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Analysis of antiinvasive and antimetastatic effects of antimetasatic agents and cytotoxic drugs in a metastasis model of human breast cancer

抗转移剂和细胞毒药物在人乳腺癌转移模型中的抗侵袭和抗转移作用分析

基本信息

批准号：
06671233
负责人：
KUREBAYASHI Junichi
金额：
$ 0.26万
依托单位：
KAWASAKI MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671233/
关键词：
Breast cancer Metastasis Angiogenesis Nude mice TNP-470 UFT IIF-2 Human cell line 浸潤画像解析

项目摘要

We recently established a novel metastasis model using an MKL-4 human breast cancer cell line, a transfectant of MCF-7 cell line with fgf-4 and lac Z.In this model, micrometastases, which were stained for beta-galactosidase activity, into lymph nodes and distant organs can be quantitatively observed with a dissecting microscope. In this research project, we have obtained research results as follows : 1. Sublines were established from metastatic foci at lymph nodes and lungs. One of the sublines from lymph node metastases, MKL-4-L1 exhibited a more rapid growth and higher metastatic potential in nude mice. 2. An antiangiogenic agent, TNP-470 inhibited angiogenesis, growth and spontaneous metastasis of the MKL-4 cells transplanted into nude mice. TNP-470 was suggested to be useful in treating more aggressive and hormone-independent breast cancers.3. An antimetabolite, UFT inhibited growth and metastasis. This drug induced a massive necrosis inside the transplanted tumors. 4. A novel anti … More invasive agent, invasion-inhibiting factor 2 inhibited invasion and spontaneous metastasis without affecting primary tumor growth and angiogenesis. A newly-developed computer-assisted analysis of tumor invasiveness may be useful in the quantitative measurement of tumor cell invasion in vivo. 5. A primary tumor removal was suggested to induce progression of micrometastasis in this metastasis model. We have a plan to establish a new postsurgical metastasis model using this technique. In addition, we have established two new human breast cancer cell lines, KPL-1 and KPL-3C.KPL-1 cells secrete a large amount of tissue polypeptide antigens both in vitro and in vivo. Interestingly, KPL-1 cells have estrogen receptors but are hormone-independent. KPL-3C cells stably secrete parathyroid hormone-related protein. Both cell lines are tumorigenic in nude mice. Interestingly, KPL-3C cells produce transplanted tumors associated with microcalcifications in nude mice. These new cell lines may be useful research resources to investigate breast cancer cell biology. Less

我们最近建立了一个新的转移模型，使用MKL-4人乳腺癌细胞系，MCF-7细胞系与FGF-4和乳糖Z的转染子。在这个模型中，微转移，这是染色的β-半乳糖苷酶活性，到淋巴结和远处器官可以定量观察解剖显微镜。在本研究项目中，我们取得了如下研究成果：1.从淋巴结和肺的转移灶建立亚系。MKL-4-L1是淋巴结转移的亚系之一，在裸鼠体内生长更快，转移能力更强。2.抗血管生成剂TNP-470可抑制移植于裸鼠体内的MKL-4细胞的血管生成、生长和自发转移。提示TNP-470可用于治疗更具侵袭性和非依赖性乳腺癌. UFT是一种抗代谢药，可抑制肿瘤生长和转移。这种药物在移植的肿瘤内部引起了大量的坏死。4.一种新颖的反 ...更多信息侵袭剂，侵袭抑制因子2抑制侵袭和自发转移，而不影响原发性肿瘤生长和血管生成。计算机辅助肿瘤侵袭性分析技术的发展为定量检测肿瘤细胞在体内的侵袭能力提供了新的思路。5.在该转移模型中，建议原发性肿瘤切除以诱导微转移的进展。我们计划利用这种技术建立一种新的术后转移模型。另外，我们建立了两个新的人乳腺癌细胞系KPL-1和KPL-3C。KPL-1细胞在体内外均能分泌大量的组织多肽抗原。有趣的是，KPL-1细胞具有雌激素受体，但不依赖于雌激素受体。KPL-3C细胞稳定分泌甲状旁腺激素相关蛋白。两种细胞系在裸鼠中均具有致瘤性。有趣的是，KPL-3C细胞在裸鼠中产生与微钙化相关的移植肿瘤。这些新的细胞系可能是研究乳腺癌细胞生物学的有用研究资源。少