FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4312075898> ?p ?o ?g. }

• W4312075898 abstract "Introduction: Glioblastoma (GBM) is invariably resistant to temozolomide (TMZ) chemotherapy. Inhibiting the proteasomal pathway is an emerging strategy to accumulate damaged proteins and inhibit their lysosomal degradation. We hypothesized that pre-treatment of glioblastoma with bortezomib (BTZ) might sensitize glioblastoma to temozolomide by abolishing autophagy survival signals to augment DNA damage and apoptosis. Methods: P3 patient-derived glioblastoma cells, as well as the tumour cell lines U87, HF66, A172, and T98G were investigated for clonogenic survival after single or combined treatment with temozolomide and bortezomib in vitro . We investigated the requirement of functional autophagy machinery by utilizing pharmacological inhibitors or CRISPR-Cas9 knockout (KO) of autophagy-related genes -5 and -7 (ATG5 and ATG7) in glioblastoma cells and monitored changes in autophagic flux after temozolomide and/or bortezomib treatments. P3 wild-type and P3 ATG5−/− (ATG5 KO) cells were implanted orthotopically into NOD-SCID mice to assess the efficacy of bortezomib and temozolomide combination therapy with and without functional autophagy machinery. Results: The chemo-resistant glioblastoma cells increased autophagic flux during temozolomide treatment as indicated by increased degradation of long-lived proteins, diminished expression of autophagy markers LC3A/B-II and p62 (SQSTM1), increased co-localisation of LC3A/B-II with STX17, augmented and no induction of apoptosis. In contrast, bortezomib treatment abrogated autophagic flux indicated by the accumulation of LC3A/B-II and p62 (SQSTM1) positive autophagosomes that did not fuse with lysosomes and thus reduced the degradation of long-lived proteins. Bortezomib synergistically enhanced temozolomide efficacy by attenuating cell proliferation, increased DNA double-strand breaks, and apoptosis in an autophagy-dependent manner. Abolishing autophagy in ATG5 KOs reversed the bortezomib-induced toxicity, rescued glioblastoma cell death and reduced animal survival. Discussion: We conclude that bortezomib abrogates temozolomide induced autophagy flux through an ATG5 dependent pathway." @default.
• W4312075898 created "2023-01-04" @default.
• W4312075898 creator A5006645265 @default.
• W4312075898 creator A5021408421 @default.
• W4312075898 creator A5037572599 @default.
• W4312075898 creator A5047255388 @default.
• W4312075898 creator A5055064502 @default.
• W4312075898 creator A5064110734 @default.
• W4312075898 creator A5064953838 @default.
• W4312075898 creator A5073036493 @default.
• W4312075898 creator A5078008340 @default.
• W4312075898 creator A5087890221 @default.
• W4312075898 date "2022-12-22" @default.
• W4312075898 modified "2023-10-05" @default.
• W4312075898 title "Bortezomib abrogates temozolomide-induced autophagic flux through an ATG5 dependent pathway" @default.
• W4312075898 cites W111616551 @default.
• W4312075898 cites W1486428308 @default.
• W4312075898 cites W1523693806 @default.
• W4312075898 cites W1526705543 @default.
• W4312075898 cites W1599096704 @default.
• W4312075898 cites W1678795445 @default.
• W4312075898 cites W1864544636 @default.
• W4312075898 cites W1890655587 @default.
• W4312075898 cites W1963521777 @default.
• W4312075898 cites W1967809393 @default.
• W4312075898 cites W1968825280 @default.
• W4312075898 cites W1970637701 @default.
• W4312075898 cites W1989560554 @default.
• W4312075898 cites W1992951702 @default.
• W4312075898 cites W2004396698 @default.
• W4312075898 cites W2005142336 @default.
• W4312075898 cites W2009128541 @default.
• W4312075898 cites W2009656063 @default.
• W4312075898 cites W201795241 @default.
• W4312075898 cites W2021242983 @default.
• W4312075898 cites W2025665129 @default.
• W4312075898 cites W2037646515 @default.
• W4312075898 cites W2045122835 @default.
• W4312075898 cites W2052032313 @default.
• W4312075898 cites W2053144360 @default.
• W4312075898 cites W2053668604 @default.
• W4312075898 cites W2055807959 @default.
• W4312075898 cites W2064037082 @default.
• W4312075898 cites W2077731318 @default.
• W4312075898 cites W2077945404 @default.
• W4312075898 cites W2079351077 @default.
• W4312075898 cites W2096287682 @default.
• W4312075898 cites W2099198727 @default.
• W4312075898 cites W2101228747 @default.
• W4312075898 cites W2102073216 @default.
• W4312075898 cites W2104072199 @default.
• W4312075898 cites W2104697581 @default.
• W4312075898 cites W2105100844 @default.
• W4312075898 cites W2107840513 @default.
• W4312075898 cites W2111013340 @default.
• W4312075898 cites W2116936013 @default.
• W4312075898 cites W2120134578 @default.
• W4312075898 cites W2122402825 @default.
• W4312075898 cites W2128603027 @default.
• W4312075898 cites W2132834292 @default.
• W4312075898 cites W2138077682 @default.
• W4312075898 cites W2143983454 @default.
• W4312075898 cites W2150168624 @default.
• W4312075898 cites W2152007057 @default.
• W4312075898 cites W2158892689 @default.
• W4312075898 cites W2164778558 @default.
• W4312075898 cites W2165079404 @default.
• W4312075898 cites W2236811429 @default.
• W4312075898 cites W2328946792 @default.
• W4312075898 cites W2410468716 @default.
• W4312075898 cites W2473146109 @default.
• W4312075898 cites W2533025094 @default.
• W4312075898 cites W2566416357 @default.
• W4312075898 cites W2602035017 @default.
• W4312075898 cites W2621728938 @default.
• W4312075898 cites W2740618823 @default.
• W4312075898 cites W2781557781 @default.
• W4312075898 cites W2791853559 @default.
• W4312075898 cites W2792784918 @default.
• W4312075898 cites W2804444580 @default.
• W4312075898 cites W2899760200 @default.
• W4312075898 cites W2902909335 @default.
• W4312075898 cites W2915043410 @default.
• W4312075898 cites W2964728112 @default.
• W4312075898 cites W2968977249 @default.
• W4312075898 cites W2985373649 @default.
• W4312075898 cites W2995199710 @default.
• W4312075898 cites W2997327255 @default.
• W4312075898 cites W3003946372 @default.
• W4312075898 cites W3037178718 @default.
• W4312075898 cites W3108936441 @default.
• W4312075898 cites W4211225580 @default.
• W4312075898 cites W4223582144 @default.
• W4312075898 doi "https://doi.org/10.3389/fcell.2022.1022191" @default.
• W4312075898 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36619857" @default.
• W4312075898 hasPublicationYear "2022" @default.
• W4312075898 type Work @default.
• W4312075898 citedByCount "3" @default.
• W4312075898 countsByYear W43120758982023 @default.
• W4312075898 crossrefType "journal-article" @default.

• next