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K A Hahn

Publications and source records attributed to K A Hahn.

38 records · Page 3Linked to original sources

In vitro reversal of glutathione-S-transferase-mediated resistance in canine osteosarcoma (COS31) cells.

BACKGROUND: In this report we describe the establishment, characterization, and research utility of a cell line derived from a dog having a spontaneously occurring osteosarcoma (COS) made resistant to the cytotoxic effects of cisplatin chemotherapy. MATERIALS AND METHODS: Established cells from passage 31 (COS31) were exposed to increasing sublethal concentrations of cisplatin in vitro. RESULTS: A 2.2-fold increase in glutathione-S-transferase (GST) activity was found to be induced in this cell line (COS31/rCDDP) compared to parent cells. Furthermore, these cells were 7.8-fold more resistant to the cytotoxic effects of higher concentrations of cisplatin compared to parent cells. Ethacrynic acid was found to inhibit GST enzymatic activity and increase cisplatin cytotoxicity in resistant COS31 (COS31/rCDDP) cells. CONCLUSIONS: Inhibiting the function of GST with ethacrynic acid pretreatment in humans and dogs with osteosarcoma may result in more tumor cells than normal cells killed in vivo by cisplatin, thus significantly prolonging lifespan without increasing host toxicity.

Animals↗

An in vivo/in vitro experimental model system for the study of human osteosarcoma: canine osteosarcoma cells (COS31) which retain osteoblastic and metastatic properties in nude mice.

BACKGROUND: In this report we describe the establishment, characterization, and research utility of a cell line derived from a dog having a spontaneously occurring osteosarcoma. MATERIALS AND METHODS: Tumor samples were collected from a dog with a naturally occurring osteosarcoma and processed for light microscopy, electron microscopy, immunocytochemistry, immunohistochemistry, karyology, and cell culture. Established cells from passage 31 (COS31; canine Qsteosarcoma cells from passage 31) were inoculated subcutaneously between the scapula and in the right abdominal side of athymic nude mice and evaluated similarly. RESULTS: COS31 cells derived in cell culture and in nude mice had morphological and biochemical properties comparable in all respects to the original canine tumor specimen. CONCLUSIONS: The ability of COS31 cells to produce tumors in nude mice (i.e. a small animal model) typical of canine osteosarcoma (i.e. a large animal model) with a similar pathological and biological behavior (e.g. alkaline phosphatase and osteocalcin positive immunostaining, osteoid production, rapid growth, and wide spread metastases) demonstrates the potential utility of COS31 cells as a in vitro and in vivo model system in the development of new strategies in the treatment of human osteosarcoma.

Alkaline Phosphatase↗