OSTEOSARCOMA WITH A PATHOLOGIC FRACTURE IN A SIX-MONTH-OLD DOG

This case history report describes the clinical, radiographic, and histopathologic features of an osteosarcoma with an associated pathologic fracture in a 6-month-old dog. A 6-month-old intact male Bloodhound was presented with a primary complaint of a right forelimb lameness of one month's duration. In radiographs, a minimally displaced transverse fracture of the proximal humeral metaphysis was seen. There was extensive cortical bone destruction at the fracture site and minimal periosteal new bone suggestive of a primary bone tumor with a pathologic fracture. Biopsy specimens demonstrated neoplastic mesenchymal cells producing osteoid compatible with a diagnosis of osteosarcoma. This case history report constitutes the youngest reported canine osteosarcoma.     

Survival analysis of one versus two treatments of local delivery cisplatin in a biodegradable polymer for canine osteosarcoma

The purpose of this study was to evaluate one versus two doses of local delivery cisplatin in a biodegradable polymer (OPLA‐Pt) for the treatment of osteosarcoma (OSA) after amputation in dogs. Medical records were reviewed retrospectively, and 105 dogs were included in the study; 39% of dogs received one treatment (surgical implantation) of OPLA‐Pt and 61% of dogs received two treatments of OPLA‐Pt after amputation. Administration of two doses of OPLA‐Pt did not have a significant effect on disease‐free interval or survival time compared to one dose. The anatomic site of the tumour was identified as a prognostic factor, and dogs with proximal humeral OSA had the shortest disease‐free interval and survival times. There was no advantage to giving a second dose of local delivery cisplatin following amputation for the treatment of OSA in dogs.     

Adjuvant therapy with carboplatin and pamidronate for canine appendicular osteosarcoma

Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.     

Knockdown of Notch-1 augments inhibitory effect of dihydroartemisinin on viability of human osteosarcoma cell line U-2OS

AIM: To investigate the effect of Notch-1 knockdown on the growth of dihydroartemisinin-inhibited human osteosarcoma cell line U-2OS. METHODS: U-2OS cells treated with different concentrations of dihydroartemisinin (5, 10, 15 and 20 μmol/L) were collected. The expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels was measured by real-time PCR and Western blotting, respectively. U-2OS cells were transfected with Notch-1 siRNA for 24 h and incubated with dihydroartemisinin for another 24 h. The cell apoptotic rate, protein expression of MMP-2, MMP-9 and Hes-1, and the migration ability were measured by MTT assay, Western blotting and Transwell experiment, respectively. RESULTS: Dihydroartemisinin (5, 10, 15 and 20 μmol/L) decreased the expression of Notch-1, MMP-2, MMP-9 and Hes-1 at mRNA and protein levels in a dose-dependent manner. Down-regulation of Notch-1 significantly enhanced the effect of dihydroartemisinin on the cell apoptosis, the protein expression of MMP-2, MMP-9 and Hes-1, and migration ability (P<0.05). CONCLUSION: Notch-1 pathway is involved in the process of dihydroartemisinin-inhibited U-2OS cell growth. Knockdown of Notch-1 augments the inhibitory effect of dihydroartemisinin on U-2OS cell viability.     

Antineoplastic effect of the cyclooxygenase inhibitor meloxicam on canine osteosarcoma cells

A decisive role in cancer development has been attributed to cyclooxygenase-2 (COX-2) activity, but the significance of COX-2 inhibitors in cancer treatment still needs to be thoroughly investigated. We studied the influence of meloxicam, a non-steroidal antiinflammatory drug with preferential inhibitory effects on COX-2 compared to COX-1, on canine osteosarcoma (D-17) cells. We demonstrated that D-17 cells expressed mRNA and COX-2 protein. Treatment with meloxicam induced a time- and dose-dependent inhibition of cellular growth. To determine if apoptosis plays a role in meloxicam-induced cell death, we performed agarose gel electrophoresis and found a DNA-ladder pattern, typically seen in apoptosis, as well as early apoptotic changes by Annexin V tests. Furthermore, electron microscopy revealed ultrastructural alterations typical of apoptosis. Quantification of apoptotic cells by immunohistochemical staining of caspase 3 confirmed the results. However, further studies with meloxicam are necessary to assess its potential use for treatment of osteosarcomas in dogs.     

Nuclear scanning with 99mTc-HDP for the initial evaluation of osseous metastasis in canine osteosarcoma

The purpose of this retrospective analysis was to evaluate the use of nuclear scintigraphy in determining the rate of secondary sites of osseous malignancy at initial presentation in dogs with osteosarcoma. Radiographs of suspicious secondary lesions were reviewed and placed into four separate categories: benign lesions; no lesion seen on radiographs; subtle radiographic changes suggestive of, but not conclusive for, metastasis; and metastatic lesions highly suspected on radiographs. Three hundred and ninety‐nine dogs were evaluated by technetium nuclear scanning for suspected osteosarcoma. Three hundred and twenty‐six of 399 dogs (82%) had only one apparent site on the nuclear scan, whereas 72 dogs (18%) had more than one suspicious site on the nuclear scans. Highly suspected secondary metastatic lesions were detected by nuclear scans in 7.8% of cases. Although interpretation of nuclear scans is subjective, this study showed a 7.8% chance of detecting unsuspected osseous metastasis with nuclear scans in canine osteosarcoma patients on initial presentation.     

SCINTIGRAPHIC DETECTION OF SUBCUTANEOUS METASTASIS IN A DOG WITH APPENDICULAR OSTEOSARCOMA

This report describes the detection of subclinical soft tissue metastasis of an appendicular osteosarcoma in a dog using bone scintigraphy. A 7-year-old spayed female Rottweiler was presented with a biopsy confirmed diagnosis of osteosarcoma. Initial radiographs revealed an aggressive bone lesion of the left distal radius. At presentation, there was no clinical or radiographic evidence of metastasis; however, a nuclear bone scan showed the primary bone lesion of the distal left radius and numerous soft tissue lesions consistent with diffuse soft tissue metastases. A left foreleg amputation was performed and cisplatin chemotherapy was given post-operatively. A second bone scan performed one month following initial presentation showed progression in size and number of soft tissue masses. Many of the lesions had become apparent on physical exam and survey radiographs. Excisional biopsy was performed on one of the soft tissue masses and a diagnosis of metastatic osteosarcoma was made. The dog was euthanized 2 months after initial presentation at the owners request due to deterioration of the animals physical condition.