Browsing by Author "Beaudry, Paul"

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    Congenital Bands with Intestinal Malrotation after Propylthiouracil Exposure in Early Pregnancy
    (2015-11-18) Leung, Alexander A.; Yamamoto, Jennifer; Luca, Paola; Beaudry, Paul; McKeen, Julie
    Exposure to propylthiouracil in early pregnancy may be associated with an increased risk of birth defects. But the spectrum of associated congenital anomalies is not yet well defined. While preliminary reports suggest that most cases of propylthiouracil-associated birth defects are restricted to the preauricular and urinary systems, careful consideration should be given to other possible manifestations of teratogenicity. We propose that congenital bands may potentially represent a rare yet serious complication of propylthiouracil exposure in early pregnancy, possibly arising from an early mesenteric developmental anomaly. We report a case of a 17-day-old girl that presented with acute small bowel obstruction associated with intestinal malrotation arising from several anomalous congenital bands. Her mother was treated for Graves’ disease during pregnancy with first trimester exposure to propylthiouracil but remained clinically and biochemically euthyroid at conception and throughout the duration of pregnancy. This case suggests that the use of propylthiouracil in early pregnancy may be associated with congenital bands and intestinal malrotation. More reports are needed to further support this association.
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    Oncolytic Vesicular Stomatitis Virus and Sunitinib Combination Therapy for Treating Neuroblastoma
    (2017) Rakic, Andrea; Beaudry, Paul; Mahoney, Douglas; Morris, Donald; Liao, Shan; Strother, Douglas
    Neuroblastoma is the most common extracranial solid tumour in infants and long-term survival for high-risk patients is below 50%. Generating antitumour immune responses have indicated potential. We hypothesized that sunitinib would modulate immune responses to improve oncolytic virus (VSVΔM51) productivity in the tumour and enhance the activity of antitumour immunity activated by VSVΔM51. Using an immunocompetent mouse model of neuroblastoma (neuro-2a), we found that VSVΔM51/sunitinib combination therapy elicited superior tumour regression and durable cure rates compared to either agent alone. We tested sunitinib’s ability to enhance infection in neuro-2a tumours, however, we found that infection with or without sunitinib was identical. We further tested whether sunitinib augmented antitumour immunity generated by VSVΔM51. We found that CD8+ T-cell depletion abolished the survival advantage elicited by VSVΔM51/sunitinib, indicating that sunitinib promoted adaptive immune responses. Collectively our results show that sunitinib improves VSVΔM51 therapy in neuro-2A tumours and is dependent on CD8+ T-cells.
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    Use of Novel Anti-inflammatory Agents to Inhibit Osteosarcoma Lung Metastasis
    (2016) Wierenga, Lauren; Senger, Donna; Beaudry, Paul; McCafferty, Donna-Marie
    Currently the 5-year survival rate for osteosarcoma patients with pulmonary metastasis is less than 30%, identifying a need for novel approaches to inhibit metastasis. Consistent with an emerging understanding of the cancer-inflammation relationship, a requirement for neutrophils in metastasis was recently proposed. Here we assessed the potential requisite of neutrophils and the effects of two novel anti-inflammatory agents in osteosarcoma metastasis: LT-peptide and GML (GM1-Targeted Linoleate-Containing TLR2 Ligand). Using an osteosarcoma lung metastatic mouse model, we found increased neutrophil levels in the lungs in the presence of osteosarcoma cells and reduced metastatic burden following antibody-mediated neutrophil depletion or GML treatment. These preclinical studies identify targeting neutrophils as a novel therapeutic paradigm in osteosarcoma metastasis and contribute to our understanding of the mechanisms involved in metastatic osteosarcoma, thus supporting the development of anti-inflammatory therapies as a promising approach to improve the outcomes of osteosarcoma patients.