human ews cell line a 673  (ATCC)

Journal: Molecular Therapy Oncology

Article Title: Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma

doi: 10.1016/j.omton.2024.200886

Figure Lengend Snippet: oHSV+trabectedin synergizes to increase the disease control rate and reduce tumor burden in human xenograft models The best response for each treated tumor through 28 days, the average tumor burden, and spider plots tracking individual tumor volumes over the full study period are shown for (A) CHLA-258 (Ewing sarcoma), (B) EW5 (Ewing sarcoma), (C) PDX-0027 (rhabdomyosarcoma), (D) A673 (Ewing sarcoma), and (E) A673 in NSG-SGM3 NK-deficient mice (lack T, B, and NK cells). PBS and oHSV (1.0 × 10 7 pfu) were given intratumorally (i.Tu.) on days 0 and 2. Trabectedin (0.15 mg/kg) was given intravenously (i.v.) on days 0 and 7. Statistical analyses of the disease control rates (CR + PR + SD) were performed using a pairwise Fisher’s exact test with p values adjusted using the Benjamini-Hochberg procedure; ∗ p ≤ 0.05, ∗∗ p ≤ 0.01, ∗∗∗ p ≤ 0.001. Summarized data with error bars depict mean ± SEM.

Article Snippet: The A673 human Ewing sarcoma cell line (Cat# CCL-81), Vero green monkey kidney cell line (Cat# CRL-1598), and K7M2 mouse osteosarcoma cell line (Cat# CRL-2836) were purchased from the American Type Culture Collection (ATCC) (Manassas, VA).

Techniques: Control

Journal: Molecular Therapy Oncology

Article Title: Trabectedin promotes oncolytic virus antitumor efficacy, viral gene expression, and immune effector function in models of bone sarcoma

doi: 10.1016/j.omton.2024.200886

Figure Lengend Snippet: Trabectedin increases viral intracellular prevalence and decreases antiviral gene expression in immunodeficient Ewing sarcoma models (A) Treatment schema for scRNA-seq tumor collection: PBS and oHSV (1.0 × 10 7 pfu) were given i.Tu. on days 0 and 2, trabectedin (0.15 mg/kg) was given i.v. on day 0, and scRNA-seq samples were collected on day 3 to ensure sufficient cell viability for sequencing ( n = 2 per treatment group). (B) oHSV viral titer (pfu) from A673 tumors 3 days or 6 days following treatment with a single dose of oHSV or oHSV+trabectedin. Error bars indicate standard deviation and the p values from a Student’s unpaired t test between treatment groups at each time point are shown. (C) UMAP plots of oHSV transcript presence in all tumor cells, split by treatment group, from the merged scRNA-seq datasets. (D) Violin plot of the expression level (log-transformed) of all oHSV transcripts for all tumor cells in each treatment group. (E) Expression level of HSV time-dependent gene modules shown as a feature plot (UMAP) for all tumor cells and split by treatment groups that contained oHSV. A relative expression cutoff of 1 minimized color skewing by high-expressing outlier cells and maintained color scale consistency between feature plots. (F) Violin plot of the expression level (log-transformed) of HSV time-dependent gene modules for all tumor cells in treatment groups that contained oHSV. (G) Results from gene set enrichment analysis showing the running enrichment score for the “Herpes simplex virus 1 infection” pathway, which represents the intrinsic cellular response to HSV-1. Gene set enrichment analysis was performed on a gene list which was ranked by the gene expression fold change (log2FC) calculated for tumor cells treated with oHSV+trabectedin compared with those treated with oHSV monotherapy. The schema displays key genes from the “Herpes simplex virus 1 infection” pathway with their respective percent change shown in parentheses (a negative value indicates lower expression in tumors treated with oHSV+trabectedin, as compared to oHSV-treated tumors).

Article Snippet: The A673 human Ewing sarcoma cell line (Cat# CCL-81), Vero green monkey kidney cell line (Cat# CRL-1598), and K7M2 mouse osteosarcoma cell line (Cat# CRL-2836) were purchased from the American Type Culture Collection (ATCC) (Manassas, VA).

Techniques: Gene Expression, Sequencing, Standard Deviation, Expressing, Transformation Assay, Virus, Infection