=4), 200 mg (n=3), 400 mg (n=3), 600 mg (n=7), and 800 mg (n=8). Seven patients discontinued treatment during cycle 1 for various reasons other than study drug-related adverse events. Among 18 patients who were evaluable for dose-limiting toxicity (DLT), three DLTs were observed: one DLT (grade 3 vomiting) at 600 mg and two DLTs (grade 3 vomiting, grade 3 diarrhea) at 800 mg. The MTD was determined as 800 mg/day. Common adverse events were gastrointestinal adverse event including nausea (84%), vomiting (80%), and diarrhea (72%). Pharmacokinetics did not demonstrate dose-proportionality of OPB-31121. Eight patients had stable disease and 10 patients had disease progression. Two patients (1 colon cancer, 1 rectal cancer) showed tumor shrinkage. One gastric cancer patient continued treatment up to cycle 13 before disease progression. Conclusion This study demonstrates feasibility of STAT3 inhibition in patients with advanced solid tumor. OPB-31121, at the MTD of 800 mg/day, was safe and relatively well tolerated, and has a preliminary antitumor activity.

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Expression of STAT3, IL27p28 and IL12p35 is deregulated and linked to autoimmune markers in chronic spontaneous urticaria
Sahar Rastgoo, Mojgan Mohammadi, Marcus Maurer, Mahdi Atabaki, Jalil Tavakkol-Afshari, Maryam Khoshkhui
Clinical and Experimental Dermatology.2025; 50(2): 357. CrossRef
Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy
Win Lwin Thuya, Yang Cao, Paul Chi-Lui Ho, Andrea Li-Ann Wong, Lingzhi Wang, Jianbiao Zhou, Christophe Nicot, Boon Cher Goh
Cytokine & Growth Factor Reviews.2025;[Epub] CrossRef
CTSL Promotes Autophagy in Laryngeal Cancer Through the IL6‐JAK‐STAT3 Signalling Pathway
Xueying Wang, Junrong Wang, Lei Wang, Ming Song, Hongxue Meng, Erliang Guo, Susheng Miao
Journal of Cellular and Molecular Medicine.2025;[Epub] CrossRef
Hepatocellular carcinoma: signaling pathways and therapeutic advances
Jiaojiao Zheng, Siying Wang, Lei Xia, Zhen Sun, Kui Ming Chan, René Bernards, Wenxin Qin, Jinhong Chen, Qiang Xia, Haojie Jin
Signal Transduction and Targeted Therapy.2025;[Epub] CrossRef
STAT3 Inhibition Prevents Adaptive Resistance and Augments NK Cell Cytotoxicity to KRASG12C Inhibitors in Nonsmall Cell Lung Cancer
Zehao Pan, Yuxian Qian, Yajing Wang, Te Zhang, Xuming Song, Hanling Ding, Rutao Li, Yijian Zhang, Zi Wang, Hui Wang, Wenjie Xia, Lei Wei, Lin Xu, Gaochao Dong, Feng Jiang
Cancer Science.2025; 116(5): 1375. CrossRef
STAT signaling in the pathogenesis and therapy of acute myeloid leukemia and myelodysplastic syndromes
Zoe King, Sudhamsh Reddy Desai, David A. Frank, Aditi Shastri
Neoplasia.2025; 61: 101137. CrossRef
Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery
Yamei Hu, Zigang Dong, Kangdong Liu
Journal of Experimental & Clinical Cancer Research.2024;[Epub] CrossRef
Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets
Greta Pessino, Claudia Scotti, Maristella Maggi
Cancers.2024; 16(5): 901. CrossRef
Impact of STAT-signaling pathway on cancer-associated fibroblasts in colorectal cancer and its role in immunosuppression
Damián Sánchez-Ramírez, Mónica G Mendoza-Rodríguez, Omar R Alemán, Fernando A Candanedo-González, Miriam Rodríguez-Sosa, Juan José Montesinos-Montesinos, Mauricio Salcedo, Ismael Brito-Toledo, Felipe Vaca-Paniagua, Luis I Terrazas
World Journal of Gastrointestinal Oncology.2024; 16(5): 1705. CrossRef
Targeted Treatment against Cancer Stem Cells in Colorectal Cancer
Julia Martínez-Pérez, Carlos Torrado, María A. Domínguez-Cejudo, Manuel Valladares-Ayerbes
International Journal of Molecular Sciences.2024; 25(11): 6220. CrossRef
Interleukin-6 serves as a critical factor in various cancer progression and therapy
Asma’a H. Mohamed, Abdulrahman T. Ahmed, Waleed Al Abdulmonem, Dmitry Olegovich Bokov, Alaa Shafie, Hussein Riyadh Abdul Kareem Al-Hetty, Chou-Yi Hsu, Mohammed Alissa, Shahid Nazir, Mohammad Chand Jamali, Mustafa Mudhafar
Medical Oncology.2024;[Epub] CrossRef
Targeting cytokine and chemokine signaling pathways for cancer therapy
Ming Yi, Tianye Li, Mengke Niu, Haoxiang Zhang, Yuze Wu, Kongming Wu, Zhijun Dai
Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
Recent advances in targeted drug delivery systems for multiple myeloma
Ashruti Pant, Aayushi Laliwala, Sarah A. Holstein, Aaron M. Mohs
Journal of Controlled Release.2024; 376: 215. CrossRef
A strategic review of STAT3 signaling inhibition by phytochemicals for cancer prevention and treatment: Advances and insights
Suryaa Manoharan, Ekambaram Perumal
Fitoterapia.2024; 179: 106265. CrossRef
The STAT family: Key transcription factors mediating crosstalk between cancer stem cells and tumor immune microenvironment
Mengxuan Zhu, Suyao Li, Xin Cao, Khalid Rashid, Tianshu Liu
Seminars in Cancer Biology.2023; 88: 18. CrossRef
Dual inhibition of MYC and SLC39A10 by a novel natural product STAT3 inhibitor derived from Chaetomium globosum suppresses tumor growth and metastasis in gastric cancer
Xiaoqing Guan, Jing Yang, Weiyi Wang, Bing Zhao, Shiyu Hu, Dehua Yu, Li Yuan, Yunfu Shi, Jingli Xu, Jinyun Dong, Jinxin Wang, Xiang-Dong Cheng, Jiang-Jiang Qin
Pharmacological Research.2023; 189: 106703. CrossRef
JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens
Qian Hu, Qihui Bian, Dingchao Rong, Leiyun Wang, Jianan Song, Hsuan-Shun Huang, Jun Zeng, Jie Mei, Peng-Yuan Wang
Frontiers in Bioengineering and Biotechnology.2023;[Epub] CrossRef
Brevilin A is a potent anti-metastatic CRC agent that targets the VEGF-IL6-STAT3 axis in the HSCs-CRC interplay
Xueying Fan, Mingjing Meng, Baoting Li, Hui Chen, Jincheng Tan, Keyang Xu, Shilin Xiao, Hiu-Yee Kwan, Zhongqiu Liu, Tao Su
Journal of Translational Medicine.2023;[Epub] CrossRef
Application of Nano-Antibodies for Cancer Immunotherapy
Sunanda Singh, Samara P. Singh, Ashutosh S. Parihar
Current Tissue Microenvironment Reports.2023; 4(2): 17. CrossRef
Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies
Yan-Ruide Li, Ying Fang, Zibai Lyu, Yichen Zhu, Lili Yang
Journal of Translational Medicine.2023;[Epub] CrossRef
C188-9, a specific inhibitor of STAT3 signaling, prevents thermal burn-induced skeletal muscle wasting in mice
Yuko Ono, Masafumi Saito, Kazuho Sakamoto, Yuko Maejima, Shingen Misaka, Kenju Shimomura, Nobuto Nakanishi, Shigeaki Inoue, Joji Kotani
Frontiers in Pharmacology.2022;[Epub] CrossRef
Signaling Pathways and Targeted Therapies for Stem Cells in Prostate Cancer
Madhuvanthi Giridharan, Vasu Rupani, Satarupa Banerjee
ACS Pharmacology & Translational Science.2022; 5(4): 193. CrossRef
Insights into the role of STAT3 in intrahepatic cholangiocarcinoma (Review)
Ranzhiqiang Yang, Yinghui Song, Kashif Shakoor, Weimin Yi, Chuang Peng, Sulai Liu
Molecular Medicine Reports.2022;[Epub] CrossRef
Inhibition of STAT3-ferroptosis negative regulatory axis suppresses tumor growth and alleviates chemoresistance in gastric cancer
Shumin Ouyang, Huaxuan Li, Linlin Lou, Qiuyao Huang, Zhenhua Zhang, Jianshan Mo, Min Li, Jiaye Lu, Kai Zhu, Yunjie Chu, Wen Ding, Jianzheng Zhu, Ziyou Lin, Lin Zhong, Junjian Wang, Peibin Yue, James Turkson, Peiqing Liu, Yuanxiang Wang, Xiaolei Zhang
Redox Biology.2022; 52: 102317. CrossRef
Digesting the Role of JAK-STAT and Cytokine Signaling in Oral and Gastric Cancers
Yanhong Ni, Jun T. Low, John Silke, Lorraine A. O’Reilly
Frontiers in Immunology.2022;[Epub] CrossRef
A Broad-Based Characterization of a Cell-Penetrating, Single Domain Camelid Bi-Specific Antibody Monomer That Targets STAT3 and KRAS Dependent Cancers
Sunanda Singh, Genoveva Murillo, Justin Richner, Samara P. Singh, Erica Berleth, Vijay Kumar, Rajendra Mehta, Vijay Ramiya, Ashutosh S. Parihar
International Journal of Molecular Sciences.2022; 23(14): 7565. CrossRef
Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy
Elham Patrad, Solmaz Khalighfard, Taghi Amiriani, Vahid Khori, Ali Mohammad Alizadeh
Cellular Oncology.2022; 45(6): 1073. CrossRef
STAT3 and Its Targeting Inhibitors in Oral Squamous Cell Carcinoma
Mingjing Jiang, Bo Li
Cells.2022; 11(19): 3131. CrossRef
The Role of IL-6 in Cancer Cell Invasiveness and Metastasis—Overview and Therapeutic Opportunities
Magdalena Rašková, Lukáš Lacina, Zdeněk Kejík, Anna Venhauerová, Markéta Skaličková, Michal Kolář, Milan Jakubek, Daniel Rosel, Karel Smetana, Jan Brábek
Cells.2022; 11(22): 3698. CrossRef
An update on investigational therapies that target STAT3 for the treatment of cancer
Matteo Santoni, Francesca Miccini, Alessia Cimadamore, Francesco Piva, Francesco Massari, Liang Cheng, Antonio Lopez-Beltran, Rodolfo Montironi, Nicola Battelli
Expert Opinion on Investigational Drugs.2021; 30(3): 245. CrossRef
RETRACTED: GATA4 Regulates Inflammation-Driven Pancreatic Ductal Adenocarcinoma Progression
Weiliang Jiang, Congying Chen, Li Huang, Jie Shen, Lijuan Yang
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Phytochemicals Targeting JAK–STAT Pathways in Inflammatory Bowel Disease: Insights from Animal Models
Sun Young Moon, Kwang Dong Kim, Jiyun Yoo, Jeong-Hyung Lee, Cheol Hwangbo
Molecules.2021; 26(9): 2824. CrossRef
Development and Validation of an IL6/JAK/STAT3-Related Gene Signature to Predict Overall Survival in Clear Cell Renal Cell Carcinoma
Chuanchuan Zhan, Chao Xu, Jiajun Chen, Chong Shen, Jinkun Li, Zichu Wang, Xiangrong Ying, Zhengang Luo, Yu Ren, Gangfeng Wu, Haojie Zhang, Manfei Qian
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Emerging role of signal transducer and activator of transcription 3 (STAT3) in pituitary adenomas
Cyndy Liu, Tae Nakano-Tateno, Motoyasu Satou, Constance Chik, Toru Tateno
Endocrine Journal.2021; 68(10): 1143. CrossRef
The JAK/STAT signaling pathway: from bench to clinic
Xiaoyi Hu, Jing li, Maorong Fu, Xia Zhao, Wei Wang
Signal Transduction and Targeted Therapy.2021;[Epub] CrossRef
Interleukin-6 and colorectal cancer development
I.А. Hromakova, P.P. Sorochan, N.E. Prokhach, I.S. Hromakova
Український радіологічний та онкологічний журнал.2021; 29(4): 89. CrossRef
Ailanthone suppresses the activity of human colorectal cancer cells through the STAT3 signaling pathway
Haixiang Ding, Xiuchong Yu, Zhilong Yan
International Journal of Molecular Medicine.2021;[Epub] CrossRef
Radiation induces an inflammatory response that results in STAT3-dependent changes in cellular plasticity and radioresistance of breast cancer stem-like cells
Kimberly M. Arnold, Lynn M. Opdenaker, Nicole J. Flynn, Daniel Kwesi Appeah, Jennifer Sims-Mourtada
International Journal of Radiation Biology.2020; 96(4): 434. CrossRef
Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization
Jan Jamroskovic, Mara Doimo, Karam Chand, Ikenna Obi, Rajendra Kumar, Kristoffer Brännström, Mattias Hedenström, Rabindra Nath Das, Almaz Akhunzianov, Marco Deiana, Kazutoshi Kasho, Sebastian Sulis Sato, Parham L. Pourbozorgi, James E. Mason, Paolo Medini
Journal of the American Chemical Society.2020; 142(6): 2876. CrossRef
Phosphotyrosine isosteres: past, present and future
Robert A. Cerulli, Joshua A. Kritzer
Organic & Biomolecular Chemistry.2020; 18(4): 583. CrossRef
Anticancer activity of dietary xanthone α-mangostin against hepatocellular carcinoma by inhibition of STAT3 signaling via stabilization of SHP1
Hai Zhang, Yu-ping Tan, Lin Zhao, Lun Wang, Nai-jie Fu, Song-ping Zheng, Xiao-fei Shen
Cell Death & Disease.2020;[Epub] CrossRef
JAK/STAT signaling in hepatocellular carcinoma
Justin Jit Hin Tang, Dexter Kai Hao Thng, Jhin Jieh Lim, Tan Boon Toh
Hepatic Oncology.2020;[Epub] CrossRef
JAK–STAT pathway targeting for the treatment of inflammatory bowel disease
Azucena Salas, Cristian Hernandez-Rocha, Marjolijn Duijvestein, William Faubion, Dermot McGovern, Severine Vermeire, Stefania Vetrano, Niels Vande Casteele
Nature Reviews Gastroenterology & Hepatology.2020; 17(6): 323. CrossRef
Targeting STAT3 in cancer and autoimmune diseases
Tohid Gharibi, Zohreh Babaloo, Arezoo Hosseini, Meghdad Abdollahpour-alitappeh, Vida Hashemi, Faroogh Marofi, Kazem Nejati, Behzad Baradaran
European Journal of Pharmacology.2020; 878: 173107. CrossRef
Betacellulin drives therapy resistance in glioblastoma
Qiwen Fan, Zhenyi An, Robyn A Wong, Xujun Luo, Edbert D Lu, Albert Baldwin, Manasi K Mayekar, Franziska Haderk, Kevan M Shokat, Trever G Bivona, William A Weiss
Neuro-Oncology.2020; 22(4): 457. CrossRef
A novel small molecule STAT3 inhibitor SLSI-1216 suppresses proliferation and tumor growth of triple-negative breast cancer cells through apoptotic induction
Soo Kyung Park, Woong Sub Byun, Seungbeom Lee, Young Taek Han, Yoo-Seong Jeong, Kyungkuk Jang, Suk-Jae Chung, Jeeyeon Lee, Young-Ger Suh, Sang Kook Lee
Biochemical Pharmacology.2020; 178: 114053. CrossRef
STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects
Milad Ashrafizadeh, Ali Zarrabi, Sima Orouei, Vahideh Zarrin, Ebrahim Rahmani Moghadam, Amirhossein Zabolian, Shima Mohammadi, Kiavash Hushmandi, Yashar Gharehaghajlou, Pooyan Makvandi, Masoud Najafi, Reza Mohammadinejad
Biology.2020; 9(6): 126. CrossRef
Towards the Inhibition of Protein–Protein Interactions (PPIs) in STAT3: Insights into a New Class of Benzothiadiazole Derivatives
Matteo Mori, Ettore Gilardoni, Luca Regazzoni, Alessandro Pedretti, Diego Colombo, Gary Parkinson, Akira Asai, Fiorella Meneghetti, Stefania Villa, Arianna Gelain
Molecules.2020; 25(15): 3509. CrossRef
STAT3, the Challenge for Chemotherapeutic and Radiotherapeutic Efficacy
Ping-Lian Yang, Lu-Xin Liu, En-Min Li, Li-Yan Xu
Cancers.2020; 12(9): 2459. CrossRef
Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer

Yan Lin, Ziqin He, Jiazhou Ye, Ziyu Liu, Xiaomin She, Xing Gao, Rong Liang
OncoTargets and Therapy.2020; Volume 13: 13023. CrossRef
Systemic Therapy for Hepatocellular Carcinoma: Advances and Hopes
Chen-Hao Zhang, Ming Li, You-Pei Lin, Qiang Gao
Current Gene Therapy.2020; 20(2): 84. CrossRef
Decoration of Anti-CD38 on Nanoparticles Carrying a STAT3 Inhibitor Can Improve the Therapeutic Efficacy Against Myeloma
Yung-Hsing Huang, Mohammad Reza Vakili, Ommoleila Molavi, Yuen Morrissey, Chengsheng Wu, Igor Paiva, Amir Hasan Soleimani, Forugh Sanaee, Afsaneh Lavasanifar, Raymond Lai
Cancers.2019; 11(2): 248. CrossRef
Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma
Changhoon Yoo, Jihoon Kang, Ho Yeong Lim, Jee Hyun Kim, Myung-Ah Lee, Kyung-Hun Lee, Tae-You Kim, Baek-Yeol Ryoo
Cancer Research and Treatment.2019; 51(2): 510. CrossRef
IL-6 signaling contributes to radioresistance of prostate cancer through key DNA repair-associated molecules ATM, ATR, and BRCA 1/2
Xiaodong Chen, Feng Chen, Yu Ren, Guobin Weng, Lijun Xu, Xiang Xue, Peter C. Keng, Soo Ok Lee, Yuhchyau Chen
Journal of Cancer Research and Clinical Oncology.2019; 145(6): 1471. CrossRef
Proton pump inhibitor: The dual role in gastric cancer
Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
World Journal of Gastroenterology.2019; 25(17): 2058. CrossRef
Transcriptional Reprogramming and Novel Therapeutic Approaches for Targeting Prostate Cancer Stem Cells
Gianluca Civenni, Domenico Albino, Dheeraj Shinde, Ramiro Vázquez, Jessica Merulla, Aleksandra Kokanovic, Sarah N. Mapelli, Giuseppina M. Carbone, Carlo V. Catapano
Frontiers in Oncology.2019;[Epub] CrossRef
STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review
Jiang-Jiang Qin, Li Yan, Jia Zhang, Wei-Dong Zhang
Journal of Experimental & Clinical Cancer Research.2019;[Epub] CrossRef
JAK/STAT inhibition in macrophages promotes therapeutic resistance by inducing expression of protumorigenic factors
Emily A. Irey, Chelsea M. Lassiter, Nicholas J. Brady, Pavlina Chuntova, Ying Wang, Todd P. Knutson, Christine Henzler, Thomas S. Chaffee, Rachel I. Vogel, Andrew C. Nelson, Michael A. Farrar, Kathryn L. Schwertfeger
Proceedings of the National Academy of Sciences.2019; 116(25): 12442. CrossRef
Elevated HOX gene expression in acute myeloid leukemia is associated with NPM1 mutations and poor survival
Ádám Nagy, Ágnes Ősz, Jan Budczies, Szilvia Krizsán, Gergely Szombath, Judit Demeter, Csaba Bödör, Balázs Győrffy
Journal of Advanced Research.2019; 20: 105. CrossRef
Antitumor activity of novel pyrazole-based small molecular inhibitors of the STAT3 pathway in patient derived high grade glioma cells
Liang Zhang, Timothy E. Peterson, Victor M. Lu, Ian F. Parney, David J. Daniels, Ilya Ulasov
PLOS ONE.2019; 14(7): e0220569. CrossRef
Inhibition of Stat3 Signaling Pathway by Natural Product Pectolinarigenin Attenuates Breast Cancer Metastasis
Yali Li, Cailing Gan, Yange Zhang, Yan Yu, Chen Fan, Yuanle Deng, Qianyu Zhang, Xi Yu, Yiwen Zhang, Liqun Wang, Fang He, Yongmei Xie, Tinghong Ye, Wenya Yin
Frontiers in Pharmacology.2019;[Epub] CrossRef
Impact of combination therapy with anti-PD-1 blockade and a STAT3 inhibitor on the tumor-infiltrating lymphocyte status
Tadashi Ashizawa, Akira Iizuka, Chie Maeda, Emiko Tanaka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Takuya Kawata, Shoichi Deguchi, Koichi Mitsuya, Nakamasa Hayashi, Akira Asai, Mamoru Ito, Ken Yamaguchi, Yasuto Akiyama
Immunology Letters.2019; 216: 43. CrossRef
Signal Transducer and Activator of Transcription Protein 3 (STAT3): An Update on its Direct Inhibitors as Promising Anticancer Agents
Arianna Gelain, Matteo Mori, Fiorella Meneghetti, Stefania Villa
Current Medicinal Chemistry.2019; 26(27): 5165. CrossRef
The effects of signal transducer and activator of transcription three mutations on human platelets
Floor E. Aleva, Frank L. van de Veerdonk, Yang Li, Rahajeng N. Tunjungputri, Sami Simons, Philip G. De Groot, Mihai M. Netea, Yvonne F. Heijdra, Quirijn de Mast, André J.A.M. van der Ven
Platelets.2018; 29(6): 602. CrossRef
Mechanisms Linking Obesity and Thyroid Cancer Development and Progression in Mouse Models
Won Gu Kim, Sheue-yann Cheng
Hormones and Cancer.2018; 9(2): 108. CrossRef
Targeting the IL-6/JAK/STAT3 signalling axis in cancer
Daniel E. Johnson, Rachel A. O'Keefe, Jennifer R. Grandis
Nature Reviews Clinical Oncology.2018; 15(4): 234. CrossRef
Arsenic trioxide attenuates STAT-3 activity and epithelial-mesenchymal transition through induction of SHP-1 in gastric cancer cells
Sung Ho Kim, Hyo Soon Yoo, Moon Kyung Joo, Taehyun Kim, Jong-Jae Park, Beom Jae Lee, Hoon Jai Chun, Sang Woo Lee, Young-Tae Bak
BMC Cancer.2018;[Epub] CrossRef
Linker Variation and Structure–Activity Relationship Analyses of Carboxylic Acid-based Small Molecule STAT3 Inhibitors
Francisco Lopez-Tapia, Christine Brotherton-Pleiss, Peibin Yue, Heide Murakami, Ana Carolina Costa Araujo, Bruna Reis dos Santos, Erin Ichinotsubo, Anna Rabkin, Raj Shah, Megan Lantz, Suzie Chen, Marcus A. Tius, James Turkson
ACS Medicinal Chemistry Letters.2018; 9(3): 250. CrossRef
Decoy-Based, Targeted Inhibition of STAT3: A New Step forward for B Cell Lymphoma Immunotherapy
Mario M. Soldevilla, Fernando Pastor
Molecular Therapy.2018; 26(3): 675. CrossRef
Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we?
Jenny D. Beebe, Jing-Yuan Liu, Jian-Ting Zhang
Pharmacology & Therapeutics.2018; 191: 74. CrossRef
Translational and clinical advances in JAK-STAT biology: The present and future of jakinibs
Massimo Gadina, Catrina Johnson, Daniella Schwartz, Michael Bonelli, Sarfaraz Hasni, Yuka Kanno, Paul Changelian, Arian Laurence, John J O’Shea
Journal of Leukocyte Biology.2018; 104(3): 499. CrossRef
Targeting JAK-STAT signal transduction in IBD
Christoffer Soendergaard, Fredrik Holmberg Bergenheim, Jakob Tveiten Bjerrum, Ole Haagen Nielsen
Pharmacology & Therapeutics.2018; 192: 100. CrossRef
“Do We Know Jack” About JAK? A Closer Look at JAK/STAT Signaling Pathway
Emira Bousoik, Hamidreza Montazeri Aliabadi
Frontiers in Oncology.2018;[Epub] CrossRef
Plasticity of Type I Interferon-Mediated Responses in Cancer Therapy: From Anti-tumor Immunity to Resistance
Megha Budhwani, Roberta Mazzieri, Riccardo Dolcetti
Frontiers in Oncology.2018;[Epub] CrossRef
STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context
Ilenia Segatto, Gustavo Baldassarre, Barbara Belletti
International Journal of Molecular Sciences.2018; 19(9): 2818. CrossRef
Suppression of STAT3 signaling promotes cellular reprogramming into insulin-producing cells induced by defined transcription factors
Masaki Miura, Takeshi Miyatsuka, Takehiro Katahira, Shugo Sasaki, Luka Suzuki, Miwa Himuro, Yuya Nishida, Yoshio Fujitani, Taka-aki Matsuoka, Hirotaka Watada
EBioMedicine.2018; 36: 358. CrossRef
Aptamer-iRNAs as Therapeutics for Cancer Treatment
Mario M. Soldevilla, Daniel Meraviglia-Crivelli de Caso, Ashwathi P. Menon, Fernando Pastor
Pharmaceuticals.2018; 11(4): 108. CrossRef
A First-in-Human Phase I Study of OPB-111077, a Small-Molecule STAT3 and Oxidative Phosphorylation Inhibitor, in Patients with Advanced Cancers
Anthony Tolcher, Keith Flaherty, Geoffrey I. Shapiro, Jordan Berlin, Thomas Witzig, Thomas Habermann, Andrea Bullock, Edwin Rock, Agnes Elekes, Chester Lin, Dusan Kostic, Naoto Ohi, Drew Rasco, Kyriakos P. Papadopoulos, Amita Patnaik, Lon Smith, Gregory M
The Oncologist.2018; 23(6): 658. CrossRef
Impact of STAT3 phosphorylation in glioblastoma stem cells radiosensitization and patient outcome
Konstantin Masliantsev, Baptiste Pinel, Anaïs Balbous, Pierre-Olivier Guichet, Gaëlle Tachon, Serge Milin, Julie Godet, Mathilde Duchesne, Antoine Berger, Christos Petropoulos, Michel Wager, Lucie Karayan-Tapon
Oncotarget.2018; 9(3): 3968. CrossRef
Discovery of an Orally Selective Inhibitor of Signal Transducer and Activator of Transcription 3 Using Advanced Multiple Ligand Simultaneous Docking
Wenying Yu, Chenglong Li, Wenda Zhang, Yuanzheng Xia, Shanshan Li, Jia-yuh Lin, Keqin Yu, Mu Liu, Lei Yang, Jianguang Luo, Yijun Chen, Hongbin Sun, Lingyi Kong
Journal of Medicinal Chemistry.2017; 60(7): 2718. CrossRef
Exploiting the Ref-1-APE1 node in cancer signaling and other diseases: from bench to clinic
Fenil Shah, Derek Logsdon, Richard A. Messmann, Jill C. Fehrenbacher, Melissa L. Fishel, Mark R. Kelley
npj Precision Oncology.2017;[Epub] CrossRef
Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells
Davide Genini, Lara Brambilla, Erik Laurini, Jessica Merulla, Gianluca Civenni, Shusil Pandit, Rocco D'Antuono, Laurent Perez, David E. Levy, Sabrina Pricl, Giuseppina M. Carbone, Carlo V. Catapano
Proceedings of the National Academy of Sciences.2017;[Epub] CrossRef
Identification of novel small molecules that inhibit STAT3-dependent transcription and function
Iryna Kolosenko, Yasmin Yu, Sander Busker, Matheus Dyczynski, Jianping Liu, Martin Haraldsson, Caroline Palm Apergi, Thomas Helleday, Katja Pokrovskaja Tamm, Brent D. G. Page, Dan Grander, Aamir Ahmad
PLOS ONE.2017; 12(6): e0178844. CrossRef
Antineoplastic effects of CPPTL via the ROS/JNK pathway in acute myeloid leukemia
Hui-Er Gao, Yue Sun, Ya-Hui Ding, Jing Long, Xiao-Lei Liu, Ming Yang, Qing Ji, Ying-Hui Li, Yue Chen, Quan Zhang, Ying-Dai Gao
Oncotarget.2017; 8(24): 38990. CrossRef
Stattic and metformin inhibit brain tumor initiating cells by reducing STAT3-phosphorylation
Verena Leidgens, Judith Proske, Lisa Rauer, Sylvia Moeckel, Kathrin Renner, Ulrich Bogdahn, Markus J. Riemenschneider, Martin Proescholdt, Arabel Vollmann-Zwerenz, Peter Hau, Corinna Seliger
Oncotarget.2017; 8(5): 8250. CrossRef
Identification of antipsychotic drug fluspirilene as a potential anti-glioma stem cell drug
Yu Dong, Takuya Furuta, Hemragul Sabit, Tomohiro Kitabayashi, Shabierjiang Jiapaer, Masahiko Kobayashi, Yasushi Ino, Tomoki Todo, Lei Teng, Atsushi Hirao, Shi-Guang Zhao, Mitsutoshi Nakada
Oncotarget.2017; 8(67): 111728. CrossRef
Feedback Activation of STAT3 as a Cancer Drug-Resistance Mechanism
Chengguang Zhao, Huameng Li, Huey-Jen Lin, Shulin Yang, Jiayuh Lin, Guang Liang
Trends in Pharmacological Sciences.2016; 37(1): 47. CrossRef
Targeting transcription factor STAT3 for cancer prevention and therapy
Edna Zhi Pei Chai, Muthu K. Shanmugam, Frank Arfuso, Arunasalam Dharmarajan, Chao Wang, Alan Prem Kumar, Ramar Perumal Samy, Lina H.K. Lim, Lingzhi Wang, Boon Cher Goh, Kwang Seok Ahn, Kam Man Hui, Gautam Sethi
Pharmacology & Therapeutics.2016; 162: 86. CrossRef
Molecular Bases for Combinatorial Treatment Strategies in Patients with KRAS Mutant Lung Adenocarcinoma and Squamous Cell Lung Carcinoma
Chiara Lazzari, Alberto Verlicchi, Anastasios Gkountakos, Sara Pilotto, Mariacarmela Santarpia, Imane Chaib, Jose Luis Ramirez Serrano, Santiago Viteri, Daniela Morales-Espinosa, Claudio Dazzi, Filippo de Marinis, Peng Cao, Niki Karachaliou, Rafael Rosell
Pulmonary Therapy.2016; 2(1): 1. CrossRef
Preclinical Characterization of 3β-(N-Acetyl l-cysteine methyl ester)-2aβ,3-dihydrogaliellalactone (GPA512), a Prodrug of a Direct STAT3 Inhibitor for the Treatment of Prostate Cancer
Zilma Escobar, Anders Bjartell, Giacomo Canesin, Susan Evans-Axelsson, Olov Sterner, Rebecka Hellsten, Martin H Johansson
Journal of Medicinal Chemistry.2016; 59(10): 4551. CrossRef
A Positive TGF-β/c-KIT Feedback Loop Drives Tumor Progression in Advanced Primary Liver Cancer
Andres Rojas, Pingyu Zhang, Ying Wang, Wai Chin Foo, Nina M. Muñoz, Lianchun Xiao, Jing Wang, Gregory J. Gores, Mien-Chie Hung, Boris Blechacz
Neoplasia.2016; 18(6): 371. CrossRef
Novel STAT 3 inhibitors for treating gastric cancer
Catherine Cafferkey, Ian Chau
Expert Opinion on Investigational Drugs.2016; 25(9): 1023. CrossRef
‘Acute myeloid leukemia: a comprehensive review and 2016 update’
I De Kouchkovsky, M Abdul-Hay
Blood Cancer Journal.2016; 6(7): e441. CrossRef
Recent updates of precision therapy for gastric cancer: Towards optimal tailored management
Moon Kyung Joo, Jong-Jae Park, Hoon Jai Chun
World Journal of Gastroenterology.2016; 22(19): 4638. CrossRef
Targeted inhibition of STATs and IRFs as a potential treatment strategy in cardiovascular disease
Malgorzata Szelag, Anna Piaszyk-Borychowska, Martyna Plens-Galaska, Joanna Wesoly, Hans A.R. Bluyssen
Oncotarget.2016; 7(30): 48788. CrossRef
Cell-cell and cell-matrix adhesion in survival and metastasis: Stat3 versus Akt
Maximilian Niit, Victoria Hoskin, Esther Carefoot, Mulu Geletu, Rozanne Arulanandam, Bruce Elliott, Leda Raptis
Biomolecular Concepts.2015; 6(5-6): 383. CrossRef
Phase 1 and pharmacological trial of OPB‐31121, a signal transducer and activator of transcription‐3 inhibitor, in patients with advanced hepatocellular carcinoma
Takuji Okusaka, Hideki Ueno, Masafumi Ikeda, Shuichi Mitsunaga, Masato Ozaka, Hiroshi Ishii, Osamu Yokosuka, Yoshihiko Ooka, Ryo Yoshimoto, Yasuo Yanagihara, Kiwamu Okita
Hepatology Research.2015; 45(13): 1283. CrossRef
STAT3 Inhibition Enhances the Therapeutic Efficacy of Immunogenic Chemotherapy by Stimulating Type 1 Interferon Production by Cancer Cells
Heng Yang, Takahiro Yamazaki, Federico Pietrocola, Heng Zhou, Laurence Zitvogel, Yuting Ma, Guido Kroemer
Cancer Research.2015; 75(18): 3812. CrossRef

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Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors: Do-Youn Oh, Tae-Min Kim, Sae-Won Han, Dong-Yeop Shin, Yun Gyoo Lee, Keun-Wook Lee, Jee Hyun Kim, Tae-You Kim, In-Jin Jang, Jong-Seok Lee, Yung-Jue Bang; Cancer Res Treat. 2016;48(1):28-36. Published online February 23, 2015; DOI: https://doi.org/10.4143/crt.2014.258

Abstract PDF PubReader ePub

Purpose
CKD-516 is a newly developed vascular disrupting agent. This phase I dose-escalation study of CKD-516 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. Materials and Methods Patients received CKD-516 intravenously on D1 and D8 every 3 weeks, in a standard 3+3 design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.02 and response was assessed by Response Evaluation Criteria in Solid Tumor ver. 1.1.
Results
Twenty-three patients were treated with CKD-516 at seven dosing levels: 1 mg/m2/day (n=3), 2 mg/m2/day (n=3), 3.3 mg/m2/day (n=3), 5 mg/m2/day (n=3), 7 mg/m2/day (n=3), 9 mg/m2/day (n=6), and 12 mg/m2/day (n=2). Mean age was 54 and 56.5% of patients were male. Two dose-limiting toxicities, which were both grade 3 hypertension, were observed in two patients at 12 mg/m2/day. The MTD was determined as 12 mg/m2/day. Most common adverse events were gastrointestinal adverse events (diarrhea, 34.8% [30.4% grade 1/2, 13.0% grade 3]; nausea, 21.7% [all grade 1/2]; vomiting, 21.7% [all grade 1/2]), myalgia (17.4%, all grade 1/2), and abdominal pain (21.7% [21.7% grade 1/2, 4.3% grade 3]). The pharmacokinetic study showed the dose-linearity of all dosing levels. Among 23 patients, six patients (26.1%) showed stable disease. Median progression-free survival was 39 days (95% confidence interval, 37 to 41 days). Conclusion This study demonstrates feasibility of CKD-516, novel vascular disrupting agent, in patients with advanced solid tumor. MTD of CKD-516 was defined as 12 mg/m2/day on D1 and D8 every 3 weeks.

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First-in-human phase 1 study of an orally bioavailable vascular-disrupting agent DX1002 in patients with advanced solid tumors
Xiao-Li Wei, Hao-Xiang Wu, Dan-Yun Ruan, Feng Wang, Li Xu, Yu-Hong Li, Yu-Xiang Ma, Zhi-Qiang Wang, Yun-Peng Yang, Liang-Wei Tang, Bao-Lin Chen, Zhi-Quan Yong, Rui-Hua Xu, Hong-Yun Zhao
Cell Reports Medicine.2025; 6(2): 101969. CrossRef
Natural‐Product‐Inspired Discovery of Trimethoxyphenyl‐1,2,4‐triazolosulfonamides as Potent Tubulin Polymerization Inhibitors
Vajja Krishna Rao, Anvesh Ashtam, Dulal Panda, Sankar K. Guchhait
ChemMedChem.2024;[Epub] CrossRef
Thiazole, Isatin and Phthalimide Derivatives Tested in vivo against Cancer Models: A Literature Review of the Last Six Years
Aline Ferreira Pinto, Janine Siqueira Nunes, José Eduardo Severino Martins, Amanda Calazans Leal, Carla Cauanny Vieira Costa Silva, Anderson José Firmino Santos da Silva, Daiane Santiago da Cruz Olímpio, Elineide Tayse Noberto da Silva, Thiers Araújo Camp
Current Medicinal Chemistry.2024; 31(20): 2991. CrossRef
CKD-516 potentiates the anti-cancer activity of docetaxel against epidermal growth factor receptor tyrosine kinase inhibitor-resistant lung cancer
Soo Jin Kim, Kyunghyeon Lee, Jaewoo Park, Miso Park, U. Ji Kim, Se-mi Kim, Keun Ho Ryu, Keon Wook Kang
Toxicological Research.2023; 39(1): 61. CrossRef
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Lance B. Augustin, Liming Milbauer, Sara E. Hastings, Arnold S. Leonard, Daniel A. Saltzman, Janet L. Schottel
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A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer
Hyehyun Jeong, Yong Sang Hong, Jeong Eun Kim, Hyeong-Seok Lim, Joong Bae Ahn, Sang Joon Shin, Young Suk Park, Seung Tae Kim, Sae-Won Han, Tae-You Kim, Tae Won Kim
Investigational New Drugs.2021; 39(5): 1335. CrossRef
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M. Shaheer Malik, Saleh A. Ahmed, Ismail I. Althagafi, Mohammed Azam Ansari, Ahmed Kamal
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Haiyang Yu, Na Shen, Yanli Bao, Li Chen, Zhaohui Tang
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Phase I and pharmacokinetic study of the vascular‐disrupting agent CKD‐516 (NOV120401) in patients with refractory solid tumors
Hark Kyun Kim, Jeong Won Kang, Young‐Whan Park, Jung Young Kim, Minchae Kim, Soo Jin Kim, Se‐mi Kim, Keun Ho Ryu, Seonghae Yoon, Yun Kim, Joo‐Youn Cho, Keun Seok Lee, Tak Yun, Kiwon Kim, Mi Hyang Kwak, Tae‐Sung Kim, Jinsoo Chung, Joong‐Won Park
Pharmacology Research & Perspectives.2020;[Epub] CrossRef
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Mai F. Tolba
International Journal of Cancer.2020; 147(11): 2996. CrossRef
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Jian Song, Qiu-Lei Gao, Bo-Wen Wu, Ting Zhu, Xin-Xin Cui, Cheng-Jun Jin, Shu-Yu Wang, Sheng-Hui Wang, Dong-Jun Fu, Hong-Min Liu, Sai-Yang Zhang, Yan-Bing Zhang, Yong-Chun Li
European Journal of Medicinal Chemistry.2020; 203: 112618. CrossRef
Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma
Min-Young Kim, Jung-Young Shin, Jeong-Oh Kim, Kyoung-Hwa Son, Yeon Sil Kim, Chan Kwon Jung, Jin-Hyoung Kang
BMC Cancer.2020;[Epub] CrossRef
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Fang Yang, Cai-Ping He, Peng-Cheng Diao, Kwon Ho Hong, Jin-Jun Rao, Pei-Liang Zhao
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Jason H. Gill, Kimberly L. Rockley, Carol De Santis, Asma K. Mohamed
Pharmacology & Therapeutics.2019; 202: 18. CrossRef
Combretastatin A4 Nanoparticles Combined with Hypoxia-Sensitive Imiquimod: A New Paradigm for the Modulation of Host Immunological Responses during Cancer Treatment
Na Shen, Jing Wu, Chenguang Yang, Haiyang Yu, Shengcai Yang, Tete Li, Jingtao Chen, Zhaohui Tang, Xuesi Chen
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Ling Li, Sibo Jiang, Xiaoxun Li, Yao Liu, Jing Su, Jianjun Chen
European Journal of Medicinal Chemistry.2018; 151: 482. CrossRef
Combination of anti-vascular agent - DMXAA and HIF-1α inhibitor - digoxin inhibits the growth of melanoma tumors
Ryszard Smolarczyk, Tomasz Cichoń, Ewelina Pilny, Magdalena Jarosz-Biej, Aleksandra Poczkaj, Natalia Kułach, Stanisław Szala
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Chemoembolization with Vascular Disrupting Agent CKD-516 Dissolved in Ethiodized Oil in Combination with Doxorubicin: A VX2 Tumor Model Study
In Joon Lee, Myungsu Lee, Soo Jin Kim, You Kyung Kim, Jong Yun Won, Jin Wook Chung
Journal of Vascular and Interventional Radiology.2018; 29(8): 1078. CrossRef
Enhanced efficacy of radiofrequency ablation for hepatocellular carcinoma using a novel vascular disrupting agent, CKD-516
Su Jung Ham, YoonSeok Choi, Seul-I Lee, Jinil Kim, Young Il Kim, Jin Wook Chung, Kyung Won Kim
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Kunal Nepali, Ritu Ojha, Hsueh-Yun Lee, Jing-Ping Liou
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María-Jesús Pérez-Pérez, Eva-María Priego, Oskía Bueno, Maria Solange Martins, María-Dolores Canela, Sandra Liekens
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Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis
Souvik Banerjee, Dong-Jin Hwang, Wei Li, Duane Miller
Molecules.2016; 21(11): 1468. CrossRef

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Regorafenib as Salvage Treatment in Korean Patients with Refractory Metastatic Colorectal Cancer: Seung Tae Kim, Tae Won Kim, Kyu-pyo Kim, Tae-You Kim, Sae-Won Han, Ji Yun Lee, Sung Hee Lim, Min-Young Lee, Haesu Kim, Young Suk Park; Cancer Res Treat. 2015;47(4):790-795. Published online December 2, 2014; DOI: https://doi.org/10.4143/crt.2014.126

Abstract PDF PubReader ePub

Purpose
Regorafenib, an oral multi-targeted tyrosine kinase inhibitor, is considered the new standard of care in patients with chemotherapy-refractory colorectal cancers (CRCs). However, there are no data on this drug in Korean patients.
Materials and Methods
We evaluated patients who received oral regorafenib 160 mg once daily during the first 3 weeks of each 4-week cycle between August 2013 and September 2013. All patients had previously progressed fluorouracil, irinotecan, and oxaliplatin with or without biologic agents such as cetuximab or bevacizumab.
Results
Thirty-two patients were enrolled (median age, 57 years; male:female ratio, 20:12; Eastern Cooperative Oncology Group performance status [0-1:2], 31:1; colon:rectum, 21:11). The overall response rate was 3.1% and the disease control rate was 50.0% (95% confidence interval [CI]) with one partial response and 15 patients with stable disease. The median progression-free survival was 4.2 months (95% CI, 3.1 to 5.2 months) and the median overall survival has not yet been reached. The most common adverse events of grade two or higher related to regorafenib were hand-foot skin reaction (25%), mucositis (19%), abdominal pain (9%), and liver function test (LFT) abnormalities (9%). Grade 3 or 4 toxicities included LFT abnormalities (9%), abdominal pain (9%), rash (6%), anemia (3%), leukopenia (3%), neutropenic fever (3%), and fatigue (3%). There was no treatment-related death.
Conclusion
Regorafenib appears to have promising activity and tolerable toxicity profiles in Korean patients with refractory CRC, consistent with the CORRECT trial findings.

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Salvage Treatment Option for Metastatic Colorectal Cancer:Regorafenib
Havva YESİL CİNKİR
SDÜ Tıp Fakültesi Dergisi.2020; 27(4): 471. CrossRef
Efficacy and safety of regorafenib in the treatment of metastatic colorectal cancer: A systematic review
Maria Røed Skårderud, Anne Polk, Kirsten Kjeldgaard Vistisen, Finn Ole Larsen, Dorte Lisbet Nielsen
Cancer Treatment Reviews.2018; 62: 61. CrossRef
The real-world use of regorafenib for metastatic colorectal cancer: multicentre analysis of treatment pattern and outcomes in Hong Kong
Ka-On Lam, Kin-Chung Lee, Joanne Chiu, Victor Ho-Fun Lee, Roland Leung, T S Choy, Thomas Yau
Postgraduate Medical Journal.2017; 93(1101): 395. CrossRef
Pseudocirrhosis caused by regorafenib in an advanced rectal cancer patient with multiple liver metastases
Kensuke Kumamoto, Shungo Endo, Noriyuki Isohata, Azuma Nirei, Daiki Nemoto, Kenichi Utano, Takuro Saito, Kazutomo Togashi
Molecular and Clinical Oncology.2017; 6(1): 63. CrossRef
Incidence and risk of hematologic toxicities in cancer patients treated with regorafenib
Bin Zhao, Hong Zhao
Oncotarget.2017; 8(55): 93813. CrossRef
Efficacy, Safety and Cost of Regorafenib in Patients with Metastatic Colorectal Cancer in French Clinical Practice
Fabien Calcagno, Sabrina Lenoble, Zaher Lakkis, Thierry Nguyen, Samuel Limat, Christophe Borg, Marine Jary, Stefano Kim, Virginie Nerich
Clinical Medicine Insights: Oncology.2016;[Epub] 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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Milk: A Natural Guardian for the Gut Barrier
Yanli Wang, Yiyao Gong, Muhammad Salman Farid, Changhui Zhao
Journal of Agricultural and Food Chemistry.2024; 72(15): 8285. CrossRef
Tristetraprolin, a Potential Safeguard Against Carcinoma: Role in the Tumor Microenvironment
Diwen Zhang, Zhigang Zhou, Ruixia Yang, Sujun Zhang, Bin Zhang, Yanxuan Tan, Lingyao Chen, Tao Li, Jian Tu
Frontiers in Oncology.2021;[Epub] CrossRef
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 Research and Treatment.2019; 51(2): 451. CrossRef
Transforming Growth Factor β Activation Primes Canonical Wnt Signaling Through Down‐Regulation of Axin‐2
Justin Gillespie, Rebecca L. Ross, Clarissa Corinaldesi, Filomena Esteves, Emma Derrett‐Smith, Michael F. McDermott, Gina M. Doody, Christopher P. Denton, Paul Emery, Francesco Del Galdo
Arthritis & Rheumatology.2018; 70(6): 932. CrossRef
Cyclin E overexpression confers resistance to the CDK4/6 specific inhibitor palbociclib in gastric cancer cells
Ahrum Min, Jung Eun Kim, Yu-Jin Kim, Jee Min Lim, Seongyeong Kim, Jin Won Kim, Kyung-Hun Lee, Tae-Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im
Cancer Letters.2018; 430: 123. CrossRef
Identification of SMAD3 as a Novel Mediator of Inflammation in Human Myometrium In Vitro
Martha Lappas
Mediators of Inflammation.2018; 2018: 1. CrossRef
Tristetraprolin activation by resveratrol inhibits the proliferation and metastasis of colorectal cancer cells
Se-Ra Lee, Hua Jin, Won-Tae Kim, Won-Jung Kim, Sung Zoo Kim, Sun-Hee Leem, Soo Mi Kim
International Journal of Oncology.2018;[Epub] CrossRef
Androgen Receptor Inhibitor Enhances the Antitumor Effect of PARP Inhibitor in Breast Cancer Cells by Modulating DNA Damage Response
Ahrum Min, Hyemin Jang, Seongyeong Kim, Kyung-Hun Lee, Debora Keunyoung Kim, Koung Jin Suh, Yaewon Yang, Paul Elvin, Mark J. O'Connor, Seock-Ah Im
Molecular Cancer Therapeutics.2018; 17(12): 2507. CrossRef
Anti‐tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells
Hee‐Jun Kim, Ahrum Min, Seock‐Ah Im, Hyemin Jang, Kyung Hun Lee, Alan Lau, Miso Lee, Seongyeong Kim, Yaewon Yang, Jungeun Kim, Tae Yong Kim, Do‐Youn Oh, Jeffrey Brown, Mark J. O'Connor, Yung‐Jue Bang
International Journal of Cancer.2017; 140(1): 109. CrossRef
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,
Cancer Research and Treatment.2017; 49(3): 643. CrossRef
AZD6738, A Novel Oral Inhibitor of ATR, Induces Synthetic Lethality with ATM Deficiency in Gastric Cancer Cells
Ahrum Min, Seock-Ah Im, Hyemin Jang, Seongyeong Kim, Miso Lee, Debora Keunyoung Kim, Yaewon Yang, Hee-Jun Kim, Kyung-Hun Lee, Jin Won Kim, Tae-Yong Kim, Do-Youn Oh, Jeff Brown, Alan Lau, Mark J. O'Connor, Yung-Jue Bang
Molecular Cancer Therapeutics.2017; 16(4): 566. CrossRef
HSP90 Inhibition Suppresses PGE2 Production via Modulating COX-2 and 15-PGDH Expression in HT-29 Colorectal Cancer Cells
A. Mohammadi, M.M. Yaghoobi, A. Gholamhoseinian Najar, B. Kalantari-Khandani, H. Sharifi, M. Saravani
Inflammation.2016;[Epub] CrossRef
Dysregulation of TTP and HuR plays an important role in cancers
Hao Wang, Nannan Ding, Jian Guo, Jiazeng Xia, Yulan Ruan
Tumor Biology.2016; 37(11): 14451. CrossRef
Low tristetraprolin expression promotes cell proliferation and predicts poor patients outcome in pancreatic cancer
Zi-Ran Wei, Chao Liang, Dan Feng, Ya-Jun Cheng, Wei-Min Wang, De-Jun Yang, Yue-Xiang Wang, Qing-Ping Cai
Oncotarget.2016; 7(14): 17737. 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
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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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