FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2538480114> ?p ?o ?g. }

• W2538480114 abstract "Abstract Glucocorticoids like Prednisolone (PRED) and dexamethasone is one of the most powerful group of drugs for treatment of childhood ALL; when used alone, it can achieve morphological remission in &gt; 60% of patients. However glucocorticoids have severe immunosuppressive effects increasing the risk of severe bacterial and fungal infections and severe psychosomatic effects like bad tempers, bad dreams and a veracious appetite. However, despite extensive use, the mechanism of PRED induced apoptosis remains unclear. Understanding the mechanism of PRED action and resistance in ALL will greatly enhance our ability to fully harness the potency of this important drug. Here, we investigated the mechanism of PRED induced apoptosis using four clinically important pre-B ALL cell lines: REH, 697, RS4;11, SUPB-15 and validated this in 45 paired bone marrow samples before and after 7 days of PRED induction for newly diagnosed children with ALL. Our results show that after treatment with PRED (10.0μg/ml) for 24h, the four cell lines can be separated into resistant (REH) and sensitive (697, RS4;11, SUPB-15) using apoptosis assay ( Cell Death Detection ELISA, Roche) and MTS assay (Promega). We studied the BCL-2 family members which are known to play an important regulatory role in the intrinsic apoptotic pathway in executing cell death program induced by glucocorticoids. We examined 6 members of the BCL-2 family - BIM, BCL-2, BAX, BAD, MCL-1, BCL-xl - using RQ-PCR and western blots. Only BIM, a pro-apoptotic member of the BCL-2 family, was up-regulated after PRED treatment in the 3 sensitive cell lines, both in terms of gene and protein expression levels. In contrast, it remains unchanged in REH resistant cell line. When co-treated with Ru486, a glucocorticoid receptor antagonist, PRED induced apoptosis was inhibited and the expression level of BIM was no longer elevated in the 3 sensitive cell lines, indicating the importance of BIM in PRED induced apoptosis and its potential role as a prognostic biomarker. To confirm this clinically, we studied the changes in expression levels of BIM in serial paired bone marrow after 7 days of PRED induction in 45 patients (35 good PRED responders and 10 poor PRED responders ) using Affymetrix U133 Plus 2 chips. Statistical analysis was performed using a two-sided Student’s t test. After 7 days of PRED, good PRED responders showed BIM was significantly up-regulated compared to PRED poor responders (p&lt;0.05). We conclude that BIM plays an essential regulatory role in PRED induced intrinsic apoptosis pathway in pre-B ALL cells in a glucocorticoid receptor dependent manner. BIM could act as a potential prognostic biomarker of steroid response in treatment of childhood ALL allowing clinicians to clearly identify patients who are resistant early during therapy so that other drugs can be introduced early during induction so to maximise leukemia cell kill and improve the outcome of therapy. It will also provide the rationale to avoid the severe immunesuppressive and psychosomatic side-effects of steroid in patients whose leukemia are resistant to PRED." @default.
• W2538480114 created "2016-10-28" @default.
• W2538480114 creator A5008867819 @default.
• W2538480114 creator A5028955627 @default.
• W2538480114 creator A5038324149 @default.
• W2538480114 creator A5039006439 @default.
• W2538480114 creator A5042688244 @default.
• W2538480114 creator A5067364293 @default.
• W2538480114 date "2008-11-16" @default.
• W2538480114 modified "2023-09-28" @default.
• W2538480114 title "BIM Regulates Prednisolone-Induced Apoptosis in B-Lineage ALL: A Potential Biomarker." @default.
• W2538480114 doi "https://doi.org/10.1182/blood.v112.11.1505.1505" @default.
• W2538480114 hasPublicationYear "2008" @default.
• W2538480114 type Work @default.
• W2538480114 sameAs 2538480114 @default.
• W2538480114 citedByCount "0" @default.
• W2538480114 crossrefType "journal-article" @default.
• W2538480114 hasAuthorship W2538480114A5008867819 @default.
• W2538480114 hasAuthorship W2538480114A5028955627 @default.
• W2538480114 hasAuthorship W2538480114A5038324149 @default.
• W2538480114 hasAuthorship W2538480114A5039006439 @default.
• W2538480114 hasAuthorship W2538480114A5042688244 @default.
• W2538480114 hasAuthorship W2538480114A5067364293 @default.
• W2538480114 hasConcept C126322002 @default.
• W2538480114 hasConcept C190283241 @default.
• W2538480114 hasConcept C203014093 @default.
• W2538480114 hasConcept C2776715498 @default.
• W2538480114 hasConcept C2776789625 @default.
• W2538480114 hasConcept C2780401358 @default.
• W2538480114 hasConcept C31573885 @default.
• W2538480114 hasConcept C502942594 @default.
• W2538480114 hasConcept C54355233 @default.
• W2538480114 hasConcept C71924100 @default.
• W2538480114 hasConcept C81885089 @default.
• W2538480114 hasConcept C86803240 @default.
• W2538480114 hasConceptScore W2538480114C126322002 @default.
• W2538480114 hasConceptScore W2538480114C190283241 @default.
• W2538480114 hasConceptScore W2538480114C203014093 @default.
• W2538480114 hasConceptScore W2538480114C2776715498 @default.
• W2538480114 hasConceptScore W2538480114C2776789625 @default.
• W2538480114 hasConceptScore W2538480114C2780401358 @default.
• W2538480114 hasConceptScore W2538480114C31573885 @default.
• W2538480114 hasConceptScore W2538480114C502942594 @default.
• W2538480114 hasConceptScore W2538480114C54355233 @default.
• W2538480114 hasConceptScore W2538480114C71924100 @default.
• W2538480114 hasConceptScore W2538480114C81885089 @default.
• W2538480114 hasConceptScore W2538480114C86803240 @default.
• W2538480114 hasLocation W25384801141 @default.
• W2538480114 hasOpenAccess W2538480114 @default.
• W2538480114 hasPrimaryLocation W25384801141 @default.
• W2538480114 hasRelatedWork W2002697338 @default.
• W2538480114 hasRelatedWork W2057580638 @default.
• W2538480114 hasRelatedWork W2170788438 @default.
• W2538480114 hasRelatedWork W2240367598 @default.
• W2538480114 hasRelatedWork W2316128687 @default.
• W2538480114 hasRelatedWork W2316611023 @default.
• W2538480114 hasRelatedWork W2417191938 @default.
• W2538480114 hasRelatedWork W2478990223 @default.
• W2538480114 hasRelatedWork W2521688950 @default.
• W2538480114 hasRelatedWork W2550669303 @default.
• W2538480114 hasRelatedWork W2551002076 @default.
• W2538480114 hasRelatedWork W2555225703 @default.
• W2538480114 hasRelatedWork W2560668046 @default.
• W2538480114 hasRelatedWork W2576782710 @default.
• W2538480114 hasRelatedWork W2911568111 @default.
• W2538480114 hasRelatedWork W2916062086 @default.
• W2538480114 hasRelatedWork W2986341305 @default.
• W2538480114 hasRelatedWork W2994193302 @default.
• W2538480114 hasRelatedWork W303996508 @default.
• W2538480114 hasRelatedWork W65177702 @default.
• W2538480114 isParatext "false" @default.
• W2538480114 isRetracted "false" @default.
• W2538480114 magId "2538480114" @default.
• W2538480114 workType "article" @default.