scholarly journals Role of MicroRNAs in BCG Therapy by the Induction of Neutrophil Extracellular Traps in Bladder Cancer

2020 ◽  
pp. 17-28
Author(s):  
Mohammad Mehdi Adibzadeh Sereshgi ◽  
Ali Mohammad Mohseni Majd ◽  
Sahar Salimi ◽  
Hassan Noorbazargan
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Surashri Shinde-Jadhav ◽  
Jose Joao Mansure ◽  
Roni F. Rayes ◽  
Gautier Marcq ◽  
Mina Ayoub ◽  
...  

AbstractRadiation therapy (RT) is used in the management of several cancers; however, tumor radioresistance remains a challenge. Polymorphonuclear neutrophils (PMNs) are recruited to the tumor immune microenvironment (TIME) post-RT and can facilitate tumor progression by forming neutrophil extracellular traps (NETs). Here, we demonstrate a role for NETs as players in tumor radioresistance. Using a syngeneic bladder cancer model, increased NET deposition is observed in the TIME of mice treated with RT and inhibition of NETs improves overall radiation response. In vitro, the protein HMGB1 promotes NET formation through a TLR4-dependent manner and in vivo, inhibition of both HMGB1 and NETs significantly delays tumor growth. Finally, NETs are observed in bladder tumors of patients who did not respond to RT and had persistent disease post-RT, wherein a high tumoral PMN-to-CD8 ratio is associated with worse overall survival. Together, these findings identify NETs as a potential therapeutic target to increase radiation efficacy.


2021 ◽  
Vol 8 ◽  
Author(s):  
Chenyu Mao ◽  
Xin Xu ◽  
Yongfeng Ding ◽  
Nong Xu

Bladder cancer (BC) is the ninth most common cancer and the thirteenth most common cause of mortality worldwide. Bacillus Calmette Guerin (BCG) instillation is a common treatment option for BC. BCG therapy is associated with the less adversary effects, compared to chemotherapy, radiotherapy, and other conventional treatments. BCG could inhibit the progression and recurrence of BC by triggering apoptosis pathways, arrest cell cycle, autophagy, and neutrophil extracellular traps (NETs) formation. However, BCG therapy is not efficient for metastatic cancer. NETs and autophagy were induced by BCG and help to suppress the growth of tumor cells especially in the primary stages of BC. Activated neutrophils can stimulate autophagy pathway and release NETs in the presence of microbial pathogenesis, inflammatory agents, and tumor cells. Autophagy can also regulate NETs formation and induce production of reactive oxygen species (ROS) and NETs. Moreover, miRNAs are important regulator of gene expression. These small non-coding RNAs are also considered as an essential factor to control the levels of tumor development. However, the interaction between BCG and miRNAs has not been well-understood yet. Therefore, the present study discusses the roles of miRNAs in regulations of autophagy and NETs formation in BCG therapy in the treatment of BC. The roles of autophagy and NETs formation in BC treatment and efficiency of BCG are also discussed.


2019 ◽  
Vol 39 (1) ◽  
Author(s):  
César Díaz-Godínez ◽  
Julio C. Carrero

AbstractNeutrophil extracellular traps (NETs) are DNA fibers associated with histones, enzymes from neutrophil granules and anti-microbial peptides. NETs are released in a process denominated NETosis, which involves sequential steps that culminate with the DNA extrusion. NETosis has been described as a new mechanism of innate immunity related to defense against different pathogens. The initial studies of NETs were carried out with bacteria and fungi, but currently a large variety of microorganisms capable of inducing NETs have been described including protozoan and helminth parasites. Nevertheless, we have little knowledge about how NETosis process is carried out in response to the parasites, and about its implication in the resolution of this kind of disease. In the best case, the NETs entrap and kill parasites in vitro, but in others, immobilize the parasites without affecting their viability. Moreover, insufficient studies on the NETs in animal models of infections that would help to define their role, and the association of NETs with chronic inflammatory pathologies such as those occurring in several parasitic infections have left open the possibility of NETs contributing to pathology instead of protection. In this review, we focus on the reported mechanisms that lead to NET release by protozoan and helminth parasites and the evidence that support the role of NETosis in the resolution or pathogenesis of parasitic diseases.


2019 ◽  
Vol 201 ◽  
pp. 4-14 ◽  
Author(s):  
Kangkang Liu ◽  
Erlin Sun ◽  
Mingde Lei ◽  
Limin Li ◽  
Jingda Gao ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Yilu Zhou ◽  
Weimin Tao ◽  
Fuyi Shen ◽  
Weijia Du ◽  
Zhendong Xu ◽  
...  

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.


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