Browsing by Author "Yu, Ching-Fang"

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Gene expression profiling of tumor-associated macrophages after exposure to single-dose irradiation
(2017-08-01)
Kung, Wei-Hsiang
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Yu, Ching-Fang
;
Lee, Andy Chi-Lung
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Yang, Chi-Dung
;
Liu, Yu-Chen
Radiotherapy (RT) is a common cancer treatment approach that accounts for nearly 50% of patient treatment; however, tumor relapse after radiotherapy is still a major issue. To study the crucial role of tumor-associated macrophages (TAMs) in the regulation of tumor progression post-RT, microarray experiments comparing TAM gene expression profiles between unirradiated and irradiated tumors were conducted to discover possible roles of TAMs in initiation or contribution to tumor recurrence following RT, taking into account the relationships among gene expression, tumor microenvironment, and immunology. A single dose of 25 Gy was given to TRAMP C-1 prostate tumors established in C57/B6 mice. CD11b-positive macrophages were extracted from the tumors at one, two and three weeks post-RT. Gene ontology (GO) term analysis using the DAVID database revealed that genes that were differentially expressed at one and two weeks after irradiation were associated with biological processes such as morphogenesis of a branching structure, tube development, and cell proliferation. Analysis using Short Time-Series Expression Miner (STEM) revealed the temporal gene expression profiles and identified 13 significant patterns in four main groups of profiles. The genes in the upregulated temporal profile have diverse functions involved in the intracellular signaling cascade, cell proliferation, and cytokinemediated signaling pathway. We show that tumor irradiation with a single 25-Gy dose can initiate a time series of differentially expressed genes in TAMs, which are associated with the immune response, DNA repair, cell cycle arrest, and apoptosis. Our study helps to improve our understanding of the function of the group of genes whose expression changes temporally in an irradiated tumor microenvironment. (C) 2017 Elsevier Ltd. All rights reserved.
Integrated microRNA and mRNA expression profile analysis of tumor-associated macrophages after exposure to single-dose irradiation
(2018-06-01)
Kung, Wei-Hsiang
;
Lee, Chi-Lung
;
Yang, Chi-Dung
;
Yu, Ching-Fang
;
Chiew, Men-Yee
Background: Radiotherapy (RT) is a common approach that accounts for nearly 50% of cancer patient treatment and has the potential for long-term tumor control Recently, we published a research article on gene expression profiling of tumor-associated macrophages (TAM) that were exposed to ionizing radiation (IR). Single-dose irradiation of tumors could initiate differentially expressed genes in TAM as a time series from irradiated tumors that are associated with the immune response. It is also well known that human cancers are associated with microRNA (miRNA) alterations that are involved in cancer progression. However, the role of miRNA on TAM after exposure to irradiation remains unclear. Results: In this study, miRNA expression profiles from microarrays were used to identify the key miRNAs and correlating pathways involved in the role of TAMs in tumor progression and recurrence after RT. Using a mouse tumor model, we identified miRNA pattern changes over time in response to irradiation. Based on our results, we hypothesize that miRNA expression in the irradiated tumor may be used as a distinguishing marker to indicate the best time for therapeutic intervention to prevent tumor recurrence after RT. Conclusions: We established a murine model irradiated with a single dose of 25 Gy that could initiate temporal changes in the expression of miRNAs associated with cell proliferation and the immune response, as evidenced by macrophages directly extracted from irradiated tumors after two weeks of IR. Statistical analyses were conducted by comparing the miRNA expression in macrophages from non-lrradiated versus irradiated tumors. Thus, our study could lead to a better understanding of the function of miRNA expressions, which changed temporally in an irradiated tumor microenvironment. (C) 2018 Elsevier Ltd. All rights reserved.