患者来源的肿瘤干细胞异种移植物作为个体化胰腺癌研究的临床前模型。

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Benedikt J Wagner, Andreas Ettner-Sitter, Nicolas A Ihlo, Merle Behr, Sebastian Koelbl, Stefan M Brunner, Florian Weber, Bettina M Rau, Hans J Schlitt, Christoph Brochhausen, Rebecca Schoenmehl, Annalena Artinger, Dorothea Schott, Monika Pizon, Katharina Pachmann, Thiha Aung, Silke Haerteis, Christina Hackl
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引用次数: 0

摘要

患者源性异种移植物(PDXs)为胰腺癌精准医学治疗策略的发展提供了生物学相关模型和潜在平台。此外,循环上皮肿瘤细胞(CETCs/ ctc)被实体肿瘤释放到血液中,一种罕见的亚群-循环癌症干细胞(cCSCs) -被认为是导致复发的原因,并在转移中起关键作用。为了鉴定cCSCs,本研究建立了一种创新的体外肿瘤球生成实验。分析了25例胰腺癌患者围手术期肿瘤球数和癌细胞/癌细胞数。此外,使用个体体内绒毛膜尿囊膜(CAM)培养系统从这些肿瘤球中产生pdx。虽然ctc / ctc与临床病理参数的总体相关性没有达到统计学意义,但在UICC分期较低和较高的患者亚组之间,肿瘤球数存在显著差异。这一发现强调了它们作为生物标志物的潜力,为临床决策和肿瘤进展提供了有价值的见解。肿瘤球在CAM上的应用在7天内成功建立了pdx。这些异种移植物与原发肿瘤的组织学特征非常相似。因此,该模型代表了PDAC新疗法个性化测试的一种新颖而快速的选择。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Patient-derived xenografts from circulating cancer stem cells as a preclinical model for personalized pancreatic cancer research.

Patient-derived xenografts (PDXs) provide biologically relevant models and potential platforms for the development of treatment strategies for precision medicine in pancreatic cancer. Furthermore, circulating epithelial tumor cells (CETCs/CTCs) are released into the bloodstream by solid tumors and a rare subpopulation-circulating cancer stem cells (cCSCs) - is considered to be responsible for recurrence and plays a key role in metastasis. For the identification of cCSCs, an innovative in vitro assay to generate tumorspheres was established in this study. The number of tumorspheres and CETCs/CTCs was analyzed perioperatively in 25 pancreatic cancer patients. Additionally, an individual in vivo chorioallantoic membrane (CAM) culture system was used to generate PDXs from these tumorspheres. While overall correlations of CETCs/CTCs with clinicopathological parameters did not reach statistical significance, a significant difference in the number of tumorspheres was observed between patient subgroups with lower and higher UICC stages. This finding underscores their potential as biomarkers, providing valuable insights into clinical decision-making and tumor progression. The application of tumorspheres on the CAM successfully established PDXs within 7 days. These xenografts closely resembled the histological features of the primary tumor. Hence, this model represents a novel and fast option for individualized testing of new therapies for PDAC.

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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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