Hypoxia-Induced Epithelial-Mesenchymal Transition in Cancers: HIF-1α and Beyond

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 10

Published: April 8, 2020

Metastasis is the main cause of cancer-related mortality. Although actual process metastasis remains largely elusive, epithelial-mesenchymal transition (EMT) has been considered as a major event in metastasis. Besides, hypoxia common solid cancers and an important factor for adverse treatment outcomes including Since EMT potentially share several signaling pathways, many recent studies focused on investigate issue hypoxia-induced EMT. Among all potential mediators EMT, hypoxia-inducible factor-1α (HIF-1α) studied extensively. Moreover, there are other that may also contribute to process. This review aims summarize reports by HIF-1α or provide insights further investigations this issue. Ultimately, better understanding allow us develop anti-metastatic strategies improve outcomes.

Language: Английский

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Hypoxia/pseudohypoxia‐mediated activation of hypoxia‐inducible factor‐1α in cancer

Cancer Science, Journal Year: 2019, Volume and Issue: 110(5), P. 1510 - 1517

Published: March 7, 2019

Since the first identification of hypoxic cells in sections carcinomas 1950s, hypoxia has been known as a central hallmark cancer and their microenvironment. Indeed, benefits growth, survival, metastasis. The historical discovery hypoxia-inducible factor-1α (HIF1A) early 1990s had great influence on field many phenomena could be explained by HIF1A. However, not all regions or types tumors are necessarily hypoxic. Thus, it is difficult to explain whole pathobiology hypoxia, especially stage cancer. Upregulation glucose metabolism well known. Oxygen-independent glycolysis activated even normoxia condition, which Warburg effect. Accumulating evidence recent advances research suggest that hypoxia-independent mechanisms for HIF signaling activation There various generate pseudohypoxic conditions, normoxia. Given importance HIF1A pathobiology, pseudohypoxia concept shed light longstanding mystery effect accelerate better understanding diverse seen variety cancers.

Language: Английский

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Ca2+ Fluxes and Cancer

Molecular Cell, Journal Year: 2020, Volume and Issue: 78(6), P. 1055 - 1069

Published: June 1, 2020

Language: Английский

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HIF-1α inducing exosomal microRNA-23a expression mediates the cross-talk between tubular epithelial cells and macrophages in tubulointerstitial inflammation

Kidney International, Journal Year: 2018, Volume and Issue: 95(2), P. 388 - 404

Published: Dec. 11, 2018

Language: Английский

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A General Overview on the Hyperbaric Oxygen Therapy: Applications, Mechanisms and Translational Opportunities

Medicina, Journal Year: 2021, Volume and Issue: 57(9), P. 864 - 864

Published: Aug. 24, 2021

Hyperbaric oxygen therapy (HBOT) consists of using pure at increased pressure (in general, 2-3 atmospheres) leading to augmented levels in the blood (Hyperoxemia) and tissue (Hyperoxia). The bioavailability might be related a plethora applications, particularly hypoxic regions, also exerting antimicrobial, immunomodulatory angiogenic properties, among others. In this review, we will discuss detail physiological relevance therapeutical basis HBOT, collecting current indications underlying mechanisms. Furthermore, potential areas research examined, including inflammatory systemic maladies, COVID-19 cancer. Finally, adverse effects contraindications associated with future directions considered. Overall, encourage further field extend possible uses procedure. inclusion HBOT clinical could an additional support management multiple pathologies.

Language: Английский

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FOXO3a from the Nucleus to the Mitochondria: A Round Trip in Cellular Stress Response

Cells, Journal Year: 2019, Volume and Issue: 8(9), P. 1110 - 1110

Published: Sept. 19, 2019

Cellular stress response is a universal mechanism that ensures the survival or negative selection of cells in challenging conditions. The transcription factor Forkhead box protein O3 (FOXO3a) core regulator cellular homeostasis, response, and longevity since it can modulate variety responses upon nutrient shortage, oxidative stress, hypoxia, heat shock, DNA damage. FOXO3a activity regulated by post-translational modifications drive its shuttling between different compartments, thereby determining inactivation (cytoplasm) activation (nucleus mitochondria). Depending on stimulus subcellular context, activated induce specific sets nuclear genes, including cell cycle inhibitors, pro-apoptotic reactive oxygen species (ROS) scavengers, autophagy effectors, gluconeogenic enzymes, others. On other hand, glucose restriction, 5′-AMP-activated kinase (AMPK) mitogen (MEK)/extracellular signal-regulated (ERK) -dependent mitochondrial translocation allows phosphorylation (OXPHOS) restoring ATP levels, while cancer cells, mediates genotoxic induced chemotherapy. Interestingly, these target genes their related pathways are diverse sometimes antagonistic, suggesting an adaptable player dynamic homeostasis normal stressed cells. In this review, we describe multiple roles with focus both functions.

Language: Английский

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Biomimetic Liposomal Nanoplatinum for Targeted Cancer Chemophototherapy

Advanced Science, Journal Year: 2021, Volume and Issue: 8(8)

Published: March 1, 2021

Photodynamic therapy (PDT) of cancer is limited by tumor hypoxia. Platinum nanoparticles (nano-Pt) as a catalase-like nanoenzyme can enhance PDT through catalytic oxygen supply. However, the cytotoxic activity nano-Pt not comprehensively considered in existing methods to exert their multifunctional antitumor effects. Here, are loaded into liposomes via reverse phase evaporation. The clinical photosensitizer verteporfin (VP) lipid bilayer confer activity. Murine macrophage cell membranes hybridized liposomal membrane biomimetic and targeting features. resulting system, termed "nano-Pt/VP@MLipo," investigated for chemophototherapy vitro vivo mouse models. At site, produced catalyzation improves VP-mediated PDT, which turn triggers release permeabilization. ultrasmall 3-5 nm enables better penetration tumors, also facilitated generated gas, enhanced chemotherapy. Chemophototherapy with single injection nano-Pt/VP@MLipo light irradiation inhibits growth aggressive 4T1 tumors lung metastasis, prolongs animal survival without overt toxicity.

Language: Английский

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Tumor angiogenesis: Current challenges and therapeutic opportunities

Cancer Treatment and Research Communications, Journal Year: 2021, Volume and Issue: 28, P. 100422 - 100422

Published: Jan. 1, 2021

Angiogenesis plays an important role in the development of cancer since it allows for delivery oxygen, nutrients, and growth factors as well tumor dissemination to distant organs. Inhibition angiogenesis is strategy prevention multiple solid tumors that depend on cutting or at least reducing blood supply micro-regions, resulting pan-hypoxia pan-necrosis within tissues. These drugs are part treatment some types cancer. As a stand-alone therapy, inhibition can arrest halt growth, but will not eliminate tumor. Therefore, anti-angiogenic combinations with another anti-cancer method, like chemotherapy, lead being critical optimum patient outcomes. Over last two decades, investigations have been made improve efficacy drugs, recognize their potential drug interactions, come up plausible explanations possible resistance. This review offer overview varying concepts angiogenesis, several angiogenic factors; focus anti-angiogenesis strategies treatment.

Language: Английский

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Innate immunological pathways in COVID-19 pathogenesis

Science Immunology, Journal Year: 2022, Volume and Issue: 7(67)

Published: Jan. 7, 2022

Coronavirus disease 2019 (COVID-19) is a characterized by profound dysregulation of the innate immune system. This knowledge has emerged from large body single-cell omics studies patients with COVID-19, which have provided one most detailed cellular atlases human ever. However, we are only beginning to understand immunological pathways that govern host defense and immunopathology in COVID-19. In this review, discuss emerging understanding how SARS-CoV-2 host-derived molecules activate specific pattern recognition receptors elicit protective interferon responses pathological cytokine responses, particular focus on acute infection lung pathophysiology critical addition, these modulated virus-host interactions stress-sensing pathways. In-depth mechanisms will likely uncover molecular targets for treatment COVID-19 other viral infections. it reveal fine balance between beneficial versus causing responses.

Language: Английский

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Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 25, 2023

Abstract Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder in which the airways narrow or collapse during sleep, causing obstructive apnea. The prevalence of OSAS continues to rise worldwide, particularly middle-aged and elderly individuals. mechanism upper airway incompletely understood but associated with several factors, including obesity, craniofacial changes, altered muscle function airway, pharyngeal neuropathy, fluid shifts neck. main characteristics are recurrent pauses respiration, lead intermittent hypoxia (IH) hypercapnia, accompanied by blood oxygen desaturation arousal sharply increases risk diseases. This paper first briefly describes epidemiology, incidence, pathophysiological mechanisms OSAS. Next, alterations relevant signaling pathways induced IH systematically reviewed discussed. For example, can induce gut microbiota (GM) dysbiosis, impair intestinal barrier, alter metabolites. These ultimately secondary oxidative stress, systemic inflammation, sympathetic activation. We then summarize effects on disease pathogenesis, cardiocerebrovascular disorders, neurological metabolic diseases, cancer, reproductive COVID-19. Finally, different therapeutic strategies for caused causes proposed. Multidisciplinary approaches shared decision-making necessary successful treatment future, more randomized controlled trials needed further evaluation define what treatments best specific patients.

Language: Английский

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