Journal: Cancers

Article Title: Potent Antitumor Activity of Liposomal Irinotecan in an Organoid- and CRISPR-Cas9-Based Murine Model of Gallbladder Cancer

doi: 10.3390/cancers11121904

Figure Lengend Snippet: Mutant ERBB2 cooperates with loss of p53 and leads to papillary GBC in recipient mice. ( A ) Top: Schematic of human ERBB2, indicating the location of two point mutants (S310F and V777L). Bottom: retroviral vector used to transduce organoids, that had been treated with an sgp53-containing plasmid (px459) to induce loss of p53. ( B ) Immunofluorescence for ERBB2 (top) and phospho-ERBB2 (bottom) on organoids harboring the indicated genetic alterations. ( C ) Tumor volumes 36 days after s.c. implantation of the respective organoids into recipient mice. All mice transplanted with sgp53;ERBB2 S310F - and sgp53;ERBB2 V777L organoids exhibited tumor development, whereas sgp53;empty vector- and sgp53;ERBB2 wildtype organoids did not give rise to tumors over a four-month observation period. There was no significant difference in the tumor burden of mice transplanted with sgp53;ERBB2 S310F - and sgp53;ERBB2 V777L organoids ( p = 0.999). ( D ) Mice transplanted with sgp53;ERBB2 S310F - and sgp53;ERBB2 V777L organoids reached endpoint criteria with a median survival of 79.5 days and 58.5 days, respectively. ( E ) H&E and IHC for CK19 and EGFP on tumors generated with sgp53;ERBB2 S310 - and sgp53;ERBB2 V777L organoids.

Article Snippet: The pMSCV- ERBB2 -IRES- EGFP was a gift from Martine Roussel (Addgene, Watertown, MA, USA, plasmid #91888).

Techniques: Mutagenesis, Retroviral, Plasmid Preparation, Transduction, Immunofluorescence, Generated