دورية أكاديمية
Combination bromo- and extraterminal domain and poly (ADP-ribose) polymerase inhibition synergistically enhances DNA damage and inhibits neuroblastoma tumorigenesis.
| العنوان: | Combination bromo- and extraterminal domain and poly (ADP-ribose) polymerase inhibition synergistically enhances DNA damage and inhibits neuroblastoma tumorigenesis. |
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| المؤلفون: | Jacobson JC; Department of Pediatric Surgery, University of Texas Southwestern Medical Center and Children's Health, 1935 Medical District Dr. Mailstop F3.66, Dallas, TX, 75235, USA., Qiao J; Department of Pediatric Surgery, University of Texas Southwestern Medical Center and Children's Health, 1935 Medical District Dr. Mailstop F3.66, Dallas, TX, 75235, USA., Clark RA; Department of Pediatric Surgery, University of Texas Southwestern Medical Center and Children's Health, 1935 Medical District Dr. Mailstop F3.66, Dallas, TX, 75235, USA., Chung DH; Department of Pediatric Surgery, University of Texas Southwestern Medical Center and Children's Health, 1935 Medical District Dr. Mailstop F3.66, Dallas, TX, 75235, USA. dai.chung@utsouthwestern.edu. |
| المصدر: | Discover. Oncology [Discov Oncol] 2022 Oct 13; Vol. 13 (1), pp. 103. Date of Electronic Publication: 2022 Oct 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: United States NLM ID: 101775142 Publication Model: Electronic Cited Medium: Internet ISSN: 2730-6011 (Electronic) Linking ISSN: 27306011 NLM ISO Abbreviation: Discov Oncol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: [New York] : Springer, [2021]- |
| مستخلص: | Purpose: JQ1 is a bromo- and extraterminal (BET) domain inhibitor that downregulates MYC expression and impairs the DNA damage response. Poly (ADP-ribose) polymerase (PARP) inhibitors prevent DNA damage sensing and repair. We hypothesized that JQ1 would promote a DNA repair-deficient phenotype that sensitizes neuroblastoma cells to PARP inhibition. Methods: Four human neuroblastoma cell lines were examined: two MYCN-amplified (BE(2)-C and IMR-32), and two non-MYCN-amplified (SK-N-SH and SH-SY5Y). Cells were treated with JQ1 (BET inhibitor), Olaparib (PARP inhibitor), or in combination to assess for therapeutic synergy of JQ1 and Olaparib. Treated cells were harvested and analyzed. Quantitative assessment of combination treatment synergy was performed using the median effect principle of Chou and Talalay. Results: Combination treatment with Olaparib decreased the IC Conclusions: Combination BET and PARP inhibition synergistically inhibited neuroblastoma tumorigenesis in vitro. In MYCN-amplified neuroblastoma cells, this effect may be induced by downregulation of MYCN transcription, defects in DNA repair, accumulation of DNA damage, and apoptosis. In non-MYCN-amplified cell lines, combination treatment induced cell cycle arrest. (© 2022. The Author(s).) |
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| معلومات مُعتمدة: | 1018897 Burroughs Wellcome Fund; R01 DK61470 United States NH NIH HHS |
| فهرسة مساهمة: | Keywords: BET; JQ1; Neuroblastoma; Olaparib; PARP |
| تواريخ الأحداث: | Date Created: 20221013 Latest Revision: 20221017 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC9562984 |
| DOI: | 10.1007/s12672-022-00563-5 |
| PMID: | 36227363 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2730-6011 |
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| DOI: | 10.1007/s12672-022-00563-5 |