FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W32879009> ?p ?o ?g. }

• W32879009 abstract "The current outlook for patients suffering malignant glioma is poor, with suboptimal delivery of agents across the blood-brain barrier, migration of tumour cells to areas that are not exposed to chemotherapeutic assault and the ability of tumour cells to repair DNA damage caused by anti-proliferative agents. The objectives were to demonstrate the potential of targeting the mitochondria of glioma cells through the use of tricyclic antidepressants and to show that the success of this approach is largely dependent on the metabolic capacity of the patient and the expression of the norepinephrine transporter on glioma cells. A range of tricyclic agents were screened against a panel of tumours using MTT, ATP-TCA and Annexin-V assays; the metabolic capacity of seventeen glioma patients was assessed through HPLC-MS/MS sampling of plasma Clomipramine concentrations and cytochrome P450 drug metabolism enzyme genotyping viareal-time PCR; the presence of the norepinephrine transporter was elucidated through immunohistochemical, immunocytochemical, Western blotting and realtime PCR techniques and finally apoptotic potential was determined by screening tumours (retrospectively and prospectively) via real-time PCR. Chemosensitivity results show that Clomipramine (the range for five tumours tested was 42.57 ±16.58 μM) and Nortriptyline (the range for four tumours tested was 30.22 ± 14.81 μM) were the most effective agents when tested in the MTT assay and Norclomipramine (the range for five tumours tested was 7.65 ±3.53 μM) and Nortriptyline (the range for five tumours tested was 33.15 ± 13.72 μM) were the most effective agents when tested using the ATP-TCA assay. Annexin-V flow cytometry supported these results and further evidenced that Clomipramine induces apoptosis in malignant glioma.The genotypic status of CYP2D6 and CYP2C19, combined with plasma levels of Clomipramine/Norclomipramine achieved in vivo, showed that mutations in the CYP2D6*2X3 allele significantly affect the metabolism of Norclomipramine (p<0.05). Immunohistochemical, immunocytochemical and Western blotting techniques demonstrated the presence of the norepinephrine transporter (encoded by the SLC6A2 gene) on glioma cells, however real-time PCR results suggest that the exons within the SLC6A2 gene contain splice variants. Taqman low density array of retrospective tumour samples revealed variation in the expression of apoptotic genes, with no discernable pattern, and that it is possible to modulate the expression of these genes by exposing SNB-19, DK-MG and UPAB glioma cells to tricyclic antidepressants, Procarbazine, Dexamethasone and Valproic acid. Evidence from this study demonstrates that tricyclic antidepressants provide a new approach to mitochondrially-mediated therapy for malignant glioma that express the Norepinephrine transporter, which overcomes the resistance to targeting proliferation and growth facto" @default.
• W32879009 created "2016-06-24" @default.
• W32879009 creator A5023333208 @default.
• W32879009 date "2011-01-01" @default.
• W32879009 modified "2023-09-26" @default.
• W32879009 title "Sensitivity to and functional effects of tricyclic agents on glioma: an immunohistochemical and in vitro study" @default.
• W32879009 cites W114310229 @default.
• W32879009 cites W115092695 @default.
• W32879009 cites W139355624 @default.
• W32879009 cites W142297450 @default.
• W32879009 cites W1441877074 @default.
• W32879009 cites W1486528432 @default.
• W32879009 cites W1486607502 @default.
• W32879009 cites W1491979926 @default.
• W32879009 cites W1503005497 @default.
• W32879009 cites W1504011557 @default.
• W32879009 cites W1519566744 @default.
• W32879009 cites W1522339760 @default.
• W32879009 cites W1523733420 @default.
• W32879009 cites W1530222274 @default.
• W32879009 cites W1531654035 @default.
• W32879009 cites W1531816383 @default.
• W32879009 cites W1531962115 @default.
• W32879009 cites W1534337735 @default.
• W32879009 cites W1536306303 @default.
• W32879009 cites W1539220078 @default.
• W32879009 cites W1541845741 @default.
• W32879009 cites W1544229812 @default.
• W32879009 cites W1547863599 @default.
• W32879009 cites W1550666015 @default.
• W32879009 cites W1557315818 @default.
• W32879009 cites W1566260450 @default.
• W32879009 cites W1582805634 @default.
• W32879009 cites W1591646293 @default.
• W32879009 cites W1593219141 @default.
• W32879009 cites W1595720718 @default.
• W32879009 cites W1598404519 @default.
• W32879009 cites W1617532721 @default.
• W32879009 cites W1621124914 @default.
• W32879009 cites W1624342207 @default.
• W32879009 cites W1630545408 @default.
• W32879009 cites W1675006565 @default.
• W32879009 cites W1679888853 @default.
• W32879009 cites W1731940515 @default.
• W32879009 cites W1745634660 @default.
• W32879009 cites W1748218710 @default.
• W32879009 cites W1781676997 @default.
• W32879009 cites W1785362826 @default.
• W32879009 cites W17969427 @default.
• W32879009 cites W1809723326 @default.
• W32879009 cites W1849819493 @default.
• W32879009 cites W1855056902 @default.
• W32879009 cites W1856415312 @default.
• W32879009 cites W1857696717 @default.
• W32879009 cites W1864905496 @default.
• W32879009 cites W1898063915 @default.
• W32879009 cites W1914432880 @default.
• W32879009 cites W1916943047 @default.
• W32879009 cites W1924733673 @default.
• W32879009 cites W1928423351 @default.
• W32879009 cites W1932668123 @default.
• W32879009 cites W1933598261 @default.
• W32879009 cites W1937235214 @default.
• W32879009 cites W1941056101 @default.
• W32879009 cites W1944104521 @default.
• W32879009 cites W1963656895 @default.
• W32879009 cites W1963782830 @default.
• W32879009 cites W1963842583 @default.
• W32879009 cites W1964037605 @default.
• W32879009 cites W1964126982 @default.
• W32879009 cites W1964483580 @default.
• W32879009 cites W1964511841 @default.
• W32879009 cites W1965141098 @default.
• W32879009 cites W1965296739 @default.
• W32879009 cites W1965345502 @default.
• W32879009 cites W1965417311 @default.
• W32879009 cites W1965482698 @default.
• W32879009 cites W1965490017 @default.
• W32879009 cites W1966213558 @default.
• W32879009 cites W1966241472 @default.
• W32879009 cites W1967079243 @default.
• W32879009 cites W1968054914 @default.
• W32879009 cites W1968407153 @default.
• W32879009 cites W1968616393 @default.
• W32879009 cites W1968909205 @default.
• W32879009 cites W1968963925 @default.
• W32879009 cites W1969285468 @default.
• W32879009 cites W1969394140 @default.
• W32879009 cites W1969825491 @default.
• W32879009 cites W1970297715 @default.
• W32879009 cites W1970369074 @default.
• W32879009 cites W1970972818 @default.
• W32879009 cites W1971713350 @default.
• W32879009 cites W1972627828 @default.
• W32879009 cites W1972664118 @default.
• W32879009 cites W1973043379 @default.
• W32879009 cites W1973087709 @default.
• W32879009 cites W1973541913 @default.
• W32879009 cites W1973710560 @default.
• W32879009 cites W1974315180 @default.

• next