Cancer Research and Treatment

Original Articles

Gastrointestinal cancer

Molecular and Immune Profiling of Syngeneic Mouse Models Predict Response to Immune Checkpoint Inhibitors in Gastric Cancer: Dagyeong Lee, Junyong Choi, Hye Jeong Oh, In-Hye Ham, Sung Hak Lee, Sachiyo Nomura, Sang-Uk Han, Hoon Hur; Cancer Res Treat. 2023;55(1):167-178. Published online May 20, 2022; DOI: https://doi.org/10.4143/crt.2022.094

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Purpose
Appropriate preclinical mouse models are needed to evaluate the response to immunotherapeutic agents. Immunocompetent mouse models have rarely been reported for gastric cancer. Thus, we investigated immunophenotypes and responses to immune checkpoint inhibitor (ICI) in immunocompetent mouse models using various murine gastric cancer cell lines.
Materials and Methods
We constructed subcutaneous syngeneic tumors with murine gastric cancer cell lines, YTN3 and YTN16, in C57BL/6J mice. Mice were intraperitoneally treated with IgG isotype control or an anti–programmed death-ligand 1 (PD-L1) neutralizing antibody. We used immunohistochemistry to evaluate the tumor-infiltrating immune cells of formalin-fixed paraffin-embedded mouse tumor tissues. We compared the protein and RNA expression between YTN3 and YTN16 cell lines using a mouse cytokine array and RNA sequencing.
Results
The mouse tumors revealed distinct histological and molecular characteristics. YTN16 cells showed upregulation of genes and proteins related to immunosuppression, such as Ccl2 (CCL2) and Csf1 (M-CSF). Macrophages and exhausted T cells were more enriched in YTN16 tumors than in YTN3 tumors. Several YTN3 tumors were completely regressed by the PD-L1 inhibitor, whereas YTN16 tumors were unaffected. Although treatment with a PD-L1 inhibitor increased infiltration of T cells in both the tumors, the proportion of exhausted immune cells did not decrease in the non-responder group.
Conclusion
We confirmed the histological and molecular features of cancer cells with various responses to ICI. Our models can be used in preclinical research on ICI resistance mechanisms to enhance clinical efficacy.

Citations

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Tubulointerstitial nephritis antigen-like 1 from cancer-associated fibroblasts contribute to the progression of diffuse-type gastric cancers through the interaction with integrin β1
Dagyeong Lee, In-Hye Ham, Hye Jeong Oh, Dong Min Lee, Jung Hwan Yoon, Sang-Yong Son, Tae-Min Kim, Jae-Young Kim, Sang-Uk Han, Hoon Hur
Journal of Translational Medicine.2024;[Epub] CrossRef
Safety and Efficacy of Neoadjuvant Chemoimmunotherapy in Gastric Cancer Patients with a PD-L1 Positive Status: A Case Report
Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Liudmila V. Spirina, Alexander M. Volkov
Current Issues in Molecular Biology.2023; 45(9): 7642. CrossRef
Targeting GAS6/AXL signaling improves the response to immunotherapy by restoring the anti-immunogenic tumor microenvironment in gastric cancer
Tae Hoon Kim, Dagyeong Lee, Hye Jeong Oh, In-Hye Ham, Dong Min Lee, Yulim Lee, Zhang Zhang, Ding Ke, Hoon Hur
Life Sciences.2023; 335: 122230. CrossRef

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Gastrointestinal Cancer

Development and Validation of a Symptom-Focused Quality of Life Questionnaire (KOQUSS-40) for Gastric Cancer Patients after Gastrectomy: Bang Wool Eom, Joongyub Lee, In Seob Lee, Young-Gil Son, Keun Won Ryu, Sung Geun Kim, Hyoung-Il Kim, Young-Woo Kim, Seong-Ho Kong, Oh Kyoung Kwon, Ji-Ho Park, Ji Yeong An, Chang Hyun Kim, Byoung-Jo Suh, Hong Man Yoon, Myoung Won Son, Ji Yeon Park, Jong-Min Park, Sang-Ho Jeong, Moon-Won Yoo, Geum Jong Song, Han-Kwang Yang, Yun-Suhk Suh, Ki Bum Park, Sang-Hoon Ahn, Dong Woo Shin, Ye Seob Jee, Hye-Seong Ahn, Sol Lee, Jae Seok Min, Haejin In, Ahyoung Kim, Hoon Hur, Hyuk-Joon Lee, on behalf of KOrean QUality of life in Stomach cancer patients Study group (KOQUSS); Cancer Res Treat. 2021;53(3):763-772. Published online December 29, 2020; DOI: https://doi.org/10.4143/crt.2020.1270

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Purpose
Patients who have undergone gastrectomy have unique symptoms that are not appropriately assessed using currently available tools. This study developed and validated a symptom-focused quality of life (QoL) questionnaire for patients who have received gastrectomy for gastric cancer. Materials and Methods Based on a literature review, patient interviews, and expert consultation by the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS), the initial item pool was developed. Two large-scale developmental studies were then sequentially conducted for exploratory factor analyses for content validity and item reduction. The final item pool was validated in a separate cohort of patients and assessed for internal consistency, test-retest reliability, construct validity, and clinical validity.
Results
The initial questionnaire consisted of 46-items in 12 domains. Data from 465 patients at 11 institutions, followed by 499 patients at 13 institutions, were used to conduct item reduction and exploratory factor analyses. The final questionnaire (KOQUSS-40) comprised 40 items within 11 domains. Validation of KOQUSS-40 was conducted on 413 patients from 12 hospitals. KOQUSS-40 was found to have good model fit. The mean summary score of the KOQUSS-40 was correlated with the EORTC QLQ-C30 and STO22 (correlation coefficients, 0.821 and 0.778, respectively). The KOQUSS-40 score was also correlated with clinical factors, and had acceptable internal consistency (> 0.7). Test-retest reliability was greater than 0.8. Conclusion The KOQUSS-40 can be used to assess QoL of gastric cancer patients after gastrectomy and allows for a robust comparison of surgical techniques in clinical trials.

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Global status of research on gastrointestinal cancer patients’ quality of life: A bibliometric and visual analysis from 2003 to 2023
Xiaoqin Wang, Caihua Wang, Wenjin Han, Jiaru Sun, Zhaozhao Hui, Shuangyan Lei, Huili Wu, Xiaohong Liu
Heliyon.2024; 10(1): e23377. CrossRef
Development and Feasibility Assessment of Mobile Application-Based Digital Therapeutics for Postoperative Supportive Care in Gastric Cancer Patients Following Gastrectomy
Ji-Hyeon Park, Hyuk-Joon Lee, JeeSun Kim, Yo-Seok Cho, Sunjoo Lee, Seongmin Park, Hwinyeong Choe, Eunhwa Song, Youngran Kim, Seong-Ho Kong, Do Joong Park, Byung-Ho Nam, Han-Kwang Yang
Journal of Gastric Cancer.2024; 24(4): 420. CrossRef
Effect of Four Main Gastrectomy Procedures for Proximal Gastric Cancer on Patient Quality of Life: A Nationwide Multi-Institutional Study
Koji Nakada, Akitoshi Kimura, Kazuhiro Yoshida, Nobue Futawatari, Kazunari Misawa, Kuniaki Aridome, Yoshiyuki Fujiwara, Kazuaki Tanabe, Hirofumi Kawakubo, Atsushi Oshio, Yasuhiro Kodera
Journal of Gastric Cancer.2023; 23(2): 275. CrossRef
Quality of life after gastric cancer surgery
Jae Kyun Park, Hyuk-Joon Lee
Foregut Surgery.2023; 3(2): 27. CrossRef
Long-term Functional and Patient-reported Outcomes Between Intra-corporeal Delta-shaped Gastroduodenostomy and Gastrojejunostomy After Laparoscopic Distal Gastrectomy
Sin Hye Park, Hong Man Yoon, Keun Won Ryu, Young-Woo Kim, Mira Han, Bang Wool Eom
Journal of Gastric Cancer.2023; 23(4): 561. CrossRef
Potential Applicability of Local Resection With Prophylactic Left Gastric Artery Basin Dissection for Early-Stage Gastric Cancer in the Upper Third of the Stomach
Yoshimasa Akashi, Koichi Ogawa, Katsuji Hisakura, Tsuyoshi Enomoto, Yusuke Ohara, Yohei Owada, Shinji Hashimoto, Kazuhiro Takahashi, Osamu Shimomura, Manami Doi, Yoshihiro Miyazaki, Kinji Furuya, Shoko Moue, Tatsuya Oda
Journal of Gastric Cancer.2022; 22(3): 184. CrossRef
Systematic review of health-related quality of life (HRQoL) issues associated with gastric cancer: capturing cross-cultural differences
Alison Rowsell, Samantha C. Sodergren, Vassilios Vassiliou, Anne-Sophie Darlington, Marianne G. Guren, Bilal Alkhaffaf, Chantelle Moorbey, Kristopher Dennis, Mitsumi Terada
Gastric Cancer.2022; 25(4): 665. CrossRef
Patient-reported gastrointestinal symptoms following surgery for gastric cancer and the relative risk factors
Rui Xu, Qiong Gu, Shuomeng Xiao, Ping Zhao, Zhi Ding
Frontiers in Oncology.2022;[Epub] CrossRef
Prospective multicentre randomised clinical trial comparing survival rates, quality of life and nutritional status between advanced gastric cancer patients with different follow-up intensities: study protocol for the STOFOLUP trial
Bang Wool Eom, Dong-Hoe Koo, Ji Yeong An, Han Hong Lee, Hyoung-Il Kim, Hoon Hur, Moon-Won Yoo, Min-Hee Ryu, Hyuk-Joon Lee, Su Mi Kim, Ji-Ho Park, Jae Seok Min, Kyung Won Seo, Sang-Ho Jeong, Oh Jeong, Oh Kyoung Kwon, Seung Wan Ryu, Chang Hak Yoo, Jae Moon
BMJ Open.2021; 11(12): e056187. CrossRef

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Outcomes of Modified FOLFOX-6 as First Line Treatment in Patients with Advanced Gastric Cancer in a Single Institution; Retrospective Analysis: Han Hong Lee, Hoon Hur, Soo Hong Kim, Ae Ryung Park, Wook Kim, Hae Myung Jeon; Cancer Res Treat. 2010;42(1):18-23. Published online March 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.1.18

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Purpose

Treatment options for patients with advanced gastric cancer remain limited. Few studies have investigated the efficacy and tolerability of the combination regimen of oxaliplatin and 5-fluorouracil with leucovorin for patients with advanced gastric cancer. The goal of this study was to examine the efficacy and toxicity of a modified FOLFOX-6 (mFOLFOX-6) regimen as a first-line chemotherapy regimen for patients with advanced gastric cancer.

Materials and Methods

From March, 2006, to December, 2007, 82 patients with advanced gastric cancer received 100 mg/m² oxaliplatin and 100 mg/m² leucovorin on the first day of treatment, followed by 2,400 mg/m² of 5-fluorouracil on the first and second days of treatment every 2 weeks as a first-line treatment.

Results

The median age of the enrolled patients was 62 years (range; 30~75). Out of 82 patients, 34 cases (41.5%) were recurrent cases after curative resection, and the other 48 cases were unresectable or non-curative resectable cases. Their response was evaluated every 6 weeks. The overall response rate was 40.2%, with 2 (2.4%) complete response and 31 (37.8%) partial responses. The median time to progression (TTP) and overall survival (OS) time were 6.0 months (95% confidence interval [CI]: 4.69~7.31) and 13.0 months (7.99~18.0), respectively. The grade 3~4 hematologic toxicities observed included neutropenia (34.1%), thrombocytopenia (7.3%), and anemia (1.2%). The gastrointestinal toxicities observed included grade 3~4 nausea (9.8%) and vomiting (7.3%). Six patients (7.3%) experienced grade 3 neuropathy. No treatment-related deaths were recorded.

Conclusion

The modified FOLFOX-6 regimen is effective and well tolerated as a first-line chemotherapy regimen for patients with advanced gastric cancer.

Citations

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Nanoparticle Polymeric Micellar Paclitaxel Versus Paclitaxel for Patients with Advanced Gastric Cancer
Fei-Yu Wang, Xiang-Ming Huang, Yu-Qing Cao, Jie Cao, Jie Ni, Ke Li, Min Lu, Xin-En Huang
Journal of Gastrointestinal Cancer.2024; 55(3): 1105. CrossRef
Prognostic significance of interim 18F‐fluorodeoxyglucose positron emission tomography–computed tomography volumetric parameters in metastatic or recurrent gastric cancer
Suk‐young Lee, Hyo Jung Seo, Sungeun Kim, Jae Seon Eo, Sang Cheul Oh
Asia-Pacific Journal of Clinical Oncology.2018;[Epub] CrossRef
Combination chemotherapy with paclitaxel and oxaliplatin as first-line treatment in patients with advanced gastric cancer
Yan-qin Lan, Ling-jun Kong, Xiao-yan Lin, Qian Xu, Xin-yan Gao, Ri-ping Wu, Xin-li Wang, Dong-ta Zhong
Cancer Chemotherapy and Pharmacology.2018; 81(6): 1007. CrossRef
Paclitaxel, oxaliplatin, 5-fluorouracil and leucovorin combination chemotherapy in patients with recurrent or metastatic gastric cancer
Yan-qin Lan, Ri-ping Wu, Xiao-bing Huang, Xin-li Wang, Dong-ta Zhong, Chuan-yong Huang, Jin-tian Song
Tumori Journal.2018; 104(1): 22. CrossRef
Comparative Analysis of the Efficacy and Safety of Oxaliplatin Plus 5-Fluorouracil/Leucovorin (Modified FOLFOX6) with Advanced Gastric Cancer Patients having a Good or Poor Performance Status
Ilhan Hacibekiroglu, Hilmi Kodaz, Bulent Erdogan, Esma Turkmen, Asim Esenkaya, Sernaz Uzunoglu, Irfan Cicin
Asian Pacific Journal of Cancer Prevention.2015; 16(6): 2355. CrossRef
Comparative analysis of the efficacy and safety of modified FOLFOX-6 and DCF regimens as first-line treatment in advanced gastric cancer
ILHAN HACIBEKIROGLU, HILMI KODAZ, BULENT ERDOGAN, ESMA TURKMEN, ASIM ESENKAYA, YILMAZ ONAL, SERNAZ UZUNOGLU, IRFAN CICIN
Molecular and Clinical Oncology.2015; 3(5): 1160. CrossRef
Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer
Zhan-Dong Zhang, Ye Kong, Wei Yang, Bin Zhang, Yong-Lei Zhang, Er-Min Ma, Hong-Xing Liu, Xiao-Bin Chen, Ya-Wei Hua
World Journal of Surgical Oncology.2014;[Epub] CrossRef
Management of advanced gastric cancer
Timothy J Price, Jeremy D Shapiro, Eva Segelov, Christos S Karapetis, Nick Pavlakis, Eric Van Cutsem, Manish A Shah, Yoon-Koo Kang, Niall C Tebbutt
Expert Review of Gastroenterology & Hepatology.2012; 6(2): 199. CrossRef
Outcomes of Third-Line Docetaxel-Based Chemotherapy in Advanced Gastric Cancer Who Failed Previous Oxaliplatin-Based and Irinotecan-Based Chemotherapies
Min Jeong Lee, In Gyu Hwang, Joung-Soon Jang, Jin Hwa Choi, Byeong-Bae Park, Myung Hee Chang, Seung Tae Kim, Se Hoon Park, Myoung Hee Kang, Jung Hun Kang
Cancer Research and Treatment.2012; 44(4): 235. CrossRef
Modified FOLFOX-6 Therapy for Heavily Pretreated Advanced Gastric Cancer Refractory to Fluorouracil, Irinotecan, Cisplatin and Taxanes: A Retrospective Study
K. Tsuji, H. Yasui, Y. Onozawa, N. Boku, H. Doyama, A. Fukutomi, K. Yamazaki, N. Machida, A. Todaka, H. Taniguchi, T. Tsushima, T. Yokota
Japanese Journal of Clinical Oncology.2012; 42(8): 686. CrossRef
A rare case of acute kidney injury associated with autoimmune hemolytic anemia and thrombocytopenia after long-term usage of oxaliplatin
Isao Ito, Yasuhiko Ito, Masashi Mizuno, Yasuhiro Suzuki, Kaoru Yasuda, Takenori Ozaki, Tomoki Kosugi, Yoshinari Yasuda, Waichi Sato, Naotake Tsuboi, Shoichi Maruyama, Enyu Imai, Seiichi Matsuo
Clinical and Experimental Nephrology.2012; 16(3): 490. CrossRef
Oxaliplatin, 5-fluorouracil and leucovorin (modified FOLFOX-6) as first-line chemotherapy for advanced gastric cancer patients with poor performance status
HYEONG SU KIM, JUNG HAN KIM, HEE JUN KIM, HYUN JOO JANG, JIN BAE KIM, JI WON KIM, SO YOUNG JUNG, BYUNG CHUN KIM, DAE HYUN YANG, SOAH PARK, KEONG JU KIM, SOON IL LEE, DAE YOUNG ZANG
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Targeted Therapies for Gastric Cancer
Jaclyn Yoong, Michael Michael, Trevor Leong
Drugs.2011; 71(11): 1367. CrossRef

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