Targeting Vessels in Tumors

靶向肿瘤血管

• 批准号: 7692222
• 负责人: MARK A TALAMINI
• 金额: $ 271.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-16 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7692222
• 关键词: Targeting; Vessels; Tumors

DESCRIPTION (provided by applicant): This program project grant is designed to integrate the activities of 4 projects and 4 core facilities toward potentiating the overall goal of this PPG which is to discover selective tumor vascular targets and to develop and test tumor vascular targeting agents for cancer treatment. Each of the projects involves a strategy designed to target vessels associated with solid cancer tissue. Studies which have been carried out to date reveal that the cell surface of blood vessels associated with tumor tissue contain proteins which are not found on the surface of vessels of normal tissues. These differences may be caused by angiogenic and other trophic factors that are released by tumor cells in the vicinity of the endothelial cells and that induce proliferation of the endothelial cells with poor vessel remodeling. The cancer center has developed a unique concentration of investigators avidly interested in tumor vascular biology and dedicated to translating lab bench discoveries to clinical applications at the patient's bedside. Targeting of the tumor vasculature can accomplish two very important goals by generating: i) a new and more sensitive imaging diagnostic tool for the early detection of cancer and ii) a new modality of site-directed therapy for cancer that permits better access and effectiveness in vivo and that avoids the evolution of resistance. In addition to these applied goals, this program project grant will deepen our understanding of the mechanisms in the tumor neovasculature governing drug efficacy, induction of apoptosis, caveolae function, and proliferation of endothelial cells. The integration of the projects and the cores is designed not only to demonstrate the specificity of the binding of tumor-homing peptides, proteins and antibodies to the endothelial cell surface of the tumor vasculature, but also to understand what are the cell biological events which occur following binding including possible trafficking into the endothelium and beyond to the tumor cells as well as the mechanisms by which tumor cell death and vessel occur following binding. The cores provide an unique opportunity to utilize total body imaging to track targeting in vivo, intravital microscopy to study mechanisms and specificity at the tissue level, and light, fluorescence confocal and electron microscopy to define target localization and to follow probes directed to, and incorporated into, the tumor at the cellular and subcellular level. The administrative core will promote the integration of the projects and cores over 3 local institutions: SKCC, The Scripps Research Institute, and The Burnham Institute in San Diego as well as Yale University School of Medicine in New Haven, CI. The integrative potentiation of each project may lead to new strategies, including single and combined therapies for clinical translation in the future.

描述（由申请人提供）：该计划项目赠款旨在整合4个项目和4个核心设施的活动，以增强该PPG的整体目标，即发现选择性肿瘤血管靶标，并开发和测试肿瘤血管靶向剂进行癌症治疗。 每个项目都涉及旨在针对与固体癌组织相关的血管的策略。 迄今已进行的研究表明，与肿瘤组织相关的血管的细胞表面含有在正常组织血管表面未发现的蛋白质。 这些差异可能是由肿瘤细胞在内皮细胞附近释放的血管生成和其他营养因子引起的，并通过较差的血管重塑诱导内皮细胞的增殖。 癌症中心已经开发了对肿瘤血管生物学感兴趣的独特研究人员，并致力于将实验室长凳发现转化为患者床边的临床应用。 靶向肿瘤脉管系统可以通过产生以下方式实现两个非常重要的目标：i）一种新的，更敏感的成像诊断工具，用于早期癌症和ii）癌症现场指导的疗法的新方式，可以在体内更好地进入和有效性，并避免抗药性的演变。除了这些应用目标外，该计划项目赠款还将加深我们对有关药物疗效，凋亡诱导，小窝功能和内皮细胞增殖的肿瘤新生血管内机制的理解。 项目和核心的整合不仅旨在证明肿瘤共肽，蛋白质和抗体与肿瘤脉管系统的内皮细胞表面的结合的特异性，而且还了解细胞生物学事件是什么是发生在肿瘤中的结合，包括在肿瘤中的结合以及肿瘤的结合，以及发生在肿瘤中的结合，以及随后发生的肿瘤及其及其及其机制的结合。 这些核心提供了一个独特的机会，可以利用总体成像来跟踪靶向靶向体内的靶向，在组织水平上研究机制和特异性，以及光，荧光共焦和电子显微镜来定义目标定位，并遵循针对细胞和亚细胞层的探针，并掺入细胞和肿瘤。 行政核心将促进3个本地机构的项目和核心的整合：SKCC，SCRIPPS研究所和圣地亚哥的Burnham Institute以及CI纽黑文的耶鲁大学医学院。 每个项目的综合增强性可能会导致新的策略，包括将来的临床翻译单一和联合疗法。

项目成果

Range Charts for Agreement in Measurement Comparison Studies, With Application to Replicate Mass Spectrometry Experiments.

测量比较研究中协议的范围图，并应用于重复质谱实验。

• DOI: 10.4172/jpb.1000036
• 发表时间: 2008
• 期刊: Journal of proteomics & bioinformatics
• 作者: Koziol,JamesA;Feng,AnneC;Yu,Jingyi;Griffin,NoelleM;Schnitzer,JanE
• 通讯作者: Schnitzer,JanE

Lessons from the Past: Methodological Issues Arising from Comparison of the Disease Burden of the Influenza A (H1N1) Pandemic 2009-10 and Seasonal Influenza 2010-2019 in the United States.

过去的教训：美国 2009-10 年甲型 H1N1 流感大流行和 2010-2019 年季节性流感疾病负担比较所产生的方法学问题。

• DOI: 10.23937/2474-3658/1510218
• 发表时间: 2021
• 期刊: Journal of infectious diseases and epidemiology
• 作者: Koziol,JamesA;Schnitzer,JanE
• 通讯作者: Schnitzer,JanE

Targeting of albumin-embedded paclitaxel nanoparticles to tumors.

• DOI: 10.1016/j.nano.2008.07.007
• 发表时间: 2009-03
• 期刊: NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
• 影响因子: 5.4
• 作者: Karmali, Priya Prakash;Kotamraju, Venkata Ramana;Kastantin, Mark;Black, Matthew;Missirlis, Dimitris;Tirrell, Matthew;Ruoslahti, Erkki
• 通讯作者: Ruoslahti, Erkki

III. Cellular ultrastructures in situ as key to understanding tumor energy metabolism: biological significance of the Warburg effect.

• DOI: 10.12688/f1000research.2-10.v1
• 发表时间: 2013
• 期刊: F1000Research
• 作者: Witkiewicz H;Oh P;Schnitzer JE
• 通讯作者: Schnitzer JE

The rank product method with two samples.

• DOI: 10.1016/j.febslet.2010.10.012
• 发表时间: 2010-11-05
• 期刊: FEBS letters
• 影响因子: 3.5
• 作者: Koziol JA