HYALURONIDASE AND CD44 VARIANTS IN ORAL CANCER
口腔癌中的透明质酸酶和 CD44 变体
基本信息
- 批准号:6336500
- 负责人:
- 金额:$ 10.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-09-21 至 2000-07-31
- 项目状态:已结题
- 来源:
- 关键词:CD44 molecule antineoplastics athymic mouse biomarker disease /disorder model flow cytometry hyaluronate hyaluronidase immunocytochemistry neoplasm /cancer invasiveness neoplastic process oral pharyngeal neoplasm polymerase chain reaction protein isoforms receptor binding squamous cell carcinoma tissue /cell culture
项目摘要
Hyaluronic acid (HA), the predominant glycosaminoglycan on malignant
tumor cells, is bound to the cell surface by its receptor CD44. Levels
of HA correlate with enhanced metastatic behavior, as do certain of the
isoforms of CD44. Human breast cancer cell tumors grown in SCID mice
decrease in size following i.v. hyaluronidase treatment, a 50% decrease
occurring in four days. Brief exposure of cultured breast cancer cells
in vitro to hyaluronidase eliminates not only the cell-associated HA,
but also all of the malignant variants of CD44, leaving only two
"benign" forms, CD44S and CD44E. It is now proposed to develop an animal
model of oral squamous cell carcinoma (OSCC) using human cell lines
grown orthotopically in nude mice, and to determine whether
hyaluronidase can also cause tumor regression in this model.
Simultaneously, coordinated studies using immunohistochemistry, FACS
analyses, and RT-PCR will be performed to document modulation of HA and
CD44 isoforms with hyaluronidase. It is postulated that the enzyme is a
previously unrecognized anticancer therapeutic, that HA stabilizes its
own receptor, and that eradication of HA by hyaluronidase causes down
regulation of CD44 metastatic variant isoforms, thereby causing tumor
regression, and prevention of further cancer spread. Furthermore, it is
suspect that saliva creates an HA-rich environment in the oral cavity,
and underlies the particularly aggressive course of OSCC's.
In conjunction with these studies, levels and localization of HA,
hyaluronidase, CD44, and its isoforms will be documented in an array of
cultured OSCC cells of increasing aggressiveness, as well as in human
biopsy specimens obtained from the oral cancer tissue and histopathology
core. OSCC, comprising the vast majority of oral cancers, metastasizes
widely. The degree of aggressiveness, unlike other human cancers, does
not correlate with the histological appearance. Nor can it be predicted
which patients with dysplasia or leukoplakia will go on to develop OSCC.
The contention of this proposal is that the metabolism of HA is
fundamental to the process of malignant progression, and that among the
parameters measured in this proposal will be those that can function as
predictive and prognostic indicators. Such potential markers will be of
enormous clinical value in identifying not only patients at increased
risk for developing malignancy, but also those with existing lesions
that have particularly aggressive potential.
透明质酸(HA)是恶性肿瘤中的主要糖胺聚糖
肿瘤细胞通过其受体 CD44 与细胞表面结合。级别
HA 的增加与转移行为增强相关,某些
CD44 的亚型。 SCID 小鼠体内生长的人乳腺癌细胞肿瘤
静脉注射后尺寸减小透明质酸酶治疗,减少 50%
发生在四天内。短暂暴露培养的乳腺癌细胞
体外透明质酸酶不仅消除了细胞相关的 HA,
还有 CD44 的所有恶性变体,只留下两个
“良性”形式,CD44S 和 CD44E。现在提议开发一种动物
使用人类细胞系的口腔鳞状细胞癌(OSCC)模型
在裸鼠中原位生长,并确定是否
在此模型中,透明质酸酶还可以导致肿瘤消退。
同时,使用免疫组织化学、FACS 进行协调研究
分析,并进行 RT-PCR 来记录 HA 和
CD44 亚型与透明质酸酶。据推测,该酶是
以前未被认识的抗癌疗法,HA 可以稳定其
自己的受体,并且通过透明质酸酶消除 HA 会导致下降
调节 CD44 转移变异亚型,从而引起肿瘤
消退,并预防癌症进一步扩散。此外,它是
怀疑唾液在口腔中创造了富含透明质酸的环境,
这也是 OSCC 特别激进的做法的基础。
结合这些研究、HA 的水平和定位,
透明质酸酶、CD44 及其亚型将记录在一系列
培养的 OSCC 细胞的攻击性不断增强,以及人类的 OSCC 细胞
从口腔癌组织和组织病理学中获得的活检标本
核。 OSCC 占口腔癌的绝大多数,会发生转移
广泛。与其他人类癌症不同,其侵袭性程度确实
与组织学外观无关。也无法预测
患有异型增生或白斑的患者将继续发展为 OSCC。
该提案的论点是HA的代谢是
恶性进展过程的基础,并且
本提案中测量的参数将是那些可以充当
预测和预后指标。这些潜在的标记将是
不仅在识别增加的患者方面具有巨大的临床价值
发生恶性肿瘤的风险,以及已有病变的风险
具有特别激进的潜力。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
ROBERT STERN其他文献
ROBERT STERN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('ROBERT STERN', 18)}}的其他基金
HYALURONIDASE AND CD44 VARIANTS IN ORAL CANCER
口腔癌中的透明质酸酶和 CD44 变体
- 批准号:
6500415 - 财政年份:2001
- 资助金额:
$ 10.58万 - 项目类别:
FOLLOW-UP STUDY OF PATIENTS RECEIVING ORAL PSORALEN
接受口服补骨脂素治疗的患者的随访研究
- 批准号:
6339734 - 财政年份:2000
- 资助金额:
$ 10.58万 - 项目类别:
HYALURONIDASE AND CD44 VARIANTS IN ORAL CANCER
口腔癌中的透明质酸酶和 CD44 变体
- 批准号:
6471773 - 财政年份:2000
- 资助金额:
$ 10.58万 - 项目类别:
HYALURONIDASE AND CD44 VARIANTS IN ORAL CANCER
口腔癌中的透明质酸酶和 CD44 变体
- 批准号:
6218974 - 财政年份:1999
- 资助金额:
$ 10.58万 - 项目类别:
HYALURONIDASE AND CD44 VARIANTS IN ORAL CANCER
口腔癌中的透明质酸酶和 CD44 变体
- 批准号:
6104932 - 财政年份:1998
- 资助金额:
$ 10.58万 - 项目类别:
HYALURONIDASE AND CD44 VARIANTS IN ORAL CANCER
口腔癌中的透明质酸酶和 CD44 变体
- 批准号:
6270369 - 财政年份:1998
- 资助金额:
$ 10.58万 - 项目类别:
HYALURONIDASE AND CD44 VARIANTS IN ORAL CANCER
口腔癌中的透明质酸酶和 CD44 变体
- 批准号:
6238603 - 财政年份:1997
- 资助金额:
$ 10.58万 - 项目类别:
HYALURONIDASE AND CD44 VARIANTS IN ORAL CANCER
口腔癌中的透明质酸酶和 CD44 变体
- 批准号:
6355568 - 财政年份:1996
- 资助金额:
$ 10.58万 - 项目类别:
ORAL PSORALEN PHOTOCHEMOTHERAPY FOR PSORIASIS--FOLLOWUP
口服补骨脂素光化疗治疗银屑病——随访
- 批准号:
2298427 - 财政年份:1994
- 资助金额:
$ 10.58万 - 项目类别:
ORAL PSORALEN PHOTOCHEMOTHERAPY FOR PSORIASIS--FOLLOWUP
口服补骨脂素光化疗治疗银屑病——随访
- 批准号:
2298430 - 财政年份:1994
- 资助金额:
$ 10.58万 - 项目类别:
相似海外基金
The analysis of proteinuria caused by antineoplastics and the preventative effects with antihypertensive medications using the Japanese medical database
利用日本医学数据库分析抗肿瘤药物引起的蛋白尿及抗高血压药物的预防效果
- 批准号:
21K17258 - 财政年份:2021
- 资助金额:
$ 10.58万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Expediting Drug Development by Profiling Novel Antineoplastics by Mass Spectrometry-based Biomarker Profiling
通过基于质谱的生物标志物分析来分析新型抗肿瘤药物,加速药物开发
- 批准号:
499958-2016 - 财政年份:2016
- 资助金额:
$ 10.58万 - 项目类别:
Engage Grants Program
Combinatorial Peptidomimetics as Antineoplastics
作为抗肿瘤药的组合肽模拟物
- 批准号:
6623455 - 财政年份:2002
- 资助金额:
$ 10.58万 - 项目类别:
Combinatorial Peptidomimetics as Antineoplastics
作为抗肿瘤药的组合肽模拟物
- 批准号:
6465958 - 财政年份:2002
- 资助金额:
$ 10.58万 - 项目类别:
Novel Nanoparticle Delivery System for Antineoplastics
新型抗肿瘤纳米颗粒输送系统
- 批准号:
6483914 - 财政年份:2002
- 资助金额:
$ 10.58万 - 项目类别:
GLYCOLIPIDS AND CYTOTOXIC RESPONSE TO ANTINEOPLASTICS
糖脂和抗肿瘤药物的细胞毒性反应
- 批准号:
6124630 - 财政年份:1998
- 资助金额:
$ 10.58万 - 项目类别:
GLYCOLIPIDS AND CYTOTOXIC RESPONSE TO ANTINEOPLASTICS
糖脂和抗肿瘤药物的细胞毒性反应
- 批准号:
6329037 - 财政年份:1998
- 资助金额:
$ 10.58万 - 项目类别:
GLYCOLIPIDS AND CYTOTOXIC RESPONSE TO ANTINEOPLASTICS
糖脂和抗肿瘤药物的细胞毒性反应
- 批准号:
2747737 - 财政年份:1998
- 资助金额:
$ 10.58万 - 项目类别:
POLYMORPHIC METABOLISM OF ANTINEOPLASTICS IN CHILDREN
儿童抗肿瘤药物的多态性代谢
- 批准号:
3459680 - 财政年份:1990
- 资助金额:
$ 10.58万 - 项目类别:
POLYMORPHIC METABOLISM OF ANTINEOPLASTICS IN CHILDREN
儿童抗肿瘤药物的多态性代谢
- 批准号:
3459678 - 财政年份:1990
- 资助金额:
$ 10.58万 - 项目类别: