Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse SCIDs subcutaneously injected with human Farage DLBCL cells. When tumors reached 1 cm in diameter, four mice were administered PU-H71 (75mg/kg) by intra-peritoneal injectionThe purine scaffold HSP90 inhibitor PU-H71 induces specific changes in gene expression in DLBCL xenografts.


ABSTRACT: Heat shock protein 90 (Hsp90) is an emerging therapeutic target in cancer. We report that Hsp90 inhibitors selectively kill DLBCLs that are biologically dependent on the BCL6 transcriptional repressor. We examined the pharmacokinetics, toxicity and efficacy of PUH71, a recently developed purine scaffold Hsp90 inhibitor. PUH71 preferentially accumulated in tumors vs. normal tissues, and unlike the widely used benzoquinone Hsp90 inhibitors, displayed no signs of organ toxicity. PUH71 selectively and potently induced the regression of BCL6-dependent DLBCLs in vivo, through reactivation of key BCL6 target genes and apoptosis. Experiment Overall Design: Six SCID mice were subcutaneously injected with human Farage DLBCL cells. When tumors reached 1 cm in diameter, four mice were administered PU-H71 (75mg/kg) by intra-peritoneal injection and two mice served as no-treatment controls. Animals were sacrificed by cervical dislocation under anesthesia at 6 and 12 h after the administration of PU-H71.

ORGANISM(S): Homo sapiens

SUBMITTER: Ana Robles 

PROVIDER: E-GEOD-13401 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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