BREAST CANCER AND BONE METASTASIS

乳腺癌和骨转移

• 批准号: 2856368
• 负责人: TOSHIYUKI YONEDA
• 金额: $ 16.91万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-03-10 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2856368
• 关键词: athymic mouse; bone neoplasms; breast neoplasms; cadherins; disease /disorder model; histology; laminin; metastasis; protease inhibitor; tissue /cell culture; transfection

DESCRIPTION: (Adapted From Investigator's Abstract) Some solid tumors such as breast cancer have a special predilection to cause osteolytic metastases. The investigators have developed an in vivo model to study the capacity of human breast cancer cells to form osteolytic bone lesions in vivo using a modification of a technique developed by others to study mechanisms of bone metastasis by animal tumors. Human breast cancer cells are inoculated into the left ventricle of the heart of nude mice, and osteolytic bone lesions are then assessed during the following 4 weeks in the vertebrae and extremities by x-ray and quantitative histology. The applicants plan to use this model to characterize the properties of human breast cancer cells which are responsible for bone metastasis and osteolytic bone destruction. In particular, they plan to study specific properties of cultured human breast cancer cells which may be related to metastasis to bone and osteolysis, including expression of cell attachment proteins which bind to laminin, to E-cadherin and the production of proteolytic enzymes or their inhibitors. They also plan to use this model to examine potential therapeutic approaches to prevent or inhibit the development of osteolytic bone lesions. With this model, they will select subpopulations of cells with enhanced capacity to cause osteolytic bone destruction, investigate the role of cell attachment proteins such as laminin and E-cadherin by the use of specific antagonists, antibodies and transfected cells, and the role of matrix metalloproteases and their inhibitors in osteolysis caused by human breast cancer cells in this model. The overall goal is to identify some of these molecular mechanisms which are responsible for osteolysis in vivo, so that rational therapeutic approaches can be devised to prevent or reverse bone destruction associated with metastatic breast cancer.

描述：（根据研究者的摘要进行了改编）一些实体瘤 例如乳腺癌具有特殊的偏爱来引起溶性 转移。 研究人员已经开发了一个体内模型来研究 人类乳腺癌细胞形成骨骨的能力 使用他人开发的技术的修改在体内病变 研究动物肿瘤骨转移的机制。 人乳房 将癌细胞接种到裸体心脏的左心室中 然后在以下时评估小鼠和骨骨病变 X射线和定量的椎骨和四肢的4周 组织学。 申请人计划使用此模型来表征 负责骨骼的人类乳腺癌细胞的特性 转移和骨骨破坏。 他们特别计划 研究培养的人类乳腺癌细胞的特定特性 可能与转移到骨骼和骨溶解有关，包括表达 与层粘连蛋白结合的细胞附着蛋白与E-钙粘蛋白和 产生蛋白水解酶或其抑制剂。 他们也计划 使用此模型检查潜在的治疗方法以防止 或抑制骨骨病变的发展。 使用此模型，他们将选择具有增强的细胞亚群 引起骨骨破坏的能力，研究 通过使用 特定的拮抗剂，抗体和转染的细胞，以及 基质金属蛋白酶及其在骨溶解中的抑制剂 该模型中的人类乳腺癌细胞。 总体目标是 确定其中一些分子机制 体内的溶解性，因此可以理性的治疗方法是 设计以防止或反向与 转移性乳腺癌。

项目成果

Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2.

双膦酸盐伊班膦酸盐和基质金属蛋白酶-2组织抑制剂联合治疗抑制乳腺癌溶骨性骨转移。

• DOI: 10.1172/jci119435
• 发表时间: 1997
• 期刊: The Journal of clinical investigation
• 作者: Yoneda,T;Sasaki,A;Dunstan,C;Williams,PJ;Bauss,F;DeClerck,YA;Mundy,GR
• 通讯作者: Mundy,GR

Cellular and molecular mechanisms of breast and prostate cancer metastasis to bone.

• DOI: 10.1016/s0959-8049(97)10132-0
• 发表时间: 1998-02
• 期刊: European journal of cancer
• 影响因子: 8.4
• 作者: T. Yoneda

E-cadherin expression in human breast cancer cells suppresses the development of osteolytic bone metastases in an experimental metastasis model.

在实验性转移模型中，人乳腺癌细胞中 E-钙粘蛋白的表达可抑制溶骨性骨转移的发展。

• 发表时间: 1996
• 期刊: Cancer research.
• 作者: Mbalaviele,G;Dunstan,CR;Sasaki,A;Williams,PJ;Mundy,GR;Yoneda,T
• 通讯作者: Yoneda,T

Accumulation of p53 protein is frequent in ovarian cancers associated with BRCA1 and BRCA2 germline mutations.

p53 蛋白的积累在与 BRCA1 和 BRCA2 种系突变相关的卵巢癌中很常见。

• DOI: 10.1136/jcp.52.5.372
• 发表时间: 1999
• 期刊: Journal of clinical pathology
• 影响因子: 3.4
• 作者: Zweemer,RP;Shaw,PA;Verheijen,RM;Ryan,A;Berchuck,A;Ponder,BA;Risch,H;McLaughlin,JR;Narod,SA;Menko,FH;Kenemans,P;Jacobs,IJ
• 通讯作者: Jacobs,IJ