지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2015.1
- 수록면
- 329 - 338 (10page)
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초록· 키워드
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Purpose: Trabectedin induces synthetic lethality in tumor cells carrying defects in homologous recombinant DNA repair. We evaluated the effect of concomitant inhibition of nucleotide-excision repair and poly (ADP-ribose) polymerase (PARP) activity with trabectedin and PARP inhibitors, respectively, and whether the synthetic lethality effect had the potential for a synergistic effect in breast cancer cell lines. Additionally, we investigated if this approach remained effective in BRCA1-positive breast tumor cells. Methods: We have evaluated the in vitro synergistic effect of combinations of trabectedin and three different PARP inhibitors (veliparib, olaparib, and iniparib) in four breast cancer cell lines, each presenting a different BRCA1 genetic background. Antiproliferative activity, DNA damage, cell cycle perturbations and poly(ADP-ribosyl)ation were assessed by MTT assay, comet assay, flow cytometry and western blot, respectively. Results: The combination of trabectedin and olaparib was synergistic in all the breast cancer cell lines tested. Our data indicated that the synergy persisted regardless of the BRCA1 status of the tumor cells. Combination treatment was associated with a strong accumulation of double-stranded DNA breaks, G2/M arrest, and apoptotic cell death. Synergistic effects were not observed when trabectedin was combined with veliparib or iniparib. Conclusion: Collectively, our results indicate that the combination of trabectedin and olaparib induces an artificial synthetic lethality effect that can be used to kill breast cancer cells, independent of BRCA1 status.
목차
등록된 정보가 없습니다.
참고문헌 (28)
참고문헌 신청
D’Incalci M / 2010 / A review of trabectedin(ET-743) : a unique mechanism of action / Mol Cancer Ther 9:2157~2163
Demetri GD / 2009 / Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide : results of a randomized phase II study of two different schedules / J Clin Oncol 27:4188~4196
Monk BJ / 2010 / Trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer / J Clin Oncol 28:3107~3114
Di Giandomenico S / 2014 / Mode of action of trabectedin in myxoid liposarcomas / Oncogene 33:5201~5210
Galmarini CM / 2014 / Trabectedin and plitidepsin : drugs from the sea that strike the tumor microenvironment / Mar Drugs 12:719~733
Demetri GD / 2009 / Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide : results of a randomized phase II study of two different schedules / J Clin Oncol 27:4188~4196
Monk BJ / 2010 / Trabectedin plus pegylated liposomal doxorubicin in recurrent ovarian cancer / J Clin Oncol 28:3107~3114
Di Giandomenico S / 2014 / Mode of action of trabectedin in myxoid liposarcomas / Oncogene 33:5201~5210
Galmarini CM / 2014 / Trabectedin and plitidepsin : drugs from the sea that strike the tumor microenvironment / Mar Drugs 12:719~733
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