从血管肉瘤患者体内生成肉瘤瘤体,作为一种以系统为基础的合理治疗方法。

IF 29.5 1区 医学 Q1 HEMATOLOGY
Da Jung Jung, Jae Hee Byeon, Young Chul Kim, Woo Shik Jeong, Jong-Woo Choi, Gi Seok Jeong
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引用次数: 0

摘要

血管肉瘤是一种源自血管或淋巴内皮细胞的罕见亚型恶性肿瘤;其低发病率为通过体外和体内模型全面研究其发病机制和开发创新治疗模式带来了重大挑战。最近,由患者参与的研究计划旨在利用生物全息方法阐明血管肉瘤的复杂性,其首要目标是增强这种不常见病理的预后指标和治疗方案。为了缩小临床前研究与转化应用之间的差距,我们从手术切除的原发肿瘤中提取了血管肉瘤衍生有机体(以下简称 "sarconoids"),作为概念验证模型。我们开发并验证了建立这些肉瘤的新方案。为确保sarconoids忠实再现患者原始肿瘤的异质性和复杂性,包括转录组特征、细胞类型特异性和形态特征,我们进行了详尽的组织学和转录组分析。随后,我们扩大了研究范围,纳入了对基于肉毒杆菌的药物筛选平台的评估;为此,我们使用 96 孔板筛选了由美国国家癌症研究所开发治疗项目提供的药物库(AOD IX)。我们的研究结果表明,肉瘤可以从血管肉瘤患者的组织中可靠地生成,并可作为评估治疗反应的精确模型,从而对转化研究和临床应用产生深远影响,旨在促进我们对血管肉瘤的了解和治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Generation of sarconoids from angiosarcoma patients as a systematic-based rational approach to treatment.

Angiosarcoma is a rare subtype of malignant neoplasm originating from vascular or lymphatic endothelial cells; its low incidence has posed significant challenges for comprehensive investigations into its pathogenic mechanisms and the development of innovative treatment modalities through in vitro and in vivo models. Recent endeavors spearheaded by patient-partnered research initiatives have aimed to elucidate the intricacies of angiosarcomas by leveraging biological omics approaches, with the overarching objective of enhancing prognostic indicators and therapeutic options for this uncommon pathology. To bridge the gap between preclinical research and translational applications, we engineered angiosarcoma-derived organoids from surgically resected primary tumors, hereafter referred to as "sarconoids," as a proof-of-concept model. A novel protocol for the establishment of these sarconoids has been developed and validated. To ensure that the sarconoids faithfully recapitulate the heterogeneity and complexities of the patients' original tumors, including transcriptomic signatures, cell-type specificity, and morphological traits, exhaustive histological and transcriptomic analyses were conducted. Subsequently, we expanded the scope of our study to include an evaluation of a sarconoid-based drug screening platform; for this purpose, a drug library (AOD IX), supplied by the National Cancer Institute's Developmental Therapeutics Program, was screened using 96-well plates. Our findings suggest that sarconoids can be reliably generated from angiosarcoma patient-derived tissues and can serve as accurate models for evaluating therapeutic responses, thereby holding far-reaching implications for translational research and clinical applications aimed at advancing our understanding and treatment of angiosarcoma.

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来源期刊
CiteScore
48.10
自引率
2.10%
发文量
169
审稿时长
6-12 weeks
期刊介绍: The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts. Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.
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