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建立患者来源的原位异种移植(PDX)模型用于胰腺导管腺癌。

Establishment of Patient-derived Orthotopic Xenografts (PDX) as Models for Pancreatic Ductal Adenocarcinoma.

机构信息

Department of Cardiothoracic Surgery, University of Thessaly, Biopolis, Larissa, Greece.

Department of Pharmacology, University of Thessaly, Biopolis, Larissa, Greece.

出版信息

In Vivo. 2022 May-Jun;36(3):1114-1119. doi: 10.21873/invivo.12809.

Abstract

BACKGROUND/AIM: Pancreatic cancer (PC) is one of the leading causes of cancer-related death. The purpose of the present study was to establish a patient-derived orthotopic xenograft model (PDOX) for pancreatic ductal adenocarcinoma (PDAC), thus providing a tumor microenvironment resembling that of the human pancreas to identify novel potential biomarkers and treatment regimens.

MATERIALS AND METHODS

PDAC tissue samples were received from 35 patients, following informed consent, and three mouse strains were implemented.

RESULTS

Successful PDOX engraftment was performed in nonobese diabetic/severe combined immunodeficient (NOD/SCID) and NOD/SCID gamma (NSG) mice. Nonetheless, we found a higher rate of successful engraftment and tumor growth in NSG compared to NOD/SCID mice, possibly owning to the different level of immunosuppression and more specifically of the natural killer cells presence.

CONCLUSION

Our suggested PDOX model represents a preclinical cancer research model with a high affinity for the patient's tumor microenvironment, thus enabling the acceleration of PDAC research.

摘要

背景/目的:胰腺癌(PC)是癌症相关死亡的主要原因之一。本研究的目的是建立胰腺导管腺癌(PDAC)的患者来源的原位异种移植模型(PDOX),从而提供类似于人类胰腺的肿瘤微环境,以鉴定新的潜在生物标志物和治疗方案。

材料和方法

从 35 名患者获得 PDAC 组织样本,并在知情同意后使用了三种小鼠品系。

结果

在非肥胖型糖尿病/重症联合免疫缺陷(NOD/SCID)和 NOD/SCID 伽马(NSG)小鼠中成功进行了 PDOX 移植。然而,我们发现 NSG 小鼠中的移植成功率和肿瘤生长率高于 NOD/SCID 小鼠,这可能归因于不同程度的免疫抑制,特别是自然杀伤细胞的存在。

结论

我们提出的 PDOX 模型代表了一种具有高亲和力的患者肿瘤微环境的临床前癌症研究模型,从而加速了 PDAC 的研究。

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The cancer-inhibitory effects of proliferating tumor-residing fibroblasts.增殖性肿瘤驻留成纤维细胞的抑癌作用。
Biochim Biophys Acta Rev Cancer. 2022 Jan;1877(1):188673. doi: 10.1016/j.bbcan.2021.188673. Epub 2021 Dec 22.

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