摘要

Metastasis is a major cause of cancer-related deaths. A dearth of preclinical models that recapitulate the metastatic microenvironment has impeded the development of therapeutic agents that are effective against metastatic disease. Because the majority of solid tumors metastasize to the lung, we developed a multicellular lung organoid that mimics the lung microenvironment with air sac-like structures and production of lung surfactant protein. We used these cultures, called primitive lung-in-a-dish (PLiD), to recreate metastatic disease using primary and established cancer cells. The metastatic tumor-in-a-dish (mTiD) cultures resemble the architecture of metastatic tumors in the lung, including angiogenesis. Pretreating PLiD with tumor exosomes enhanced cancer cell colonization. We next tested the response of primary and established cancer cells to current chemotherapeutic agents and an anti-VEGF antibody in mTiD against cancer cells in two-dimensional (2D) or 3D cultures. The response of primary patient-derived colon and ovarian tumor cells to therapy in mTiD cultures matched the response of the patient in the clinic, but not in 2D or single-cell-type 3D cultures. The sensitive mTiD cultures also produced significantly lower circulating markers for cancer similar to that seen in patients who responded to therapy. Thus, we have developed a novel method for lung colonization in vitro, a final stage in tumor metastasis. Moreover, the technique has significant utility in precision/personalized medicine, wherein this phenotypic screen can be coupled with current DNA pharmacogenetics to identify the ideal therapeutic agent, thereby increasing the probability of response to treatment while reducing unnecessary side effects. SIGNIFICANCE: A lung organoid that exhibits characteristics of a normal human lung is developed to study the biology of metastatic disease and therapeutic intervention.

译文

转移是癌症相关死亡的主要原因。缺乏概括转移微环境的临床前模型阻碍了对转移性疾病有效的治疗药物的开发。因为大多数实体肿瘤转移到肺部,我们开发了一种多细胞的肺部器官样物,它通过气囊样结构和肺表面活性蛋白的产生来模拟肺部微环境。我们使用这些被称为原始盘中肺 (PLiD) 的培养物,利用原代和已建立的癌细胞来重建转移性疾病。培养皿中的转移性肿瘤 (mTiD) 培养类似于肺部转移性肿瘤的结构,包括血管生成。用肿瘤 exosomes 预处理 PLiD 可增强癌细胞定植。我们接下来在二维 (2D) 或三维培养物中测试了原代和已建立的癌细胞对当前化疗药物和 mTiD 中抗 VEGF 抗体对癌细胞的反应。原发性患者来源的结肠和卵巢肿瘤细胞对 mTiD 培养物治疗的反应与患者在临床上的反应相匹配,但在 2D 或单细胞类型的 3D 培养物中没有。敏感的 mTiD 培养物也产生了与对治疗有反应的患者相似的显著较低的癌症循环标志物。因此,我们开发了一种新的体外肺定植方法,这是肿瘤转移的最后阶段。此外,该技术在精准/个性化医学中具有显著效用,其中该表型筛选可以与当前的 DNA 药物遗传学相结合,以确定理想的治疗剂, 从而增加治疗反应的概率,同时减少不必要的副作用。意义: 一种具有正常人类肺特征的肺类器官被开发用于研究转移性疾病的生物学和治疗干预。

Metastatic tumor

骨科 肿瘤 临床研究术语
概述  :  

随着医学技术的发展,肿瘤患者生存期逐渐延长,临床骨转移瘤患者随之增多,5%-10%恶性肿瘤患者存在椎体转移。一旦骨转移引起疼痛、骨折、不稳定或脊柱神经损害等,可能需要放射治疗或介入治疗。病因及解剖基础血流丰富:癌细胞的转移,常常发生在血流丰富而缓慢的地方,例如脑部、肺部、肝脏及骨骼。骨骼内部的骨髓负责身体内的造血功能,特别是红骨髓,因此骨头内部的血流量是非常惊人的。癌细胞喜欢骨头。对于癌细胞来说,骨骼内丰富的血流量及旺盛的生长因子,也会让癌细胞觉得比较舒适。所以,当癌细胞随着血液流经骨髓内时

metastatic 英 /,metə'stætɪk/  美 /,mɛtə'stætɪk/    

释义   adj. (癌细胞的)转移性的;变形的;新陈代谢的

例句   Some research shows that only about 25% of newly discovered metastatic breast cancer patients live for 5 years. 有些研究表明只有大约25%初期的已经转移的乳腺癌患者可以生存5年。

 

tumor 英 /'tju:mə(r)/  美 /'tjʊmɚ/     

释义   n. 肿瘤;肿块;赘生物

例句   So anti-angiogenesis will be an efficient method in the inhibition of the growth and metastasis of tumor. 所以抗血管生成药将是一种很有希望的对抑制肿瘤生长和转移的有效方法。


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