FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3086363865> ?p ?o ?g. }

• W3086363865 abstract "Novel targeted agents to inhibit DNA repair pathways to sensitize tumors to irradiation (IR) are being investigated as an alternative to chemoradiation for locally-advanced HPV negative head and neck squamous cell carcinoma (HNSCC). Two well-characterized targets that when inhibited exhibit potent IR sensitization are PARP1 and DNA-PKcs. However, their cooperation in sensitizing Human Papilloma Virus negative (HPV negative) HNSCC to IR remains to be explored, given PARP1 and DNA-PkCS bind to unresected stalled DNA replication forks and cooperate to recruit XRCC1 to facilitate DSB repair. Here, we showed that the combination of the DNA-PK inhibitor NU7441 and the PARP inhibitor olaparib significantly decreased proliferation (61-78%) compared to no reduction with either agent alone (p<0.001) in both SCC1 and SCC6 cell lines. Adding IR to the combination further decreased cell proliferation (91-92%, p<0.001) in SCC1 and SCC6. Similar results were observed using long-term colony formation assays (dose enhancement ratio [DER] 2.3 – 3.2 at 4Gy, p<0.05). Reduced cell survival was attributed to increased apoptosis and G2/M cell cycle arrest. Kinomic analysis using tyrosine (PTK) and Serine/Threonine (STK) arrays revealed that combination treatment resulted in most potent inhibition of kinases involved in the CDK and ERK pathways, compared to either agent alone. In vivo, a significant delay of tumor growth was observed in UM-SCC1 xenografts receiving IR with olaparib and/or NU7441, which was similar to the cisplatin-IR group. Both regimens were less toxic than cisplatin-IR as assessed by loss of mouse body weight. Taken together, these results demonstrate that the combination of NU7441 and olaparib with IR enhances HPV negative HNSCC inhibition in both cell culture and in mice, suggesting a potential innovative combination for effectively treating patients with HPV negative HNSCC." @default.
• W3086363865 created "2020-09-21" @default.
• W3086363865 creator A5013854802 @default.
• W3086363865 creator A5025228395 @default.
• W3086363865 creator A5027224128 @default.
• W3086363865 creator A5031531252 @default.
• W3086363865 creator A5039699766 @default.
• W3086363865 creator A5043979995 @default.
• W3086363865 creator A5067067884 @default.
• W3086363865 creator A5068526964 @default.
• W3086363865 creator A5069596466 @default.
• W3086363865 creator A5070231585 @default.
• W3086363865 creator A5072016490 @default.
• W3086363865 creator A5075553640 @default.
• W3086363865 date "2020-09-10" @default.
• W3086363865 modified "2023-09-24" @default.
• W3086363865 title "Combining PARP and DNA-PK Inhibitors With Irradiation Inhibits HPV-Negative Head and Neck Cancer Squamous Carcinoma Growth" @default.
• W3086363865 cites W1517498529 @default.
• W3086363865 cites W1628408467 @default.
• W3086363865 cites W1927461076 @default.
• W3086363865 cites W1964071325 @default.
• W3086363865 cites W1976872531 @default.
• W3086363865 cites W1989445129 @default.
• W3086363865 cites W1994073149 @default.
• W3086363865 cites W2001997645 @default.
• W3086363865 cites W2007369689 @default.
• W3086363865 cites W2007773961 @default.
• W3086363865 cites W2013793743 @default.
• W3086363865 cites W2017541448 @default.
• W3086363865 cites W2030335946 @default.
• W3086363865 cites W2035992391 @default.
• W3086363865 cites W2061001563 @default.
• W3086363865 cites W2074156138 @default.
• W3086363865 cites W2075124520 @default.
• W3086363865 cites W2076583198 @default.
• W3086363865 cites W2083533688 @default.
• W3086363865 cites W2101816193 @default.
• W3086363865 cites W2123241821 @default.
• W3086363865 cites W2125037952 @default.
• W3086363865 cites W2127414222 @default.
• W3086363865 cites W2137174176 @default.
• W3086363865 cites W2139674628 @default.
• W3086363865 cites W2140562572 @default.
• W3086363865 cites W2146331622 @default.
• W3086363865 cites W2146750548 @default.
• W3086363865 cites W2150089707 @default.
• W3086363865 cites W2151499633 @default.
• W3086363865 cites W2164872561 @default.
• W3086363865 cites W2169031119 @default.
• W3086363865 cites W2171208628 @default.
• W3086363865 cites W2178442747 @default.
• W3086363865 cites W2253016623 @default.
• W3086363865 cites W2462299929 @default.
• W3086363865 cites W2523005380 @default.
• W3086363865 cites W2527062344 @default.
• W3086363865 cites W2527281379 @default.
• W3086363865 cites W2562712448 @default.
• W3086363865 cites W2580602635 @default.
• W3086363865 cites W2795465941 @default.
• W3086363865 cites W2808408940 @default.
• W3086363865 cites W2971556441 @default.
• W3086363865 cites W2974330297 @default.
• W3086363865 cites W2985561224 @default.
• W3086363865 cites W3010406759 @default.
• W3086363865 cites W3013811673 @default.
• W3086363865 cites W3027631273 @default.
• W3086363865 doi "https://doi.org/10.3389/fgene.2020.01036" @default.
• W3086363865 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7511754" @default.
• W3086363865 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33133138" @default.
• W3086363865 hasPublicationYear "2020" @default.
• W3086363865 type Work @default.
• W3086363865 sameAs 3086363865 @default.
• W3086363865 citedByCount "12" @default.
• W3086363865 countsByYear W30863638652021 @default.
• W3086363865 countsByYear W30863638652022 @default.
• W3086363865 countsByYear W30863638652023 @default.
• W3086363865 crossrefType "journal-article" @default.
• W3086363865 hasAuthorship W3086363865A5013854802 @default.
• W3086363865 hasAuthorship W3086363865A5025228395 @default.
• W3086363865 hasAuthorship W3086363865A5027224128 @default.
• W3086363865 hasAuthorship W3086363865A5031531252 @default.
• W3086363865 hasAuthorship W3086363865A5039699766 @default.
• W3086363865 hasAuthorship W3086363865A5043979995 @default.
• W3086363865 hasAuthorship W3086363865A5067067884 @default.
• W3086363865 hasAuthorship W3086363865A5068526964 @default.
• W3086363865 hasAuthorship W3086363865A5069596466 @default.
• W3086363865 hasAuthorship W3086363865A5070231585 @default.
• W3086363865 hasAuthorship W3086363865A5072016490 @default.
• W3086363865 hasAuthorship W3086363865A5075553640 @default.
• W3086363865 hasBestOaLocation W30863638651 @default.
• W3086363865 hasConcept C121608353 @default.
• W3086363865 hasConcept C126322002 @default.
• W3086363865 hasConcept C134935766 @default.
• W3086363865 hasConcept C143425029 @default.
• W3086363865 hasConcept C153911025 @default.
• W3086363865 hasConcept C182979987 @default.
• W3086363865 hasConcept C185592680 @default.
• W3086363865 hasConcept C190283241 @default.
• W3086363865 hasConcept C2776530083 @default.
• W3086363865 hasConcept C2776694085 @default.

• next