Cancer Research and Treatment

Original Articles

Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer: Li-jun Liang, Chen-xi Hu, Yi-xuan Wen, Xiao-wei Geng, Ting Chen, Guo-qing Gu, Lei Wang, You-you Xia, Yong Liu, Jia-yan Fei, Jie Dong, Feng-hua Zhao, Yiliyar Ahongjiang, Kai-yuan Hui, Xiao-dong Jiang; Cancer Res Treat. 2020;52(2):406-418. Published online September 3, 2019; DOI: https://doi.org/10.4143/crt.2019.296

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Purpose
This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma.
Materials and Methods
Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed.
Results
For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved.
Conclusion
Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

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Antiangiogenic Treatment Facilitates the Abscopal Effect of Radiation Therapy Combined With Anti-PD-1 in Hepatocellular Carcinoma
Hailong Sheng, Yongyi Luo, Liting Zhong, Zhiyi Wang, Zhichao Sun, Xinna Gao, Xinrong He, Zhenru Zhu, Dehua Wu, Jingyuan Sun, Chuanhui Cao
International Journal of Radiation Oncology*Biology*Physics.2025; 121(2): 534. CrossRef
Interactions between radiotherapy resistance mechanisms and the tumor microenvironment
Dengxiong Li, Jie Wang, Xinrui Li, Zhipeng Wang, Qingxin Yu, Siang Boon Koh, Ruicheng Wu, Luxia Ye, Yiqing Guo, Uzoamaka Okoli, Alisha Pati-Alam, Eduardo Mota, Wuran Wei, Koo Han Yoo, William C. Cho, Dechao Feng, Susan Heavey
Critical Reviews in Oncology/Hematology.2025; 210: 104705. CrossRef
Combination of potassium oxonate with anti-PD-1 for the treatment of colorectal cancer
Yuanyuan Wang, Chenxi Hu, Tianpeng Du, Jiawen Li, Kaiyuan Hui, Xiaodong Jiang
Frontiers in Oncology.2025;[Epub] CrossRef
Comparison of Efficacy and Safety of Different Second-line Therapies for Patients With Advanced Thymic Carcinoma
K. Shao, Y. Hao, M. Xu, Z. Shi, G. Lin, C. Xu, Y. Zhang, Z. Song
Clinical Oncology.2024; 36(11): 710. CrossRef
Immune effect and prognosis of transcatheter arterial chemoembolization and tyrosine kinase inhibitors therapy in patients with hepatocellular carcinoma
Yuan Guo, Ru-Chun Li, Wei-Li Xia, Xiong Yang, Wen-Bo Zhu, Fang-Ting Li, Hong-Tao Hu, Hai-Liang Li
World Journal of Gastrointestinal Oncology.2024; 16(7): 3256. CrossRef
A disintegrin and metalloproteinase domain 10 expression inhibition by the small molecules adenosine, cordycepin and N6, N6-dimethyladenosine and immune regulation in malignant cancers
Wenqian Zhang, Jiewen Fu, Jiaman Du, Xiaoyan Liu, Jingliang Cheng, Chunli Wei, Youhua Xu, Junjiang Fu
Frontiers in Immunology.2024;[Epub] CrossRef
Low‐ dose Apatinib promotes vascular normalization and hypoxia reduction and sensitizes radiotherapy in lung cancer
Shanshan Jiang, Yue Zhou, Liqing Zou, Li Chu, Xiao Chu, Jianjiao Ni, Yida Li, Tiantian Guo, Xi Yang, Zhengfei Zhu
Cancer Medicine.2023; 12(4): 4434. CrossRef
Local Destruction of Tumors and Systemic Immune Effects
Karl-Göran Tranberg
Frontiers in Oncology.2021;[Epub] CrossRef
A novel role for apatinib in enhancing radiosensitivity in non-small cell lung cancer cells by suppressing the AKT and ERK pathways
Lin Li, Yuexian Li, Huawei Zou
PeerJ.2021; 9: e12356. CrossRef

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Reduction of Target Volume and the Corresponding Dose for the Tumor Regression Field after Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: Lei Wang, Zheng Wu, Dehuan Xie, Ruifang Zeng, Wanqin Cheng, Jiang Hu, Shaomin Huang, Shu Zhou, Rui Zhong, Yong Su; Cancer Res Treat. 2019;51(2):685-695. Published online August 13, 2018; DOI: https://doi.org/10.4143/crt.2018.250

Abstract PDF PubReader ePub

Purpose
This study aims to investigate the feasibility of contouring target volume according to residual tumor and decreasing the dose to the tumor regression field after induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC).
Materials and Methods
From August 2009 to August 2013, patients with stage III–IVB NPC were treated with IC and concurrent chemoradiotherapy. Gross tumor volume of nasopharynx (GTVnx)–residual and gross tumor volume of cervical lymph node (GTVnd)–residual were contoured according to post-IC residual primary tumor and any N+ disease, respectively. The tumor regression field was included in CTVnx1/CTVnd1 and prescribed a dose of 60 Gy. Outcomes and toxicities of all patients were evaluated.
Results
A total of 57 patients were enrolled. At a median follow-up of 68 months, three cases displayed locoregional recurrence and one case showed both distant metastasis and locoregional recurrence. All locoregional recurrences were in the GTVnx-residual/GTVnd-residual and in-field. The 5-year overall, locoregional relapse-free, distant metastasis-free, and progression-free survival rates were 82.2%, 87.7%, 85.8% and 80.3%, respectively.
Conclusion
After IC, contouring of GTVnx-residual/GTVnd-residual as residual tumor volume and distribution 60 Gy ofradiation dose to the tumorregression field may be feasible and need further investigation.

Citations

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Recurrent Patterns in Patients With Nasopharyngeal Caricinoma and Risks Leading to Inaccurate Delineation in Marginal Failure in the Era of Intensity‐Modulated Radiotherapy
Shu Zhang, Ni Zeng, Jiangping Yang, Jiaqi Han, Jinlan He, Baofeng Duan, Xiaoqiang Chen, Xiaofang Gou, Fubin Zhu, Huizhen Liu, Ming Zeng, Di Yan, Nianyong Chen
Head & Neck.2025; 47(3): 917. CrossRef
Efficacy and Failure Patterns Following Target Volume and Dose Reduction After Neoadjuvant Therapy in Locoregionally Advanced Head and Neck Squamous Cell Carcinoma
Xiong Zhou, Zheng Wu, Zichen Qiu, Minchuan Lin, Yalan Tao, Yong Su
Head & Neck.2025; 47(4): 1247. CrossRef
Comparison of TPF and PF induction chemotherapy combined with cisplatin concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: A systematic review and meta-analysis
Haiwen Li, Qibiao Wu, Haiqing Luo, Jiayuan Wu, Wenmei Su, Lili Yu
Medicine.2025; 104(3): e41278. CrossRef
Reduced‐volume radiotherapy versus conventional‐volume radiotherapy after induction chemotherapy in nasopharyngeal carcinoma: An open‐label, noninferiority, multicenter, randomized phase 3 trial
Ling‐Long Tang, Lin Chen, Gui‐Qiong Xu, Ning Zhang, Cheng‐Long Huang, Wen‐Fei Li, Yan‐Ping Mao, Guan‐Qun Zhou, Feng Lei, Lu‐Si Chen, Shao Hui Huang, Lei Chen, Yu‐Pei Chen, Yuan Zhang, Xu Liu, Cheng Xu, Yin Zhao, Ji‐Bin Li, Na Liu, Fang‐Yun Xie, Rui Guo, Y
CA: A Cancer Journal for Clinicians.2025; 75(3): 203. CrossRef
International Consensus Guidelines on the Delineation of Radiation Therapy Target Volumes for Nasopharyngeal Carcinoma After Induction Chemotherapy Using a 2-Round Modified Delphi Survey
Nejla Fourati, Warren Bacorro, Omar Nouri, Ryan Anthony Agas, Audrey Larnaudie, Lester Bryan Co, Hela Hammami, Clevelinda Calma, Melvin L.K. Chua, Chong Zhao, Jamel Daoud, Michael Benedict Mejia
Practical Radiation Oncology.2025;[Epub] CrossRef
Post‐induction lymph node delineation in nasopharyngeal cancer: A single‐center experience
Sezin Yuce Sari, Ecem Yigit, Gozde Yazici, Ibrahim Halil Gullu, Sercan Aksoy, Gokhan Ozyigit, Mustafa Cengiz
Head & Neck.2023; 45(3): 612. CrossRef
Tumor volume reduction after induction chemotherapy with gemcitabine plus cisplatin in nasopharyngeal carcinoma
Qian Chen, Liangfang Shen, Shan Li
European Archives of Oto-Rhino-Laryngology.2023; 280(5): 2497. CrossRef
Characteristics of local extension based on tumor distribution in nasopharyngeal carcinoma and proposed clinical target volume delineation
Zheng Wu, Bin Qi, Fei-Fei Lin, Lin Zhang, Qian He, Fei-Ping Li, Hui Wang, Ya-Qian Han, Wen-Jing Yin
Radiotherapy and Oncology.2023; 183: 109595. CrossRef
Optimizing induction chemotherapy regimens for radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma
Ying Li, Jianping Bi, Guoliang Pi, Hanping He, Yanping Li, Dandan Zheng, Zecheng Wei, Guang Han
Cancer Medicine.2023; 12(8): 9449. CrossRef
Lessons and Opportunities for Biomarker-Driven Radiation Personalization in Head and Neck Cancer
Elham Rahimy, Michael F. Gensheimer, Beth Beadle, Quynh-Thu Le
Seminars in Radiation Oncology.2023; 33(3): 336. CrossRef
Concurrent chemoradiotherapy with or without neoadjuvant chemotherapy in pediatric patients with stage III-IVa nasopharyngeal carcinoma: a real-world propensity score-matched cohort study
Ya-Nan Jin, Zhao-Hui Ruan, Wan-Wei Cao, Lin Yang, Wei Yao, Xiao-Feng Pei, Wang-Jian Zhang, Tia Marks, Ji-Jin Yao, Liang-Ping Xia
Journal of Cancer Research and Clinical Oncology.2023; 149(13): 11929. CrossRef
Failure patterns of locoregional recurrence after reducing target volumes in patients with nasopharyngeal carcinoma receiving adaptive replanning during intensity-modulated radiotherapy: a single-center experience in China
Xiate Zhou, Jian Zhu, Chao Zhou, Wei Wang, Weijun Ding, Meng Chen, Kuifei Chen, Shuling Li, Xiaofeng Chen, Haihua Yang
Radiation Oncology.2023;[Epub] CrossRef
Clinical target volume design of postoperative intensity-modulated radiotherapy for major salivary gland tumours according to surgical principles: an innovative method
Shaowen Lyu, Zheng Wu, Dehuan Xie, Zhiqing Long, Rui Zhong, Wang Lei, Wanqin Cheng, Jiang Hu, Xuekui Liu, Chuanmiao Xie, Yong Su
Journal of Cancer Research and Clinical Oncology.2022; 148(4): 921. CrossRef
Local control and failure patterns after intensity modulated radiotherapy with reduced target volume delineation after induction chemotherapy for patients with T4 nasopharyngeal carcinoma
Fang-Fang Kong, Meng-Shan Ni, Rui-Ping Zhai, Hong-Mei Ying, Chao-Su Hu
Translational Oncology.2022; 16: 101324. CrossRef
Tumor factors associated with in‐field failure for nasopharyngeal carcinoma after intensity‐modulated radiotherapy
Xixi Liu, Bian Wu, Jing Huang, You Qin, Zhanjie Zhang, Liangliang Shi, Xiaohua Hong, Qian Ding, Gang Peng, Kunyu Yang
Head & Neck.2022; 44(4): 876. CrossRef
Gemcitabine Versus Docetaxel Plus Cisplatin as Induction Chemotherapy in Nasopharyngeal Carcinoma
Qian Chen, Shan Li
The Laryngoscope.2022; 132(12): 2379. CrossRef
Individualized clinical target volume delineation and efficacy analysis in unilateral nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT): 10-year summary
De-Huan Xie, Zheng Wu, Wang-Zhong Li, Wan-Qin Cheng, Ya-Lan Tao, Lei Wang, Shao-Wen Lv, Fei-Fei Lin, Nian-Ji Cui, Chong Zhao, Jun Ma, Shao-Min Huang, Tai-Xiang Lu, Ya-Qian Han, Yong Su
Journal of Cancer Research and Clinical Oncology.2022; 148(8): 1931. CrossRef
Volumetric modulated arc therapy versus tomotherapy for late T-stage nasopharyngeal carcinoma
Qian Chen, Lingwei Tang, Zhe Zhu, Liangfang Shen, Shan Li
Frontiers in Oncology.2022;[Epub] CrossRef
Is a high-risk clinical target volume required? Evaluation of the dosimetric feasibility based on T staging
Xingxing Yuan, Chao Yan, Shiyi Peng, Zhiping Chen, Tianzhu Lu, Qiaoying Gong, Yang Qiu, Wenming Xiong, Fenghua Ao, Guoqing Li, Jingao Li, Ziwei Tu
Frontiers in Oncology.2022;[Epub] CrossRef
Long-term results of the phase II dose and volume de-escalation trial for locoregionally advanced nasopharyngeal carcinoma
Fen Xue, Dan Ou, Xiaomin Ou, Xin Zhou, Chaosu Hu, Xiayun He
Oral Oncology.2022; 134: 106139. CrossRef
Is Surgery an Inevitable Treatment for Advanced Salivary Lymphoepithelial Carcinoma? Three Case Reports
Shaowen Lv, Dehuan Xie, Zheng Wu, Lei Wang, Yong Su
Ear, Nose & Throat Journal.2021; 100(9): NP402. CrossRef
The change in tumor volume after induction chemotherapy with docetaxel plus cisplatin in 259 nasopharyngeal carcinoma patients
Shan Li, Liangfang Shen
European Archives of Oto-Rhino-Laryngology.2021; 278(8): 3027. CrossRef
Extensive pelvic and abdominal lymphadenopathy with hepatosplenomegaly treated with radiotherapy—A case report
Sahil Mittal, ShaikhA Hussain, RahulV. C Tiwari, AjithB Poovathingal, BPadma Priya, Rishabh Bhanot, Heena Tiwari
Journal of Family Medicine and Primary Care.2020; 9(2): 1215. CrossRef
Nutritional outcomes after radiotherapy target volume reduction for nasopharyngeal cancer: a Phase III trial
Li Xiang, Jin-Feng Rong, Hao-Wen Pang, Huai-Lin He, Yue Chen, Jing-Bo Wu, Yong-Sheng Wang
Future Oncology.2020; 16(9): 427. CrossRef
Quality of Life, Toxicity and Unmet Needs in Nasopharyngeal Cancer Survivors
Lachlan McDowell, June Corry, Jolie Ringash, Danny Rischin
Frontiers in Oncology.2020;[Epub] CrossRef
Impact of tumor volume enlargement after induction chemotherapy on subsequent radiotherapy in locally advanced nasopharyngeal carcinoma: A propensity‐score matching analysis
Shan Li, Liangfang Shen
Cancer Medicine.2020; 9(23): 8832. CrossRef
Target delineation and dose prescription of adaptive replanning intensity‐modulated radiotherapy for nasopharyngeal carcinoma
Dehuan Xie, Wanqin Cheng, Shaowen Lv, Rui Zhong, Lei Wang, Jiang Hu, Mingli Wang, Shaomin Huang, Yong Su, Yunfei Xia
Cancer Communications.2019; 39(1): 1. CrossRef
Cisplatin/docetaxel/fluorouracil

Reactions Weekly.2019; 1753(1): 113. CrossRef
Chemotherapy Potentially Facilitates the Occurrence of Radiation Encephalopathy in Patients With Nasopharyngeal Carcinoma Following Radiotherapy: A Multiparametric Magnetic Resonance Imaging Study
Youming Zhang, Xiaoping Yi, Jianming Gao, Li Li, Lizhi Liu, Ting Qiu, Jinlei Zhang, Yuanchao Zhang, Weihua Liao
Frontiers in Oncology.2019;[Epub] CrossRef

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MicroRNA-373 Inhibits Cell Proliferation and Invasion via Targeting BRF2 in Human Non-small Cell Lung Cancer A549 Cell Line: Lei Wang, Junfeng Qu, Li Zhou, Fei Liao, Ju Wang; Cancer Res Treat. 2018;50(3):936-949. Published online October 12, 2017; DOI: https://doi.org/10.4143/crt.2017.302

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to investigate the biological role and mechanism of miR-373 targeting of TFIIB-related factor 2 (BRF2) in the regulation of non-small cell lung cancer (NSCLC) cells. MaterialsandMethods miRNA microarray chip analysis of four paired NSCLC and adjacent non-tumor tissues was performed. Quantitative real-time polymerase chain reaction (qRT-PCR) andwestern blotting were used to detect the expression levels of miR-373 and BRF2 in NSCLC tissues and cell lines. The dual-luciferase reporter method was performed to determine if BRF2 is a target of miR-373. MTT, wound-healing, Transwell, and flow cytometric assays were conducted to examine the proliferation, migration, invasion, and cell cycle progression of NSCLC A549 cells, respectively; western blotting was used to detect the expression of epithelial-mesenchymal transition (EMT)–related proteins.
Results
The miRNA microarray chip analysis demonstrated that miR-373 was down-regulated in NSCLC tissues, and this result was confirmed by qRT-PCR. Additionally, miR-373 was confirmed to target BRF2. Moreover, miR-373 expression was inversely correlated with BRF2 expression in NSCLC tissues and cell lines; both miR-373 down-regulation and BRF2 up-regulation were strongly associated with the clinicopathological features and prognosis of NSCLC patients. In vitro, overexpression of miR-373 markedly inhibited cell proliferation, migration, and invasion; up-regulated the expression of E-cadherin; and down-regulated the expression of N-cadherin and Snail in A549 cell. Knockdown BRF2 by siRNA resulted in effects similar to those caused by overexpression of miR-373.
Conclusion
MiR-373 is decreased in NSCLC, and overexpression of miR-373 can suppress cell EMT, and inhibit the proliferation, migration, and invasion of NSCLC A549 cells by targeting BRF2.

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