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Targeted Oncology Dec 2012Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO)... (Review)
Review
Hypoxia is a critical hallmark of solid tumors and involves enhanced cell survival, angiogenesis, glycolytic metabolism, and metastasis. Hyperbaric oxygen (HBO) treatment has for centuries been used to improve or cure disorders involving hypoxia and ischemia, by enhancing the amount of dissolved oxygen in the plasma and thereby increasing O(2) delivery to the tissue. Studies on HBO and cancer have up to recently focused on whether enhanced oxygen acts as a cancer promoter or not. As oxygen is believed to be required for all the major processes of wound healing, one feared that the effects of HBO would be applicable to cancer tissue as well and promote cancer growth. Furthermore, one also feared that exposing patients who had been treated for cancer, to HBO, would lead to recurrence. Nevertheless, two systematic reviews on HBO and cancer have concluded that the use of HBO in patients with malignancies is considered safe. To supplement the previous reviews, we have summarized the work performed on HBO and cancer in the period 2004-2012. Based on the present as well as previous reviews, there is no evidence indicating that HBO neither acts as a stimulator of tumor growth nor as an enhancer of recurrence. On the other hand, there is evidence that implies that HBO might have tumor-inhibitory effects in certain cancer subtypes, and we thus strongly believe that we need to expand our knowledge on the effect and the mechanisms behind tumor oxygenation.
Topics: Animals; Cell Hypoxia; Cell Respiration; Clinical Trials as Topic; Humans; Hyperbaric Oxygenation; Neoplasms; Oxygen
PubMed: 23054400
DOI: 10.1007/s11523-012-0233-x -
Biomolecules Jun 2020Effective metabolism is highly dependent on a narrow therapeutic range of oxygen. Accordingly, low levels of oxygen, or hypoxia, are one of the most powerful inducers of... (Review)
Review
Effective metabolism is highly dependent on a narrow therapeutic range of oxygen. Accordingly, low levels of oxygen, or hypoxia, are one of the most powerful inducers of gene expression, metabolic changes, and regenerative processes, including angiogenesis and stimulation of stem cell proliferation, migration, and differentiation. The sensing of decreased oxygen levels (hypoxia) or increased oxygen levels (hyperoxia), occurs through specialized chemoreceptor cells and metabolic changes at the cellular level, which regulate the response. Interestingly, fluctuations in the free oxygen concentration rather than the absolute level of oxygen can be interpreted at the cellular level as a lack of oxygen. Thus, repeated intermittent hyperoxia can induce many of the mediators and cellular mechanisms that are usually induced during hypoxia. This is called the hyperoxic-hypoxic paradox (HHP). This article reviews oxygen physiology, the main cellular processes triggered by hypoxia, and the cascade of events triggered by the HHP.
Topics: Animals; Cell Hypoxia; Humans; Hyperoxia; Oxygen
PubMed: 32630465
DOI: 10.3390/biom10060958 -
Virology Journal Jul 2020The oxygen levels organ and tissue microenvironments vary depending on the distance of their vasculature from the left ventricle of the heart. For instance, the oxygen... (Review)
Review
The oxygen levels organ and tissue microenvironments vary depending on the distance of their vasculature from the left ventricle of the heart. For instance, the oxygen levels of lymph nodes and the spleen are significantly lower than that in atmospheric air. Cellular detection of oxygen and their response to low oxygen levels can exert a significant impact on virus infection. Generally, viruses that naturally infect well-oxygenated organs are less able to infect cells under hypoxic conditions. Conversely, viruses that infect organs under lower oxygen tensions thrive under hypoxic conditions. This suggests that in vitro experiments performed exclusively under atmospheric conditions ignores oxygen-induced modifications in both host and viral responses. Here, we review the mechanisms of how cells adapt to low oxygen tensions and its impact on viral infections. With growing evidence supporting the role of oxygen microenvironments in viral infections, this review highlights the importance of factoring oxygen concentrations into in vitro assay conditions. Bridging the gap between in vitro and in vivo oxygen tensions would allow for more physiologically representative insights into viral pathogenesis.
Topics: Cell Hypoxia; Humans; Oxygen; Virus Diseases; Viruses
PubMed: 32718318
DOI: 10.1186/s12985-020-01374-2 -
Clinical Oncology (Royal College of... Nov 2021Regions of reduced oxygenation (hypoxia) are a characteristic feature of virtually all animal and human solid tumours. Numerous preclinical studies, both in vitro and... (Review)
Review
Regions of reduced oxygenation (hypoxia) are a characteristic feature of virtually all animal and human solid tumours. Numerous preclinical studies, both in vitro and in vivo, have shown that decreasing oxygen concentration induces resistance to radiation. Importantly, hypoxia in human tumours is a negative indicator of radiotherapy outcome. Hypoxia also contributes to resistance to other cancer therapeutics, including immunotherapy, and increases malignant progression as well as cancer cell dissemination. Consequently, substantial effort has been made to detect hypoxia in human tumours and identify realistic approaches to overcome hypoxia and improve cancer therapy outcomes. Hypoxia-targeting strategies include improving oxygen availability, sensitising hypoxic cells to radiation, preferentially killing these cells, locating the hypoxic regions in tumours and increasing the radiation dose to those areas, or applying high energy transfer radiation, which is less affected by hypoxia. Despite numerous clinical studies with each of these hypoxia-modifying approaches, many of which improved both local tumour control and overall survival, hypoxic modification has not been established in routine clinical practice. Here we review the background and significance of hypoxia, how it can be imaged clinically and focus on the various hypoxia-modifying techniques that have undergone, or are currently in, clinical evaluation.
Topics: Animals; Cell Hypoxia; Humans; Hypoxia; Neoplasms; Oxygen
PubMed: 34535359
DOI: 10.1016/j.clon.2021.08.014 -
Cells Aug 2021Recently, the research on stemness and multilineage differentiation mechanisms has greatly increased its value due to the potential therapeutic impact of stem cell-based... (Review)
Review
Recently, the research on stemness and multilineage differentiation mechanisms has greatly increased its value due to the potential therapeutic impact of stem cell-based approaches. Stem cells modulate their self-renewing and differentiation capacities in response to endogenous and/or extrinsic factors that can control stem cell fate. One key factor controlling stem cell phenotype is oxygen (O). Several pieces of evidence demonstrated that the complexity of reproducing O physiological tensions and gradients in culture is responsible for defective stem cell behavior in vitro and after transplantation. This evidence is still worsened by considering that stem cells are conventionally incubated under non-physiological air O tension (21%). Therefore, the study of mechanisms and signaling activated at lower O tension, such as those existing under native microenvironments (referred to as hypoxia), represent an effective strategy to define if O is essential in preserving naïve stemness potential as well as in modulating their differentiation. Starting from this premise, the goal of the present review is to report the status of the art about the link existing between hypoxia and stemness providing insight into the factors/molecules involved, to design targeted strategies that, recapitulating naïve O signals, enable towards the therapeutic use of stem cell for tissue engineering and regenerative medicine.
Topics: Animals; Cell Differentiation; Cell Hypoxia; Humans; Oxygen; Stem Cells
PubMed: 34440930
DOI: 10.3390/cells10082161 -
The British Journal of Radiology Mar 2019Hypoxia is known to be a poor prognostic indicator for nearly all solid tumours and also is predictive of treatment failure for radiotherapy, chemotherapy, surgery and... (Review)
Review
Hypoxia is known to be a poor prognostic indicator for nearly all solid tumours and also is predictive of treatment failure for radiotherapy, chemotherapy, surgery and targeted therapies. Imaging has potential to identify, spatially map and quantify tumour hypoxia prior to therapy, as well as track changes in hypoxia on treatment. At present no hypoxia imaging methods are available for routine clinical use. Research has largely focused on positron emission tomography (PET)-based techniques, but there is gathering evidence that MRI techniques may provide a practical and more readily translational alternative. In this review we focus on the potential for imaging hypoxia by measuring changes in longitudinal relaxation [R; termed oxygen-enhanced MRI or tumour oxygenation level dependent (TOLD) MRI] and effective transverse relaxation [R*; termed blood oxygenation level dependent (BOLD) MRI], induced by inhalation of either 100% oxygen or the radiosensitising hyperoxic gas carbogen. We explain the scientific principles behind oxygen-enhanced MRI and BOLD and discuss significant studies and their limitations. All imaging biomarkers require rigorous validation in order to translate into clinical use and the steps required to further develop oxygen-enhanced MRI and BOLD MRI into decision-making tools are discussed.
Topics: Biomarkers; Contrast Media; Humans; Magnetic Resonance Imaging; Neoplasms; Oxygen; Tumor Hypoxia
PubMed: 30272998
DOI: 10.1259/bjr.20180642 -
California Medicine Oct 1952ACCURATE EVALUATION OF THE DEGREE OF IMPAIRMENT OF PULMONARY FUNCTION IN PERSONS WITH FIBROSIS AND EMPHYSEMA REQUIRES: (1) ventilatory measurements from rapid spirogram...
ACCURATE EVALUATION OF THE DEGREE OF IMPAIRMENT OF PULMONARY FUNCTION IN PERSONS WITH FIBROSIS AND EMPHYSEMA REQUIRES: (1) ventilatory measurements from rapid spirogram tracings (vital capacity, maximal breathing capacity and the time required to blow the air from the lungs); (2) determination of the degree of bronchospasm present; (3) determination of the degree of pulmonary emphysema (residual air expressed quantitatively as percent of total lung volume); (4) determination of the arterial blood oxygen saturation at rest and immediately after step-up exercise; (5) measurement of the oxygen extraction from inspired air (per cent of oxygen removed) during rest and exercise; (6) determination of the oxygen up-take during exercise; and (7) observation of the duration of dyspnea after step-up exercise. No single physiologic test is adequate in evaluating impairment of pulmonary function, and roentgenograms of the chest are unreliable as a sole basis for appraisal of disability. In industrial medicine, pulmonary function studies make possible (a) more accurate diagnosis and evaluation of pulmonary disability; and (b) earlier detection and thus prevention of prolonged exposure by susceptible individuals to environmental hazards.
Topics: Cell Respiration; Dyspnea; Emphysema; Exercise; Humans; Lung; Male; Oxygen; Pulmonary Emphysema; Respiration; Respiratory Function Tests; Vital Capacity
PubMed: 13009463
DOI: No ID Found -
Plant & Cell Physiology Nov 2021Oxygen is essential for multicellular aerobic life due to its central role in energy metabolism. The availability of oxygen can drop below the level to sustain oxidative... (Review)
Review
Oxygen is essential for multicellular aerobic life due to its central role in energy metabolism. The availability of oxygen can drop below the level to sustain oxidative phosphorylation when plants are flooded, posing a severe threat to survival. However, under non-stressful conditions, the internal oxygen concentration of most plant tissue is not in equilibrium with the environment, which is attributed to cellular respiration and diffusion constrains imposed by O2 barriers and bulky tissue. This is exemplified by the observations of steep oxygen gradients in roots, fruits, tubers, anthers and meristems. To adapt to a varying availability of oxygen, plants sense O2 via the conditional proteolysis of transcriptional regulators. This mechanism acts to switch oxidative metabolism to anaerobic fermentation, but it was also shown to play a role in plant development and pathogen defense. To investigate how dynamic and spatial distribution of O2 impacts on these processes, accurate mapping of its concentration in plants is essential. Physical oxygen sensors have been employed for decades to profile internal oxygen concentrations in plants, while genetically encoded oxygen biosensors have only recently started to see use. Driven by the critical role of hypoxia in human pathology and development, several novel oxygen-sensing devices have also been characterized in cell lines and animal model organisms. This review aims to provide an overview of available oxygen biosensors and to discuss their potential application to image oxygen levels in plants.
Topics: Biosensing Techniques; Cell Respiration; Intravital Microscopy; Oxygen; Plant Cells
PubMed: 33725087
DOI: 10.1093/pcp/pcab039 -
Experimental Cell Research Jul 2017There are numerous mechanisms by which mammals respond to hypoxia. These include acute changes in pulmonary arterial tone due to smooth muscle cell contraction, acute... (Review)
Review
There are numerous mechanisms by which mammals respond to hypoxia. These include acute changes in pulmonary arterial tone due to smooth muscle cell contraction, acute increases in respiration triggered by the carotid body chemosensory cells, and chronic changes such as induction of red blood cell proliferation and angiogenesis by hypoxia inducible factor targets erythropoietin and vascular endothelial growth factor, respectively. Mitochondria account for the majority of oxygen consumption in the cell and have recently been appreciated to serve as signaling organelles required for the initiation or propagation of numerous homeostatic mechanisms. Mitochondria can influence cell signaling by production of reactive oxygen species and metabolites. Here we review recent evidence that mitochondrial signals can imitate acute and chronic hypoxia responses.
Topics: Animals; Cell Hypoxia; Homeostasis; Humans; Hypoxia; Mitochondria; Oxygen; Reactive Oxygen Species
PubMed: 28327410
DOI: 10.1016/j.yexcr.2017.03.034 -
Nature Communications Nov 2023Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant...
Implantable cell therapies and tissue transplants require sufficient oxygen supply to function and are limited by a delay or lack of vascularization from the transplant host. Previous exogenous oxygenation strategies have been bulky and had limited oxygen production or regulation. Here, we show an electrocatalytic approach that enables bioelectronic control of oxygen generation in complex cellular environments to sustain engineered cell viability and therapy under hypoxic stress and at high cell densities. We find that nanostructured sputtered iridium oxide serves as an ideal catalyst for oxygen evolution reaction at neutral pH. We demonstrate that this approach exhibits a lower oxygenation onset and selective oxygen production without evolution of toxic byproducts. We show that this electrocatalytic on site oxygenator can sustain high cell loadings (>60k cells/mm) in hypoxic conditions in vitro and in vivo. Our results showcase that exogenous oxygen production devices can be readily integrated into bioelectronic platforms, enabling high cell loadings in smaller devices with broad applicability.
Topics: Humans; Oxygen; Hypoxia; Cell Hypoxia; Respiratory Physiological Phenomena
PubMed: 37945597
DOI: 10.1038/s41467-023-42697-2