Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361947710> ?p ?o ?g. }
Showing items 1 to 74 of
74
with 100 items per page.
- W4361947710 abstract "<div>Abstract<p><b>Purpose:</b> Conventional chemotherapy has modest efficacy in advanced adenoid cystic carcinomas (ACC). Tumor recurrence is a major challenge in the management of ACC patients. Here, we evaluated the antitumor effect of a novel small-molecule inhibitor of the MDM2–p53 interaction (MI-773) combined with cisplatin in patient-derived xenograft (PDX) ACC tumors.</p><p><b>Experimental Design:</b> Therapeutic strategies with MI-773 and/or cisplatin were evaluated in SCID mice harboring PDX ACC tumors (UM-PDX-HACC-5) and in low passage primary human ACC cells (UM-HACC-2A, -2B, -5, -6) <i>in vitro</i>. The effect of therapy on the fraction of cancer stem cells (CSC) was determined by flow cytometry for ALDH activity and CD44 expression.</p><p><b>Results:</b> Combined therapy with MI-773 with cisplatin caused p53 activation, induction of apoptosis, and regression of ACC PDX tumors. Western blots revealed induction of MDM2, p53 and downstream p21 expression, and regulation of apoptosis-related proteins PUMA, BAX, Bcl-2, Bcl-x<sub>L</sub>, and active caspase-9 upon MI-773 treatment. Both single-agent MI-773 and MI-773 combined with cisplatin decreased the fraction of CSCs in PDX ACC tumors. Notably, neoadjuvant MI-773 and surgery eliminated tumor recurrences during a postsurgical follow-up of more than 300 days. In contrast, 62.5% of mice that received vehicle control presented with palpable tumor recurrences within this time period (<i>P</i> = 0.0097).</p><p><b>Conclusions:</b> Collectively, these data demonstrate that therapeutic inhibition of MDM2–p53 interaction by MI-773 decreased the CSC fraction, sensitized ACC xenograft tumors to cisplatin, and eliminated tumor recurrence. These results suggest that patients with ACC might benefit from the therapeutic inhibition of the MDM2–p53 interaction. <i>Clin Cancer Res; 23(4); 1036–48. ©2016 AACR</i>.</p></div>" @default.
- W4361947710 created "2023-04-05" @default.
- W4361947710 creator A5020029343 @default.
- W4361947710 creator A5027131360 @default.
- W4361947710 creator A5031626209 @default.
- W4361947710 creator A5033565291 @default.
- W4361947710 creator A5045654645 @default.
- W4361947710 creator A5063728574 @default.
- W4361947710 creator A5073754378 @default.
- W4361947710 creator A5076184864 @default.
- W4361947710 creator A5084156745 @default.
- W4361947710 creator A5086323031 @default.
- W4361947710 date "2023-03-31" @default.
- W4361947710 modified "2023-10-14" @default.
- W4361947710 title "Data from Therapeutic Inhibition of the MDM2–p53 Interaction Prevents Recurrence of Adenoid Cystic Carcinomas" @default.
- W4361947710 doi "https://doi.org/10.1158/1078-0432.c.6526476" @default.
- W4361947710 hasPublicationYear "2023" @default.
- W4361947710 type Work @default.
- W4361947710 citedByCount "0" @default.
- W4361947710 crossrefType "posted-content" @default.
- W4361947710 hasAuthorship W4361947710A5020029343 @default.
- W4361947710 hasAuthorship W4361947710A5027131360 @default.
- W4361947710 hasAuthorship W4361947710A5031626209 @default.
- W4361947710 hasAuthorship W4361947710A5033565291 @default.
- W4361947710 hasAuthorship W4361947710A5045654645 @default.
- W4361947710 hasAuthorship W4361947710A5063728574 @default.
- W4361947710 hasAuthorship W4361947710A5073754378 @default.
- W4361947710 hasAuthorship W4361947710A5076184864 @default.
- W4361947710 hasAuthorship W4361947710A5084156745 @default.
- W4361947710 hasAuthorship W4361947710A5086323031 @default.
- W4361947710 hasBestOaLocation W43619477102 @default.
- W4361947710 hasConcept C126322002 @default.
- W4361947710 hasConcept C185592680 @default.
- W4361947710 hasConcept C190283241 @default.
- W4361947710 hasConcept C202751555 @default.
- W4361947710 hasConcept C203014093 @default.
- W4361947710 hasConcept C2776192174 @default.
- W4361947710 hasConcept C2776694085 @default.
- W4361947710 hasConcept C2778239845 @default.
- W4361947710 hasConcept C2780932548 @default.
- W4361947710 hasConcept C502942594 @default.
- W4361947710 hasConcept C553184892 @default.
- W4361947710 hasConcept C55493867 @default.
- W4361947710 hasConcept C71924100 @default.
- W4361947710 hasConceptScore W4361947710C126322002 @default.
- W4361947710 hasConceptScore W4361947710C185592680 @default.
- W4361947710 hasConceptScore W4361947710C190283241 @default.
- W4361947710 hasConceptScore W4361947710C202751555 @default.
- W4361947710 hasConceptScore W4361947710C203014093 @default.
- W4361947710 hasConceptScore W4361947710C2776192174 @default.
- W4361947710 hasConceptScore W4361947710C2776694085 @default.
- W4361947710 hasConceptScore W4361947710C2778239845 @default.
- W4361947710 hasConceptScore W4361947710C2780932548 @default.
- W4361947710 hasConceptScore W4361947710C502942594 @default.
- W4361947710 hasConceptScore W4361947710C553184892 @default.
- W4361947710 hasConceptScore W4361947710C55493867 @default.
- W4361947710 hasConceptScore W4361947710C71924100 @default.
- W4361947710 hasLocation W43619477101 @default.
- W4361947710 hasLocation W43619477102 @default.
- W4361947710 hasOpenAccess W4361947710 @default.
- W4361947710 hasPrimaryLocation W43619477101 @default.
- W4361947710 hasRelatedWork W2023053165 @default.
- W4361947710 hasRelatedWork W2144448045 @default.
- W4361947710 hasRelatedWork W2358507455 @default.
- W4361947710 hasRelatedWork W2371090843 @default.
- W4361947710 hasRelatedWork W2371307295 @default.
- W4361947710 hasRelatedWork W2385755382 @default.
- W4361947710 hasRelatedWork W2388658149 @default.
- W4361947710 hasRelatedWork W2391804837 @default.
- W4361947710 hasRelatedWork W3028727730 @default.
- W4361947710 hasRelatedWork W4283817505 @default.
- W4361947710 isParatext "false" @default.
- W4361947710 isRetracted "false" @default.
- W4361947710 workType "article" @default.