Franklin Peale

Abstract LB-136: Characterization of residual Basal Cell Carcinoma after vismodegib treatment

We have generated a mouse model of Superficial Basal Cell Carcinoma (BCC) to study the effect of the Smoothened inhibitor vismodegib in vivo. Despite the potency of vimodegib in blocking Hedgehog (Hh) signaling and efficacy in treatment of BCC, residual disease persists in the mouse model. To better understand the Biology of BCC and the potential mechanisms maintaining BCC during treatment, we profiled isolated untreated as well as residual tumors. We found that treated tumors change their transcriptional program to resemble the cells of skin and hair follicle structures like the Interfollicular Epidermis (IFE) and Isthmus, both of which harbor stem cell compartments. Consistent with these findings, residual disease lacks expression of epidermal differentiation markers and initiates growth upon cessation of treatment. While Wnt signaling is clearly required for BCC initiation in mouse models, we show that Wnt signaling is down-regulated in untreated full-blown disease and subsequently strongly induced in the treated tumors. We hypothesize that re-initiation of the Wnt pathway maintains BCC and study the effect of blocking both Wnt and Hh pathways with combined treatment of vismodegib and Wnt inhibitors. Citation Format: Brian Biehs, Gerrit J. Dijkgraaf, Bruno Alicke, Franklin Peale, Stephen E. Gould, Frederic J. de Sauvage. Characterization of residual Basal Cell Carcinoma after vismodegib treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-136. doi:10.1158/1538-7445.AM2017-LB-136

An analysis of the decrease in the assayed level of charged bovine estrogen receptor observed at physiological ionic strength

Lower assayed levels of heifer uterine estrogen receptor (ER) occur at physiologic ionic strength when ER is separated from [3H]estradiol by Dextran-coated charcoal treatments, or by gel filtration on Sephadex or polyacrylamide resins. The assayed level of charged ER in buffers containing 150-200 mM ionic strength is approximately one-half that of ER levels assayed in buffers either at 0-50 or 400-450 mM ionic strength. Treatment of ER with trypsin or molybdate eliminates this observed reduction. Evidence is presented that the decrease results from a preferential adsorption of ER to the assay resins at 150-200 mM ionic strength. This adsorption is likely to be mediated by a hydrophobic region of the ER, which is removed by trypsin cleavage.