Basic amd clinical study on differentiation induction of solid tumors with frequent metastasis

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Final purpose of this study is to induce differentiation of malignant solid tumor like osteosarvoma by physiologically active substances. But in veterinary medicine especially in Japn, the clinical aspects to tumor patients such as survival rates depending on the treatments are not fully investigated. We have seen various cancer patients in our hospital of Univerdity of Tokyo, therefore we have statted to investigate the prognosis of these tumor patients.During the research period, we reported a review and some original papers on the prognosis of canine oral and nasal tumors, mast cell tumors, feline mammary grand tumors. The results were almost the same as described in foreign countries before, but can be used as reference data for our further reseaches.Establishment of tumor cell lines from spontaneous animal tumors were also tried. During this period, we have establishe two other canine osteosarcoma cells, malanoma cells and canine and feline mamary gland tumor cells. These cells could be quite valuable ones for the further reseaches of induction of differentiation of malignant tumors.Differentiation induction was investigated using cloned canine osteosarcoma cells and vitamine D,TFG-beta, and recombinant human bone morphogenetic protein-2 (rhBMP-2) as physiologic substance. By addition of these substances into the culture media, ALP activity. ALp staining strength, osteocalcin concentrations, and type I collagen concentrations, as the phenotypic characteristics of osteoblasts, increased. This result suggests that osteosarcoma cells must be induced higher differentiation stages by these substances. The potency of induction was higher in vitamine D and rhBMP-2 than in TGF-beta.Differentiation was also observed by addition of retinoic acids and vitamine D derivatives in other canine osteosarcoma cells, though the results were still preliminary. Further researches including in vivo and clinical studies must be needed.