scholarly journals Extracellular Glutathione Peroxidase GPx3 and Its Role in Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2197 ◽  
Author(s):  
Caroline Chang ◽  
Beth L. Worley ◽  
Rébécca Phaëton ◽  
Nadine Hempel
Keyword(s):  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Cancer Progression ◽  
Mammalian Cells ◽  
Lipid Hydroperoxides ◽  
Therapeutic Approaches ◽  
Antioxidant Enzyme System ◽  
Disease Associations ◽  
Tumor Types

Mammalian cells possess a multifaceted antioxidant enzyme system, which includes superoxide dismutases, catalase, the peroxiredoxin/thioredoxin and the glutathione peroxidase systems. The dichotomous role of reactive oxygen species and antioxidant enzymes in tumorigenesis and cancer progression complicates the use of small molecule antioxidants, pro-oxidants, and targeting of antioxidant enzymes as therapeutic approaches for cancer treatment. It also highlights the need for additional studies to investigate the role and regulation of these antioxidant enzymes in cancer. The focus of this review is on glutathione peroxidase 3 (GPx3), a selenoprotein, and the only extracellular GPx of a family of oxidoreductases that catalyze the detoxification of hydro- and soluble lipid hydroperoxides by reduced glutathione. In addition to summarizing the biochemical function, regulation, and disease associations of GPx3, we specifically discuss the role and regulation of systemic and tumor cell expressed GPx3 in cancer. From this it is evident that GPx3 has a dichotomous role in different tumor types, acting as both a tumor suppressor and pro-survival protein. Further studies are needed to examine how loss or gain of GPx3 specifically affects oxidant scavenging and redox signaling in the extracellular tumor microenvironment, and how GPx3 might be targeted for therapeutic intervention.

Role of intracellular antioxidant enzymes after in vivo myocardial ischemia and reperfusion

2003 ◽  
Vol 284 (1) ◽  
pp. H277-H282 ◽  
Author(s):  
Steven P. Jones ◽  
Michaela R. Hoffmeyer ◽  
Brent R. Sharp ◽  
Ye-Shih Ho ◽  
David J. Lefer
Keyword(s):  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Myocardial Damage ◽  
Ischemia And Reperfusion ◽  
Myocardial Ischemia And Reperfusion

Reactive oxygen species induce myocardial damage after ischemia and reperfusion in experimental animal models. Numerous studies have investigated the deleterious effects of ischemia-reperfusion (I/R)-induced oxidant production using various pharmacological interventions. More recently, in vitro studies have incorporated gene-targeted mice to decipher the role of antioxidant enzymes in myocardial reperfusion injury. We examined the role of cellular antioxidant enzymes in the pathogenesis of myocardial I/R (MI/R) injury in vivo in gene-targeted mice. Neither deficiency nor overexpression of Cu-Zn superoxide dismutase (SOD) altered the extent of myocardial necrosis. Overexpression of glutathione peroxidase did not affect the degree of myocardial injury. Conversely, overexpression of manganese (Mn)SOD significantly attenuated myocardial necrosis after MI/R. Transthoracic echocardiography was performed on MnSOD-overexpressing and wild-type mice that were subjected to a more prolonged period of reperfusion. Cardiac output was significantly depressed in the nontransgenic but not the transgenic MnSOD-treated mice. Anterior wall motion was significantly impaired in the nontransgenic mice. These findings demonstrate an important role for MnSOD but not Cu/ZnSOD or glutathione peroxidase in mice after in vivo MI/R.

scholarly journals HIF1α stabilization in hypoxia is not oxidant-initiated

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Amit Kumar ◽  
Manisha Vaish ◽  
Saravanan S Karuppagounder ◽  
Irina Gazaryan ◽  
John W Cave ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Antioxidant Enzymes ◽  
Glutathione Peroxidase ◽  
Protein Stability ◽  
Lipid Peroxides ◽  
Second Messenger ◽  
Hypoxic Adaptation

Hypoxic adaptation mediated by HIF transcription factors requires mitochondria, which have been implicated in regulating HIF1α stability in hypoxia by distinct models that involve consuming oxygen or alternatively converting oxygen into the second messenger peroxide. Here, we use a ratiometric, peroxide reporter, HyPer to evaluate the role of peroxide in regulating HIF1α stability. We show that antioxidant enzymes are neither homeostatically induced nor are peroxide levels increased in hypoxia. Additionally, forced expression of diverse antioxidant enzymes, all of which diminish peroxide, had disparate effects on HIF1α protein stability. Moreover, decrease in lipid peroxides by glutathione peroxidase-4 or superoxide by mitochondrial SOD, failed to influence HIF1α protein stability. These data show that mitochondrial, cytosolic or lipid ROS were not necessary for HIF1α stability, and favor a model where mitochondria contribute to hypoxic adaptation as oxygen consumers.

Role of Tissue Factor in Tumor Progression and Cancer-Associated Thrombosis

2019 ◽  
Vol 45 (04) ◽  
pp. 396-412 ◽  
Author(s):  
Araci M. R. Rondon ◽  
Chantal Kroone ◽  
Maaike Y. Kapteijn ◽  
Henri H. Versteeg ◽  
Jeroen T. Buijs
Keyword(s):  
Tissue Factor ◽  
Cancer Progression ◽  
Coagulation Cascade ◽  
Clinical Phase ◽  
Transmembrane Glycoprotein ◽  
Cancer Models ◽  
Cytotoxic Compounds ◽  
Cancer Associated Thrombosis ◽  
Tumor Types

AbstractIt has been long-established that cancer and thrombosis are linked, but the exact underlying pathological mechanism remains to be unraveled. As the initiator of the coagulation cascade, the transmembrane glycoprotein tissue factor (TF) has been intensely investigated for its role in cancer-associated thrombosis and cancer progression. TF expression is regulated by both specific oncogenes and environmental factors, and it is shown to regulate primary growth and metastasis formation in a variety of cancer models. In clinical studies, TF has been shown to be overexpressed in most cancer types and is strongly associated with disease progression. While TF clearly associates with cancer progression, a prominent role for TF in the development of cancer-associated thrombosis is less clear. The current concept is that cancer-associated thrombosis is associated with the secretion of tumor-derived TF-positive extracellular vesicles in certain tumor types. To date, many therapeutic strategies to target TF—both in preclinical and clinical phase—are being pursued, including targeting TF or the TF:FVIIa complex by itself or by exploiting TF as a docking molecule to deliver cytotoxic compounds to the tumor. In this review, the authors summarize the current understanding of the role of TF in both cancer progression and cancer-associated thrombosis, and discuss novel insights on TF as a therapeutic target as well as a biomarker for cancer progression and VTE.

scholarly journals HIF Signaling Pathway in Pheochromocytoma and Other Neuroendocrine Tumors

2014 ◽  
pp. S251-S262 ◽  
Author(s):  
I. JOCHMANOVÁ ◽  
T. ZELINKA ◽  
J. WIDIMSKÝ ◽  
K. PACAK
Keyword(s):  
Neuroendocrine Tumors ◽  
Cancer Progression ◽  
Protein Translation ◽  
Hypoxia Inducible Factors ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Hereditary Tumor Syndromes ◽  
Cluster 2 ◽  
Chromaffin Tissue

Hypoxia-inducible factors (HIFs) are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. Dysregulation of these proteins contributes to tumorigenesis and cancer progression. Recent findings revealed the important role of HIFs in the pathogenesis of neuroendocrine tumors, especially pheochromocytoma (PHEO) and paraganglioma (PGL). PHEOs and PGLs are catecholamine-producing tumors arising from sympathetic- or parasympathetic-derived chromaffin tissue. To date, eighteen PHEO/PGL susceptibility genes have been identified. Based on the main signaling pathways, PHEOs/PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Recent data suggest that both clusters are interconnected via the HIF signaling and its role in tumorigenesis is supported by newly described somatic and germline mutations in HIF2A gene in patients with PHEOs/PGLs associated with polycythemia, and in some of them also with somatostatinoma. Moreover, HIFα signaling has also been shown to be upregulated in neuroendocrine tumors other than PHEO/PGL. Some of these tumors are components of hereditary tumor syndromes which can be associated with PHEO/PGL, but also in ileal carcinoids or melanoma. HIF signaling appears to be one of the crucial players in tumorigenesis, which could suggest new therapeutic approaches for treatment of neuroendocrine tumors.

scholarly journals Immunotherapy Approaches in HPV-Associated Head and Neck Cancer

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5889
Author(s):  
Ricklie Julian ◽  
Malvi Savani ◽  
Julie E. Bauman
Keyword(s):  
Head And Neck ◽  
Clinical Evidence ◽  
Tumor Antigens ◽  
Checkpoint Inhibitors ◽  
Therapeutic Approaches ◽  
Improved Outcomes ◽  
Hpv Status ◽  
Management Of Hpv ◽  
Tumor Types

Immunotherapy approaches for head and neck squamous cell carcinoma (HNSCC) are rapidly advancing. Human papillomavirus (HPV) has been identified as a causative agent in a subset of oropharyngeal cancers (OPC). HPV-positive OPC comprises a distinct clinical and pathologic disease entity and has a unique immunophenotype. Immunotherapy with anti-PD1 checkpoint inhibitors has exhibited improved outcomes for patients with advanced HNSCC, irrespective of HPV status. To date, the clinical management of HPV-positive HNSCC and HPV-negative HNSCC has been identical, despite differences in the tumor antigens, immune microenvironment, and immune signatures of these two biologically distinct tumor types. Numerous clinical trials are underway to further refine the application of immunotherapy and develop new immunotherapy approaches. The aim of this review is to highlight the developing role of immunotherapy in HPV-positive HNSCC along with the clinical evidence and preclinical scientific rationale behind emerging therapeutic approaches, with emphasis on promising HPV-specific immune activators that exploit the universal presence of foreign, non-self tumor antigens.

scholarly journals TMEM88 is a Prognostic Biomarker and Correlates With Immune Infiltrates in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Andrew Liman ◽  
Yang Gu ◽  
Pengpeng Liu ◽  
Quanyan Liu
Keyword(s):  
Liver Cancer ◽  
Cancer Progression ◽  
Prognostic Biomarker ◽  
Progression Free Survival ◽  
Free Survival ◽  
Multiple Tumor ◽  
Normal Tissues ◽  
Tumor Types ◽  
Disease Stages

Abstract BackgroundTransmembrane protein 88 (TMEM88) has emerged as a newly discovered cancer-related protein that acts as a cancer-promoting or cancer-inhibiting regulator in multiple tumor types. However, the exact role of TMEM88 in liver cancer is undetermined. The current study was designed to determine the expression of TMEM88 in liver cancer. ResultsTMEM88 expression was significantly lower in several human cancers, but higher in liver and bile cancer, than in corresponding normal tissues. TMEM88 expression in HCC tissues correlated with prognosis. Low TMEM88 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at late disease stages (grade 2 and 3). TMEM88 showed strong correlation with tumor-infiltrating B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. ConclusionThese findings demonstrate that TMEM88 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.

Role of Organ Specific Cancer Stem Cells in Organ Specific Cancer Progression

2020 ◽  
Vol 6 (2) ◽  
pp. 21
Author(s):  
Muhammad Ali ◽  
Fatima Ali ◽  
Nadia Wajid
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Cancer Therapeutics ◽  
Therapeutic Approaches ◽  
Specific Cancer ◽  
Organ Specific

Since the cancer stem cells (CSC) have been identified in 1997 by Bonnet and Dick, more than 100,000 papers have been published on the CSC. Huge research on cancer stem cells helped the scientists to rethink about the cancer therapeutics as classic way of chemotherapy is ineffective because chemotherapy failed to kill these cells, the only reason of cancer relapse. The cancer theory of stem cells is one of the most trending theory in stem cells and cancer biology focusing on the understanding of biology of cancer cells for an enhanced and improved therapeutic approaches should be applied to cure the cancer. This mini-review is a short overview on the role of organ specific cancer stem cells in the organ specific cancer progression.

Human Galectin-1 and Its Inhibitors: Privileged Target for Cancer and HIV

2019 ◽  
Vol 19 (16) ◽  
pp. 1369-1378 ◽  
Author(s):  
Narella Sridhar Goud ◽  
P.S. Lakshmi Soukya ◽  
Mahammad Ghouse ◽  
Daipule Komal ◽  
Ravi Alvala ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Viral Entry ◽  
Immune Escape ◽  
Specific Binding ◽  
Therapeutic Approaches ◽  
Therapeutic Drugs ◽  
Kinetics Of ◽  
Structural Insights ◽  
Hiv 1

Galectin 1(Gal-1), a β-galactoside binding mammalian lectin of 14KDa, is implicated in many signalling pathways, immune responses associated with cancer progression and immune disorders. Inhibition of human Gal-1 has been regarded as one of the potential therapeutic approaches for the treatment of cancer, as it plays a major role in tumour development and metastasis by modulating various biological functions viz. apoptosis, angiogenesis, migration, cell immune escape. Gal-1 is considered as a biomarker in diagnosis, prognosis and treatment condition. The overexpression of Gal-1 is well established and seen in many types of cancer progression like osteosarcoma, breast, lung, prostate, melanoma, etc. Gal-1 greatly accelerates the binding kinetics of HIV-1 to susceptible cells, leading to faster viral entry and a more robust viral replication by specific binding of CD4 cells. Hence, the Gal-1 is considered a promising molecular target for the development of new therapeutic drugs for cancer and HIV. The present review laid emphasis on structural insights and functional role of Gal-1 in the disease, current Gal-1 inhibitors and future prospects in the design of specific Gal-1 inhibitors.

scholarly journals Argonaute Proteins Take Center Stage in Cancers

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 788
Author(s):  
Iwona Nowak ◽  
Aishe A. Sarshad
Keyword(s):  
Cancer Cells ◽  
Small Rna ◽  
Therapeutic Approaches ◽  
Rna Molecules ◽  
Center Stage ◽  
Current State ◽  
Argonaute Proteins ◽  
Tumor Types ◽  
Novel Therapeutic

Argonaute proteins (AGOs) play crucial roles in RNA-induced silencing complex (RISC) formation and activity. AGOs loaded with small RNA molecules (miRNA or siRNA) either catalyze endoribonucleolytic cleavage of target RNAs or recruit factors responsible for translational silencing and target destabilization. miRNAs are well characterized and broadly studied in tumorigenesis; nevertheless, the functions of the AGOs in cancers have lagged behind. Here, we discuss the current state of knowledge on the role of AGOs in tumorigenesis, highlighting canonical and non-canonical functions of AGOs in cancer cells, as well as the biomarker potential of AGO expression in different of tumor types. Furthermore, we point to the possible application of the AGOs in development of novel therapeutic approaches.

Metabolic and functional defects in selenium deficiency

1981 ◽  
Vol 294 (1071) ◽  
pp. 105-117 ◽  
Keyword(s):  
Hydrogen Peroxide ◽  
Vitamin E ◽  
Glutathione Peroxidase ◽  
Membrane Lipids ◽  
Selenium Deficiency ◽  
Human Nutrition ◽  
Keshan Disease ◽  
Lipid Hydroperoxides ◽  
Membrane Phospholipids

This paper is concerned with present-day knowledge of the biological role of selenium, of its interaction with other nutrients including trace elements, and with the importance of selenium in human nutrition and health. Selenium has been shown to be an integral part of glutathione peroxidase, which catalyses the reduction of a large range of lipid hydroperoxides and hydrogen peroxide. The interrelation between vitamin E, selenium and polyunsaturated fatty acids is complex. First, selenium in glutathione peroxidase may control intracellular levels of hydrogen peroxide, which affect the formation of active oxygen metabolites that may serve as initiators of lipid peroxidation; this role of selenium is closely related to that of superoxide dismutases, which control intracellular levels of the superoxide anion. Secondly, vitamin E may control the formation of lipid hydroperoxides through its antioxidant function, as well as possibly entering into a structural relation with membrane phospholipids. Thirdly, glutathione peroxidase may catalyse the reduction of lipid hydroperoxides, formed from membrane lipids, to hydroxyacids without detriment to the cellular economy. In the field of human nutrition, the lack of selenium has been shown to be the cause of a cardiomyopathy known as Keshan disease, occurring in the People’s Republic of China. Blood selenium levels in patients from this area are compared with blood selenium levels in three other parts of the world and the conclusion is reached that the blood selenium level of populations in Keshan disease regions are exceptionally low and that Keshan disease is the first demonstration that selenium is an essential trace element for man.

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