Supplementary Data from Combined MEK and PI3K/p110β Inhibition as a Novel Targeted Therapy for Malignant Mesothelioma Displaying Sarcomatoid Features
This file contains Supplementary Material and Methods. Supplementary Table S1 summarizes the antibodies used for IHC and WB; Supplementary Table S2 shows the primers and the shRNAs sequences used; Supplementary Table S3 shows the Selumetinib and AZD8186 concentration ranges used for in vitro experiments; Supplementary Table S4. Summary of patient and tumor characteristics corresponding to the TMA from each institution; Supplementary Table S5. Drug sensitivity values for Selumetinib/AZD8186 responder cells. Supplementary Figure S1. Histology of the metastases of Pten;Trp53-null mouse tumors. Representative H&E staining of kidney, spleen and pancreas metastases of Pten;Trp53-null tumors. Scale bar 200µm (right panels) and 50µm (left panels). Supplementary Figure S2. Signaling analysis of Pten;Trp53-null and Pik3ca*;Trp53-null mouse tumors. Supplementary Figure S3. Characterization of cell lines derived from Pten;Trp53-null and Pik3ca*;Trp53-null tumors. Supplementary Figure S4. Effect of MEK and p110b inhibitors on signaling in Pten;Trp53-null and Pik3ca*;Trp53-null cells. Supplementary Figure S5. A fraction of Selumetinib/AZD8186 treated mice had no macroscopically detectable tumors at autopsy. Supplementary Figure S6. Analysis of synergy between Selumetinib and AZD8186 in the extended panel of primary human PMM cells. Supplementary Figure S7. Comparison of the response of human Pl-MM cultures to the Selumetinib/AZD8186 combination compared to cisplatin. Viability of primary human PMM cells after 72h exposure to serial dilutions of cisplatin or constant ratio combination of Selumetinib/AZD8186. Compound concentration range: 0.025-20µM for Selumetinib and AZD8186 and 1.25-40 µM for cisplatin. The combination ratios for Selumetinib and AZD8186 in each specific culture are specified in Supplementary table S3. Mean+ SEM (n=2-3).