Non-Invasive Evaluation of Acute Effects of Tubulin Binding Agents: A Review of Imaging Vascular Disruption in Tumors.
Non-Invasive Evaluation of Acute Effects of Tubulin Binding Agents: A Review of Imaging Vascular Disruption in Tumors.
复制标题
微管蛋白结合剂急性效应的非侵入性评价：肿瘤血管破坏成像的综述。
DOI：
10.3390/molecules26092551
复制
发表时间：
2021-04-27
期刊：
影响因子：
--
通讯作者：
Mason RP
中科院分区：
文献类型：
--
作者：
Liu L;O'Kelly D;Schuetze R;Carlson G;Zhou H;Trawick ML;Pinney KG;Mason RP
肿瘤脉管系统迅速增殖，通常缺乏周细胞覆盖，并且独特地脆弱，使其成为有吸引力的治疗靶标。小分子微管蛋白结合剂的子集引起内皮细胞骨架的解聚，导致血管通透性增强，产生增加的间质压力。由此产生的血管塌陷和缺血引起下游缺氧，最终导致细胞死亡和坏死。因此，局部损伤产生大量扩增和肿瘤破坏。肿瘤血管系统易于进入，并且可能是常见的靶点，而与体内的疾病部位无关。有效的非侵入性测定有利于开发治疗方法，特别是下一代药物。成像技术提供了不同程度的复杂性和易用性。这篇评论认为，从我们自己的实验室的例子技术的优势和劣势。方法揭示了血管的范围和通畅性，以及对组织活力，增殖和坏死的见解。时空分辨率范围从细胞显微镜到单层断层扫描和整个肿瘤的全三维视图，测量可以足够快地揭示急性变化或长期结果。由于成像是非侵入性的，每个肿瘤都可以作为自己的控制，使调查特别有效和严格。肿瘤血管破裂的概念在30多年前提出，并且它仍然是一个活跃的研究领域。
Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely fragile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage generates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular microscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations particularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.
登录
查看更多内容
影响因子：
3.8
作者：
Milanović D;Braun F;Weber W;Grosu AL;Behe M;Niedermann G
通讯作者：
Niedermann G
影响因子：
5.7
作者：
Bohndiek SE;Kettunen MI;Hu DE;Witney TH;Kennedy BW;Gallagher FA;Brindle KM
通讯作者：
Brindle KM
影响因子：
3.3
作者：
Beeman SC;Shui YB;Perez-Torres CJ;Engelbach JA;Ackerman JJ;Garbow JR
通讯作者：
Garbow JR
影响因子：
11.4
作者：
Benezra M;Phillips E;Tilki D;Ding BS;Butler J;Dobrenkov K;Siim B;Chaplin D;Rafii S;Rabbany S;Bradbury MS
通讯作者：
Bradbury MS
影响因子：
4.6
作者：
Abma, Eline;Stock, Emmelie;de Rooster, Hilde
通讯作者：
de Rooster, Hilde