American Association for Cancer Research
10780432ccr140463-sup-127486_2_supp_2650890_nbmwhl.ppt (2.66 MB)

Figure S1 and Table S1. from Doxorubicin Synergizes with 34.5ENVE to Enhance Antitumor Efficacy against Metastatic Ovarian Cancer

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posted on 2023-03-31, 18:28 authored by Chelsea Bolyard, Ji Young Yoo, Pin-Yi Wang, Uksha Saini, Kellie S. Rath, Timothy P. Cripe, Jianying Zhang, Karuppaiyah Selvendiran, Balveen Kaur

Figure S1 and Table S1. Supplementary Figure 1. (A) Typical cobblestone morphology of the ascites derived cancer cells for (deidentified sample 140) under a light microscope, 4X magnification. (B) Fluorescence microscope images for patient ascites derived cancer cells (sample 140) stained with pan-cytokeratin (red); 10X magnification, left; 20X magnification, right. (C) Fluorescence microscope images for patient ascites derived cancer cells (sample 140) stained with vimentin (green); 10X magnification. (D) FACS analysis of patient ascites derived cancer cells stained for vimentin (left) and CD14 (right). M3, total cells; M1, negative for staining; M2, positive for staining. Supplementary Table 1: Table depicting the patient demographics for the collected ascites.



Purpose: Novel therapeutic regimens are needed to improve dismal outcomes associated with late-stage ovarian cancer. Oncolytic viruses are currently being tested in patients with ovarian cancer. Here, we tested the therapeutic efficacy of combining doxorubicin with 34.5ENVE, an oncolytic herpes simplex virus transcriptionally driven by a modified stem cell–specific nestin promoter, and encoding for antiangiogenic Vasculostatin-120 (VStat120) for use against progressive ovarian cancer.Experimental Design: Antitumor efficacy of 34.5ENVE was assessed in ovarian cancer cell lines, mouse ascites–derived tumor cells, and primary patient ascites–derived tumor cells by standard MTT assay. The ability of conditioned medium derived from 34.5ENVE-infected ovarian cancer cells to inhibit endothelial cell migration was measured by a Transwell chamber assay. Scope of cytotoxic interactions between 34.5ENVE and doxorubicin were evaluated using Chou–Talalay synergy analysis. Viral replication, herpes simplex virus receptor expression, and apoptosis were evaluated. Efficacy of oncolytic viral therapy in combination with doxorubicin was evaluated in vivo in the murine xenograft model of human ovarian cancer.Results: Treatment with 34.5ENVE reduced cell viability of ovarian cancer cell lines, and mouse ascites–derived and patient ascites–derived ovarian tumor cells. Conditioned media from tumor cells infected with 34.5ENVE reduced endothelial cell migration. When combined with doxorubicin, 34.5ENVE killed synergistically with a significant increase in caspase-3/7 activation, and an increase in sub-G1 population of cells. The combination of doxorubicin and 34.5ENVE significantly prolonged survival in nude mice bearing intraperitoneal ovarian cancer tumors.Conclusions: This study indicates significant antitumor efficacy of 34.5ENVE alone, and in combination with doxorubicin against disseminated peritoneal ovarian cancer. Clin Cancer Res; 20(24); 6479–94. ©2014 AACR.

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