canine osteosarcoma
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2021 ◽  
Vol 8 ◽  
Author(s):  
Aryana M. Razmara ◽  
Sean J. Judge ◽  
Alicia A. Gingrich ◽  
Sylvia M. Cruz ◽  
William T. N. Culp ◽  
...  

Metastatic osteosarcoma has a bleak prognosis in both humans and dogs, and there have been minimal therapeutic advances in recent decades to improve outcomes. Naturally occurring osteosarcoma in dogs is shown to be a highly suitable model for human osteosarcoma, and limited data suggest the similarities between species extend into immune responses to cancer. Studies show that immune infiltrates in canine osteosarcoma resemble those of human osteosarcoma, and the analysis of tumor immune constituents as predictors of therapeutic response is a promising direction for future research. Additionally, clinical studies in dogs have piloted the use of NK transfer to treat osteosarcoma and can serve as valuable precursors to clinical trials in humans. Cytotoxic lymphocytes in dogs and humans with osteosarcoma have increased activation and exhaustion markers within tumors compared with blood. Accordingly, NK and T cells have complex interactions among cancer cells and other immune cells, which can lead to changes in pathways that work both for and against the tumor. Studies focused on NK and T cell interactions within the tumor microenvironment can open the door to targeted therapies, such as checkpoint inhibitors. Specifically, PD-1/PD-L1 checkpoint expression is conserved across tumors in both species, but further characterization of PD-L1 in canine osteosarcoma is needed to assess its prognostic significance compared with humans. Ultimately, a comparative understanding of T and NK cells in the osteosarcoma tumor microenvironment in both dogs and humans can be a platform for translational studies that improve outcomes in both dogs and humans with this frequently aggressive disease.


2021 ◽  
Vol 8 ◽  
Author(s):  
Anita K. Luu ◽  
Geoffrey A. Wood ◽  
Alicia M. Viloria-Petit

Canine osteosarcoma (OSA) is an aggressive malignancy that frequently metastasizes to the lung and bone. Not only has there been essentially no improvement in therapeutic outcome over the past 3 decades, but there is also a lack of reliable biomarkers in clinical practice. This makes it difficult to discriminate which patients will most benefit from the standard treatment of amputation and adjuvant chemotherapy. The development of reliable diagnostic biomarkers could aid in the clinical diagnosis of primary OSA and metastasis; while prognostic, and predictive biomarkers could allow clinicians to stratify patients to predict response to treatment and outcome. This review summarizes biomarkers that have been explored in canine OSA to date. The focus is on molecular biomarkers identified in tumor samples as well as emerging biomarkers that have been identified in blood-based (liquid) biopsies, including circulating tumor cells, microRNAs, and extracellular vesicles. Lastly, we propose future directions in biomarker research to ensure they can be incorporated into a clinical setting.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4890
Author(s):  
Bénédicte Brulin ◽  
John C. Nolan ◽  
Tecla Marangon ◽  
Milan Kovacevic ◽  
Mathias Chatelais ◽  
...  

Improvements in the clinical outcome of osteosarcoma have plateaued in recent decades with poor translation between preclinical testing and clinical efficacy. Organotypic cultures retain key features of patient tumours, such as a myriad of cell types organized within an extracellular matrix, thereby presenting a more realistic and personalised screening of chemotherapeutic agents ex vivo. To test this concept for the first time in osteosarcoma, murine and canine osteosarcoma organotypic models were maintained for up to 21 days and in-depth analysis identified proportions of immune and stromal cells present at levels comparable to that reported in vivo in the literature. Cytotoxicity testing of a range of chemotherapeutic drugs (mafosfamide, cisplatin, methotrexate, etoposide, and doxorubicin) on murine organotypic culture ex vivo found limited response to treatment, with immune and stromal cells demonstrating enhanced survival over the global tumour cell population. Furthermore, significantly decreased sensitivity to a range of chemotherapeutics in 3D organotypic culture relative to 2D monolayer was observed, with subsequent investigation confirming reduced sensitivity in 3D than in 2D, even at equivalent levels of drug uptake. Finally, as proof of concept for the application of this model to personalised drug screening, chemotherapy testing with doxorubicin was performed on biopsies obtained from canine osteosarcoma patients. Together, this study highlights the importance of recapitulating the 3D tumour multicellular microenvironment to better predict drug response and provides evidence for the utility and possibilities of organotypic culture for enhanced preclinical selection and evaluation of chemotherapeutics targeting osteosarcoma.


Author(s):  
Lauren Arnold ◽  
Alissa Hendricks-Wenger ◽  
Sheryl Coutermarsh-Ott ◽  
Jessica Gannon ◽  
Alayna N. Hay ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4178
Author(s):  
Salvador Padilla-Arellanes ◽  
Rafael Salgado-Garciglia ◽  
Marisol Báez-Magaña ◽  
Alejandra Ochoa-Zarzosa ◽  
Joel Edmundo López-Meza

Osteosarcoma is the most common malignant bone tumor in both children and dogs. It is an aggressive and metastatic cancer with a poor prognosis for long-term survival. The search for new anti-cancer drugs with fewer side effects has become an essential goal for cancer chemotherapy; in this sense, the bioactive compounds from avocado have proved their efficacy as cytotoxic molecules. The objective of this study was to determine the cytotoxic and antiproliferative effect of a lipid-rich extract (LEAS) from Mexican native avocado seed (Persea americana var. drymifolia) on canine osteosarcoma D-17 cell line. Also, the combined activity with cytostatic drugs was evaluated. LEAS was cytotoxic to D-17 cells in a concentration-dependent manner with an IC50 = 15.5 µg/mL. Besides, LEAS induced caspase-dependent cell apoptosis by the extrinsic and intrinsic pathways. Moreover, LEAS induced a significant loss of mitochondrial membrane potential and increased superoxide anion production and mitochondrial ROS. Also, LEAS induced the arrest of the cell cycle in the G0/G1 phase. Finally, LEAS improved the cytotoxic activity of cisplatin, carboplatin, and in less extension, doxorubicin against the canine osteosarcoma cell line through a synergistic effect. In conclusion, avocado could be a potential source of bioactive molecules in the searching treatments for osteosarcoma.


2021 ◽  
Author(s):  
Yingli Fu ◽  
Jing Yu ◽  
Ioanna Liatsou ◽  
Anders Josefsson ◽  
Yong Du ◽  
...  

2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Ioannis Oikonomidis ◽  
Theodora Tsouloufi

PICO question What is the sensitivity and specificity of cytology as a test for canine osteosarcoma when compared to histopathology as a gold standard?   Clinical bottom line Category of research question Diagnosis The number and type of study designs reviewed Overall, four diagnostic validity studies (two prospective and two retrospective) were critically appraised Strength of evidence Weak to moderate Outcomes reported There is evidence of moderate strength to support that cytology is highly sensitive and specific for diagnosing histologically confirmed osteosarcomas as mesenchymal malignant neoplasms (cytological diagnosis of sarcoma). Evidence of weak strength suggests that the sensitivity and specificity of cytology for identifying the exact histotype (cytological diagnosis of osteosarcoma) are low and high, respectively. Finally, there is currently evidence of weak strength indicating that the sensitivity and specificity of cytology are comparable to that of preoperative histopathology after incisional biopsy for the diagnosis of canine osteosarcoma Conclusion Based on the available evidence, the diagnostic accuracy of cytology in diagnosing histologically confirmed osteosarcomas as sarcomas is high, whereas a confident conclusion cannot be drawn regarding the diagnostic accuracy of cytology for the identification of the exact histotype (cytological diagnosis of osteosarcoma). There is currently scant evidence suggesting that cytology has comparable diagnostic accuracy to preoperative histopathology (i.e. after incisional biopsy) for the diagnosis of canine osteosarcomas, however, more studies are warranted to confirm these results   How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.  


2021 ◽  
Author(s):  
Magdalena Jolanta Walewska ◽  
Anna Małek ◽  
Bartłomiej Taciak ◽  
Anna Wojtalewicz ◽  
Sylwia Wilk ◽  
...  

Abstract The chick chorioallantoic membrane (CAM) assay has long been used to study the effects of drugs on angiogenesis or evaluate cancer cell invasiveness by quantifying in vivo rates of cancer cell extravasation. Extravasation plays a crucial role in the metastatic cascade, whereby circulating cancer cells derived from the primary tumor cross the endothelial barrier to reach the target metastatic site. Accordingly, we adapted an ex ovo model to study the anti-extravasation efficiency of anticancer drugs. The drugs investigated include conventional and PEG-liposomal doxorubicin. The conventional form is commonly used in chemotherapy protocols for canine appendicular osteosarcoma (OSA), although it has no specific biodistribution and a low therapeutic index. For this reason, this study compared the effects of conventional and PEG-liposomal doxorubicin on cytotoxicity and migration inhibition in the in vitro environment. Cytotoxicity was evaluated by the MTT assay, Annexin V staining and the Draq 7 test; the inhibition of migration was analyzed using the scratch assay test. Moreover the inhibitory effect of study drugs on cancer cell extravasation was analyzed in the in vivo conditions, on the ex ovo model. The results of experiments performed showed that PEG-liposomal doxorubicin has a higher inhibitory effect on the in vitro migration of canine OSA (p ≤ 0.05). Ex ovo research revealed both drugs elicited a high efficiency for inhibiting the extravasation of canine OSA (p< 0.0001). Therefore PEG-liposomal doxorubicin may be considered as a potentially useful anti-metastatic agent in canine osteosarcoma due to its inhibitory effect on both the migration and extravasation of the D-17 cell line.


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