Journal of Clinical & Experimental Pharmacology

Joseph Spernyak

Publications

• Research Article
  Anti-tumor Activity of IGF-1R Kinase Inhibitor PQIP in Colon Cancer
  Author(s): Sanjib Chowdhury *,Ivan Dominguez ,Elizabeth Sharratt ,Joseph Spernyak ,Michael G Brattain ,Ashwani RajputSanjib Chowdhury *,Ivan Dominguez ,Elizabeth Sharratt ,Joseph Spernyak ,Michael G Brattain ,Ashwani Rajput
  
  Insulin-Like Growth Factors (IGFs) and their receptor, IGF-1R, are frequently expressed in human colon cancers and play important roles in promoting malignancy. We demonstrate that colon cancer cells show dependence upon an IGF2/IGF-1R autocrine loop and have characterized the effects of an IGF1R kinase inhibitor (designated PQIP in vitroand in vivo). PQIP abrogated IGF-1R mediated activation of IRS-1/Akt to inhibit survival signaling and induce apoptosis. Furthermore, PQIP inhibited mitogenesis and anchorage-independent growth in soft agarose at concentrations consistent with inhibition of IGF-1R phosphorylation. Thus, PQIP showed potent in vitro antitumor activity in colon cancer cells. The effects of PQIP on the growth of orthotopically implanted GEO colon cancer xenografts were determined following daily treatment with 75 mg/Kg of drug by .. View More»
  DOI: 10.4172/2161-1459.S4-005

  Abstract PDF