Matches in SemOpenAlex for { <https://semopenalex.org/work/W2243007498> ?p ?o ?g. }
Showing items 1 to 80 of
80
with 100 items per page.
- W2243007498 endingPage "9549" @default.
- W2243007498 startingPage "9549" @default.
- W2243007498 abstract "9549 Background: Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm derived from cells lining serosal membranes. The characteristics of the epithelial (E) type MPM are distinct from those of the biphasic and sarcomatous (BS) type tumors. The goal of our study was to examine the molecular basis for this distinction. Methods: We used global molecular profiling with DNA microarrays to identify pathways associated with histologic subtype of 16 MPM tumor specimens acquired from patients entered into pilot multimodality protocols at our Institution. We performed immunohistochemistry on a tissue microarray and quantitative-real time PCR to validate the microarray results. Results: We performed average linkage agglomerative hierarchical clustering using microdissected MPM specimens and normal peritoneal tissue. The tumors segregated into two clades associated with histological subtype, which were distinct from the controls. 476 genes were differentially expressed between E and BS histologic classes (P < .001, with permutation test P value of .001). To identify biologically important differentially expressed genes and pathways, we examined the functional annotation of mesothelioma histologic subtype classifiers using the Pathway Comparison tool of BRB-Array. Among the differentially expressed categories was the ubiquitin-proteasome (UP) pathway, which was upregulated in BS tumors. Cytoxicity experiments by MTS assay indicated that, by the computation of combination indexes of activity, cells derived from BS tumors were exquisitely sensitive to sequential combination regimens containing the proteasome inhibitor (PI) bortezomib and oxaliplatin. The mechanism of this synergistic response, which was not detected in cells of E tumor origin, was apoptosis. Conclusions: Together, our results identify the ubiquitin-proteasome pathway as a biomarker of poor prognosis biphasic and sarcomatous malignant peritoneal mesothelioma tumors and suggest that proteasome inhibitors could increase the effectiveness of cytotoxic chemotherapy in this subset of patients. No significant financial relationships to disclose." @default.
- W2243007498 created "2016-06-24" @default.
- W2243007498 creator A5002110784 @default.
- W2243007498 creator A5019337443 @default.
- W2243007498 creator A5047808615 @default.
- W2243007498 creator A5061631795 @default.
- W2243007498 creator A5078275347 @default.
- W2243007498 creator A5079449321 @default.
- W2243007498 date "2006-06-20" @default.
- W2243007498 modified "2023-10-18" @default.
- W2243007498 title "Molecular profiling of malignant peritoneal mesothelioma identifies the ubiquitin-proteasome pathway as a therapeutic target in poor prognosis tumors" @default.
- W2243007498 doi "https://doi.org/10.1200/jco.2006.24.18_suppl.9549" @default.
- W2243007498 hasPublicationYear "2006" @default.
- W2243007498 type Work @default.
- W2243007498 sameAs 2243007498 @default.
- W2243007498 citedByCount "0" @default.
- W2243007498 crossrefType "journal-article" @default.
- W2243007498 hasAuthorship W2243007498A5002110784 @default.
- W2243007498 hasAuthorship W2243007498A5019337443 @default.
- W2243007498 hasAuthorship W2243007498A5047808615 @default.
- W2243007498 hasAuthorship W2243007498A5061631795 @default.
- W2243007498 hasAuthorship W2243007498A5078275347 @default.
- W2243007498 hasAuthorship W2243007498A5079449321 @default.
- W2243007498 hasConcept C104317684 @default.
- W2243007498 hasConcept C142724271 @default.
- W2243007498 hasConcept C150194340 @default.
- W2243007498 hasConcept C18431079 @default.
- W2243007498 hasConcept C193270364 @default.
- W2243007498 hasConcept C203014093 @default.
- W2243007498 hasConcept C204232928 @default.
- W2243007498 hasConcept C27740335 @default.
- W2243007498 hasConcept C2776364478 @default.
- W2243007498 hasConcept C2777407522 @default.
- W2243007498 hasConcept C2777478702 @default.
- W2243007498 hasConcept C2778995398 @default.
- W2243007498 hasConcept C502942594 @default.
- W2243007498 hasConcept C55493867 @default.
- W2243007498 hasConcept C71924100 @default.
- W2243007498 hasConcept C8415881 @default.
- W2243007498 hasConcept C86803240 @default.
- W2243007498 hasConcept C95444343 @default.
- W2243007498 hasConceptScore W2243007498C104317684 @default.
- W2243007498 hasConceptScore W2243007498C142724271 @default.
- W2243007498 hasConceptScore W2243007498C150194340 @default.
- W2243007498 hasConceptScore W2243007498C18431079 @default.
- W2243007498 hasConceptScore W2243007498C193270364 @default.
- W2243007498 hasConceptScore W2243007498C203014093 @default.
- W2243007498 hasConceptScore W2243007498C204232928 @default.
- W2243007498 hasConceptScore W2243007498C27740335 @default.
- W2243007498 hasConceptScore W2243007498C2776364478 @default.
- W2243007498 hasConceptScore W2243007498C2777407522 @default.
- W2243007498 hasConceptScore W2243007498C2777478702 @default.
- W2243007498 hasConceptScore W2243007498C2778995398 @default.
- W2243007498 hasConceptScore W2243007498C502942594 @default.
- W2243007498 hasConceptScore W2243007498C55493867 @default.
- W2243007498 hasConceptScore W2243007498C71924100 @default.
- W2243007498 hasConceptScore W2243007498C8415881 @default.
- W2243007498 hasConceptScore W2243007498C86803240 @default.
- W2243007498 hasConceptScore W2243007498C95444343 @default.
- W2243007498 hasIssue "18_suppl" @default.
- W2243007498 hasLocation W22430074981 @default.
- W2243007498 hasOpenAccess W2243007498 @default.
- W2243007498 hasPrimaryLocation W22430074981 @default.
- W2243007498 hasRelatedWork W2004663407 @default.
- W2243007498 hasRelatedWork W2011730160 @default.
- W2243007498 hasRelatedWork W2081773521 @default.
- W2243007498 hasRelatedWork W2102866915 @default.
- W2243007498 hasRelatedWork W2125600615 @default.
- W2243007498 hasRelatedWork W2268939928 @default.
- W2243007498 hasRelatedWork W2338340728 @default.
- W2243007498 hasRelatedWork W2438622766 @default.
- W2243007498 hasRelatedWork W4361238835 @default.
- W2243007498 hasRelatedWork W4361252383 @default.
- W2243007498 hasVolume "24" @default.
- W2243007498 isParatext "false" @default.
- W2243007498 isRetracted "false" @default.
- W2243007498 magId "2243007498" @default.
- W2243007498 workType "article" @default.