MECHANISMS BY WHICH METASTASIZING OSTEOLYTIC BREAST CANCER INTERACTS WITH BONE
转移性溶骨性乳腺癌与骨相互作用的机制
基本信息
- 批准号:6236747
- 负责人:
- 金额:$ 20.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-05-01 至 1998-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Breast cancer has a special predilection to cause osteolytic metastases.
This is a much more common problem than that of hypercalcemia, and is
responsible for considerable morbidity and mortality in patients with
many common solid tumors. We have recently modified an in vivo model of
bone metastasis to allow us to study the mechanisms involved in
osteolysis mediated by human breast cancer cells, and human breast cancer
cell metastasis to bone. We plan to use this model to characterize the
interactions which occur between metastasizing human breast cancer cells
and the bone microenvironment. Our hypothesis is that normal bone
remodeling releases factors into the bone microenvironment which
stimulate aggressive growth and behavior of human breast cancer cells in
this site, and that by altering rates of remodeling by pharmacologic
inhibitors of bone resorption, we can limit tumor growth in bone.
Our approach is to use this in vivo model and alter rates of bone
remodeling in tumor bearing nude mice. Nude mice will be inoculated with
MDA-231 human breast cancer cells and subsequent osteolysis in the
vertebrae and extremities will be assessed by x-ray and quantitative bone
histomorphometry. In the first series of experiments, we will use
inhibitors of bone resorption such as the bisphosphonates and assess the
effects of inhibition of bone remodeling on tumor growth in bone and the
development of osteolytic metastases. In the second series of experiments
we will examine the development of metastases in tumor bearing mice which
have been exposed to stimulators of bone resorption and bone remodeling
such as IL-I and PTH-rP. In a third series of experiments, we will use
in vitro techniques to examine specific factors in the bone
microenvironment which may be responsible for enhancing breast cancer
cell growth in bone. Our hope is that such studies will not only allow
us to develop better understanding of the responsible mechanisms, but
also more appropriate therapies to prevent the formation of osteolytic
lesions and to treat established osteolytic lesions, and hopefully to
eventually reverse the dismal picture this common complication of cancer
currently exhibits.
乳腺癌具有引起溶骨性转移的特殊倾向。
这是一个比高钙血症更常见的问题,而且
对患者的相当大的发病率和死亡率负有责任
许多常见的实体瘤。我们最近修改了一个体内模型
骨转移使我们能够研究参与的机制
人乳腺癌细胞介导的骨溶解和人乳腺癌
细胞转移到骨。我们计划使用这个模型来描述
转移性人乳腺癌细胞之间的相互作用
和骨骼微环境。我们的假设是正常的骨骼
重塑向骨微环境释放因子,从而
刺激人乳腺癌细胞侵袭性生长和行为
这个部位和那个部位,通过改变药物重塑的速度
骨吸收的抑制剂,我们可以限制肿瘤在骨骼中的生长。
我们的方法是使用这个活体模型并改变骨骼的速率
荷瘤裸鼠的重塑。裸鼠将接种疫苗
MDA-231人乳腺癌细胞和随后的骨溶解
椎骨和四肢将通过x光和定量骨进行评估。
组织形态计量学。在第一系列实验中,我们将使用
骨吸收抑制剂,如双膦酸类,并评估
抑制骨改建对骨肿瘤生长的影响
溶骨性转移的进展。在第二系列实验中
我们将检查荷瘤小鼠的转移发展情况
曾接触过骨吸收和骨重塑的刺激物
如IL-I、PTH-RP等。在第三系列实验中,我们将使用
检测骨骼中特定因子的体外技术
微环境可能是乳腺癌发生的原因
骨骼中的细胞生长。我们希望这样的研究不仅能让
我们需要更好地了解负责的机制,但
也有更合适的治疗方法来防止骨溶解的形成
用于治疗已确定的溶骨性病变,并有望
最终扭转这一常见癌症并发症的惨淡图景
目前正在展出。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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TOSHIYUKI YONEDA其他文献
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{{ truncateString('TOSHIYUKI YONEDA', 18)}}的其他基金
Bone derived IGFs in bone metastasis of human breast cancer
骨源性 IGF 在人乳腺癌骨转移中的作用
- 批准号:
6314027 - 财政年份:2000
- 资助金额:
$ 20.27万 - 项目类别:
Bone derived IGFs in bone metastasis of human breast cancer
骨源性 IGF 在人乳腺癌骨转移中的作用
- 批准号:
6203093 - 财政年份:1999
- 资助金额:
$ 20.27万 - 项目类别:
MECHANISMS BY WHICH METASTASIZING OSTEOLYTIC BREAST CANCER INTERACTS WITH BONE
转移性溶骨性乳腺癌与骨相互作用的机制
- 批准号:
6102225 - 财政年份:1998
- 资助金额:
$ 20.27万 - 项目类别:
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Standard Grant