Cell death genetic signature in histotripsy treated canine Osteosarcoma cells
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ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE194267 | GEO | 2022/01/24
REPOSITORIES: GEO
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Project description:Abstract. The use of large animal spontaneous models of solid cancers, such as dogs with osteosarcoma (OS), can help develop new cancer immunotherapy approaches, including chimeric antigen receptor (CAR) T cells. Therefore, the goal of the present study was to generate canine CAR T cells targeting the B7-H3 (CD276) co-stimulatory molecule overexpressed by several solid cancers, including OS and glioma in both humans and dogs, and to assess their ability to recognize B7-H3 expressed by canine OS cell lines or by canine tumors in xenograft models. A second objective was to determine whether a novel dual CAR that expressed a chemokine receptor together with the B7-H3 CAR improved the activity of the canine CAR T cells. Therefore, in the studies reported here we examined B7-H3 expression by canine OS tumors, evaluated target engagement by canine B7-H3 CAR T cells in vitro, and compared the relative effectiveness of B7-H3 CAR T cells versus B7-H3-CXCR2 dual CAR T cells in canine xenograft models. We found that most canine OS tumors expressed high levels of B7-H3, whereas levels were undetectable on normal dog tissues. In vitro, both B7-H3 CAR T cells demonstrated activation and OS-specific target killing in vitro, but there was significantly greater cytokine production by B7-H3-CXCR2 CAR T cells. In canine OS xenograft models, little antitumor activity was generated by B7-H3 CAR T cells, whereas B7-H3-CXCR2 CAR T cells significantly inhibited tumor growth, inducing complete tumor elimination in most treated mice. These findings indicated therefore that addition of a chemokine receptor could significantly improve the anti-tumor activity of canine B7-H3 CAR T cells, and that evaluation of this new dual CAR construct in dogs with primary or metastatic OS is warranted since such studies could provide a critical and realistic validation of the chemokine receptor concept.
2024-04-03 | GSE247355 | GEO
Project description:Osteosarcoma (OS) accounts for approximately 80% of all malignant bone tumors in the dog. Tumors are highly metastatic and long-term survival is poor. This study aims to investigate the prognosis associated gene expression profile in primary canine OS. Canine specific cDNA microarray representing 20,313 genes was used to analyze expression profiles in a panel of thirty-two primary osteosarcoma to identify genes associated with survival. The 32 tumours were classified into two groups of prognosis based on survival time (ST). They were defined as short survivors (dogs with poor prognosis that survived less than 6 months) and long survivors (dogs with better prognosis that survived longer than 6 months). Fifty-one genes were found to be differentially expressed, with common up regulation of these genes in the short survivors. The overexpression of these genes in short survivors suggests a possible role for increased proliferation, drug resistance or metastasis. Several deregulated pathways were identified in the present study includes Wnt signaling, Integrin signaling and Chemokine / cytokine signaling which were comparable to the pathway analysis conducted on human OS, adding more value for the dog as an excellent model to study human OS. Our results suggest that a molecular-based method for discrimination of outcome for short survivors and long survivors of canine OS may be useful for future prognostic stratification of dogs at initial diagnosis, where genes and pathways associated with cell cycle/ proliferation, drug resistance and metastasis could be potential targets for therapy that may not just be beneficial for dogs but also for humans.
2009-09-14 | GSE14033 | GEO
Project description:Cell death genetic signature in histotripsy treated canine Osteosarcoma cells
| PRJNA800029 | ENA
Project description:RNA-Seq of canine osteosarcoma tumor samples obtained from Canine Comparative Oncology and Genomics Consortium
2023-08-07 | GSE239948 | GEO
Project description:Osteosarcoma is the most common primary bone tumours of dogs. Canine osteosarcoma contains a sub-population of cancer stem cells. Here we used canine-specific microarrays to compare the global gene expression profiles of osteosarcoma stem cells to adherent cancer cells and canine mesenchymal stem cells.
2013-11-05 | GSE52063 | GEO
Project description:Osteosarcoma is the most common primary bone tumours of dogs. Canine osteosarcoma contains a sub-population of cancer stem cells. Here we used canine-specific microarrays to compare the global gene expression profiles of osteosarcoma stem cells to adherent cancer cells and canine mesenchymal stem cells. Canine osteosarcoma spheres were isolated by their ability to form tumourspheres. Spheres, adherent cells and mesenchymal stem cells were harvested and used for RNA extraction and hybridisation on Affymetrix microarrays (Canine 2.0). Four biological replicates of each sample were included.
2013-11-05 | E-GEOD-52063 | biostudies-arrayexpress
Project description:Cell lines and tumor tissues from canine osteosarcomas with accompanying survival and breed data.
2011-09-08 | GSE27217 | GEO
Project description:Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy.
2009-11-04 | GSE16087 | GEO
Project description:The recently developed COXEN method (PMID: 17666531) has been used to successfully extrapolate gene signatures of drug sensitivity across different tumor histotypes. We wanted to explore the utility of COXEN to predict chemosensitivity in canine cancer, specifically if we could extrapolate gene signatures identified in human datasets over to canine osteosarcoma tumors. This dataset of canine osteosarcoma tumor samples has available clinical outcome data after patients had infected limbs amputated and were treated with doxorubicin and/or carboplatin. We performed microarray analysis on this panel of tumor samples for validating our COXEN prediction models for doxorubicin or carboplatin sensitivity.
2015-12-18 | GSE76127 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE16087: Gene expression profiles of canine osteosarcoma GSE16088: Gene expression profiles of human osteosarcoma GSE16091: Gene expression profiles of human osteosarcoma, set2 Pulmonary metastasis continues to be the most common cause of death in osteosarcoma. Indeed, the 5-year survival for newly diagnosed osteosarcoma patients has not significantly changed in over 20 years. Further understanding of the mechanisms of metastasis and resistance for this aggressive pediatric cancer is necessary. Pet dogs naturally develop osteosarcoma providing a novel opportunity to model metastasis development and progression. Given the accelerated biology of canine osteosarcoma, we hypothesized that a direct comparison of canine and pediatric osteosarcoma expression profiles may help identify novel metastasis-associated tumor targets that have been missed through the study of the human cancer alone. Collectively, these data support the strong similarities between human and canine osteosarcoma and underline the opportunities provided by a comparative oncology approach as a means to improve our understanding of cancer biology and therapy. Two datasets consisting of canine osteosarcoma tumors, canine osteosarcoma cell lines, and three normal tissues and an analogous human dataset were used to define the similarity between human and canine osteosarcoma. A third dataset, human osteosarcoma with outcome data, was then used to suggest that some of the differences between the canine and human osteosarcoma were, perhaps, related to survival.
2009-11-03 | E-GEOD-16102 | biostudies-arrayexpress