scholarly journals Supercharged eGFP-TRAIL Decorated NETs to Ensnare and Kill Disseminated Tumor Cells

2020 ◽  
Vol 13 (4) ◽  
pp. 359-367
Author(s):  
Thong M. Cao ◽  
Michael R. King
Keyword(s):  
Tumor Cells ◽  
Chimeric Protein ◽  
Disseminated Tumor Cells ◽  
Innate Immune ◽  
Delivery Vehicle ◽  
Extracellular Traps ◽  
Microbial Infections ◽  
Activated Neutrophils ◽  
Tumor Drug Delivery ◽  
Induced Apoptosis

Abstract Background NETosis is an innate immune response elicited by activated neutrophils to fight microbial infections. Activated neutrophils release DNA fibers decorated with anti-microbial proteins called neutrophil extracellular traps (NETs) into the extracellular space to trap and kill surrounding microbes. Methods Here, we show that tumor-derived IL-8 released by cancer cells also activates the release of NETs. Until now, there have been no existing technologies that leverage NETs as an anti-tumor drug delivery vehicle. In this study, we demonstrate the re-engineering of neutrophils to express an apoptosis-inducing chimeric protein, supercharged eGFP-TRAIL, on NETs that can ensnare and kill tumor cells while retaining their anti-microbial capabilities. Results We observed significant TRAIL-induced apoptosis in tumor cells captured by TRAIL-decorated NETs. Conclusions This work demonstrates NETs as a promising technology to deliver protein in response to local cytokine signals.

scholarly journals Immune System Disequilibrium—Neutrophils, Their Extracellular Traps, and COVID-19-Induced Sepsis

2021 ◽  
Vol 8 ◽  
Author(s):  
Colm Keane ◽  
Matthew Coalter ◽  
Ignacio Martin-Loeches
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Innate Immune ◽  
Organ Injury ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Adaptive Immune ◽  
Extracellular Traps ◽  
Adaptive Immune Cells ◽  
Induced Apoptosis

Equilibrium within the immune system can often determine the fate of its host. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Immune dysregulation remains one of the main pathophysiological components of SARS-CoV-2-associated organ injury, with over-activation of the innate immune system, and induced apoptosis of adaptive immune cells. Here, we provide an overview of the innate immune system, both in general and relating to COVID-19. We specifically discuss “NETosis,” the process of neutrophil release of their extracellular traps, which may be a more recently described form of cell death that is different from apoptosis, and how this may propagate organ dysfunction in COVID-19. We complete this review by discussing Stem Cell Therapies in COVID-19 and emerging COVID-19 phenotypes, which may allow for more targeted therapy in the future. Finally, we consider the array of potential therapeutic targets in COVID-19, and associated therapeutics.

scholarly journals COVID-19: Lung-Centric Immunothrombosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Peter R. Kvietys ◽  
Hana. M. A. Fakhoury ◽  
Sana Kadan ◽  
Ahmed Yaqinuddin ◽  
Eid Al-Mutairy ◽  
...  
Keyword(s):  
Pulmonary Infection ◽  
Distress Syndrome ◽  
Cytokine Production ◽  
Coagulation Factors ◽  
Innate Immune ◽  
Defensive Strategy ◽  
Extracellular Traps ◽  
Cytoplasmic Material ◽  
Activated Platelets ◽  
Activated Neutrophils

The respiratory tract is the major site of infection by SARS-CoV-2, the virus causing COVID-19. The pulmonary infection can lead to acute respiratory distress syndrome (ARDS) and ultimately, death. An excessive innate immune response plays a major role in the development of ARDS in COVID-19 patients. In this scenario, activation of lung epithelia and resident macrophages by the virus results in local cytokine production and recruitment of neutrophils. Activated neutrophils extrude a web of DNA-based cytoplasmic material containing antimicrobials referred to as neutrophil extracellular traps (NETs). While NETs are a defensive strategy against invading microbes, they can also serve as a nidus for accumulation of activated platelets and coagulation factors, forming thrombi. This immunothrombosis can result in occlusion of blood vessels leading to ischemic damage. Herein we address evidence in favor of a lung-centric immunothrombosis and suggest a lung-centric therapeutic approach to the ARDS of COVID-19.

scholarly journals NETs and oncologic process

2021 ◽  
Vol 15 (1) ◽  
pp. 107-116
Author(s):  
E. V. Slukhanchuk
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Neutrophil Extracellular Traps ◽  
Therapeutic Strategies ◽  
Innate Immune ◽  
Systemic Lupus ◽  
Extracellular Traps ◽  
Activated Neutrophils ◽  
Autoimmune Conditions

Neutrophil Extracellular Traps (NETs) represent the networks consisting of DNA, histones, and proteins produced by activated neutrophils. Such structures have been proved to play a crucial role in inducing neutrophil innate immune response in the pathogenesis of such autoimmune conditions as systemic lupus erythematosus, rheumatoid arthritis, psoriasis, as well as in the pathogenesis of other non-infectious processes, e. g., clotting disorders, thrombosis, diabetes, atherosclerosis, vasculitis and oncology diseases. Recent studies on animal models and human pathologies have uncovered a tremendous role for NETs in tumor progression and metastasis. In this regard, NETs should be considered as pro-oncogenic substances, which further investigation will provide an opportunity to develop new therapeutic strategies.

scholarly journals Optimization of BCG Therapy Targeting Neutrophil Extracellular Traps, Autophagy, and miRNAs in Bladder Cancer: Implications for Personalized Medicine

2021 ◽  
Vol 8 ◽  
Author(s):  
Chenyu Mao ◽  
Xin Xu ◽  
Yongfeng Ding ◽  
Nong Xu
Keyword(s):  
Bladder Cancer ◽  
Tumor Cells ◽  
Metastatic Cancer ◽  
Tumor Development ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Bcg Therapy ◽  
Activated Neutrophils ◽  
Apoptosis Pathways ◽  
Important Regulator

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.

Disseminated tumor cells in bone marrow of breast cancer patients–Comparison of immunocytochemistry and RT-PCR

2006 ◽  
Vol 66 (S 01) ◽  
Author(s):  
T Fehm ◽  
S Becker ◽  
MJ Banys ◽  
G Becker-Pergola ◽  
S Duerr-Stoerzer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Disseminated Tumor Cells ◽  
Breast Cancer Patients ◽  
Rt Pcr

Hybrid Compounds & Oxidative Stress Induced Apoptosis in Cancer Therapy

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Author(s):  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben
Keyword(s):  
Oxidative Stress ◽  
Drug Resistance ◽  
Side Effects ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Drugs ◽  
Chemotherapeutic Agents ◽  
Oxidation Reactions ◽  
Hybrid Compounds ◽  
Induced Apoptosis

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

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