-
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 -
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 -
The Journal of Extra-corporeal... Jun 2018Hemolysis is a known consequence of extracorporeal membrane oxygenation (ECMO) resulting from shear force within the different components of the extracorporeal circuit....
Hemolysis is a known consequence of extracorporeal membrane oxygenation (ECMO) resulting from shear force within the different components of the extracorporeal circuit. The primary aim of this study was to evaluate the EOS PMP oxygenator for generation of plasma free hemoglobin (PfHg) over 24 hours at nominal operating range flow rates. The EOS ECMO (LivaNova, Inc.; formerly Sorin, Arvada, CO) is equipped with a plasma tight polymethylpentene (PMP) hollow fiber oxygenator. We hypothesized that PfHg generation would be elevated in circuits with higher flow rates, because of the significant pressure drop across the oxygenator according to manufacturer provided flow charts. Generated PfHg concentrations were compared with PfHg concentrations from blood not exposed to an ECMO circuit. The secondary aim was to evaluate circuit flow-rate-induced changes in platelet count and platelet function over 24 hours. Circuits contained a CentriMag (St. Jude Medical, St. Paul, MN) blood pump and an EOS ECMO PMP oxygenator. Circuits in triplicate were run continuously for 24 hours at three flow rates [1, 3, and 5 liters per minute {LPM}]. PfHg was analyzed at baseline, 6, 12, 18, and 24 hours. Platelet count and function were measured at baseline and 24 hours. Concentrations of PfHg at baseline for circuits operating at 1, 3, and 5 LPM were 24.4 ± 4.0, 38.4 ± 28.6, and 26.7 ± 6.9 mg/dL, respectively. PfHg concentrations after 24 hours were statistically compared for the three flow rates using analysis of variance; PfHg concentrations at 1 LPM (181.4 ± 29.1 mg/dL), 3 LPM (145.9 ± 8.7 mg/dL), and 5 LPM (100.1 ± 111.3 mg/dL) circuits. The -test was not statistically significant ( = .632), indicating that PfHg generation at 24 hours was similar among the three flow rates. Excessive hemolysis using PfHg levels in the EOS PMP membrane oxygenator was not observed.
Topics: Extracorporeal Membrane Oxygenation; Hemoglobins; Humans; Oxygenators, Membrane; Platelet Function Tests
PubMed: 29921987
DOI: No ID Found -
The Journal of Extra-corporeal... Mar 2020To remove gaseous microemboli (GME) using an oxygenator with an integrated arterial filter, it is recommended by some manufacturers to purge the oxygenator as an...
To remove gaseous microemboli (GME) using an oxygenator with an integrated arterial filter, it is recommended by some manufacturers to purge the oxygenator as an additional safety feature while on bypass. In this in vitro study, we evaluated whether purging of oxygenators with an integrated arterial filter is efficient in reducing GME. Five different types of commercially available contemporary oxygenators with an integrated arterial filter based on progressive filter filtration (1), cascade filtration (1), screen filtration (2), or self-venting (1) were tested for their efficiency in removing GME while keeping the purge line open or closed. A bubble counter was used for pre- and post-oxygenator GME signaling, from which the filter efficiency was computed. Freshly drawn heparinized porcine blood was used at blood flow rates of 3 and 5 L/min. Three units of each oxygenator were tested with its specific reservoir at a fixed volume level of 1,500 mL. GME load was introduced into the venous line at 1,000 mL air/min. Measurements started as soon as GME were detected by the pre-oxygenator probe and then continued for 1 minute. There was no statistically significant difference in filter efficiency between the purged and non-purged groups for specific oxygenators. At a blood flow of 3 L/min, the average filter efficiency stayed approximately invariable when comparing the non-purged and purged groups, where 89.1-88.2% indicated the largest difference between the groups. At a blood flow rate of 5 L/min, the filter efficiency changed in one screen filter group from an average of 55.7% in the non-purged group to 42.4% in the purged group. Other filter efficiencies at the blood flow rate of 5 L/min for non-purged compared with purged groups were, respectively, 98.0 vs. 98.0% (screen filtration), 88.6 vs. 85.8% (self-venting filtration), 82.8 vs. 75.5% (progressive filter filtration), and 65.4 vs. 65.1% (cascade filtration). Based on these results, purging while confronted with continuous GME challenge did not result in an increased filter efficiency.
Topics: Arteries; Cardiopulmonary Bypass; Equipment Design; Oxygenators, Membrane
PubMed: 32280141
DOI: 10.1182/ject-1900022 -
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 -
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 -
The Journal of Thoracic and... Jan 2014
Topics: Extracorporeal Membrane Oxygenation; Humans; Lung Transplantation; Oxygenators, Membrane; Respiratory Insufficiency
PubMed: 24199763
DOI: 10.1016/j.jtcvs.2013.08.079 -
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 -
PloS One 2022Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and...
Current methods for identification of oxygenator clotting during prolonged extracorporeal life support include visual inspection, evaluation of oxygenator resistance and oxygen exchange performance, and assessment of clotting-related laboratory parameters. However, these observations do not provide a quantitative assessment of oxygenator clot formation. By measuring changes in the dynamic oxygenator blood volume this study aimed to evaluate the relation to oxygenator resistance and oxygen transfer performance. Sixty-seven oxygenators were studied during adult extracorporeal life support. Oxygenator blood volume, oxygenator resistance, and oxygen transfer efficiency were monitored. Oxygenator blood volume decreased with increasing runtime (r = -0.462; p <0.001). There was a statistically significant, fair negative correlation between oxygenator blood volume and oxygenator resistance (r = -0.476; p<0.001) in all oxygenators, which became stronger analyzing only exchanged oxygenators (r = -0.680; p<0.001) and oxygenators with an oxygenator blood volume <187 mL (r = 0.831; p<0.001). No relevant correlation between oxygenator blood volume and O2 transfer was found. Oxygenator blood volume declined over time and was clearly associated with an increasing oxygenator resistance during prolonged extracorporeal life support, though O2 transfer was less affected.
Topics: Adult; Blood Volume; Carbon Dioxide; Extracorporeal Membrane Oxygenation; Female; Humans; Male; Middle Aged; Monitoring, Physiologic; Oxygen; Oxygenators; Regional Blood Flow
PubMed: 35108345
DOI: 10.1371/journal.pone.0263360