vascular disruption
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2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Dongjie Zhu ◽  
Yang Li ◽  
Zhengjia Zhang ◽  
Zeyu Xue ◽  
Zhenglai Hua ◽  
...  

AbstractTumor vessels can provide oxygen and nutrition for solid tumor tissue, create abnormal tumor microenvironment (TME), and play a vital role in the development, immune escape, metastasis and drug resistance of tumor. Tumor vessel-targeting therapy has become an important and promising direction in anti-tumor therapy, with the development of five anti-tumor therapeutic strategies, including vascular disruption, anti-angiogenesis, vascular blockade, vascular normalization and breaking immunosuppressive TME. However, the insufficient drug accumulation and severe side effects of vessel-targeting drugs limit their development in clinical application. Nanotechnology offers an excellent platform with flexible modified surface that can precisely deliver diverse cargoes, optimize efficacy, reduce side effects, and realize the combined therapy. Various nanomedicines (NMs) have been developed to target abnormal tumor vessels and specific TME to achieve more efficient vessel-targeting therapy. The article reviews tumor vascular abnormalities and the resulting abnormal microenvironment, the application of NMs in the tumor vessel-targeting strategies, and how NMs can improve these strategies and achieve multi-strategies combination to maximize anti-tumor effects. Graphical Abstract


Author(s):  
Yibin Liu ◽  
Fuan Deng ◽  
Rongrong Zheng ◽  
Xiayun Chen ◽  
Linping Zhao ◽  
...  

EBioMedicine ◽  
2021 ◽  
Vol 73 ◽  
pp. 103683
Author(s):  
Vanessa Tran ◽  
Andrea M. Weckman ◽  
Valerie M. Crowley ◽  
Lindsay S. Cahill ◽  
Kathleen Zhong ◽  
...  

2021 ◽  
pp. 109352662110296
Author(s):  
Brittany Ruschkowski ◽  
Ahmed Nasr ◽  
Irina Oltean ◽  
Sarah Lawrence ◽  
Dina El Demellawy

Introduction Gastroschisis is a congenital malformation characterized by intestinal herniation through an abdominal wall defect. Despite its unknown pathogenesis, known risk factors include maternal smoking, alcohol use, and young maternal age. Previous work has shown that gastroschisis is associated with placental delayed villous maturation, and the goal of this study was to assess for additional associated placental pathologies that may help clarify the pathogenesis of gastroschisis. Methods We conducted a retrospective slide review of 29 placentas of neonates with gastroschisis. Additionally, we reviewed pathology reports from one control group of 30 placentas with other congenital malformations. Gross and histological data were collected based on a standardized rubric. Results Gastroschisis was associated with increased placental fetal vascular malperfusion (FVM) in 62% of cases (versus 0% of controls, p < 0.0001). It was also associated with increased placental villous maldevelopment in 76% of cases (versus 3% of controls, p < 0.0001). Conclusion Our study demonstrates an association between gastroschisis and FVM. While FVM could be the consequence of vascular disruption due to the ventral location of gastroschisis, it could also reflect estrogen-induced thrombosis in early pregnancy. Further research is needed to separate these possibilities and determine the cause of the placental FVM observed in gastroschisis.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Seung-hwan Jeong ◽  
Myung Jin Yang ◽  
Seunghyeok Choi ◽  
JungMo Kim ◽  
Gou Young Koh

AbstractStimulator of interferon genes (STING) promotes anti-tumour immunity by linking innate and adaptive immunity, but it remains unclear how intratumoural treatment with STING agonists yields anti-tumour effects. Here we demonstrate that intratumoural injection of the STING agonist cGAMP induces strong, rapid, and selective apoptosis of tumour endothelial cells (ECs) in implanted LLC tumour, melanoma and breast tumour, but not in spontaneous breast cancer and melanoma. In both implanted and spontaneous tumours, cGAMP greatly increases TNFα from tumour-associated myeloid cells. However, compared to spontaneous tumour ECs, implanted tumour ECs are more vulnerable to TNFα-TNFR1 signalling-mediated apoptosis, which promotes effective anti-tumour activity. The spontaneous tumour’s refractoriness to cGAMP is abolished by co-treatment with AKT 1/2 inhibitor (AKTi). Combined treatment with cGAMP and AKTi induces extensive tumour EC apoptosis, leading to extensive tumour apoptosis and marked growth suppression of the spontaneous tumour. These findings propose an advanced avenue for treating primary tumours that are refractory to single STING agonist therapy.


Genetics ◽  
2021 ◽  
Author(s):  
Riddhiman K Garge ◽  
Hye Ji Cha ◽  
Chanjae Lee ◽  
Jimmy D Gollihar ◽  
Aashiq H Kachroo ◽  
...  

Abstract Thiabendazole (TBZ) is an FDA-approved benzimidazole widely used for its antifungal and antihelminthic properties. We showed previously that TBZ is also a potent vascular disrupting agent and inhibits angiogenesis at the tissue level by dissociating vascular endothelial cells in newly formed blood vessels. Here, we uncover TBZ’s molecular target and mechanism of action. Using human cell culture, molecular modeling, and humanized yeast, we find that TBZ selectively targets only 1 of 9 human β-tubulin isotypes (TUBB8) to specifically disrupt endothelial cell microtubules. By leveraging epidemiological pesticide resistance data and mining chemical features of commercially used benzimidazoles, we discover that a broader class of benzimidazole compounds, in extensive use for 50 years, also potently disrupt immature blood vessels and inhibit angiogenesis. Thus, besides identifying the molecular mechanism of benzimidazole-mediated vascular disruption, this study presents evidence relevant to the widespread use of these compounds while offering potential new clinical applications.


2021 ◽  
Author(s):  
Moataz Dowaidar

Customized nanomedicines can be used in a variety of ways, including angiogenesis suppression, vascular disruption, and vascular infarction. In the angiogenesis suppression approach, VEGF, VEGFR, mTOR, EGFR, bFGF, ROS, and other components have become promising therapeutic targets. The nanomedicine system has successfully inhibited tumor neovascularization using gene silencing, chemotherapy, photothermal therapy, and other therapies. In the vascular disruption approach, VDAs supplied by nanomaterials were bonded with the bonding sites of CA4, COL, PTX, and other medications on microtubules to promote rapid disintegration of tumor vascular wall cells. Combining many medicines increased the tumor treatment outcome even more. For example, disruption of tumor blood arteries caused by nanoparticle-mediated physical methods combined with chemotherapy resulted in effective treatment in a large volume tumor model. The vascular infarction methodology uses a variety of carriers, including nanoparticles, DNA nanorobots, platelet membranes, and others, to carry thrombin, tTF, and other drugs to generate local thrombosis and provide safe and effective tumor treatment.


Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2551
Author(s):  
Li Liu ◽  
Devin O’Kelly ◽  
Regan Schuetze ◽  
Graham Carlson ◽  
Heling Zhou ◽  
...  

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.


Author(s):  
li Liu ◽  
Devin O’Kelly ◽  
Regan Schuetze ◽  
Graham Carlson ◽  
Heling Zhou ◽  
...  

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely frag-ile 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 gener-ates 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 mi-croscopy 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 par-ticularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.


2021 ◽  
Vol 14 (1) ◽  
pp. e238392
Author(s):  
Nadira Shahrul Baharin ◽  
Eman Awadh Hashim ◽  
Quek Bin Huey ◽  
Suresh Chandran

A preterm female infant was admitted at birth with respiratory distress. On examination, she had an asymmetric right chest wall and ipsilateral small hand. Air entry was reduced over the right chest. A clinical diagnosis of Poland’s syndrome was made based on the hypoplasia of the right pectoral muscles, absent nipple, deformed ribs and symbrachydactyly of the ipsilateral hand. Chest X-ray suggested and ultrasound confirmed eventration of the right hemidiaphragm. ‘Subclavian artery supply disruption sequence’ (SASDS) theory by Bavnick and Weaver remains the most accepted pathogenic mechanism in Poland’s syndrome. This case reinforces SASDS theory associated with the genesis of Poland’s syndrome that relates to the pathogenicity of vascular disruption of subclavian artery, characteristics of which are unilateral pectoral defects, symbrachydactyly and eventration of the diaphragm. At 2 months, she underwent diaphragm plication. She is under review by our multidisciplinary surgical team for reconstruction of the chest deformity.


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