Cancer Research and Treatment

Original Articles

Breast cancer

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

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

Citations

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

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Gastrointestinal cancer

Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer: Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh; Cancer Res Treat. 2022;54(2):541-553. Published online August 6, 2021; DOI: https://doi.org/10.4143/crt.2021.473

Abstract PDF PubReader ePub

Purpose
Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
Materials and Methods
We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
Results
In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
Conclusion
This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

Citations

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Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma
Philipp Heumann, Andreas Albert, Karsten Gülow, Denis Tümen, Martina Müller, Arne Kandulski
Cancers.2024; 16(9): 1690. CrossRef
Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer
Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
Frontiers in Oncology.2024;[Epub] CrossRef
Update on Combination Strategies of PARP Inhibitors
Zhuoqun Lin, Lingfang Wang, Ziyu Xing, Fenfen Wang, Xiaodong Cheng
Cancer Control.2024;[Epub] CrossRef
The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer
Deqian Xie, Bowen Jiang, Shijin Wang, Qifei Wang, Guangzhen Wu
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
Cells.2022; 11(9): 1463. CrossRef
Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
Ourania N. Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis
Viruses.2022; 14(7): 1372. CrossRef
Targeted Therapy with PI3K, PARP, and WEE1 Inhibitors and Radiotherapy in HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy while Effects with APR-246 Are Limited
Karin Byskata, Monika Lukoseviciute, Filippo Tuti, Mark Zupancic, Ourania N. Kostopoulou, Stefan Holzhauser, Tina Dalianis
Cancers.2022; 15(1): 93. 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.

Citations

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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
Cell Death Discovery.2024;[Epub] CrossRef
Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center
Johannes Felix Englisch, Alexander Englisch, Dominik Dannehl, Kenneth Eissler, Christian Martin Tegeler, Sabine Matovina, Léa Louise Volmer, Diethelm Wallwiener, Sara Y. Brucker, Andreas Hartkopf, Tobias Engler
Archives of Gynecology and Obstetrics.2024;[Epub] CrossRef
A Photothermal Therapy Study Based on Electrospinning Nanofibers Blended and Coated with Polydopamine Nanoparticles
Chunhong Sui, Yijia Luo, Xiao Xiao, Jiaxue Liu, Xiaotong Shao, Yingxue Xue, Cheng Wang, Wenliang Li
ChemistrySelect.2023;[Epub] CrossRef
Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
Da Eun Lee, Hyeon Woong Kang, So Yi Kim, Myeong Jin Kim, Jae Woong Jeong, Woosol Chris Hong, Sungsoon Fang, Hyung Sun Kim, Yun Sun Lee, Hyo Jung Kim, Joon Seong Park
Frontiers in Pharmacology.2022;[Epub] CrossRef
CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1
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
Effects of Radiotherapy and Chemotherapy on Postoperative Prognosis of Patients Undergoing Radical Surgery for Pancreatic Cancer—Based on SEER Database Analysis
媛媛苏
Advances in Clinical Medicine.2022; 12(10): 9540. CrossRef
Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients
Alice Usai, Gregorio Di Franco, Margherita Piccardi, Perla Cateni, Luca Emanuele Pollina, Caterina Vivaldi, Enrico Vasile, Niccola Funel, Matteo Palmeri, Luciana Dente, Alfredo Falcone, Dimitri Giunchi, Alessandro Massolo, Vittoria Raffa, Luca Morelli
Cancers.2021; 13(16): 4131. CrossRef
Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef

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Review Article

Systemic Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors in Korea: Literature Review and Expert Opinion: Changhoon Yoo, Chung Ryul Oh, Seung-Tae Kim, Woo Kyun Bae, Hye-Jin Choi, Do-Youn Oh, Myung-Ah Lee, Baek-Yeol Ryoo; Cancer Res Treat. 2021;53(2):291-300. Published online December 29, 2020; DOI: https://doi.org/10.4143/crt.2020.1233

Abstract PDF PubReader ePub

Neuroendocrine tumors (NETs) are a group of malignancies arising from neuroendocrine cells and frequently originate in the gastrointestinal tract and pancreas. Although curative resection is the main treatment for localized disease, systemic therapy is needed for relapsed or metastatic/unresectable gastroenteropancreatic NETs (GEP-NETs). Although there are several NET treatment guidelines from various countries, the geographical discrepancies between patient clinical characteristics, the regulatory approval status for therapeutic agents, and medical practices necessitate specific guidelines for Korean patients. We here provide a consensus review of the diagnosis, staging and systemic treatment of Korean GEP-NET patients. Systemic therapy options and the current Korean expert consensus on these treatments, including somatostatin analogs, targeted therapies such as everolimus and sunitinib, peptide receptor radionuclide treatments, and cytotoxic chemotherapies are addressed.

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Efficacy and Safety of Lu-177 DOTATATE Peptide Receptor Radionuclide Therapy in Patients with Unresectable or Metastatic Neuroendocrine Tumors in Korea
Yeokyeong Shin, Bo Hyun Moon, Baek-Yeol Ryoo, Heung-Moon Chang, Kyu-pyo Kim, Yong Sang Hong, Tae Won Kim, Jin-Sook Ryu, Yong-il Kim, Changhoon Yoo
Targeted Oncology.2024; 19(1): 41. CrossRef
Effectiveness and Safety of Retreatment with177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States
Ebrahim S. Delpassand, Soheil M. Yazdi, Shashank Ghantoji, Antonio Nakasato, Corinne Strickland, Rodolfo Nunez, Afshin Shafie, Susan Cork, Clare Byrne, Jackson Tang, Jeetvan Patel
Journal of Nuclear Medicine.2024; 65(5): 746. CrossRef
Advances in hydrogel materials applied to pancreatic-related diseases
Yuan Zhou, Maoen Pan, Ronggui Lin, Heguang Huang
Journal of Pancreatology.2024; 7(3): 222. CrossRef
Prognostic value of interim [68Ga]Ga-DOTA-TOC PET/CT in patients with neuroendocrine tumour who underwent peptide receptor radionuclide therapy
Eonwoo Shin, Yong-il Kim, Changhoon Yoo, Yeokyeong Shin, Baek-Yeol Ryoo, Dong Yun Lee, Jin-Sook Ryu
European Radiology.2024;[Epub] CrossRef
Consideration of quality of life in the treatment decision-making for patients with advanced gastroenteropancreatic neuroendocrine tumors
Boris G. Naraev, Josh Mailman, Thorvardur R. Halfdanarson, Heloisa P. Soares, Erik S. Mittra, Julie Hallet
Expert Review of Anticancer Therapy.2023; 23(6): 601. CrossRef
KSNM60 in Nuclear Endocrinology: from the Beginning to the Future
Chae Moon Hong, Young Jin Jeong, Hae Won Kim, Byeong-Cheol Ahn
Nuclear Medicine and Molecular Imaging.2022; 56(1): 17. CrossRef
Efficacy of Immune Checkpoint Inhibitors against Advanced or Metastatic Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis
Eun-Joo Park, Hyo-Jung Park, Kyung-Won Kim, Chong-Hyun Suh, Changhoon Yoo, Young-Kwang Chae, Sree Harsha Tirumani, Nikhil H. Ramaiya
Cancers.2022; 14(3): 794. CrossRef
Advances in the Diagnosis and Therapeutic Management of Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NENs)
Krzysztof Kaliszewski, Maksymilian Ludwig, Maria Greniuk, Agnieszka Mikuła, Karol Zagórski, Jerzy Rudnicki
Cancers.2022; 14(8): 2028. CrossRef
Capecitabine plus temozolomide in patients with grade 3 unresectable or metastatic gastroenteropancreatic neuroendocrine neoplasms with Ki-67 index <55%: single-arm phase II study
H. Jeong, J. Shin, J.H. Jeong, K.-p. Kim, S.-M. Hong, Y.-i. Kim, J.-S. Ryu, B.-Y. Ryoo, C. Yoo
ESMO Open.2021; 6(3): 100119. CrossRef

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Original Articles

Gastrointestinal cancer

Targeting Hypoxia Using Evofosfamide and Companion Hypoxia Imaging of FMISO-PET in Advanced Biliary Tract Cancer: Jeesun Yoon, Seo Young Kang, Kyung-Hun Lee, Gi Jeong Cheon, Do-Youn Oh; Cancer Res Treat. 2021;53(2):471-479. Published online October 22, 2020; DOI: https://doi.org/10.4143/crt.2020.577

Abstract PDF Supplementary Material PubReader ePub

Purpose
Hypoxia is widely known as one of the mechanisms of chemoresistance and as an environmental condition which triggers invasion and metastasis of cancer. Evofosfamide is a hypoxia-activated prodrug of the cytotoxin bromo-isophosphoramide mustard conjugated with 2-nitroimidazole. Biliary tract cancer (BTC) is known to contain large hypoxic area. This study evaluated the efficacy and safety of evofosfamide as a second-line treatment of advanced BTC.
Materials and Methods
Patients received evofosfamide at a dose of 340 mg/m² on days 1, 8, and 15 of every 28-day cycle. Primary end-point was progression-free survival (PFS) rate at 4-months (4m-PFSR). Secondary end-points included overall survival (OS), PFS, disease control rate (DCR), metabolic response by ¹⁸F-fluorodeoxyglucose positron emission tomography (PET), hypoxic parameters evaluated by ¹⁸F-fluoromisonidazole (FMISO) PET and toxicity.
Results
Twenty patients were treated with evofosfamide, with 16 response-evaluable patients. There was no objective response; stable disease was observed in nine patients, with a DCR of 56.25%. 4m-PFSR was 40.6%. Median PFS was 3.60 months (95% confidence interval [CI], 1.68 to 5.52). Median OS was 6.37 months (95% CI, 3.94 to 8.79). Reduction of tumor metabolic activity was observed in eight of 15 patients (53.3%). High baseline hypoxic parameters were associated with poor PFS. Change of hypoxic parameters between pretreatment and post-treatment reflected hypoxic-activated drug response. There was no treatment-related death.
Conclusion
Evofosfamide as second-line treatment of advanced BTC showed acceptable safety and comparable efficacy to other agents. Changes in volumetric parameters measured with FMISO PET, showing the degree of tumor hypoxia, reflected the response to evofosfamide based on the mode of action.

Citations

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Functional Imaging of Hypoxia: PET and MRI
Ryan C. Perez, DaeHee Kim, Aaron W. P. Maxwell, Juan C. Camacho
Cancers.2023; 15(13): 3336. CrossRef
Phase Ib dose-escalation study of the hypoxia-modifier Myo-inositol trispyrophosphate in patients with hepatopancreatobiliary tumors
Marcel A. Schneider, Michael Linecker, Ralph Fritsch, Urs J. Muehlematter, Daniel Stocker, Bernhard Pestalozzi, Panagiotis Samaras, Alexander Jetter, Philipp Kron, Henrik Petrowsky, Claude Nicolau, Jean-Marie Lehn, Bostjan Humar, Rolf Graf, Pierre-Alain C
Nature Communications.2021;[Epub] CrossRef

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Prognostic Value of Serum Soluble Programmed Death-Ligand 1 and Dynamics During Chemotherapy in Advanced Gastric Cancer Patients: Woochan Park, Ju-Hee Bang, Ah-Rong Nam, Mei Hua Jin, Hyerim Seo, Jae-Min Kim, Kyoung Seok Oh, Tae-Yong Kim, Do-Youn Oh; Cancer Res Treat. 2021;53(1):199-206. Published online October 6, 2020; DOI: https://doi.org/10.4143/crt.2020.497

Abstract PDF Supplementary Material PubReader ePub

Purpose
The soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC).
Materials and Methods
We prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progressionfree survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics.
Results
The median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline.
Conclusion
sPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.

Citations

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Laccase-inspired bi-amino acid MOFs with high substrate affinity: Catalytic deposition induced “signal-down” electrochemical response towards PD-L1
Ruhui Hu, Suyun Zhong, Hezhen Liu, Yawen Liu, Hongxia Chen, Xiaojun Hu
Sensors and Actuators B: Chemical.2024; 399: 134773. CrossRef
Prognostic significance of soluble PD-L1 in prostate cancer
Margarita Zvirble, Zilvinas Survila, Paulius Bosas, Neringa Dobrovolskiene, Agata Mlynska, Gintaras Zaleskis, Jurgita Jursenaite, Dainius Characiejus, Vita Pasukoniene
Frontiers in Immunology.2024;[Epub] CrossRef
CRP and soluble CTLA4 are determinants of anti-PD1 resistance in gastrointestinal cancer
Kotoe Oshima
American Journal of Cancer Research.2024; 14(3): 1174. CrossRef
Soluble immune checkpoint molecules in cancer risk, outcomes prediction, and therapeutic applications
Lin Chen, Yuqing Chao, Wenjing Li, Zhixia Wu, Qinchuan Wang
Biomarker Research.2024;[Epub] CrossRef
Myeloid subsets impede the efficacy of anti-PD1 therapy in patients with advanced gastric cancer (WJOG10417GTR study)
Hirokazu Shoji, Chie Kudo-Saito, Kengo Nagashima, Hiroshi Imazeki, Kai Tsugaru, Naoki Takahashi, Takeshi Kawakami, Yusuke Amanuma, Takeru Wakatsuki, Naohiro Okano, Yukiya Narita, Yoshiyuki Yamamoto, Rika Kizawa, Kei Muro, Kazunori Aoki, Narikazu Boku
Journal for ImmunoTherapy of Cancer.2024; 12(11): e010174. CrossRef
Prognostic value of tumor mutation burden in patients with advanced gastric cancer receiving first-line chemotherapy
Xiao-Peng Duan, Ke Liu, Xiao-Dong Jiao, Bao-Dong Qin, Bing Li, Xi He, Yan Ling, Ying Wu, Shi-Qi Chen, Yuan-Sheng Zang
Frontiers in Oncology.2023;[Epub] CrossRef
Prognostic value of soluble PD-L1 and exosomal PD-L1 in advanced gastric cancer patients receiving systemic chemotherapy
Kabsoo Shin, Joori Kim, Se Jun Park, Myung Ah Lee, Jae Myung Park, Myung-Gyu Choi, Donghoon Kang, Kyo Young Song, Han Hong Lee, Ho Seok Seo, Sung Hak Lee, Bohyun Kim, Okran Kim, Juyeon Park, Nahyeon Kang, In-Ho Kim
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Site-specific protein biomarkers in gastric cancer: a comprehensive review of novel biomarkers and clinical applications
Takahiro Shinozuka, Mitsuro Kanda, Yasuhiro Kodera
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The predictive role of soluble programmed death ligand 1 in digestive system cancers
Jian Ruan, Zhihong Zhao, Yuting Qian, Ruilian Xu, Guixiang Liao, Feng-Ming (Spring) Kong
Frontiers in Oncology.2023;[Epub] CrossRef
Does Elevated Pre-Treatment Plasma PD-L1 Level Indicate an Increased Tumor Burden and Worse Prognosis in Metastatic Colorectal Cancer?
Magdolna Dank, Dorottya Mühl, Magdolna Herold, Lilla Hornyák, Attila Marcell Szasz, Zoltan Herold
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How to Best Exploit Immunotherapeutics in Advanced Gastric Cancer: Between Biomarkers and Novel Cell-Based Approaches
Michele Ghidini, Angelica Petrillo, Andrea Botticelli, Dario Trapani, Alessandro Parisi, Anna La Salvia, Elham Sajjadi, Roberto Piciotti, Nicola Fusco, Shelize Khakoo
Journal of Clinical Medicine.2021; 10(7): 1412. CrossRef

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

Abstract PDF Supplementary Material PubReader ePub

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

Citations

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Journal of Inflammation Research.2023; Volume 16: 4373. CrossRef
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Cancers.2021; 13(19): 4872. CrossRef

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Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer: Ah-Rong Nam, Mei-Hua Jin, Ju-Hee Bang, Kyoung-Seok Oh, Hye-Rim Seo, Do-Youn Oh, Yung-Jue Bang; Cancer Res Treat. 2020;52(3):945-956. Published online April 17, 2020; DOI: https://doi.org/10.4143/crt.2020.080

Abstract PDF Supplementary Material PubReader ePub

Purpose
Currently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC.
Materials and Methods
In this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models.
Results
AZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy.
Conclusion
Taken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.

Citations

Citations to this article as recorded by

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Inhibition of the ATR-DNAPKcs-RB axis drives G1/S-phase transition and sensitizes triple-negative breast cancer (TNBC) to DNA holliday junctions
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Combination of S-1 and the oral ATR inhibitor ceralasertib is effective against pancreatic cancer cells
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Immunomodulatory effects of trastuzumab deruxtecan through the cGAS-STING pathway in gastric cancer cells
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Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma
Giulia Anichini, Chiara Raggi, Mirella Pastore, Laura Carrassa, Luisa Maresca, Enrica Crivaro, Tiziano Lottini, Lea Duwe, Jesper B. Andersen, Lorenzo Tofani, Luca Di Tommaso, Jesus M. Banales, Annarosa Arcangeli, Fabio Marra, Barbara Stecca
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Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma
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Cancer Research and Treatment.2022; 54(1): 277. CrossRef
ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting repair of DNA damage
Takuya Suzuki, Takahisa Hirokawa, Anri Maeda, Shinnosuke Harata, Kaori Watanabe, Takeshi Yanagita, Hajime Ushigome, Nozomi Nakai, Yuzo Maeda, Kazuyoshi Shiga, Ryo Ogawa, Akira Mitsui, Masahiro Kimura, Yoichi Matsuo, Hiroki Takahashi, Shuji Takiguchi
Oncology Reports.2022;[Epub] CrossRef
Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
Cancer Research and Treatment.2022; 54(2): 541. CrossRef
DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
Öykü Gönül Geyik, Giulia Anichini, Engin Ulukaya, Fabio Marra, Chiara Raggi
Cells.2022; 11(9): 1463. CrossRef
Multiple-low-dose therapy: effective killing of high-grade serous ovarian cancer cells with ATR and CHK1 inhibitors
Anya Golder, Louisa Nelson, Anthony Tighe, Bethany Barnes, Camilla Coulson-Gilmer, Robert D Morgan, Joanne C McGrail, Stephen S Taylor
NAR Cancer.2022;[Epub] CrossRef
Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells
Gro Elise Rødland, Sissel Hauge, Grete Hasvold, Lilli T. E. Bay, Tine T. H. Raabe, Mrinal Joel, Randi G. Syljuåsen
Cancers.2021; 13(15): 3790. CrossRef
Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation
Jacqueline Nathansen, Felix Meyer, Luise Müller, Marc Schmitz, Kerstin Borgmann, Anna Dubrovska
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The Role of the Hedgehog Pathway in Cholangiocarcinoma
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Cancers.2021; 13(19): 4774. CrossRef
Targeting P53 as a Future Strategy to Overcome Gemcitabine Resistance in Biliary Tract Cancers
Chiao-En Wu, Yi-Ru Pan, Chun-Nan Yeh, John Lunec
Biomolecules.2020; 10(11): 1474. CrossRef

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Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer: Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh; Cancer Res Treat. 2020;52(1):149-166. Published online June 25, 2019; DOI: https://doi.org/10.4143/crt.2019.183

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors.
Materials and Methods
We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings.
Results
In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion.
Conclusion
Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget

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Therapeutic Targeting of the DNA Damage Response Using an ATR Inhibitor in Biliary Tract Cancer: Ah-Rong Nam, Mei Hua Jin, Ji Eun Park, Ju-Hee Bang, Do-Youn Oh, Yung-Jue Bang; Cancer Res Treat. 2019;51(3):1167-1179. Published online December 3, 2018; DOI: https://doi.org/10.4143/crt.2018.526

Abstract PDF PubReader ePub

Purpose
The DNA damage response (DDR) is a multi-complex network of signaling pathways involved in DNA damage repair, cell cycle checkpoints, and apoptosis. In the case of biliary tract cancer (BTC), the strategy of DDR targeting has not been evaluated, even though many patients have DNA repair pathway alterations. The purpose of this study was to test the DDR-targeting strategy in BTC using an ataxia-telangiectasia and Rad3-related (ATR) inhibitor.
Materials and Methods
A total of nine human BTC cell lines were used for evaluating anti-tumor effect of AZD6738 (ATR inhibitor) alone or combination with cytotoxic chemotherapeutic agents through MTT assay, colony-forming assays, cell cycle analyses, and comet assays. We established SNU478-mouse model for in vivo experiments to confirm our findings.
Results
Among nine human BTC cell lines, SNU478 and SNU869 were the most sensitive to AZD6738, and showed low expression of both ataxia-telangiectasia mutated (ATM) and p53. AZD6738 blocked p-Chk1 and p-glycoprotein and increased γH2AX, a marker of DNA damage, in sensitive cells. AZD6738 significantly increased apoptosis, G2/M arrest and p21, and decreased CDC2. Combinations of AZD6738 and cytotoxic chemotherapeutic agents exerted synergistic effects in colony-forming assays, cell cycle analyses, and comet assays. In our mouse models, AZD6738 monotherapy decreased tumor growth and the combination with cisplatin showed more potent effects on growth inhibition, decreased Ki-67, and increased terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling than monotherapy with each drug.
Conclusion
In BTC, DDR targeting strategy using ATR inhibitor demonstrated promising antitumor activity alone or in combination with cytotoxic chemotherapeutic agents. This supports further clinical development of DDR targeting strategy in BTC.

Citations

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AZD6738 promotes the tumor suppressive effects of trifluridine in colorectal cancer cells
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Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer
Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh
Cancer Research and Treatment.2022; 54(2): 541. CrossRef
DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives
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Cells.2022; 11(9): 1463. CrossRef
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Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer
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Biochemical Pharmacology.2019; 164: 273. CrossRef

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Dynamics of Soluble Programmed Death-Ligand 1 (sPDL1) during Chemotherapy and Its Prognostic Implications in Cancer Patients: Biomarker Development in Immuno-oncology: Hyerim Ha, Ju-Hee Bang, Ah-Rong Nam, Ji-Eun Park, Mei Hua Jin, Yung-Jue Bang, Do-Youn Oh; Cancer Res Treat. 2019;51(2):832-840. Published online October 5, 2018; DOI: https://doi.org/10.4143/crt.2018.311

Abstract PDF PubReader ePub

Purpose
The soluble programmed death-ligand 1 (sPDL1) has immunosuppressive activity and is a candidate biomarker for immuno-oncology drug development. In this study, we measured sPDL1 at pre- and post-chemotherapy and at disease progression to uncover the dynamics of sPDL1 during treatment in biliary tract cancer (BTC) patients.
Materials and Methods
From 90 BTC patients (training cohort, 53; validation cohort, 37) who were candidates for palliative first-line chemotherapy, blood was collected at pre- and post-chemotherapy (at the time of best response) and at disease progression. The sPDL1 levels were measured using an enzyme-linked immunosorbent assay. Responses to chemotherapy, overall survival (OS), and other prognostic factors including the neutrophil-lymphocyte ratio (NLR) were analyzed.
Results
The OS of all patients was 11.5 months (confidence interval [CI], 9.7 to 16.2). The best response was complete response in seven (7.8%), partial response in 20 (22.2%), stable disease in 52 (57.8%), and disease progression (PD) in 11 patients (12.2%). Patients with high pre-chemotherapy sPDL1 (≥ 1.30 ng/mL) showed worse OS than patients with low prechemotherapy sPDL1 (9.1 months vs. 12.5 months, p=0.003). In multivariate analyses, high pre-chemotherapy sPDL1 (hazard ratio [HR], 1.96; 95% CI, 1.2 to 3.9; p=0.011) and high pre-chemotherapy NLR (HR, 1.82; 95% CI, 1.1 to 3.0; p=0.020) were independent poor prognostic factors for OS. At the time of PD, sPDL1 was increased significantly compared with pre-chemotherapy sPDL1 (1.59 ng/mL vs. 0.72 ng/mL, p=0.003).
Conclusion
The sPDL1 at pre-chemotherapy confers the prognostic value for OS in BTC patients under palliative chemotherapy. The dynamics of sPDL1 during chemotherapy correlate with disease burden and have prognostic value.

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Jab1 Silencing Inhibits Proliferation and Sensitizes to Cisplatin in Biliary Tract Cancer: Ah-Rong Nam, Ji-Won Kim, Ji Eun Park, Ju-Hee Bang, Mei Hua Jin, Do-Youn Oh, Yung-Jue Bang; Cancer Res Treat. 2019;51(3):886-900. Published online October 1, 2018; DOI: https://doi.org/10.4143/crt.2018.375

Abstract PDF Supplementary Material PubReader ePub

Purpose
Jab1 is a coactivator of c-Jun that enhances the transcriptional function of c-Jun. Jab1 is frequently overexpressed in various cancers and is associatedwith poor prognosis of cancer patients. Thus, Jab1 could be a potential therapeutic target in cancer. However, the role of Jab1 in biliary tract cancer (BTC) has not been studied.
Materials and Methods
We performed in vitro and in vivo experiments to evaluate the therapeutic potential ofJab1 inhibition in BTC.
Results
Among 8 BTC cell lines, many showed higher Jab1 expression levels. In addition, Jab1 silencing by siRNA increased p27 expression levels. SNU478 and HuCCT-1 cells exhibited profound Jab1 knockdown and increased p27 expression by Jab1-specific siRNA transfection. Jab1 silencing induced anti-proliferative and anti-migratory effects and resulted in G1 cell cycle arrest in SNU478 and HuCCT-1 cells. In addition, Jab1 silencing potentiated the anti-proliferative and anti-migratory effects of cisplatin by increasing DNA damage. Interestingly,Jab1 knockdown increased PTEN protein half-life, resulting in increased PTEN expression. In the HuCCT-1 mouse xenograft model, stable knockdown of Jab1 by shRNA also showed anti-proliferative effects in vivo, with decreased Ki-67 expression and AKT phosphorylation and increased Terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling and p27 expression.
Conclusion
Jab1 knockdown demonstrated anti-proliferative and anti-migratory effects in BTC cells by increasing DNA damage and stabilizing PTEN, resulting in G1 cell cycle arrest. In addition, Jab1 silencing potentiated the anti-proliferative effects of cisplatin. Our data suggest that Jab1 may be a potential therapeutic target in BTC that is worthy of further investigations.

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COP9 signalosome complex is a prognostic biomarker and corresponds with immune infiltration in hepatocellular carcinoma
Jiahui Liu, Dexing Han, Junfeng Xuan, Jinye Xie, Weijia Wang, Quan Zhou, Kang Chen
Aging.2024; 16(6): 5264. CrossRef
Pan-cancer analyses of Jab1/COPS5 reveal oncogenic role and clinical outcome in human cancer
Liping Wang, Xiaojiao Zeng, Gui Yang, Guohong Liu, Yunbao Pan
Heliyon.2022; 8(12): e12553. CrossRef
Jab1/Cops5: a promising target for cancer diagnosis and therapy
Chunjue Yuan, Dong Wang, Guohong Liu, Yunbao Pan
International Journal of Clinical Oncology.2021; 26(7): 1159. CrossRef

8,482 View
225 Download
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Pan-Pim Kinase Inhibitor AZD1208 Suppresses Tumor Growth and Synergistically Interacts with Akt Inhibition in Gastric Cancer Cells: Miso Lee, Kyung-Hun Lee, Ahrum Min, Jeongeun Kim, Seongyeong Kim, Hyemin Jang, Jee Min Lim, So Hyeon Kim, Dong-Hyeon Ha, Won Jae Jeong, Koung Jin Suh, Yae-Won Yang, Tae Yong Kim, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2019;51(2):451-463. Published online June 6, 2018; DOI: https://doi.org/10.4143/crt.2017.341

Abstract PDF Supplementary Material PubReader ePub

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

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PIM1 attenuates cisplatin-induced AKI by inhibiting Drp1 activation
Yuzhen Li, Lang Shi, Fan Zhao, Yanwen Luo, Mingjiao Zhang, Xiongfei Wu, Jiefu Zhu
Cellular Signalling.2024; 113: 110969. CrossRef
Prognostic Model Construction of Disulfidptosis-Related Genes and Targeted Anticancer Drug Research in Pancreatic Cancer
Hongtao Duan, Li Gao, Aiminuer Asikaer, Lingzhi Liu, Kuilong Huang, Yan Shen
Molecular Biotechnology.2024;[Epub] CrossRef
PIM1 kinase and its diverse substrate in solid tumors
Rituparna Choudhury, Chandan Kumar Bahadi, Ipsa Pratibimbita Ray, Pragyanshree Dash, Isha Pattanaik, Suman Mishra, Soumya R. Mohapatra, Srinivas Patnaik, Kumar Nikhil
Cell Communication and Signaling.2024;[Epub] CrossRef
The evaluation of six genes combined value in glioma diagnosis and prognosis
Ping Lin, Lingyan He, Nan Tian, Xuchen Qi
Journal of Cancer Research and Clinical Oncology.2023; 149(13): 12413. CrossRef
Toxic effects of AZD1208 on mouse oocytes and its possible mechanisms
Feng‐Ze Yan, Ying‐Chun Ouyang, Tie‐Gang Meng, Hong‐Yong Zhang, Wei Yue, Xin‐Ran Zhang, Yue Xue, Zhen‐Bo Wang, Qing‐Yuan Sun
Journal of Cellular Physiology.2022; 237(9): 3661. CrossRef
Therapeutic targeting of PIM KINASE signaling in cancer therapy: Structural and clinical prospects
Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
Biochimica et Biophysica Acta (BBA) - General Subjects.2021; 1865(11): 129995. CrossRef
TDP1 and TOP1 Modulation in Olaparib-Resistant Cancer Determines the Efficacy of Subsequent Chemotherapy
Jin Won Kim, Ahrum Min, Seock-Ah Im, Hyemin Jang, Yu Jin Kim, Hee-Jun Kim, Kyung-Hun Lee, Tae-Yong Kim, Keun Wook Lee, Do-Youn Oh, Jee-Hyun Kim, Yung-Jue Bang
Cancers.2020; 12(2): 334. CrossRef
PIM1 (Moloney Murine Leukemia Provirus Integration Site) Inhibition Decreases the Nonhomologous End-Joining DNA Damage Repair Signaling Pathway in Pulmonary Hypertension
Marie-Claude Lampron, Géraldine Vitry, Valérie Nadeau, Yann Grobs, Renée Paradis, Nolwenn Samson, Ève Tremblay, Olivier Boucherat, Jolyane Meloche, Sébastien Bonnet, Steeve Provencher, François Potus, Roxane Paulin
Arteriosclerosis, Thrombosis, and Vascular Biology.2020; 40(3): 783. CrossRef
Inhibition of PIM1 attenuates the stem cell–like traits of breast cancer cells by promoting RUNX3 nuclear retention
Hui Liu, Cheng Chen, Dongshen Ma, Yubing Li, Qianqian Yin, Qing Li, Chenxi Xiang
Journal of Cellular and Molecular Medicine.2020; 24(11): 6308. CrossRef
Antitumor effect of a WEE1 inhibitor and potentiation of olaparib sensitivity by DNA damage response modulation in triple-negative breast cancer
Dong-Hyeon Ha, Ahrum Min, Seongyeong Kim, Hyemin Jang, So Hyeon Kim, Hee-Jun Kim, Han Suk Ryu, Ja-Lok Ku, Kyung-Hun Lee, Seock-Ah Im
Scientific Reports.2020;[Epub] CrossRef
Pim kinase inhibitors in cancer: medicinal chemistry insights into their activity and selectivity
Soraya Alnabulsi, Enas A. Al-Hurani
Drug Discovery Today.2020; 25(11): 2062. CrossRef
New Mechanistic Insight on the PIM-1 Kinase Inhibitor AZD1208 Using Multidrug Resistant Human Erythroleukemia Cell Lines and Molecular Docking Simulations
Maiara Bernardes Marques, Michael González-Durruthy, Bruna Félix da Silva Nornberg, Bruno Rodrigues Oliveira, Daniela Volcan Almeida, Ana Paula de Souza Votto, Luis Fernando Marins
Current Topics in Medicinal Chemistry.2019; 19(11): 914. CrossRef
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Francesca Musumeci, Chiara Greco, Giancarlo Grossi, Alessio Molinari, Silvia Schenone
Cancers.2018; 10(11): 430. CrossRef

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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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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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Review Article

Anti-angiogenic Therapy in Patients with Advanced Gastric and Gastroesophageal Junction Cancer: A Systematic Review: Li-Tzong Chen, Do-Youn Oh, Min-Hee Ryu, Kun-Huei Yeh, Winnie Yeo, Roberto Carlesi, Rebecca Cheng, Jongseok Kim, Mauro Orlando, Yoon-Koo Kang; Cancer Res Treat. 2017;49(4):851-868. Published online January 3, 2017; DOI: https://doi.org/10.4143/crt.2016.176

Abstract PDF Supplementary Material PubReader ePub

Despite advancements in therapy for advanced gastric and gastroesophageal junction cancers, their prognosis remains dismal. Tumor angiogenesis plays a key role in cancer growth and metastasis, and recent studies indicate that pharmacologic blockade of angiogenesis is a promising approach to therapy. In this systematic review, we summarize current literature on the clinical benefit of anti-angiogenic agents in advanced gastric cancer. We conducted a systematic search of PubMed and conference proceedings including the American Society of Clinical Oncology, the European Society for Medical Oncology, and the European Cancer Congress. Included studies aimed to prospectively evaluate the efficacy and safety of anti-angiogenic agents in advanced gastric or gastroesophageal junction cancer. Each trial investigated at least one of the following endpoints: overall survival, progression-free survival/time to progression, and/or objective response rate. Our search yielded 139 publications. Forty-two met the predefined inclusion criteria. Included studies reported outcomes with apatinib, axitinib, bevacizumab, orantinib, pazopanib, ramucirumab, regorafenib, sorafenib, sunitinib, telatinib, and vandetanib. Second-line therapy with ramucirumab and third-line therapy with apatinib are the only anti-angiogenic agents so far shown to significantly improve survival of patients with advanced gastric cancer. Overall, agents that specifically target the vascular endothelial growth factor ligand or receptor have better safety profile compared to multi-target tyrosine kinase inhibitors.

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Original Articles

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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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

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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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Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution: Byoung Hyuck Kim, Kyubo Kim, Eui Kyu Chie, Jeanny Kwon, Jin-Young Jang, Sun Whe Kim, Do-Youn Oh, Yung-Jue Bang; Cancer Res Treat. 2017;49(2):473-483. Published online August 23, 2016; DOI: https://doi.org/10.4143/crt.2016.166

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to evaluate the long-term outcome in patients undergoing pancreaticoduodenectomy (PD) followed by adjuvant chemoradiotherapy for distal cholangiocarcinoma (DCC) in a high-volume center and to identify the prognostic impact of clinicopathologic factors.
Materials and Methods
A total of 132 consecutive patients who met the inclusion criteria were retrieved from the institutional database from January 1995 to September 2009. All patients received adjuvant treatments at a median of 45 days after the surgery. Median follow-up duration was 57 months (range, 6 to 225 months) for all patients and 105 months for survivors (range, 13 to 225 months).
Results
The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 70.7%, 55.7%, 49.4%, and 48.1%, respectively. Univariate analysis revealed poorly differentiated (P/D) tumors and lymph node (LN) metastasis were significantly associated with DMFS and OS. Additionally, preoperative carbohydrate antigen 19-9 level was significantly correlated with DFS, LRRFS, and DMFS. Upon multivariate analysis for OS, P/D tumors (p=0.015) and LN metastasis (p=0.003) were significant prognosticators that predicted inferior OS. Grade 3 or higher late gastrointestinal toxicity occurred in only one patient (0.8%).
Conclusion
Adjuvant chemoradiotherapy after PD for DCC is an effective and tolerable strategy without significant side effects. During long-term follow-up, we found that prognosis of DCC was mainly influenced by histologic differentiation and LN metastasis. For patients with these risk factors, further research should focus on improving adjuvant strategies as well as other treatment approaches.

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Jing‐Jing Hou, Shishir K. Maithel, Sharon M. Weber, George Poultsides, Christopher L. Wolfgang, Ryan C. Fields, Jin He, Charles Scoggins, Kamron Idrees, Perry Shen, Xu‐Feng Zhang, Timothy M. Pawlik
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Pavel Skalicky, Ondrej Urban, Jiri Ehrmann, Hana Svebisova, Dusan Klos, Jana Tesarikova, Cestmir Neoral, Katerina Knapkova, Martin Lovecek
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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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Oxaliplatin‑induced changes in splenic volume and liver fibrosis indices: retrospective analyses of colon cancer patients receiving adjuvant chemotherapy
Kadriye Bir Yücel, Atiye Cenay Karabörk Kilic, Osman Sütcüoglu, Ozan Yazıcı, Koray Kilic, Gözde Savaş, Aytug Uner, Nazan Günel, Ahmet Özet, Nuriye Özdemir
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Effects of methanolic leaf extract and fractions of Irvingia gabonensis on hematological parameters in Wistar rats with splenomegaly
Fidelia Okoben, InnocentMary Ejiofor, Ikechukwu Mbagwu, Daniel Ajaghaku, Fredrick Anowi
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Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure
A. Puente, J.I. Fortea, C. Del Pozo, M. Serrano, M. Alonso-Peña, A. Giráldez, L. Tellez, J. Martinez, M. Magaz, L. Ibañez, J. Garcia, E. Llop, C. Alvarez-Navascues, M. Romero, E. Rodriguez, M.T. Arias Loste, A. Antón, V. Echavarria, C. López, A. Albillos,
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The “appearing” and “disappearing” ascites in the treatment of colorectal cancer: a case report
Hong-Ming Cui, Xin-Peng Shu, Zheng-Qiang Wei, Xing-Ye Wu
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A contrast-enhanced CT-based whole-spleen radiomics signature for early prediction of oxaliplatin-related thrombocytopenia in patients with gastrointestinal malignancies: a retrospective study
Yuhong Dai, Yiqi Cheng, Ziling Zhou, Zhen Li, Yan Luo, Hong Qiu
PeerJ.2023; 11: e16230. CrossRef
Natural Language Processing of Large-Scale Structured Radiology Reports to Identify Oncologic Patients With or Without Splenomegaly Over a 10-Year Period
Simon Sun, Kaelan Lupton, Karen Batch, Huy Nguyen, Lior Gazit, Natalie Gangai, Jessica Cho, Kevin Nicholas, Farhana Zulkernine, Varadan Sevilimedu, Amber Simpson, Richard K. G. Do
JCO Clinical Cancer Informatics.2022;[Epub] CrossRef
Model establishment and microarray analysis of mice with oxaliplatin‑induced hepatic sinusoidal obstruction syndrome
Chen Zhu, Xinwei Cheng, Ping Gao, Qianyan Gao, Ximin Wang, Dong Liu, Xiuhua Ren, Chengliang Zhang
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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Bi-Yang Cao, Le-Tian Zhang, Chen-Chen Wu, Jing Wang, Lin Yang
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Toshimichi ASANO, Satoshi HIRANO, Toru NAKAMURA, Takehiro NOJI, Keisuke OKAMURA, Takahiro TSUCHIKAWA, Yuma EBIHARA, Toshiaki SHICHINOHE
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Toshimichi Asano, Satoshi Hirano, Toru Nakamura, Keisuke Okamura, Takahiro Tsuchikawa, Takehiro Noji, Yoshitsugu Nakanishi, Kimitaka Tanaka, Toshiaki Shichinohe
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Sophie Otter, Irene Chong, Ria Kalaitzaki, Diana Tait
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Change in carbohydrate antigen 19-9 level as a prognostic marker of overall survival in locally advanced pancreatic cancer treated with concurrent chemoradiotherapy
Yi-Jun Kim, Hyeon Kang Koh, Eui Kyu Chie, Do-Youn Oh, Yung-Jue Bang, Eun Mi Nam, Kyubo Kim
International Journal of Clinical Oncology.2017; 22(6): 1069. CrossRef
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Dong S., Wang L., Guo Y. B., Ying H. F., Shen X. H., Meng Z. Q., Chen Hao, Chen Q. W., Li Z. S.
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Review Article

Gemcitabine Plus Cisplatin for Advanced Biliary Tract Cancer: A Systematic Review: Joon Oh Park, Do-Youn Oh, Chiun Hsu, Jen-Shi Chen, Li-Tzong Chen, Mauro Orlando, Jong Seok Kim, Ho Yeong Lim; Cancer Res Treat. 2015;47(3):343-361. Published online May 18, 2015; DOI: https://doi.org/10.4143/crt.2014.308

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Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin.

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Original Articles

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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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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Natural‐Product‐Inspired Discovery of Trimethoxyphenyl‐1,2,4‐triazolosulfonamides as Potent Tubulin Polymerization Inhibitors
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Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer: Do-Youn Oh, Toshihiko Doi, Kuniaki Shirao, Keun-Wook Lee, Sook Ryun Park, Ying Chen, Liqiang Yang, Olga Valota, Yung-Jue Bang; Cancer Res Treat. 2015;47(4):687-696. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.225

Abstract PDF PubReader ePub

Purpose
This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination.
Materials and Methods
Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m2 (day 1) and capecitabine 1,000 mg/m2 twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data.
Results
Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months.
Conclusion
In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable.

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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

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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
Langenbeck's Archives of Surgery.2022; 407(1): 153. CrossRef
Splenic-vasculature involvement is associated with poor prognosis in resected distal pancreatic cancer
Feng Yin, Mohammed Saad, Jingmei Lin, Christopher R Jackson, Bing Ren, Cynthia Lawson, Dipti M Karamchandani, Belen Quereda Bernabeu, Wei Jiang, Teena Dhir, Richard Zheng, Christopher W Schultz, Dongwei Zhang, Courtney L Thomas, Xuchen Zhang, Jinping Lai,
Gastroenterology Report.2021; 9(2): 139. CrossRef
Meta-analysis of recurrence pattern after resection for pancreatic cancer
M Tanaka, A L Mihaljevic, P Probst, M Heckler, U Klaiber, U Heger, M W Büchler, T Hackert
British Journal of Surgery.2019; 106(12): 1590. CrossRef
Improved Survival in Patients with Resected Pancreatic Carcinoma Using Postoperative Intensity-Modulated Radiotherapy and Regional Intra-Arterial Infusion Chemotherapy
Ningyi Ma, Zheng Wang, Jiandong Zhao, Jiang Long, Jin Xu, Zhigang Ren, Guoliang Jiang
Medical Science Monitor.2017; 23: 2315. CrossRef
Role of Adjuvant Radiotherapy in Left-Sided Pancreatic Cancer—Population-Based Analysis with Propensity Score Matching
Yu Jin Lim, Kyubo Kim, Eui Kyu Chie, BoKyong Kim, Sung W. Ha
Journal of Gastrointestinal Surgery.2015; 19(12): 2183. CrossRef

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

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

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

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

Abstract PDF PubReader ePub

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

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