Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective

Published on Mar 9, 2021in Cancers6.126
· DOI :10.3390/CANCERS13051182
Luca Possenti4
Estimated H-index: 4
(Polytechnic University of Milan),
Laura Mecchi + 8 AuthorsMatteo Moretti30
Estimated H-index: 30
Sources
Abstract
Ionizing radiation (IR) is used in radiotherapy as a treatment to destroy cancer. Such treatment also affects other tissues, resulting in the so-called normal tissue complications. Endothelial cells (ECs) composing the microvasculature have essential roles in the microenvironment’s homeostasis (ME). Thus, detrimental effects induced by irradiation on ECs can influence both the tumor and healthy tissue. In-vitro models can be advantageous to study these phenomena. In this systematic review, we analyzed in-vitro models of ECs subjected to IR. We highlighted the critical issues involved in the production, irradiation, and analysis of such radiobiological in-vitro models to study microvascular endothelial cells damage. For each step, we analyzed common methodologies and critical points required to obtain a reliable model. We identified the generation of a 3D environment for model production and the inclusion of heterogeneous cell populations for a reliable ME recapitulation. Additionally, we highlighted how essential information on the irradiation scheme, crucial to correlate better observed in vitro effects to the clinical scenario, are often neglected in the analyzed studies, limiting the translation of achieved results.
References157
Newest
#1Hyun Jung Hwang (IIT: Inha University)H-Index: 8
#2Ye Rim Lee (IIT: Inha University)H-Index: 1
Last. Jae Seon Lee (IIT: Inha University)H-Index: 27
view all 10 authors...
Abstract The effects of senescence associated secretory phenotype (SASP) from therapy-induced senescent endothelial cells on tumor microenvironment (TME) remains to be clarified. Here, we investigated effects of ionizing radiation (IR)- and doxorubicin-induced senescent HUVEC on TME. MDA-MB-231 cancer cells treated with conditioned medium (CM) from senescent HUVEC or co-cultured with senescent HUVEC significantly increased cancer cell proliferation, migration, and invasion. We found that CXCL11 ...
5 CitationsSource
FLASH radiotherapy is the delivery of ultra-high dose rate radiation several orders of magnitude higher than what is currently used in conventional clinical radiotherapy, and has the potential to revolutionize the future of cancer treatment. FLASH radiotherapy induces a phenomenon known as the FLASH effect, whereby the ultra-high dose rate radiation reduces the normal tissue toxicities commonly associated with conventional radiotherapy, while still maintaining local tumor control. The underlying...
6 CitationsSource
#1Yolande Lievens (Ghent University Hospital)H-Index: 40
#2Josep M. Borràs (University of Barcelona)H-Index: 42
Last. Cai Grau (Aarhus University Hospital)H-Index: 62
view all 3 authors...
Radiation therapy is one of the core components of multidisciplinary cancer care. Although approximately 50% of all European cancer patients have an indication for radiotherapy at least once in the course of their disease, more than one out of four cancer patients in Europe do not receive the radiotherapy they need. There are multiple reasons for this underutilisation, with limited availability of the necessary resources - in terms of both trained personnel and equipment - being a major underlyi...
8 CitationsSource
#1Verena Ziegler (HHU: University of Düsseldorf)H-Index: 4
#2Marco Deußen (HHU: University of Düsseldorf)H-Index: 1
Last. Gerhard Fritz (HHU: University of Düsseldorf)H-Index: 15
view all 5 authors...
Abstract The endothelium contributes to the pathophysiology of adverse effects caused by conventional (genotoxic) anticancer therapeutics (cAT). The relevance of structurally different types of cAT-induced DNA lesions for eliciting selected endothelial stress responses is largely unknown. Here, we analyzed the cAT-induced formation of DNA double-strand breaks (DSB), transcription blockage and DNA damage response (DDR) in time kinetic analyses employing a monolayer of primary human endothelial ce...
2 CitationsSource
#1Qibing Wu (Anhui Medical University)H-Index: 1
#2Yang Fang (Anhui Medical University)H-Index: 3
Last. Bing Shen (Anhui Medical University)H-Index: 14
view all 9 authors...
Radiation-induced brain edema is a serious adverse effect of radiotherapy. Although there are many causes of radiation-induced brain edema, the pathogenesis is not clear and clinical treatment is not ideal. Therefore, knowing the differential expression of the BMEC transcriptome after brain radiotherapy may shed light on the pathogenesis of radiation-induced brain edema. This study used RNA-Seq techniques to identify 383 BMEC transcripts differentially expressed (many twofold or higher; P< 0.05)...
2 CitationsSource
#1Shu Chen (JLU: Jilin University)H-Index: 2
#2Qian Wang (JLU: Jilin University)H-Index: 2
Last. Zhihui Liu (JLU: Jilin University)H-Index: 3
view all 8 authors...
Combined radiation-wound injury (CRWI) is characterized by blood vessel damage and pro-inflammatory cytokine deficiency. Studies have identified that the direct application of leptin plays a significant role in angiogenesis and inflammation. We established a sustained and stable leptin expression system to study the mechanism. A lentivirus method was employed to explore the angiogenic potential and peripheral inflammation of irradiated human umbilical vein endothelial cells (HUVECs). Leptin was ...
1 CitationsSource
#1Zhimin Zeng (NCU: Nanchang University)H-Index: 2
#2Hai-yang Du (NCU: Nanchang University)H-Index: 1
Last. Anwen Liu (NCU: Nanchang University)H-Index: 8
view all 8 authors...
Abstract Aims Microvascular endothelial cell dysfunction is a leading cause of radiation-induced heart disease (RIHD). BRCA1 plays an important role in DNA damage repair. The study aims to explore the effect of BRCA1 in endothelial cells involved in RIHD. Materials and methods BRCA1 and p21 expression were detected in human umbilical vein endothelial cells (HUVECs) and in mouse heart tissue after irradiation exposure. The effects of BRCA1 on cell proliferation, cell cycle and radiosensitivity we...
3 CitationsSource
#1Joseph D. Wilson (University of Oxford)H-Index: 3
#2Ester M. HammondH-Index: 10
Last. Kristoffer Petersson (University of Oxford)H-Index: 14
view all 4 authors...
Radiotherapy is a cornerstone of both curative and palliative cancer care. However, radiotherapy is severely limited by radiation-induced toxicities. If these toxicities could be reduced, a greater dose of radiation could be given therefore facilitating a better tumour response. Initial pre-clinical studies have shown that irradiation at dose rates far exceeding those currently used in clinical contexts reduce radiation-induced toxicities whilst maintaining an equivalent tumour response. This is...
53 CitationsSource
#1Ying-Hui SongH-Index: 2
#2Qin ChaiH-Index: 1
Last. Jinyue HuH-Index: 6
view all 6 authors...
AbstractPurpose: It is reported inflammatory cytokine interleukin-8 (IL-8) could predict radiation-induced lung toxicity (RILT). RILT is believed to be a consequence of a cascade of cytokine produc...
4 CitationsSource
#1Nasrollah Jabbari (Urmia University of Medical Sciences)H-Index: 9
#2Muhammad Nawaz (University of Gothenburg)H-Index: 30
Last. Jafar Rezaie (Urmia University of Medical Sciences)H-Index: 15
view all 3 authors...
Non-targeting effects of radiotherapy have become as clinical concern due to secondary tumorigenesis in the patients receiving radiotherapy. Radiotherapy also affects non-tumoral cells present in the tumor microenvironment and surrounding tissues. As such, the irradiated cells are thought to communicate the signals that promote secondary tumorigenesis by affecting the function and fate of non-irradiated cells in the vicinity including endothelial cells. This may include up-regulation of genes in...
9 CitationsSource
Cited By0
Newest