p21 (CDKN1A) expression from an IPTG-inducible promoter in HT1080 p21-9 cells was previously shown to inhibit a set of genes, many of which are involved in cell cycle progression, and to upregulate another set of genes, some of which have been implicated in cancer and age-related diseases. We have now developed Senexin A, a small-molecule inhibitor of p21-induced transcription, which we found to be a selective inhibitor of CDK8 and CDK19. Here we tested the effect of Senexin A on the induction and inhibition of transcription by p21.
Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities.
Specimen part
View SamplesGene expression profiling analysis (RNAseq) of mouse bladder epithelium from wildtype mice (Arf+/+; p53+/+; Pten+/+) or bladder tumors from Arf-wild-type (Arf+/+; p53f/f; Ptenf/f) or Arfnull (Arff/f; p53f/f; Ptenf/f) mice that had been treated with vehicle or cisplatin Overall design: Total RNA obtained from bladder epithelium or bladder tumors. Bladder tissues or tumors were harvested and processed for RNA isolation and transcriptome analysis using the MagMAX RNA isolation kit (Ambion).
ARF Confers a Context-Dependent Response to Chemotherapy in Muscle-Invasive Bladder Cancer.
Sex, Subject
View SamplesRecurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) remains one of the most difficult cancers to treat with limited chemotherapeutic options. Here, we describe a patient with HNSCC who had complete response to methotrexate (MTX) after progressing on multiple cytotoxic agents; cetuximab, a monoclonal antibody (mAb) against Epidermal Growth Factor Receptor (EGFR), and AMG 479, a mAb against Insulin-like Growth Factor-1 Receptor (IGF-1R).
Insulin-like growth factor-1 receptor inhibitor, AMG-479, in cetuximab-refractory head and neck squamous cell carcinoma.
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View SamplesDespite advances in surgery and radiotherapy of uveal melanoma (UM), many patients develop distant metastases that poorly respond to therapy. Improved therapies for the metastatic disease are therefore urgently needed. Expression of the epidermal growth factor receptor (EGFR), a target of kinase inhibitors and humanized antibodies in use for several cancers, had been reported. 48 human UMs were analyzed by expression profiling. Evidence for signaling in tumors was obtained through the application of a UM-specific EGF signature. The EGFR specific kinase inhibitor, Gefitinib, and the humanized monoclonal antibody, Cetuximab, were tested for their effect on EGFR signaling. Natural killer cell mediated antibody-dependent cellular cytotoxicity (ADCC) and TNF-alpha release was analyzed for Cetuximab. EGFR appears suited as a novel molecular drug target for therapy of uveal melanoma.
Evidence of epidermal growth factor receptor expression in uveal melanoma: inhibition of epidermal growth factor-mediated signalling by Gefitinib and Cetuximab triggered antibody-dependent cellular cytotoxicity.
Sex, Specimen part, Disease, Disease stage
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