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CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer
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Guolin Zhang, Xin Luo, Wei Zhang, Engeng Chen, Jianbin Xu, Fei Wang, Gaoyang Cao, Zhenyu Ju, Dongai Jin, Xuefeng Huang, Wei Zhou, Zhangfa Song
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Cancer Res Treat. 2020;52(2):622-633. Published online December 31, 2019
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DOI: https://doi.org/10.4143/crt.2019.593
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Abstract
PDFPubReaderePub
- Purpose
5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy for patients with advanced colorectal cancer, but many patients still suffer from treatment failure due to 5-Fu resistance. Emerging observations revealed the important role of chemokine (C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosis in patients with colorectal cancer. This study is designed to reveal the important role of CXCL-13 in causing colorectal cancer resistance to 5-Fu.
Materials and Methods
CXCL-13 levels of patient's serum or cell culture supernatants were measured separately by enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell Counting Kit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expression in cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells.
Results
In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistant cells. Clinical studies showed that CXCL-13 is highly expressed in the serum of 5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome. The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibody overcame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced 5-Fu resistance, which can be saved by added recombination CXCL-13.
Conclusion
These results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but also provide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatment strategies.
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Patient and Care Delays of Breast Cancer in China
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Yue-Lin Li, Ya-Chao Qin, Lu-Ying Tang, Yu-Huang Liao, Wei Zhang, Xiao-Ming Xie, Qiang Liu, Ying Lin, Ze-Fang Ren
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Cancer Res Treat. 2019;51(3):1098-1106. Published online November 6, 2018
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DOI: https://doi.org/10.4143/crt.2018.386
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
This study differentiates patient and care delays of breast cancer and explores the related factors as well as the associations with the prognosis in Guangzhou, a southern city of China.
Methods
A cohort of female incident breast cancer patients (n=1,551) was recruited from October 2008 to March 2012 and followed up until January 1, 2016 (n=1,374) in the affiliated hospitals of Sun Yat-sen University. The factors associated with patient and care delays were analyzed with multivariable logistic models. Cox proportional hazards regression models were constructed to estimate the impacts of the delays on the prognosis.
Results
There were 40.4% patient delay (≥3 months) and 15.5% care delay (≥1 month). The patient delay, but not the care delay, was significantly related to the clinical stage and consequently worsened the prognosis of breast cancer (hazard ratio, 1.45; 95% confidence interval, 1.09 to 1.91 for progression-free survival). The factors related to an increased patient delay included premenopausal status, history of benign breast disease, and less physical examination.
Conclusion
Patient delay was the main type of delay in Guangzhou and resulted in higher clinical stage and poor prognosis of breast cancer. Screening for breast cancer among premenopausal women may be an effective way to reduce this delay.
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