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Identification of carbon-ion responsive genes in murine tumor models
https://repo.qst.go.jp/records/62867
https://repo.qst.go.jp/records/62867a6760229-05b9-422a-8a37-c424fb5ba9b5
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2008-11-25 | |||||
| タイトル | ||||||
| タイトル | Identification of carbon-ion responsive genes in murine tumor models | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Iwakawa, Mayumi
× Iwakawa, Mayumi× Nojiri, Kazunori× Tamaki, Tomoaki× Imadome, Kaori× Nakawatari, Miyako× Sakai, Minako× Imai, Takashi× 岩川 眞由美× 野尻 和典× 田巻 倫明× 今留 香織× 中渡 美也子× 酒井 美奈子× 今井 高志 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Developments in radiation technology have lead to the clinical improvement of Carbon ion (C-ion) irradiation with well-localized energy distributions (high LET). While the development of high LET has a number of advantages over the more traditional radiation technology for the treatment of cancer, the mechanisms underlying the superior biological effectiveness of C-ion irradiation is not fully understood. Several studies have investigated the biological mechanism of C-ion irradiation in vitro. The main disadvantage of these in vitro studies includes significant differences in the gene expression profile between cell lines in vitro and the same cell lines growing in vivo and the effect of other factors related to the cellular microenvironment on the gene expression profile. Previous studies suggest that more appropriate in vivo tumor models allowing translation of findings to the clinical setting are required. We used microarray technology to examine the fate of multiple C-ion-irradiated tumors in vivo to gain a comprehensive overview of the changes in gene expression induced by C-ion irradiation. Four murine tumors were irradiated in vivo with C-ions at a single dose, and gamma-rays were used as a reference beam. \nObjective: To elucidate the in vivo biological effects induced by carbon-ion irradiation using comprehensive expression analysis. Materials and Methods: We examined gene expression changes after C-ion irradiation (290 MeV/m, SOBP 6 cm middle) with a single dose of 30 Gy in four mouse tumors (NR-S1, SCCVII, NFSa, and #8520) transplanted into the hind legs of C3H/HeNrs mice, using 44K single-color oligo-microarrays at 6 hours (h), 1 day, and 3 days after irradiation. Gamma-rays of 30 Gy and 50 Gy were used as a reference beam. Identification of C-ion-responsive genes was based on a false discovery rate of < 5% using the Wilcoxon test (P < 0.001) and the Benjamini-Hochberg correction. Results: The first finding of this study was that C-ion irradiation causes significant changes in the expression of genes that are already known to be related to radiation-induced tumor regression. A hypothetical C-ion-induced pathway indicated that a well known radiation-induced mechanism of tumor regression was similarly activated by C-ion irradiation. Radiation-induced apoptosis related genes, including Casp4, Bcl2a1b, and TNF family were also listed as C-ion responsive genes. Second, at 6 h and 1 day following C-ion irradiation, several stress-responsive genes or cell communication-related genes were also upregulated. In all tumors, the level of expression of several tens of genes, including Ccl3, Ccng1, Cd80, Cdkn1a, Cxcl2, IL7r, Lrdd, Mgmt, Mmp8, and Polk, was significantly altered 6 h and day 1 following C-ion irradiation. Third, at day 3, several hundred genes, many of which are also classified as stress-response or cell-communication genes, including Tnfrsf5, Ikbke, and Icam1, were upregulated following C-ion irradiation. The expression level of the majority of these genes was similar following gamma-ray treatment, although the change was not as extensive and intertumor variance was apparent. Several genes, including Ikbke, Serpina3n, and Saa3, responded differentially following C-ion irradiation than after gamma-ray irradiation. Pathological investigation and immunohistochemical analysis of Cdkn1a revealed cell cycle arrest with mitotic catastrophe in tumors irradiated by C-ions. \nConclusions: This study revealed significant C-ion induced up-regulation of stress-responsive and cell-communication genes common to different tumor types. These findings provide evidence for the efficacy of this modality for the treatment of local tumors. In addition, antimetastatic effects of local C-ion irradiation in murine model and evaluation of C-ion responsive genes in clinical biopsy samples taken from cervical cancer patients would be presented. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | NIRS International Workshop on Particle Radiation Science | |||||
