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Book
Tumor Hypoxia: Impact in Tumorigenesis, Diagnosis, Prognosis and Therapeutics
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Year: 2017 Publisher: Frontiers Media SA

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Abstract

Hypoxic regions have been identified within tumors and its presence has been linked to malignant progression, metastasis, resistance to therapy, and poor clinical outcomes following treatment. Acute and chronic hypoxia are integral components of tumor microenvironment and conduce to metabolic adaptations of tumor cells leading to genetic instability, intratumor heterogeneity and malignant progression. On the success of our fight against cancer, the continued adaptability of tumors to their microenvironmental stresses, such as hypoxia, must be considered. Tumor cells are endowed with a very high plasticity and capacity to adapt. It is our challenge to find populations and conditions of the tumor microenvironment germane for target success. Interdisciplinary work will be the key for achievement of these goals. This e-book is a compendium of original reports and review articles contributed by world-class experts in the field of tumor hypoxia. This material will be useful to foster discussion and increase understanding of the involvement of hypoxia in tumorigenesis, biomarker development, and therapeutics.Hypoxic regions have been identified within tumors and its presence has been linked to malignant progression, metastasis, resistance to therapy, and poor clinical outcomes following treatment. Acute and chronic hypoxia are integral components of tumor microenvironment and conduce to metabolic adaptations of tumor cells leading to genetic instability, intratumor heterogeneity and malignant progression. On the success of our fight against cancer, the continued adaptability of tumors to their microenvironmental stresses, such as hypoxia, must be considered. Tumor cells are endowed with a very high plasticity and capacity to adapt. It is our challenge to find populations and conditions of the tumor microenvironment germane for target success. Interdisciplinary work will be the key for achievement of these goals. This e-book is a compendium of original reports and review articles contributed by world-class experts in the field of tumor hypoxia. This material will be useful to foster discussion and increase understanding of the involvement of hypoxia in tumorigenesis, biomarker development, and therapeutics.

Keywords

microenvironment --- Stem Cells --- hypoxia --- stress --- HIF --- tumor --- Leukemia --- biomarkers --- therapy --- pH --- microenvironment --- Stem Cells --- hypoxia --- stress --- HIF --- tumor --- Leukemia --- biomarkers --- therapy --- pH


Book
Tumor Hypoxia: Impact in Tumorigenesis, Diagnosis, Prognosis and Therapeutics
Author:
Year: 2017 Publisher: Frontiers Media SA

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Abstract

Hypoxic regions have been identified within tumors and its presence has been linked to malignant progression, metastasis, resistance to therapy, and poor clinical outcomes following treatment. Acute and chronic hypoxia are integral components of tumor microenvironment and conduce to metabolic adaptations of tumor cells leading to genetic instability, intratumor heterogeneity and malignant progression. On the success of our fight against cancer, the continued adaptability of tumors to their microenvironmental stresses, such as hypoxia, must be considered. Tumor cells are endowed with a very high plasticity and capacity to adapt. It is our challenge to find populations and conditions of the tumor microenvironment germane for target success. Interdisciplinary work will be the key for achievement of these goals. This e-book is a compendium of original reports and review articles contributed by world-class experts in the field of tumor hypoxia. This material will be useful to foster discussion and increase understanding of the involvement of hypoxia in tumorigenesis, biomarker development, and therapeutics.Hypoxic regions have been identified within tumors and its presence has been linked to malignant progression, metastasis, resistance to therapy, and poor clinical outcomes following treatment. Acute and chronic hypoxia are integral components of tumor microenvironment and conduce to metabolic adaptations of tumor cells leading to genetic instability, intratumor heterogeneity and malignant progression. On the success of our fight against cancer, the continued adaptability of tumors to their microenvironmental stresses, such as hypoxia, must be considered. Tumor cells are endowed with a very high plasticity and capacity to adapt. It is our challenge to find populations and conditions of the tumor microenvironment germane for target success. Interdisciplinary work will be the key for achievement of these goals. This e-book is a compendium of original reports and review articles contributed by world-class experts in the field of tumor hypoxia. This material will be useful to foster discussion and increase understanding of the involvement of hypoxia in tumorigenesis, biomarker development, and therapeutics.

Keywords

microenvironment --- Stem Cells --- hypoxia --- stress --- HIF --- tumor --- Leukemia --- biomarkers --- therapy --- pH


Book
Tumor Hypoxia: Impact in Tumorigenesis, Diagnosis, Prognosis and Therapeutics
Author:
Year: 2017 Publisher: Frontiers Media SA

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Abstract

Hypoxic regions have been identified within tumors and its presence has been linked to malignant progression, metastasis, resistance to therapy, and poor clinical outcomes following treatment. Acute and chronic hypoxia are integral components of tumor microenvironment and conduce to metabolic adaptations of tumor cells leading to genetic instability, intratumor heterogeneity and malignant progression. On the success of our fight against cancer, the continued adaptability of tumors to their microenvironmental stresses, such as hypoxia, must be considered. Tumor cells are endowed with a very high plasticity and capacity to adapt. It is our challenge to find populations and conditions of the tumor microenvironment germane for target success. Interdisciplinary work will be the key for achievement of these goals. This e-book is a compendium of original reports and review articles contributed by world-class experts in the field of tumor hypoxia. This material will be useful to foster discussion and increase understanding of the involvement of hypoxia in tumorigenesis, biomarker development, and therapeutics.Hypoxic regions have been identified within tumors and its presence has been linked to malignant progression, metastasis, resistance to therapy, and poor clinical outcomes following treatment. Acute and chronic hypoxia are integral components of tumor microenvironment and conduce to metabolic adaptations of tumor cells leading to genetic instability, intratumor heterogeneity and malignant progression. On the success of our fight against cancer, the continued adaptability of tumors to their microenvironmental stresses, such as hypoxia, must be considered. Tumor cells are endowed with a very high plasticity and capacity to adapt. It is our challenge to find populations and conditions of the tumor microenvironment germane for target success. Interdisciplinary work will be the key for achievement of these goals. This e-book is a compendium of original reports and review articles contributed by world-class experts in the field of tumor hypoxia. This material will be useful to foster discussion and increase understanding of the involvement of hypoxia in tumorigenesis, biomarker development, and therapeutics.

Keywords

microenvironment --- Stem Cells --- hypoxia --- stress --- HIF --- tumor --- Leukemia --- biomarkers --- therapy --- pH


Dissertation
Thesis, COLLÉGIALITÉ
Authors: --- --- --- ---
Year: 2022 Publisher: Liège Université de Liège (ULiège)

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Abstract

Non-small cell lung cancer (NSCLC) is one of the deadliest cancers worldwide, with patients presenting an overall 5-year survival lower than 15%. NSCLC is characterized by a multitude of tumor-promoting genetic alterations, such as mutations in KRAS, EGFR and TP53 genes. The high heterogeneity and plasticity of lung cancers is one of the main reasons for the failure of current treatment strategies. Importantly, genomic amplification of RICTOR frequently occurs in lung cancer. RICTOR is the defining component of mTOR complex 2 (mTORC2). Moreover, RICTOR-dependent activation of mTORC2 is essential to support lung cancer cell survival and tumor growth in vivo. Despite high therapeutic potential, directly targeting mTORC2 activity in patients remains challenging. Therefore, targeting mTORC2-dependent liabilities may represent a better option for the development of anticancer treatments. Preliminary work from our lab and results from the literature have positioned mTORC2 signaling at the crossroad between translation and metabolism. Hence, deciphering the mechanisms linking mTORC2-dependent translation to the acquisition of specific metabolic liabilities will highlight new therapeutic strategies for the treatment of lung cancer. In this study, I focused on understanding the molecular mechanisms that sustain the rewiring of cancer cell metabolism in the clinically relevant context of RICTOR-overexpressing (RICTOR OE) lung cancer. Using several models, I first evidenced an active role for RICTOR/mTORC2 in the regulation of cancer associated mRNA translation. Preliminary data from the lab indicated that RICTOR silencing in human lung cancer cells was associated with a negative enrichment of hypoxia signatures. Therefore, I first assessed the expression of the different hypoxia-inducible factors (HIF-1α, HIF-2α and HIF-1β) in RICTOR-depleted lung cancer cells. Strikingly, I found that expression of the transcription factor HIF-1β was significantly and consistently decreased upon RICTOR silencing. Importantly, RICTOR-dependent modulation of HIF-1β expression occurred at protein level and was observed in multiple cancer cell lines, highlighting HIF-1β as a potential RICTOR-dependent translational target in lung cancer. Using pharmacological and genetic inhibition of mTOR signaling (RICTOR, RAPTOR and SIN1 siRNAs; mTOR, AKT and PKC inhibitors) I further showed that RICTOR controlled HIF-1β expression through an mTOR-PKC signaling axis, independently of AKT activity. Finally, I demonstrated that HIF-1β levels correlated with mTORC2 activation in vivo, in a mouse model of RICTOR OE. Taken together, my results highlight HIF-1β as a clinically relevant target and support targeting of hypoxia-mediated metabolism as a potential therapeutic approach for the treatment of lung cancer.


Book
High-Intensity Exercise in Hypoxia - Beneficial Aspects and Potential Drawbacks
Authors: --- ---
Year: 2018 Publisher: Frontiers Media SA

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In the past, ‘traditional’ moderate-intensity continuous training (60-75% peak heart rate) was the type of physical activity most frequently recommended for both athletes and clinical populations (cf. American College of Sports Medicine guidelines). However, growing evidence indicates that high-intensity interval training (80-100% peak heart rate) could actually be associated with larger cardiorespiratory fitness and metabolic function benefits and, thereby, physical performance gains for athletes. Similarly, recent data in obese and hypertensive individuals indicate that various mechanisms – further improvement in endothelial function, reductions in sympathetic neural activity, or in arterial stiffness – might be involved in the larger cardiovascular protective effects associated with training at high exercise intensities. Concerning hypoxic training, similar trends have been observed from ‘traditional’ prolonged altitude sojourns (‘Live High Train High’ or ‘Live High Train Low’), which result in increased hemoglobin mass and blood carrying capacity. Recent innovative ‘Live Low Train High’ methods (‘Resistance Training in Hypoxia’ or ‘Repeated Sprint Training in Hypoxia’) have resulted in peripheral adaptations, such as hypertrophy or delay in muscle fatigue. Other interventions inducing peripheral hypoxia, such as vascular occlusion during endurance/resistance training or remote ischemic preconditioning (i.e. succession of ischemia/reperfusion episodes), have been proposed as methods for improving subsequent exercise performance or altitude tolerance (e.g. reduced severity of acute-mountain sickness symptoms). Postulated mechanisms behind these metabolic, neuro-humoral, hemodynamics, and systemic adaptations include stimulation of nitric oxide synthase, increase in anti-oxidant enzymes, and down-regulation of pro-inflammatory cytokines, although the amount of evidence is not yet significant enough. Improved O2 delivery/utilization conferred by hypoxic training interventions might also be effective in preventing and treating cardiovascular diseases, as well as contributing to improve exercise tolerance and health status of patients. For example, in obese subjects, combining exercise with hypoxic exposure enhances the negative energy balance, which further reduces weight and improves cardio-metabolic health. In hypertensive patients, the larger lowering of blood pressure through the endothelial nitric oxide synthase pathway and the associated compensatory vasodilation is taken to reflect the superiority of exercising in hypoxia compared to normoxia. A hypoxic stimulus, in addition to exercise at high vs. moderate intensity, has the potential to further ameliorate various aspects of the vascular function, as observed in healthy populations. This may have clinical implications for the reduction of cardiovascular risks. Key open questions are therefore of interest for patients suffering from chronic vascular or cellular hypoxia (e.g. work-rest or ischemia/reperfusion intermittent pattern; exercise intensity; hypoxic severity and exposure duration; type of hypoxia (normobaric vs. hypobaric); health risks; magnitude and maintenance of the benefits). Outside any potential beneficial effects of exercising in O2-deprived environments, there may also be long-term adverse consequences of chronic intermittent severe hypoxia. Sleep apnea syndrome, for instance, leads to oxidative stress and the production of reactive oxygen species, and ultimately systemic inflammation. Postulated pathophysiological changes associated with intermittent hypoxic exposure include alteration in baroreflex activity, increase in pulmonary arterial pressure and hematocrit, changes in heart structure and function, and an alteration in endothelial-dependent vasodilation in cerebral and muscular arteries. There is a need to explore the combination of exercising in hypoxia and association of hypertension, developmental defects, neuro-pathological and neuro-cognitive deficits, enhanced susceptibility to oxidative injury, and possibly increased myocardial and cerebral infarction in individuals sensitive to hypoxic stress. The aim of this Research Topic is to shed more light on the transcriptional, vascular, hemodynamics, neuro-humoral, and systemic consequences of training at high intensities under various hypoxic conditions.


Book
High-Intensity Exercise in Hypoxia - Beneficial Aspects and Potential Drawbacks
Authors: --- ---
Year: 2018 Publisher: Frontiers Media SA

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Abstract

In the past, ‘traditional’ moderate-intensity continuous training (60-75% peak heart rate) was the type of physical activity most frequently recommended for both athletes and clinical populations (cf. American College of Sports Medicine guidelines). However, growing evidence indicates that high-intensity interval training (80-100% peak heart rate) could actually be associated with larger cardiorespiratory fitness and metabolic function benefits and, thereby, physical performance gains for athletes. Similarly, recent data in obese and hypertensive individuals indicate that various mechanisms – further improvement in endothelial function, reductions in sympathetic neural activity, or in arterial stiffness – might be involved in the larger cardiovascular protective effects associated with training at high exercise intensities. Concerning hypoxic training, similar trends have been observed from ‘traditional’ prolonged altitude sojourns (‘Live High Train High’ or ‘Live High Train Low’), which result in increased hemoglobin mass and blood carrying capacity. Recent innovative ‘Live Low Train High’ methods (‘Resistance Training in Hypoxia’ or ‘Repeated Sprint Training in Hypoxia’) have resulted in peripheral adaptations, such as hypertrophy or delay in muscle fatigue. Other interventions inducing peripheral hypoxia, such as vascular occlusion during endurance/resistance training or remote ischemic preconditioning (i.e. succession of ischemia/reperfusion episodes), have been proposed as methods for improving subsequent exercise performance or altitude tolerance (e.g. reduced severity of acute-mountain sickness symptoms). Postulated mechanisms behind these metabolic, neuro-humoral, hemodynamics, and systemic adaptations include stimulation of nitric oxide synthase, increase in anti-oxidant enzymes, and down-regulation of pro-inflammatory cytokines, although the amount of evidence is not yet significant enough. Improved O2 delivery/utilization conferred by hypoxic training interventions might also be effective in preventing and treating cardiovascular diseases, as well as contributing to improve exercise tolerance and health status of patients. For example, in obese subjects, combining exercise with hypoxic exposure enhances the negative energy balance, which further reduces weight and improves cardio-metabolic health. In hypertensive patients, the larger lowering of blood pressure through the endothelial nitric oxide synthase pathway and the associated compensatory vasodilation is taken to reflect the superiority of exercising in hypoxia compared to normoxia. A hypoxic stimulus, in addition to exercise at high vs. moderate intensity, has the potential to further ameliorate various aspects of the vascular function, as observed in healthy populations. This may have clinical implications for the reduction of cardiovascular risks. Key open questions are therefore of interest for patients suffering from chronic vascular or cellular hypoxia (e.g. work-rest or ischemia/reperfusion intermittent pattern; exercise intensity; hypoxic severity and exposure duration; type of hypoxia (normobaric vs. hypobaric); health risks; magnitude and maintenance of the benefits). Outside any potential beneficial effects of exercising in O2-deprived environments, there may also be long-term adverse consequences of chronic intermittent severe hypoxia. Sleep apnea syndrome, for instance, leads to oxidative stress and the production of reactive oxygen species, and ultimately systemic inflammation. Postulated pathophysiological changes associated with intermittent hypoxic exposure include alteration in baroreflex activity, increase in pulmonary arterial pressure and hematocrit, changes in heart structure and function, and an alteration in endothelial-dependent vasodilation in cerebral and muscular arteries. There is a need to explore the combination of exercising in hypoxia and association of hypertension, developmental defects, neuro-pathological and neuro-cognitive deficits, enhanced susceptibility to oxidative injury, and possibly increased myocardial and cerebral infarction in individuals sensitive to hypoxic stress. The aim of this Research Topic is to shed more light on the transcriptional, vascular, hemodynamics, neuro-humoral, and systemic consequences of training at high intensities under various hypoxic conditions.


Book
High-Intensity Exercise in Hypoxia - Beneficial Aspects and Potential Drawbacks
Authors: --- ---
Year: 2018 Publisher: Frontiers Media SA

Loading...
Export citation

Choose an application

Bookmark

Abstract

In the past, ‘traditional’ moderate-intensity continuous training (60-75% peak heart rate) was the type of physical activity most frequently recommended for both athletes and clinical populations (cf. American College of Sports Medicine guidelines). However, growing evidence indicates that high-intensity interval training (80-100% peak heart rate) could actually be associated with larger cardiorespiratory fitness and metabolic function benefits and, thereby, physical performance gains for athletes. Similarly, recent data in obese and hypertensive individuals indicate that various mechanisms – further improvement in endothelial function, reductions in sympathetic neural activity, or in arterial stiffness – might be involved in the larger cardiovascular protective effects associated with training at high exercise intensities. Concerning hypoxic training, similar trends have been observed from ‘traditional’ prolonged altitude sojourns (‘Live High Train High’ or ‘Live High Train Low’), which result in increased hemoglobin mass and blood carrying capacity. Recent innovative ‘Live Low Train High’ methods (‘Resistance Training in Hypoxia’ or ‘Repeated Sprint Training in Hypoxia’) have resulted in peripheral adaptations, such as hypertrophy or delay in muscle fatigue. Other interventions inducing peripheral hypoxia, such as vascular occlusion during endurance/resistance training or remote ischemic preconditioning (i.e. succession of ischemia/reperfusion episodes), have been proposed as methods for improving subsequent exercise performance or altitude tolerance (e.g. reduced severity of acute-mountain sickness symptoms). Postulated mechanisms behind these metabolic, neuro-humoral, hemodynamics, and systemic adaptations include stimulation of nitric oxide synthase, increase in anti-oxidant enzymes, and down-regulation of pro-inflammatory cytokines, although the amount of evidence is not yet significant enough. Improved O2 delivery/utilization conferred by hypoxic training interventions might also be effective in preventing and treating cardiovascular diseases, as well as contributing to improve exercise tolerance and health status of patients. For example, in obese subjects, combining exercise with hypoxic exposure enhances the negative energy balance, which further reduces weight and improves cardio-metabolic health. In hypertensive patients, the larger lowering of blood pressure through the endothelial nitric oxide synthase pathway and the associated compensatory vasodilation is taken to reflect the superiority of exercising in hypoxia compared to normoxia. A hypoxic stimulus, in addition to exercise at high vs. moderate intensity, has the potential to further ameliorate various aspects of the vascular function, as observed in healthy populations. This may have clinical implications for the reduction of cardiovascular risks. Key open questions are therefore of interest for patients suffering from chronic vascular or cellular hypoxia (e.g. work-rest or ischemia/reperfusion intermittent pattern; exercise intensity; hypoxic severity and exposure duration; type of hypoxia (normobaric vs. hypobaric); health risks; magnitude and maintenance of the benefits). Outside any potential beneficial effects of exercising in O2-deprived environments, there may also be long-term adverse consequences of chronic intermittent severe hypoxia. Sleep apnea syndrome, for instance, leads to oxidative stress and the production of reactive oxygen species, and ultimately systemic inflammation. Postulated pathophysiological changes associated with intermittent hypoxic exposure include alteration in baroreflex activity, increase in pulmonary arterial pressure and hematocrit, changes in heart structure and function, and an alteration in endothelial-dependent vasodilation in cerebral and muscular arteries. There is a need to explore the combination of exercising in hypoxia and association of hypertension, developmental defects, neuro-pathological and neuro-cognitive deficits, enhanced susceptibility to oxidative injury, and possibly increased myocardial and cerebral infarction in individuals sensitive to hypoxic stress. The aim of this Research Topic is to shed more light on the transcriptional, vascular, hemodynamics, neuro-humoral, and systemic consequences of training at high intensities under various hypoxic conditions.


Book
Cadmium Sources and Toxicity
Author:
ISBN: 3038979856 3038979848 Year: 2019 Publisher: MDPI - Multidisciplinary Digital Publishing Institute

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Abstract

Cadmium (Cd) is an environmental toxicant of continuing public health concern worldwide, because total diet studies have shown that Cd is present in virtually all foodstuffs. Consequently, foods that are frequently consumed in large quantities, such as rice, potatoes, wheat, leafy salad vegetables, and other cereal crops, are the most significant dietary Cd sources. Moreover, Cd has chemical propensities that confer the potential to interfere with the physiological functions of calcium and zinc. Evidence of a wide range of diverse, toxic effects of Cd is increasingly apparent. In this collection, environmental Cd exposure is linked to an increased risk of chronic kidney disease that is known to be a cause of morbidity and mortality worldwide. Cd is also implicated in an early onset of menarche and deaths from cancer, especially in the uterus, kidney, and urinary tract. Moreover, Cd-induced kidney injury is replicated in Sprague Dawley rats, as is Cd-induced periodontal disease. Experimental studies suggest that the development of kidneys in fetuses and the function of insulin-producing cells may be adversely affected by Cd and that metformin, an anti-diabetic drug, is ineffective in Cd-intoxicated Wistar rats.


Book
Pleiotropic Action of Selenium in the Prevention and Treatment of Cancer, and Related Diseases
Author:
Year: 2019 Publisher: MDPI - Multidisciplinary Digital Publishing Institute

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This book will cover topics related to the preparation and use of heterogeneous catalytic systems for the transformation of renewable sources, as well as of materials deriving from agro-industrial wastes and by-products. At the same time, the ever-increasing importance of bioproducts, due to the acceptance and request of consumers, makes the upgrade of biomass into chemicals and materials not only an environmental issue, but also an economical advantage.


Book
Marine Bioactive Natural Product Studies—A Southern Hemisphere Perspective
Author:
Year: 2020 Publisher: Basel, Switzerland MDPI - Multidisciplinary Digital Publishing Institute

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The search for bioactive secondary metabolites from marine organisms has been an active area of research since the 1950s. The distinct biodiversity of the marine environment has afforded a vast array of unique secondary metabolites, many of which possess potent biological activities. This Special Issue of Marine Drugs will highlight recent bioactive marine natural product studies conducted by southern hemisphere scientists on an array of marine organisms.

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