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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술대회자료
- 저자정보
- 발행연도
- 2015.10
- 수록면
- 155 - 168 (14page)
이용수
이 논문의 연구 히스토리 (3)
2016
Engineered neural stem cells expressing cytosine deaminase and interferon-beta restrain melanoma cells from proliferating
Kyung-Chul Choi
,
Jae-Rim Heo
한국실험동물학회 학술발표대회 논문집
2016.08
학술대회자료
Inhibition of the proliferation of K562 human leukemia cells by therapeutic neural stem cells expressing cytosine deaminase and interferon-β in cellular and xenografte mouse models
Kyung-Chul Choi
,
Geon-Tae Pa
,
k
한국실험동물학회 학술발표대회 논문집
2016.08
학술대회자료
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As an approach to improve treatment of breast cancer metastasis to the brain, we employed genetically engineered stem cells (GESTECs) consisting of neural stem cells (NSCs) expressing cytosine deaminase and the interferon-beta genes, HB1.F3.CD and HB1.F3.CD.IFN-b. In this model, MDA-MB-231/Luc breast cancer cells were implanted in the right hemisphere of the mouse brain, while CM-Dil pre-stained GESTECs were implanted in the contralateral brain. Two days after stem cells injection, 5-FC was administrated via intraperitoneal injection. Histological analysis of extracted brain confirmed the therapeutic efficacy of GESTECs in the presence of 5-FC based on reductions in density and aggressive tendency of breast cancer cells, as well as pyknosis, karyorrhexis, and karyolysis relative to a negative control. Additionally, expression of PCNA decreased in the stem cells treated group. Treatment of breast cancer cells with 5-FU increased the expression of pro-apoptotic and anti-proliferative factor. BAX and p21 protein through phosphorylation of p53 and p38. Moreover, analysis of stem cell migratory ability revealed that MDA-MB-231 cells endogenously secreted VEGF, and stem cells expressed their receptor (VEGFR2). To confirm the role of VEGF/VEGFR2 signaling in tumor tropism of stem cells, samples were treated with the VEGFR2 inhibitor. KRN633. The number of migrated stem cells decreased significantly in response to KRN633 due to Erkl/2 activation and PI3K/Akt inhibition. Taken together, these results indicate that treatment with GESTECs, particularly HB1 .F3.CD.IFN-b co-expressing CD.IFN-b. may be a useful strategy for treating breast cancer metastasis to the brain in the presence of a prodrug. [This work was supported by a National Research Foundation of Korea (NRF) grant (2013R1A1A2059092) funded by the Ministry of Education, Science and Technology (MEST) of the Republic of Korea.]
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UCI(KEPA) : I410-ECN-0101-2016-519-002373841