Matches in SemOpenAlex for { <https://semopenalex.org/work/W3023720512> ?p ?o ?g. }
- W3023720512 endingPage "1561" @default.
- W3023720512 startingPage "1550" @default.
- W3023720512 abstract "Abstract Glioma is one of the most common primary malignant tumors of the central nervous system accounting for approximately 40% of all intracranial tumors. Temozolomide is a conventional chemotherapy drug for adjuvant treatment of patients with high-risk gliomas, including grade II to grade IV. Our bioinformatic analysis of The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets and immunoblotting assay show that SLC12A2 gene and its encoded Na+-K+-2Cl− cotransporter isoform 1 (NKCC1) protein are abundantly expressed in grade II–IV gliomas. NKCC1 regulates cell volume and intracellular Cl− concentration, which promotes glioma cell migration, resistance to temozolomide, and tumor-related epilepsy in experimental glioma models. Using mouse syngeneic glioma models with intracranial transplantation of two different glioma cell lines (GL26 and SB28), we show that NKCC1 protein in glioma tumor cells as well as in tumor-associated reactive astrocytes was significantly upregulated in response to temozolomide monotherapy. Combination therapy of temozolomide with the potent NKCC1 inhibitor bumetanide reduced tumor proliferation, potentiated the cytotoxic effects of temozolomide, decreased tumor-associated reactive astrogliosis, and restored astrocytic GLT-1 and GLAST glutamate transporter expression. The combinatorial therapy also led to suppressed tumor growth and prolonged survival of mice bearing GL26 glioma cells. Taken together, these results demonstrate that NKCC1 protein plays multifaceted roles in the pathogenesis of glioma tumors and presents as a therapeutic target for reducing temozolomide-mediated resistance and tumor-associated astrogliosis." @default.
- W3023720512 created "2020-05-13" @default.
- W3023720512 creator A5009370574 @default.
- W3023720512 creator A5009622274 @default.
- W3023720512 creator A5011136143 @default.
- W3023720512 creator A5022169733 @default.
- W3023720512 creator A5022478300 @default.
- W3023720512 creator A5026429908 @default.
- W3023720512 creator A5047233885 @default.
- W3023720512 creator A5047438878 @default.
- W3023720512 creator A5049938481 @default.
- W3023720512 creator A5049944456 @default.
- W3023720512 creator A5058988458 @default.
- W3023720512 creator A5073621366 @default.
- W3023720512 creator A5080232382 @default.
- W3023720512 creator A5086872650 @default.
- W3023720512 creator A5088231950 @default.
- W3023720512 date "2020-07-01" @default.
- W3023720512 modified "2023-10-16" @default.
- W3023720512 title "Blockade of Cell Volume Regulatory Protein NKCC1 Increases TMZ-Induced Glioma Apoptosis and Reduces Astrogliosis" @default.
- W3023720512 cites W1966273336 @default.
- W3023720512 cites W1980429211 @default.
- W3023720512 cites W1984050978 @default.
- W3023720512 cites W1990590292 @default.
- W3023720512 cites W1998439025 @default.
- W3023720512 cites W2010573862 @default.
- W3023720512 cites W2015007332 @default.
- W3023720512 cites W2019787798 @default.
- W3023720512 cites W2029843335 @default.
- W3023720512 cites W2062928140 @default.
- W3023720512 cites W2073880277 @default.
- W3023720512 cites W2082713658 @default.
- W3023720512 cites W2104048484 @default.
- W3023720512 cites W2112200068 @default.
- W3023720512 cites W2123046490 @default.
- W3023720512 cites W2131589269 @default.
- W3023720512 cites W2145580834 @default.
- W3023720512 cites W2148161418 @default.
- W3023720512 cites W2149840758 @default.
- W3023720512 cites W2149924125 @default.
- W3023720512 cites W2154201731 @default.
- W3023720512 cites W2157338202 @default.
- W3023720512 cites W2208897378 @default.
- W3023720512 cites W2366536035 @default.
- W3023720512 cites W2432909692 @default.
- W3023720512 cites W2492055361 @default.
- W3023720512 cites W2556335366 @default.
- W3023720512 cites W2594733019 @default.
- W3023720512 cites W2596261790 @default.
- W3023720512 cites W2701436143 @default.
- W3023720512 cites W2754972833 @default.
- W3023720512 cites W2769204493 @default.
- W3023720512 cites W2801154762 @default.
- W3023720512 cites W2805027290 @default.
- W3023720512 cites W2834911070 @default.
- W3023720512 cites W2883020951 @default.
- W3023720512 cites W2889469198 @default.
- W3023720512 cites W2892490166 @default.
- W3023720512 cites W2892697024 @default.
- W3023720512 cites W2921594363 @default.
- W3023720512 doi "https://doi.org/10.1158/1535-7163.mct-19-0910" @default.
- W3023720512 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32393472" @default.
- W3023720512 hasPublicationYear "2020" @default.
- W3023720512 type Work @default.
- W3023720512 sameAs 3023720512 @default.
- W3023720512 citedByCount "16" @default.
- W3023720512 countsByYear W30237205122020 @default.
- W3023720512 countsByYear W30237205122021 @default.
- W3023720512 countsByYear W30237205122022 @default.
- W3023720512 countsByYear W30237205122023 @default.
- W3023720512 crossrefType "journal-article" @default.
- W3023720512 hasAuthorship W3023720512A5009370574 @default.
- W3023720512 hasAuthorship W3023720512A5009622274 @default.
- W3023720512 hasAuthorship W3023720512A5011136143 @default.
- W3023720512 hasAuthorship W3023720512A5022169733 @default.
- W3023720512 hasAuthorship W3023720512A5022478300 @default.
- W3023720512 hasAuthorship W3023720512A5026429908 @default.
- W3023720512 hasAuthorship W3023720512A5047233885 @default.
- W3023720512 hasAuthorship W3023720512A5047438878 @default.
- W3023720512 hasAuthorship W3023720512A5049938481 @default.
- W3023720512 hasAuthorship W3023720512A5049944456 @default.
- W3023720512 hasAuthorship W3023720512A5058988458 @default.
- W3023720512 hasAuthorship W3023720512A5073621366 @default.
- W3023720512 hasAuthorship W3023720512A5080232382 @default.
- W3023720512 hasAuthorship W3023720512A5086872650 @default.
- W3023720512 hasAuthorship W3023720512A5088231950 @default.
- W3023720512 hasBestOaLocation W30237205122 @default.
- W3023720512 hasConcept C126322002 @default.
- W3023720512 hasConcept C142724271 @default.
- W3023720512 hasConcept C2777389519 @default.
- W3023720512 hasConcept C2778227246 @default.
- W3023720512 hasConcept C2779130545 @default.
- W3023720512 hasConcept C2779965356 @default.
- W3023720512 hasConcept C502942594 @default.
- W3023720512 hasConcept C529278444 @default.
- W3023720512 hasConcept C71924100 @default.
- W3023720512 hasConcept C86803240 @default.
- W3023720512 hasConcept C98274493 @default.