Hypoxia Cancer Research Results
Hypoxia, Hypoxia: Click to Expand ⟱
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Deprived of adequate oxygen supply at the tissue level.
Hypoxia, a condition characterized by insufficient oxygen levels in tissues.
Cancer cells can adapt to hypoxic conditions through various mechanisms. They may activate hypoxia-inducible factors (HIFs), which are transcription factors that help cells respond to low oxygen levels. HIFs promote the expression of genes involved in angiogenesis (formation of new blood vessels), metabolism, and survival.
Tumors with high levels of hypoxia may be more aggressive and less responsive to treatment.
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Scientific Papers found: Click to Expand⟱
TumCP↓, β-caryophyllene (BCP) exhibits anti-proliferative properties in cancer cells.
CB2 / CNR2↓, BCP is able to interact with the CB2 receptor with nM affinity although the concentrations that affect signaling are in the low μM range
STAT3↓, BCP also reduces proliferation by blocking the STAT3/mTOR/AKT signaling path
mTOR↓,
Akt↓,
Hypoxia↓, we hypothesized that BCP might reverse the hypoxic phenotype of TNBC cells.
other↝, Cancer cells exhibit a unique metabolic preference for the glycolytic pathway over oxidative phosphorylation for maintaining the tumor microenvironment.
Glycolysis↓, Diclofenac (DCF), a nonsteroidal anti-inflammatory drug, has been shown to exhibit anticancer effects by interfering with the glucose metabolism pathway.
LDHA↓, DCF binds to LDHA adjacent to the substrate binding site and inhibits its activity in a dose-dependent and allosteric manner in HeLa cells.
Hypoxia↓, Thus, DCF inhibits the hypoxic microenvironment and induces apoptosis-mediated cell death.
Apoptosis↑,
lactateProd↓, DCF-induced LDHA inhibition alters pyruvate, lactate, NAD+, and ATP production in cells, and this could be a possible mechanism through which DCF inhibits glucose uptake in cancer cells.
ATP↓, DCF-induced ATP deprivation leads to mitochondria-mediated oxidative stress, which results in DNA damage, lipid peroxidation, and apoptosis-mediated cell death.
mt-ROS↑,
DNAdam↑,
lipid-P↑,
AMPK↑, Reduction in intracellular ATP levels additionally activates the sensor kinase, adenosine monophosphate-activated protein kinase (AMPK), which further downregulates phosphorylated ribosomal S6 kinase (p-S6K), leading to apoptosis-mediated cell death.
p‑S6K↓,
TumCP↓, DCF inhibits proliferation in HeLa cells
Dose↝, HeLa cells with an IC50 dose of 175 ± 4.86 μm on 24 h of incubation
selectivity↑, DCF did not significantly affect the viability of normal cervical cells at 175 μm (IC50 dose in HeLa cells), where the IC50 value was found to be greater than 1 mm concentration of DCF (
i-MDA↑, The result showed that DCF treatment in HeLa cells led to a significant increase in MDA levels, suggesting an increased level of lipid peroxidation
mtDam↑, Many reports suggest that there is a strong correlation between the inhibition of LDHA and the induction of oxidative stress (ROS production) via mitochondrial damage
*Hypoxia↓, Neurotrophin-3, originating from Müller glial cells in the retina, plays a key role in protecting photoreceptors from damage induced by light or hypoxia.
*NTF3/NT-3↑, we demonstrated that the water extract of E. longifolia roots enhanced neurotrophin-3 gene expression in primary rat Müller cells.
*other↑, this study suggests that E. longifolia may be promising for improving eye health and must be further investigated.
*Half-Life↓, However, their clinical application presents challenges owing to their short plasma half-life (1.28 and 0.92 min for NT3 and BDNF, respectively) after intravenous administration
Dose↝, Body temperature during heating was maintained at 39.5 ± 0.5 °C for 4 h
BloodF↑, Heating tumour-bearing mice resulted in significant decrease in intratumoural IFP, increased the number of perfused tumour blood vessels as well as relative tumour perfusion in both tumour models
Hypoxia↓, Intratumoural hypoxia was also reduced in tumours of mice that received heat treatment.
RadioS?, Mice bearing FaDu tumours heated 24 h prior to five daily radiation treatments exhibited significantly enhanced tumour response compared to tumours in control mice.
NA↑, As an adjunct to radiotherapy and chemotherapy, hyperthermia enhances the therapeutic efficacy against both primary and recurrent tumors.
RadioS↑, The present review explores the mechanisms underlying the synergy between radiotherapy and hyperthermia, while reviewing the outcomes of relevant clinical trials.
DNArepair↓, Key mechanisms of action include inhibition of DNA repair, reduction of hypoxic tumor cell populations, enhancement of drug uptake and improved perfusion and oxygenation.
Hypoxia↓,
EPR↑,
LC↑, Its application has improved both local control and overall survival (OS),
OS↑,
*toxicity↓, Randomized clinical trials (4–6) have demonstrated that combined therapy effectively prolongs disease-free survival and ensures local tumor control without added toxicity.
Dose↝, fever-range temperatures (39–40°C), moderate heating to induce cellular stress (41–43°C) and high-intensity thermal ablation >43°C for cell destruction.
BloodF↑, Hyperthermia is particularly toxic to cells in acidic environments (29), and increased blood flow helps clear acidic metabolites, restore normal extracellular pH
pH↝,
Imm↑, Under heat stress, tumor cells release heat shock protein 70 (HSP70), triggering antitumor immune responses
HSP70/HSPA5↑,
RadioS↑, mild hyperthermia (HT) represents an old, but recently revived opportunity to increase the efficacy of radiotherapy (RT) without increasing side effects, thereby widening the therapeutic window.
DNArepair↓, associated to DNA damage and repair, hypoxia, stemness and immunostimulation.
Hypoxia↓,
CSCs↓, Some evidences suggests that HT may be able to radiosensitize CSCs, as well as quiescent tumor cells,
Imm↑, Heat-induced activation of the immune system is mediated by heat shock proteins (HSPs); they increase antigen presentation and maturation of dendritic cells,
pH↝, regains a normal oxygen partial pressure (pO2), a normal concentration of nutrients and a normal pH, which reverse the established radioresistance
HSPs↑,
ROS↑, Hyperthermia potentializes the effects of irradiation by reducing DNA damage repair, increasing oxygen levels by vessel dilation, increasing ROS,
eff↑, An increasing number of preclinical and clinical studies are focusing on heating tumors with nanoparticles
LC↑, moderate RHT in improving local tumour control, survival outcomes and quality of life scores were observed across the different cancer subsites with minimal increase in toxicities.
OS↑,
QoL↑,
toxicity↓,
Dose↝, Various heating methods include direct (e.g., intracavitary and whole-body waterbed), infrared, perfusional (e.g., isolated limb perfusion, intravesical and intraperitoneal), nanoparticles, ultrasound and regional radiofrequency (RF) radiation
Dose↝, Moderate HT is usually described at a range of 39–44 °C a
ROS↑, Figure 1
DNArepair↓,
EPR↑,
DNAdam↑,
HSP70/HSPA5↑,
BloodF↑,
Hypoxia↓,
RadioS↑, Mild hyperthermia (mHT, 39–42 °C) is a potent modality when combined with existing radio-, chemo-, or immunotherapy, leading to enhanced microcirculatory blood flow and improved tumor oxygenation
ChemoSen↑, Hyperthermia enhances cytotoxicity of anticancer drugs:
Imm↑,
BloodF↑,
Hypoxia↓, HT-induced improvements of tumor oxygenation status (“reversal of tumor hypoxia”) a
Dose↝, Mild hyperthermia (mHT, 39–42 °C) is a potent cancer treatment modality when delivered in conjunction with radiotherapy.
DNArepair↓, Hyperthermia inhibits DNA repair enzymes: In the upper range of mHT (41–43 °C), several DNA damage repair enzymes responsible for the repair
e-pH↓, Tissue exposure to mHT triggers a series of events that aggravate tumor tissue acidosis (pH↓), finally reaching extracellular pH values of ≈ 6.20:
Hypoxia↓, There is now abundant evidence that oxygenation in rodent, canine and human tumors is improved during and for up to 1-2 days after heating at mild temperatures.
OCR↓, An increase in tumor blood perfusion along with a decline in the oxygen consumption rate appears to account for the improvement of tumor oxygenation by mild hyperthermia
RadioS↑, However, mild hyperthermia is far more effective than carbogen breathing in increasing the radiation response of experimental tumors,
eff↑, The combination of mild hyperthermia with carbogen or nicotinamide is highly effective in reducing the hypoxic cell fraction in tumors and increasing the radiation response of experimental tumors.
Dose↝, However, it is relatively easy to raise the temperature of human tumors into the range of 39-42 degrees C, which is a temperature that can improve tumor oxygenation for up to 1-2 days.
Hypoxia↓,
mitResp↓,
ROS↑, the production of reactive oxygen species would be increase which, in turn, improves the efficacy of PDT against hypoxic tumors.
Showing Research Papers: 1 to 10 of 10
* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 10
Pathway results for Effect on Cancer / Diseased Cells:
NA, unassigned(tgid=0) ⓘ
LC↑, 2, NA↑, 1,
Redox & Oxidative Stress(tgid=1) ⓘ
lipid-P↑, 1, i-MDA↑, 1, ROS↑, 3, mt-ROS↑, 1,
Mitochondria & Bioenergetics(tgid=3) ⓘ
ATP↓, 1, mitResp↓, 1, mtDam↑, 1, OCR↓, 1,
Core Metabolism/Glycolysis(tgid=4) ⓘ
AMPK↑, 1, Glycolysis↓, 1, lactateProd↓, 1, LDHA↓, 1, p‑S6K↓, 1,
Cell Death(tgid=5) ⓘ
Akt↓, 1, Apoptosis↑, 1,
Transcription & Epigenetics(tgid=7) ⓘ
other↝, 1,
Protein Folding & ER Stress(tgid=8) ⓘ
HSP70/HSPA5↑, 2, HSPs↑, 1,
DNA Damage & Repair(tgid=10) ⓘ
DNAdam↑, 2, DNArepair↓, 4,
Proliferation, Differentiation & Cell State(tgid=12) ⓘ
CSCs↓, 1, mTOR↓, 1, STAT3↓, 1,
Migration(tgid=13) ⓘ
TumCP↓, 2,
Angiogenesis & Vasculature(tgid=14) ⓘ
EPR↑, 2, Hypoxia↓, 9,
Immune & Inflammatory Signaling(tgid=16) ⓘ
CB2 / CNR2↓, 1, Imm↑, 3,
Cellular Microenvironment(tgid=17) ⓘ
pH↝, 2, e-pH↓, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
ChemoSen↑, 1, Dose↝, 7, eff↑, 2, RadioS?, 1, RadioS↑, 4, selectivity↑, 1,
Clinical Biomarkers(tgid=22) ⓘ
BloodF↑, 4,
Functional Outcomes(tgid=23) ⓘ
OS↑, 2, QoL↑, 1, toxicity↓, 1,
Total Targets: 42
Pathway results for Effect on Normal Cells:
Transcription & Epigenetics(tgid=7) ⓘ
other↑, 1,
Angiogenesis & Vasculature(tgid=14) ⓘ
Hypoxia↓, 1,
Immune & Inflammatory Signaling(tgid=16) ⓘ
NTF3/NT-3↑, 1,
Drug Metabolism & Resistance(tgid=21) ⓘ
Half-Life↓, 1,
Functional Outcomes(tgid=23) ⓘ
toxicity↓, 1,
Total Targets: 5
Scientific Paper Hit Count for: Hypoxia, Hypoxia
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include :
-low or high Dose
-format for product, such as nano of lipid formations
-different cell line effects
-synergies with other products
-if effect was for normal or cancerous cells
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