Matches in SemOpenAlex for { <https://semopenalex.org/work/W2556491431> ?p ?o ?g. }
Showing items 1 to 64 of
64
with 100 items per page.
- W2556491431 abstract "Abstract Background: Bortezomib (Bor), a proteasome inhibitor, and Thalidomide (Thal), an anti-angiogenic and immunomodulatory drug, have a remarkable effect in patients with relapsed or refractory MM with 30–40% response rates. In newly diagnosed patients the response rates vary from 70–85%. However, 15–30% of newly diagnosed patients do not respond to Bor or Thal. Secondly, 30% of the patients treated with these novel agents have to stop prematurely because of intolerable side effects, such as polyneuropathy, thrombocytopenia, thrombosis and gastro-intestinal symptoms. Aim: To gain new insights regarding the mechanisms of drug response and toxicity associated with these agents, we have embarked on a prospective study to analyze gene expression profiles (GEP) of myeloma specific genes in plasma cells purified from bone marrow from myeloma patients at diagnosis who have been treated with these novel agents in order to learn which genes govern outcome upon treatment with Bor and Thal. Methods: GEP of CD138 magnetic cell selected (MACS) myeloma plasma cells was performed using Affymetrix GeneChip Human Genome U133 plus 2.0 arrays. This program has been initiated in a large multicenter, prospective, randomized phase III trial, comparing Bor in combination with Adriamycin, Dex (PAD, arm A) followed by high dose therapy with stem cell rescue and maintenance therapy with Bor vs. Vincristine, Adriamycin and Dex (VAD, arm B) followed by high dose therapy with stem cell rescue and maintenance therapy with Thalidomide (HOVON65/GMMG-HD4). This cooperative trial in the Netherlands and Germany has started in April 2005 and has included 600 patients. Gene arrays were analyzed using correlation analysis in Omniviz. Differentially expressed genes in the different groups and in Bor responders were determined using a t-test with adjusted p-value (p<0.0001) and a 1000 permutation analysis (BRB tool). Results: Based on correlated GEPs we divided myeloma patients into 10 clusters. We determined differentially expressed genes in the different clusters and correlated the clusters with chromosomal aberrations like 13q loss, 9 and 11 gain and translocations. Three clusters showed high expression of MMSET/FGFR3, MAF downstream targets and CCND1, respectively. Conclusion: unsupervised cluster analysis led to the subdivision of myeloma patients into clusters, each with a specific gene expression signature. We determined differentially expressed genes in the different clusters and could confirm 3 subgroups (MMSET/FGFR3, MAF/MAFB, and a group with high CCND1 expression) as have been published before." @default.
- W2556491431 created "2016-11-30" @default.
- W2556491431 creator A5002972322 @default.
- W2556491431 creator A5007067641 @default.
- W2556491431 creator A5049532216 @default.
- W2556491431 creator A5055916434 @default.
- W2556491431 creator A5058429057 @default.
- W2556491431 creator A5080712446 @default.
- W2556491431 creator A5089637265 @default.
- W2556491431 date "2007-11-16" @default.
- W2556491431 modified "2023-10-16" @default.
- W2556491431 title "Gene Expression Profiles as Prognostic Factors in Patients with Multiple Myeloma Treated with Conventional Versus Novel Agents in Correlation with Outcome." @default.
- W2556491431 doi "https://doi.org/10.1182/blood.v110.11.3173.3173" @default.
- W2556491431 hasPublicationYear "2007" @default.
- W2556491431 type Work @default.
- W2556491431 sameAs 2556491431 @default.
- W2556491431 citedByCount "0" @default.
- W2556491431 crossrefType "journal-article" @default.
- W2556491431 hasAuthorship W2556491431A5002972322 @default.
- W2556491431 hasAuthorship W2556491431A5007067641 @default.
- W2556491431 hasAuthorship W2556491431A5049532216 @default.
- W2556491431 hasAuthorship W2556491431A5055916434 @default.
- W2556491431 hasAuthorship W2556491431A5058429057 @default.
- W2556491431 hasAuthorship W2556491431A5080712446 @default.
- W2556491431 hasAuthorship W2556491431A5089637265 @default.
- W2556491431 hasConcept C126322002 @default.
- W2556491431 hasConcept C143998085 @default.
- W2556491431 hasConcept C2776063141 @default.
- W2556491431 hasConcept C2776364478 @default.
- W2556491431 hasConcept C2776694085 @default.
- W2556491431 hasConcept C2776755627 @default.
- W2556491431 hasConcept C2777478702 @default.
- W2556491431 hasConcept C2778283404 @default.
- W2556491431 hasConcept C2779429289 @default.
- W2556491431 hasConcept C2779609412 @default.
- W2556491431 hasConcept C71924100 @default.
- W2556491431 hasConceptScore W2556491431C126322002 @default.
- W2556491431 hasConceptScore W2556491431C143998085 @default.
- W2556491431 hasConceptScore W2556491431C2776063141 @default.
- W2556491431 hasConceptScore W2556491431C2776364478 @default.
- W2556491431 hasConceptScore W2556491431C2776694085 @default.
- W2556491431 hasConceptScore W2556491431C2776755627 @default.
- W2556491431 hasConceptScore W2556491431C2777478702 @default.
- W2556491431 hasConceptScore W2556491431C2778283404 @default.
- W2556491431 hasConceptScore W2556491431C2779429289 @default.
- W2556491431 hasConceptScore W2556491431C2779609412 @default.
- W2556491431 hasConceptScore W2556491431C71924100 @default.
- W2556491431 hasLocation W25564914311 @default.
- W2556491431 hasOpenAccess W2556491431 @default.
- W2556491431 hasPrimaryLocation W25564914311 @default.
- W2556491431 hasRelatedWork W1913878759 @default.
- W2556491431 hasRelatedWork W1986021912 @default.
- W2556491431 hasRelatedWork W2000304045 @default.
- W2556491431 hasRelatedWork W2087887347 @default.
- W2556491431 hasRelatedWork W2099349054 @default.
- W2556491431 hasRelatedWork W2106101491 @default.
- W2556491431 hasRelatedWork W2150885028 @default.
- W2556491431 hasRelatedWork W2154021003 @default.
- W2556491431 hasRelatedWork W2483966113 @default.
- W2556491431 hasRelatedWork W2981054797 @default.
- W2556491431 isParatext "false" @default.
- W2556491431 isRetracted "false" @default.
- W2556491431 magId "2556491431" @default.
- W2556491431 workType "article" @default.