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Dasatinib Modulates Invasive and Migratory Properties of Canine Osteosarcoma and has Therapeutic Potential in Affected Dogs.

Marley K, Gullaba J, Seguin B, Gelberg HB, Helfand SC - Transl Oncol (2015)

Bottom Line: HGF induces secretion of different forms of MMP in different cell lines.The HGF-driven increase in viability and metastatic behaviors we observed are more uniformly inhibited by dasatinib.These observations suggest a potential clinical benefit of adjuvant dasatinib treatment for dogs with OS.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences Oregon State University, 105 Magruder Hall, Corvallis OR, 97331, USA. Electronic address: kevin.marley@oregonstate.edu.

No MeSH data available.


Related in: MedlinePlus

Case studies. (A) Histopathology of right tibial OS from the Great Pyrenees shows that the medullary cavity was invaded by streams of tightly-packed, infiltrating, spindloid cells. These cells had fibrillar, eosinophilic, indistinctly-bordered cytoplasm and elongate nuclei with undulant membranes, coarse, dispersed chromatin, and multiple nucleoli. (B) The cells became more rounded (arrow) along seams of osteoid (asterisk) where they were trapped in lacunae. Multinucleated cells were present and there was 1 mitotic figure in 10 contiguous 400 × fields. (A) 200 ×, (B) 400 ×. (C) Radiographic image (lateral view) of the Great Pyrenees’ tibia shows marked destruction of bone within the medullary space giving the appearance of patchy bone loss (top arrow). There is a pathological fracture of the cortex (lower arrow). (D) Radiographic image of lung metastasis that appeared resolved after 3 months of dasatinib treatment (E). This dog remains alive 33 months after diagnosis.
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f0040: Case studies. (A) Histopathology of right tibial OS from the Great Pyrenees shows that the medullary cavity was invaded by streams of tightly-packed, infiltrating, spindloid cells. These cells had fibrillar, eosinophilic, indistinctly-bordered cytoplasm and elongate nuclei with undulant membranes, coarse, dispersed chromatin, and multiple nucleoli. (B) The cells became more rounded (arrow) along seams of osteoid (asterisk) where they were trapped in lacunae. Multinucleated cells were present and there was 1 mitotic figure in 10 contiguous 400 × fields. (A) 200 ×, (B) 400 ×. (C) Radiographic image (lateral view) of the Great Pyrenees’ tibia shows marked destruction of bone within the medullary space giving the appearance of patchy bone loss (top arrow). There is a pathological fracture of the cortex (lower arrow). (D) Radiographic image of lung metastasis that appeared resolved after 3 months of dasatinib treatment (E). This dog remains alive 33 months after diagnosis.

Mentions: The starting dose of dasatinib in all dogs has been 0.5 mg/kg given every day or every other day (Table 1). Oral antiemetics were given on treatment days if needed (maropitant 2 mg/kg once and/or ondansetron 0.2 mg/kg two to three times a day). The primary adverse effects have been inappetence and gastrointestinal upset with diarrhea. In most cases, this has not precluded dasatinib treatment. After 2 weeks without significant adverse effects, the 0.5-mg/kg dose was increased to 0.75 mg/kg and continued indefinitely or until the owner’s decision to stop. Doses higher than 0.75 mg/kg were generally not tolerated. Table 1 contains details of the dogs’ signalment, tumor location, treatments, and survival times. Two dogs’ tumors had been profiled against a panel of drugs, and dasatinib was predicted to be the most effective in these animals. These dogs had the longest survival times (Table 1). Details have been previously published for the golden retriever in the table [16]. The dogs in this report were all of large stature, which is typical of canine and human OS patients. All developed OS in the proximal tibia, a common site for OS in humans, whereas the distal radius is the most common site in the dog. Histopathological examination by a board-certified veterinary pathologist confirmed the diagnosis of OS in each dog’s tumor. Representative histological sections from the tibial OS of the Great Pyrenees (Table 1) are shown in Figure 8(A and B). The radiographic image of this tumor is shown in Figure 8(C). It is primarily an osteolytic tumor with destruction of bone within the medullary space and a pathological fracture of the cortex (Figure 8C, lower arrow).


Dasatinib Modulates Invasive and Migratory Properties of Canine Osteosarcoma and has Therapeutic Potential in Affected Dogs.

Marley K, Gullaba J, Seguin B, Gelberg HB, Helfand SC - Transl Oncol (2015)

Case studies. (A) Histopathology of right tibial OS from the Great Pyrenees shows that the medullary cavity was invaded by streams of tightly-packed, infiltrating, spindloid cells. These cells had fibrillar, eosinophilic, indistinctly-bordered cytoplasm and elongate nuclei with undulant membranes, coarse, dispersed chromatin, and multiple nucleoli. (B) The cells became more rounded (arrow) along seams of osteoid (asterisk) where they were trapped in lacunae. Multinucleated cells were present and there was 1 mitotic figure in 10 contiguous 400 × fields. (A) 200 ×, (B) 400 ×. (C) Radiographic image (lateral view) of the Great Pyrenees’ tibia shows marked destruction of bone within the medullary space giving the appearance of patchy bone loss (top arrow). There is a pathological fracture of the cortex (lower arrow). (D) Radiographic image of lung metastasis that appeared resolved after 3 months of dasatinib treatment (E). This dog remains alive 33 months after diagnosis.
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Related In: Results  -  Collection

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f0040: Case studies. (A) Histopathology of right tibial OS from the Great Pyrenees shows that the medullary cavity was invaded by streams of tightly-packed, infiltrating, spindloid cells. These cells had fibrillar, eosinophilic, indistinctly-bordered cytoplasm and elongate nuclei with undulant membranes, coarse, dispersed chromatin, and multiple nucleoli. (B) The cells became more rounded (arrow) along seams of osteoid (asterisk) where they were trapped in lacunae. Multinucleated cells were present and there was 1 mitotic figure in 10 contiguous 400 × fields. (A) 200 ×, (B) 400 ×. (C) Radiographic image (lateral view) of the Great Pyrenees’ tibia shows marked destruction of bone within the medullary space giving the appearance of patchy bone loss (top arrow). There is a pathological fracture of the cortex (lower arrow). (D) Radiographic image of lung metastasis that appeared resolved after 3 months of dasatinib treatment (E). This dog remains alive 33 months after diagnosis.
Mentions: The starting dose of dasatinib in all dogs has been 0.5 mg/kg given every day or every other day (Table 1). Oral antiemetics were given on treatment days if needed (maropitant 2 mg/kg once and/or ondansetron 0.2 mg/kg two to three times a day). The primary adverse effects have been inappetence and gastrointestinal upset with diarrhea. In most cases, this has not precluded dasatinib treatment. After 2 weeks without significant adverse effects, the 0.5-mg/kg dose was increased to 0.75 mg/kg and continued indefinitely or until the owner’s decision to stop. Doses higher than 0.75 mg/kg were generally not tolerated. Table 1 contains details of the dogs’ signalment, tumor location, treatments, and survival times. Two dogs’ tumors had been profiled against a panel of drugs, and dasatinib was predicted to be the most effective in these animals. These dogs had the longest survival times (Table 1). Details have been previously published for the golden retriever in the table [16]. The dogs in this report were all of large stature, which is typical of canine and human OS patients. All developed OS in the proximal tibia, a common site for OS in humans, whereas the distal radius is the most common site in the dog. Histopathological examination by a board-certified veterinary pathologist confirmed the diagnosis of OS in each dog’s tumor. Representative histological sections from the tibial OS of the Great Pyrenees (Table 1) are shown in Figure 8(A and B). The radiographic image of this tumor is shown in Figure 8(C). It is primarily an osteolytic tumor with destruction of bone within the medullary space and a pathological fracture of the cortex (Figure 8C, lower arrow).

Bottom Line: HGF induces secretion of different forms of MMP in different cell lines.The HGF-driven increase in viability and metastatic behaviors we observed are more uniformly inhibited by dasatinib.These observations suggest a potential clinical benefit of adjuvant dasatinib treatment for dogs with OS.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Sciences Oregon State University, 105 Magruder Hall, Corvallis OR, 97331, USA. Electronic address: kevin.marley@oregonstate.edu.

No MeSH data available.


Related in: MedlinePlus