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Impact of hypoxia on chemoresistance of mesothelioma mediated by the proton-coupled folate transporter, and preclinical activity of new anti-LDH-A compounds
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Background: Expression of proton-coupled folate transporter (PCFT) is associated with survival of mesothelioma patients treated with pemetrexed, and is reduced by hypoxia, prompting studies to elucidate their correlation.
Methods:
Insights into the therapeutic potential of hypoxia-inducible factor-1α small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes.
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Malignant melanoma (MM) represents the most dangerous form of skin cancer, and its incidence is expected to rise in the coming time. However, therapy for MM is limited by low topical drug concentration and multidrug resistance. This article aimed to develop folate-decorated cationic liposomes
Truncal ataxia in chronic anticonvulsant treatment. Association with drug-induced folate deficiency.
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The association of truncal ataxia with a number of different factors has been studied in a group of 95 epileptic outpatients on chronic anticonvulsant treatment. The 28 patients showing truncal ataxia had been epileptic for a longer period of time, received a significantly larger number of drugs,
Multi-Omics Integration Reveals Short and Long-Term Effects of Gestational Hypoxia on the Heart Development.
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Antenatal hypoxia caused epigenetic reprogramming of methylome and transcriptome in the developing heart and increased the risk of heart disease later in life. Herein, we investigated the impact of gestational hypoxia in proteome and metabolome in the hearts of fetus and adult offspring. Pregnant
Environmental restrictions within tumor ecosystems select for a convergent, hypoxia-resistant phenotype of cancer stem cells.
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Tumors are ecosystems which develop from stem cells endowed with unlimited self-renewal and genetic instability, under the effects of mutagenesis and natural selection imposed by environmental changes. While changes and variations made possible by genetic instability are practically unlimited, the
Cerebral perfusion and oxygenation are impaired by folate deficiency in rat: absolute measurements with noninvasive near-infrared spectroscopy.
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Brain microvascular pathology is a common finding in Alzheimer's disease and other dementias. However, the extent to which microvascular abnormalities cause or contribute to cognitive impairment is unclear. Noninvasive near-infrared spectroscopy (NIRS) can address this question, but its use for
Mild neonatal hypoxia exacerbates the effects of vitamin-deficient diet on homocysteine metabolism in rats.
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Elevated plasma homocysteine has been linked to pregnancy complications and developmental diseases. Whereas hyperhomocysteinemia is frequently observed in populations at risk of malnutrition, hypoxia may alter the remethylation of homocysteine in hepatocytes. We aimed to investigate the combined
Influence of preconditioning-like hypoxia on the liver of developing methyl-deficient rats.
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Deficiency in nutritional determinants of homocysteine (HCY) metabolism, such as vitamin B(12) and folate, during pregnancy is known to influence HCY levels in the progeny, which in turn may exert adverse effects during development, including liver defects. Since short hypoxia has been shown to
Folate pathways mediating the effects of ethanol in tumorigenesis.
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Folate and alcohol are dietary factors affecting the risk of cancer development in humans. The interaction between folate status and alcohol consumption in carcinogenesis involves multiple mechanisms. Alcoholism is typically associated with folate deficiency due to reduced dietary folate intake.
Hypoxia-resistant profile implies vulnerability of cancer stem cells to physiological agents, which suggests new therapeutic targets.
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We have previously shown that peculiar metabolic features of cell adaptation and survival in hypoxia imply growth restriction points that are typical of embryonic stem cells and disappear with differentiation. Here we provide evidence that such restrictions can be exploited as specific antiblastic
Hypoxia-stimulated tumor therapy associated with the inhibition of cancer cell stemness
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Cancer stem cells (CSCs) possess self-renewal and clonal tumor initiation capacities, which lead to drug resistance and tumor recurrence. In this work, a hypoxia-stimulated strategy based on a smart triblock vector was developed to enhance therapeutic efficacy through the inhibition of cancer
Molecular expression and functional activity of efflux and influx transporters in hypoxia induced retinal pigment epithelial cells.
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A decrease in tissue oxygen levels (aka hypoxia) mediates a number of vascular retinal diseases. Despite introduction of novel therapeutics, treatment of retinal disorders remains challenging, possibly due to complex nature of hypoxia signaling. To date, the differential effect of hypoxia on
Severe hypoxia induces complete antifolate resistance in carcinoma cells due to cell cycle arrest.
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Antifolates have a crucial role in the treatment of various cancers by inhibiting key enzymes in purine and thymidylate biosynthesis. However, the frequent emergence of inherent and acquired antifolate resistance in solid tumors calls for the development of novel therapeutic strategies to overcome
Multi-Vitamin B Supplementation Reverses Hypoxia-Induced Tau Hyperphosphorylation and Improves Memory Function in Adult Mice.
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Hypobaric hypoxia (HH) leads to reduced oxygen delivery to brain. It could trigger cognitive dysfunction and increase the risk of dementia including Alzheimer's disease (AD). The present study was undertaken in order to examine whether B vitamins (B6, B12, folate, and choline) could exert protective
Short hypoxia could attenuate the adverse effects of hyperhomocysteinemia on the developing rat brain by inducing neurogenesis.
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Gestational deficiency in methyl donors such as folate and vitamin B12 impairs homocysteine metabolism and can alter brain development in the progeny. Since short hypoxia has been shown to be neuroprotective in preconditioning studies, we aimed to investigate the effects of brief, non-lesioning
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