Second Harmonic Generation imaging and optical scattering probes of ovarian cancer.

卵巢癌的二次谐波成像和光学散射探针。

基本信息

  • 批准号:
    1402757
  • 负责人:
  • 金额:
    $ 41.08万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2014
  • 资助国家:
    美国
  • 起止时间:
    2014-05-01 至 2019-04-30
  • 项目状态:
    已结题

项目摘要

Proposal Number: 1402757P.I.: Campagnola, Paul J.Title: Second Harmonic Generation imaging and optical scattering probes of ovarian cancerSignificance and Importance of Project:Five year survival rates of ovarian cancer remain poor (~30%), where this arises in part due to inadequate screening technologies as well as poor understanding of how cancer cells interact with the host tissue. There remains a compelling need for new technologies that have both sufficient resolution and specificity to image microscopic malignant ovarian tumors or precursor lesions. It is also equally important to understand how these changes occur and how they evolve between early stage and advanced disease. This project will develop new microscope-based methods that address these needs. The methods to be developed will be applicable to other cancers as well.Technical Description of the ProjectIt is important to understand the changes that occur in the extracellular matrix (ECM) in the tumor microenvironment in ovarian cancer and how these evolve between early stage and advanced disease and between disease grades (e.g. borderline vs high grade). In this project, we will implement multimodal forms of Second Harmonic Generation (SHG) microscopy with optical scattering measurements to address this need by characterizing macromolecular changes in collagen and also in the 3D fibrillar architecture. The methods will i) compliment histology which primarily focuses on cells, where a non-negligible fraction of tissues are mis-classified; ii) provide prognostic information based on ECM changes from other patients; and iii) afford the development of an ex vivo or ultimately in vivo imaging/screening device of either ovaries or fallopian tubes. SHG has already been shown to be a highly sensitive and specific imaging tool for quantitatively describing changes in the collagen organization in several diseases, including many cancers, fibroses, and connective tissue disorders. This success is due to the coherent nature of the process where detailed information on fibrillar assembly can be obtained through analysis of morphology, polarization properties, and emission directionality. Similarly, optical scattering measurements have proven to be powerful for delineating cancers from normal tissue in several organs. We will now leverage our previous results on ex vivo human ovarian tissues and develop new tools to further understand changes in the collagen architecture, both in terms of collagen macromolecular assembly and 3D fibrillar organization. These are both important considerations as: i) we have demonstrated that dramatic morphological changes occur between normal and high grade malignant tissues, and ii) it has been reported that several minor isoforms become up-regulated in ovarian cancer and these may be effective biomarkers. We will also interrogate the collagen fibrillar architecture using SHG and optical scattering probes, separately and in conjunction and will compare remodeling across a spectrum of ovarian cancer types (e.g. serous vs endometroid, high grade vs low grade, fallopian tube vs primary ovary) as well as primary vs metastatic tumors. Measuring the wavelength dependences of optical scattering and SHG will provide detailed structural information across different length scales and delineate different tumor types based on their structural characteristics. To this end, a classification system based on the collagen molecular changes and fibrillar architecture alterations will be developed. Key to this work is the development of a suite of new label free SHG polarization analyses to specifically probe changes in collagen molecular alignment within fibrils, the á-helix pitch angle, and the overall chirality of the collagen triple helix. All these properties can change due to increased protease activity or changes in collagen isoform incorporation (e.g. Col III) in carcinogenesis and tumor growth. These will be benchmarked in self-assembled fibrillar gels that mimic the collagen assembly in the ovarian stroma and extended to ex vivo human tissues. In sum, this project will develop tools that probe all levels of collagen organization and will serve as new label-free biomarkers for ovarian cancer. Moreover, these methods will be generally applicable to other cancers and diseases characterized by changes in collagen architecture.
提案编号:1402757 P.I.:坎帕尼奥拉,保罗·J。标题:卵巢癌的二次谐波成像和光学散射探针项目的意义和重要性:卵巢癌的五年生存率仍然很低(~30%),部分原因是由于筛查技术不足以及对癌细胞如何与宿主组织相互作用的理解不足。 仍然迫切需要具有足够分辨率和特异性的新技术来成像显微镜下的恶性卵巢肿瘤或前驱病变。同样重要的是要了解这些变化是如何发生的,以及它们是如何在早期和晚期疾病之间演变的。该项目将开发新的基于显微镜的方法来满足这些需求。该项目的技术说明了解卵巢癌肿瘤微环境中细胞外基质(ECM)的变化以及这些变化在早期和晚期疾病之间以及疾病等级之间(例如边界与高等级)的演变是很重要的。 在这个项目中,我们将实施多模态形式的二次谐波发生(SHG)显微镜与光学散射测量,以满足这一需求,通过表征胶原蛋白和3D纤维结构中的大分子变化。所述方法将i)补充主要集中于细胞的组织学,其中不可忽略的组织部分被错误分类; ii)基于来自其他患者的ECM变化提供预后信息;和iii)提供卵巢或输卵管的离体或最终体内成像/筛选装置的开发。 SHG已经被证明是一种高度敏感和特异的成像工具,用于定量描述多种疾病(包括许多癌症、纤维化和结缔组织疾病)中胶原组织的变化。这一成功是由于该过程的连贯性,其中通过分析形态、偏振特性和发射方向性可以获得关于原纤组装的详细信息。同样,光学散射测量已被证明是强大的描绘癌症从正常组织在几个器官。我们现在将利用我们以前对离体人类卵巢组织的研究结果,并开发新的工具来进一步了解胶原蛋白结构的变化,包括胶原蛋白大分子组装和3D纤维组织。这些都是重要的考虑因素,因为:i)我们已经证明了在正常和高度恶性组织之间发生显著的形态学变化,和ii)已经报道了几种次要的同种型在卵巢癌中上调,并且这些可能是有效的生物标志物。 我们还将使用SHG和光学散射探针分别和联合询问胶原纤维结构,并将比较卵巢癌类型(例如浆液性与子宫内膜样,高级别与低级别,输卵管与原发性卵巢)以及原发性与转移性肿瘤的重塑。 测量光散射和SHG的波长依赖性将提供不同长度尺度上的详细结构信息,并根据其结构特征描绘不同的肿瘤类型。 为此,将开发基于胶原分子变化和纤维结构改变的分类系统。 这项工作的关键是开发一套新的无标记SHG偏振分析,以特异性地探测原纤维内胶原分子排列、α-螺旋螺距角和胶原三螺旋的整体手性的变化。 所有这些性质都可能由于蛋白酶活性的增加或致癌和肿瘤生长中胶原异构体掺入(例如Col III)的变化而发生变化。这些将在自组装纤维凝胶中进行基准测试,该自组装纤维凝胶模拟卵巢基质中的胶原蛋白组装并延伸至离体人体组织。 总之,该项目将开发探测所有水平胶原组织的工具,并将作为卵巢癌的新的无标记生物标志物。此外,这些方法通常适用于以胶原结构变化为特征的其他癌症和疾病。

项目成果

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Paul Campagnola其他文献

P4. Poorly structured bone matrix, reminiscent of an “osteoblastic” lesion, promotes an aggressive gene expression profile in prostate carcinoma cells in vitro
  • DOI:
    10.1016/j.ctrv.2008.03.045
  • 发表时间:
    2008-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Anne Delany;Katherine Lowther;Kristen Kapinas;Catherine Kessler;Oleg Nadiarnykh;Paul Campagnola
  • 通讯作者:
    Paul Campagnola

Paul Campagnola的其他文献

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{{ truncateString('Paul Campagnola', 18)}}的其他基金

3D analysis of collagen alterations in idiopathic pulmonary fibrosis by Second Harmonic Generation Excitation and Emission Tomography
通过二次谐波产生激发和发射断层扫描对特发性肺纤维化中的胶原蛋白变化进行 3D 分析
  • 批准号:
    2203403
  • 财政年份:
    2022
  • 资助金额:
    $ 41.08万
  • 项目类别:
    Standard Grant
EAGER: Development of 3D Second Harmonic Generation Tomography and Deep Learning Algorithms for Classification of Human Ovarian Cancer
EAGER:开发用于人类卵巢癌分类的 3D 二次谐波生成断层扫描和深度学习算法
  • 批准号:
    1830964
  • 财政年份:
    2018
  • 资助金额:
    $ 41.08万
  • 项目类别:
    Standard Grant
MRI: Development of Multiscale Imaging Platform for Quantitative Analysis of Collagen Organization
MRI:开发用于胶原组织定量分析的多尺度成像平台
  • 批准号:
    1429045
  • 财政年份:
    2014
  • 资助金额:
    $ 41.08万
  • 项目类别:
    Standard Grant
Optical imaging studies of ovarian epithelial cell migration and invasion using microfabricated models of the extracellular matrix
使用细胞外基质微制造模型进行卵巢上皮细胞迁移和侵袭的光学成像研究
  • 批准号:
    1057766
  • 财政年份:
    2010
  • 资助金额:
    $ 41.08万
  • 项目类别:
    Standard Grant
MRI-R2: Development of an long wavelength nonlinear optical microscope for harmonic and autofluorescence imaging of biological tissues
MRI-R2:开发用于生物组织谐波和自发荧光成像的长波长非线性光学显微镜
  • 批准号:
    0959525
  • 财政年份:
    2010
  • 资助金额:
    $ 41.08万
  • 项目类别:
    Standard Grant
Optical imaging studies of ovarian epithelial cell migration and invasion using microfabricated models of the extracellular matrix
使用细胞外基质微制造模型进行卵巢上皮细胞迁移和侵袭的光学成像研究
  • 批准号:
    0853949
  • 财政年份:
    2009
  • 资助金额:
    $ 41.08万
  • 项目类别:
    Standard Grant
SGER: Biophotonics: Nanoscale Fabrication of Tissue Engineering Scaffolds by Stimulated Emission Depletion Microscopy
SGER:生物光子学:通过受激发射损耗显微镜纳米级制造组织工程支架
  • 批准号:
    0630545
  • 财政年份:
    2006
  • 资助金额:
    $ 41.08万
  • 项目类别:
    Standard Grant

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3D analysis of collagen alterations in idiopathic pulmonary fibrosis by Second Harmonic Generation Excitation and Emission Tomography
通过二次谐波产生激发和发射断层扫描对特发性肺纤维化中的胶原蛋白变化进行 3D 分析
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