scholarly journals Important roles of C5a and C5aR in tumor development and cancer treatment

2019 ◽  
Vol 136 ◽  
pp. 06012
Author(s):  
Wang Yuxuan
Keyword(s):  
Complement System ◽  
Tumor Therapy ◽  
Tumor Development ◽  
Tumor Formation ◽  
Complement Component ◽  
Innate Defense ◽  
And Migration ◽  
And Control ◽  
The Complement System

The complement system is part of the body's innate defense immune system, which can identify and eliminate invasive pathogenic microorganisms to maintain normal life activities. Complement Component 5a (C5a) is an active anaphylatoxin produced after complement system activation, closely related to tumor formation. C5a is highly expressed in a variety of tumors, and combines with its Complement Component 5a Receptor (C5aR) to increase the proliferation and migration of tumor cells. This review will comprehensively elaborate the important role of C5a/C5aR in the process of tumor genesis and development from the three aspects of signal transduction pathways related to tumor, C5a/C5aR and tumor formation, and C5a/C5aR inhibitors and tumor therapy. Finally, the principle of complement inhibition is used to inhibit tumor metastasis, reduce the rate of tumor diffusion, and control the trend of tumor deterioration.

scholarly journals Special Issue: The Role of Complement in Cancer Immunotherapy

Antibodies ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 29
Author(s):  
Ronald P. Taylor
Keyword(s):  
Cancer Immunotherapy ◽  
Complement System ◽  
Immune Defense ◽  
Special Issue ◽  
The Complement System ◽  
Critical Aspects

The complement system plays an important role in critical aspects of immune defense and in the maintenance of homeostasis in the bloodstream, as well as in essentially all tissues and organs [...]

The role of the complement system in hereditary angioedema

2017 ◽  
Vol 89 ◽  
pp. 59-68 ◽  
Author(s):  
Dorottya Csuka ◽  
Nóra Veszeli ◽  
Lilian Varga ◽  
Zoltán Prohászka ◽  
Henriette Farkas
Keyword(s):  
Complement System ◽  
Hereditary Angioedema ◽  
The Complement System

The role of paramyosin from blood fluke Schistosoma mansoni in inhibition of the complement system

2008 ◽  
Vol 45 (16) ◽  
pp. 4172
Author(s):  
Lina Grekin ◽  
Ram Cohen ◽  
James M. Sodetz ◽  
Daniel Gold ◽  
Zvi Fishelson
Keyword(s):  
Schistosoma Mansoni ◽  
Complement System ◽  
Blood Fluke ◽  
The Complement System

TMOD-26. MYC OVEREXPRESSION AND SMARCA4 LOSS IN GRANULE CELL PRECURSORS COOPERATE TO DRIVE MEDULLOBLASTOMA FORMATION IN MICE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi221-vi221
Author(s):  
Carolin Göbel ◽  
Dörthe Holdhof ◽  
Melanie Schoof ◽  
Catena Kresbach ◽  
Ulrich Schüller
Keyword(s):  
Granule Cell ◽  
Clinical Course ◽  
Tumor Development ◽  
Tumor Formation ◽  
Human Group ◽  
Group 4 ◽  
Small Cohort ◽  
Group 3 ◽  
Granule Cell Precursors

Abstract Mutations in SMARCA4 are frequently identified in medulloblastoma, the most common pediatric malignant brain tumor. However, the functional significance of these mutations and their suitability as a therapeutic target remain largely unclear. Medulloblastomas are divided into 4 subgroups according to their localization, molecular biology, and clinical course: WNT, SHH, Group 3, and Group 4. Group 3 medulloblastomas are associated with the poorest outcome and frequently show amplifications of the oncogene MYC. Additionally, SMARCA4 is mutated in around 15 % of cases. The few mouse models developed for this entity so far all involve the overexpression of MYC, mostly in combination with other drivers. However, none of these models include alterations in Smarca4. In our approach, we combined an overexpression of MYC with a loss of SMARCA4 in granule cell precursors, which successfully induced tumor formation in mice. For this purpose, granule cell precursors were isolated from 7-day-old Math1-creER T2 ::Smarca4 fl/fl pups after tamoxifen induced loss of SMARCA4. MYC overexpression was achieved by lentiviral transduction and transduced cells were transplanted into immunodeficient CD1 nu/nu mice. Preliminary results within a small cohort showed tumor formation in 5/19 transplanted mice (26 %) after 6 months. Immunohistochemically, tumors all stained negative for SMARCA4. In a next step, additional cohorts will elucidate if tumor development is indeed accelerated by or even dependent on the loss of SMARCA4. Additionally, the neoplastic potential of tumor cells will be verified with the aid of secondary recipient mice. To evaluate to what extent the generated tumors are comparable to human Group 3 medulloblastomas, tumors will be extensively analyzed on a morphological, transcriptional, and epigenetic level. Altogether, we hope to establish a suitable mouse model for SMARCA4 mutated Group 3 medulloblastoma that will help to elucidate the role of SMARCA4 in tumor development and to identify new therapeutic targets.

scholarly journals Activation of the complement system by pathogenic fungi.

1996 ◽  
Vol 9 (1) ◽  
pp. 34-46 ◽  
Author(s):  
T R Kozel
Keyword(s):  
Complement System ◽  
Host Resistance ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Complement Cascade ◽  
Experimental Animals ◽  
Molecular Bases ◽  
The Complement System

Fungi have been studied as prototype activators of the complement cascade since the early 1900s. More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. The interactions of Cryptococcus neoformans and Candida albicans with the complement system are the most widely characterized; however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. The molecular bases for such differences remain to be identified. Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. Contributions to host resistance include opsonization and generation of inflammatory mediators. Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections.

scholarly journals The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury

2020 ◽  
Author(s):  
Mineia Alessandra Scaranello Malaquias ◽  
Ana Carolina Gadotti ◽  
Jarbas da Silva Motta-Junior ◽  
Ana Paula Camargo Martins ◽  
Marina Luise Viola Azevedo ◽  
...  
Keyword(s):  
Lung Injury ◽  
Complement System ◽  
Lectin Pathway ◽  
The Complement System

scholarly journals Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Lisa E. Gralinski ◽  
Timothy P. Sheahan ◽  
Thomas E. Morrison ◽  
Vineet D. Menachery ◽  
Kara Jensen ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Host Defense ◽  
Complement System ◽  
Complement Activation ◽  
Fungal Infections ◽  
Central Component ◽  
Lung Pathology ◽  
Inflammatory Monocytes ◽  
The Complement System

ABSTRACT Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3–/–), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3–/– mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3–/– mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3–/– mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic. IMPORTANCE The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.

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