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

多转移实体瘤分化诱导的基础与临床研究

• 批准号: 07456141
• 负责人: SASAKI Nobuo
• 金额: $ 1.41万
• 依托单位: THE UNIVERSITY OF TOKYO
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07456141/
• 关键词: differentiation induction; canine oseosarcoma cell; vitamine D; TFD-beta; rhBMP-2; ALP activity; osteocalcin; retinoic acid; 骨肉腫細胞; ビタミンD_3; TGF-β_1; 抗腫瘍剤感受性; 放射線感受性; 転移能; 分化誘導療法; 骨肉腫細胞株; I型コラーゲン; アポトーシス

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.

本研究的最终目的是通过生理活性物质诱导恶性实体瘤如骨肉瘤的分化。但是在兽医学中，特别是在日本，对肿瘤患者的临床方面，如取决于治疗的存活率，还没有充分研究。我们在东京大学医院看到了各种癌症患者，因此我们开始调查这些肿瘤患者的预后。在研究期间，我们报道了关于犬口腔和鼻腔肿瘤，肥大细胞肿瘤，猫乳腺大肿瘤预后的综述和一些原创论文。本研究结果与国外报道的结果基本一致，但可作为进一步研究的参考资料。在此期间，我们建立了另外两个犬骨肉瘤细胞，恶性肿瘤细胞和犬猫乳腺肿瘤细胞。本研究以克隆化的犬骨肉瘤细胞为研究对象，以维生素D、TGF-β和重组人骨形态发生蛋白-2（rhBMP-2）为诱导分化的生理物质，对犬骨肉瘤细胞进行了诱导分化研究。通过向培养基中添加这些物质，ALP活性。成骨细胞表型特征的ALP染色强度、骨钙素浓度和I型胶原浓度增加。这一结果表明，骨肉瘤细胞必须由这些物质诱导更高的分化阶段。维生素D和rhBMP-2的诱导效力高于TGF-β。在其他犬骨肉瘤细胞中加入维甲酸和维生素D衍生物也观察到分化，但结果仍是初步的。必须进行进一步的研究，包括体内和临床研究。

项目成果

伊東 輝夫: "Prognosis of malignant mammary tumor in 53 cats" J.Vet,Med.Sci. 58. 723-726 (1996)

Teruo Ito：“53 只猫的恶性乳腺肿瘤的预后”J.Vet,Med.Sci. 58. 723-726 (1996)

Ito, T.et al: "Prognosis of malignant mammary tumor in 53 cats" J.Vet.Med.Sci.58. 723-726 (1996)

Ito, T. 等人：“53 只猫的恶性乳腺肿瘤的预后”J.Vet.Med.Sci.58。

T.ITO et al.: "Prognosis of malignant mammary tumor in 53 cats" J.Vet.Med.Sci.58. 723-726 (1996)

T.ITO 等人：“53 只猫的恶性乳腺肿瘤的预后”J.Vet.Med.Sci.58。

廉澤 剛: "小動物腫瘍の診断と治療" 日本獣医師会雑誌. 48. 735-742 (1995)

Tsuyoshi Renzawa：“小动物肿瘤的诊断和治疗”日本兽医协会杂志 48. 735-742 (1995)。

廉澤 剛: "小動物腫瘍の診断と治療" 日本獣医師会誌. 48巻. 735-742 (1995)

Tsuyoshi Renzawa：“小动物肿瘤的诊断和治疗”日本兽医协会杂志第 48 卷 735-742（1995 年）。