Characterization of the dissemination of canine cancer misinformation on YouTube.

YouTube is the third most popular app in the world and continues to grow each year while it reaches over 2 billion users a month. A variety of veterinary topics are addressed on YouTube but to date there have been no studies analysing misinformation of various canine cancer topics on YouTube or social media. This study described the characteristics of 99 unique videos and used the validated DISCERN quality criteria for consumer health information and the Patient Education Materials Assessment Tool (PEMAT) to characterize their usefulness. The overall median DISCERN quality score was 3 (out of 5), the median PEMAT understandability score was 72%, and 61% of videos contained little to no misinformation. 53% of videos were created by veterinarians and this subset had significantly higher PEMAT understandability and DISCERN quality scores compared with client-created content (p = .0228 and p ≤ .0001, respectively). Videos with little to no misinformation had statistically significant higher DISCERN quality scores (3 vs. 2, p = .0001). There was no statistical significance between misinformation levels and video length, PEMAT understandability, thumbs up/view, or views/mo. These data reveal similar rates of misinformation in videos on canine cancer compared to that reported for various human cancer topics. This study highlights the need for veterinarians to guide clients to more reliable and understandable information regarding their pet's health.

Effect of stimulator of interferon genes (STING) signaling on radiation-induced chemokine expression in human osteosarcoma cells.

Cancer cell-intrinsic mechanisms affecting radiation immunomodulation could be exploited to optimize systemic effects of localized radiation. Radiation-induced DNA damage is sensed by cyclic GMP-AMP synthase (cGAS), which ultimately activates stimulator of interferon (IFN) genes (STING). Resultant expression of soluble mediators such as CCL5 and CXCL10 can facilitate recruitment of dendritic cells and immune effector cells into the tumor. The primary objectives of this study were to determine the baseline expression levels of cGAS and STING in OSA cells and evaluate the dependence of OSA cells on STING signaling for eliciting radiation-induced expression of CCL5 and CXCL10. cGAS and STING expression, and CCL5/CXCL10 expression in control cells, STING-agonist treated cells, and cells treated with 5 Gy ionizing radiation were assessed utilizing RTqPCR, Western blot, and ELISA. U2OS and SAOS-2 OSA cells were deficient in STING relative to human osteoblasts (hObs), while SAOS-2-LM6 and MG63 OSA cells expressed equivalent amounts of STING compared to hObs. A dependence on baseline or induced STING expression was observed for STING-agonist, and radiation-induced, expression of CCL5 and CXCL10. This finding was confirmed by performing siRNA knockdown of STING in MG63 cells. These results show that STING signaling is necessary for radiation-induced expression of CCL5 and CXCL10 in OSA cells. Additional studies are necessary to determine whether STING expression in OSA cells in vivo alters immune cell infiltrates after radiation exposure. These data may also have implications for other potentially STING-dependent characteristics such as resistance to oncolytic virus cytotoxicity.

Synergistic and targeted therapy with a procaspase-3 activator and temozolomide extends survival in glioma rodent models and is feasible for the treatment of canine malignant glioma patients.

PURPOSE: Glioblastoma is a deadly brain cancer with a median survival time of ∼15 months. Ionizing radiation plus the DNA alkylator temozolomide (TMZ) is the current standard therapy. PAC-1, a procaspase-3 activating small molecule, is blood-brain barrier penetrant and has previously demonstrated ability to synergize with diverse pro-apoptotic chemotherapeutics. We studied if PAC-1 could enhance the activity of TMZ, and whether addition of PAC-1 to standard treatment would be feasible in spontaneous canine malignant gliomas. EXPERIMENTAL DESIGN: Using cell lines and online gene expression data, we identified procaspase-3 as a potential molecular target for most glioblastomas. We investigated PAC-1 as a single agent and in combination with TMZ against glioma cells in culture and in orthotopic rodent models of glioma. Three dogs with spontaneous gliomas were treated with an analogous human glioblastoma treatment protocol, with concurrent PAC-1. RESULTS: Procaspase-3 is expressed in gliomas, with higher gene expression correlating with increased tumor grade and decreased prognosis. PAC-1 is cytotoxic to glioma cells in culture and active in orthotopic rodent glioma models. PAC-1 added to TMZ treatments in cell culture increases apoptotic death, and the combination significantly increases survival in orthotopic glioma models. Addition of PAC-1 to TMZ and radiation was well-tolerated in 3 out of 3 pet dogs with spontaneous glioma, and partial to complete tumor reductions were observed. CONCLUSIONS: Procaspase-3 is a clinically relevant target for treatment of glioblastoma. Synergistic activity of PAC-1/TMZ in rodent models and the demonstration of feasibility of the combined regime in canine patients suggest potential for PAC-1 in the treatment of glioblastoma.

Fat necrosis simulating recurrent neoplasia following external beam radiotherapy in a dog.

A 4.5-year-old neutered male dog was diagnosed with incompletely excised well-differentiated lymphangiosarcoma in the right inguinal subcutaneous region. The mass had metastasized to the right hypogastric and medial iliac lymph nodes. Surgery followed by definitive radiation therapy was administered to the primary site and the sites of metastasis. The dog had a complete response to radiotherapy, and minimal acute side effects. Doxorubicin was administered after radiotherapy. Approximately 4 months following radiation therapy, the dog developed a mass, presumed recurrent tumor, in the original site. In a biopsy only steatitis and fibrosis were found. The mass continued to grow and conservative surgical excision was elected. Histopathologically the diagnosis was fat necrosis and steatitis, with a microscopic focus of lymphangiosarcoma. Fat necrosis is an uncommon sequelum to breast irradiation in people and also appears to be rare in animals. Fat necrosis should be considered as a differential diagnosis when recurrent tumor is suspected in a previously irradiated subcutaneous site in a dog.