Dataset Information

Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression-Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study.

ABSTRACT: Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. Considering that hyperoxic exposure results in reactive oxygen species (ROS) formation, increased oxidative stress and increased Brain-Derived Neurotrophic Factor (BDNF) expression, BDNF may mediate hyperoxia effects offering cancer cells a survival advantage by increased angiogenesis and epithelial mesenchymal transition (EMT). Human breast epithelial MCF10A, human MDA-MB-231 and murine 4T1 TNBC were investigated in 2D in vitro system. Cells were exposed to normoxia or hyperoxia (40%, 60%, 80% O2) for 6 h. We evaluated ROS levels, cell viability and the expression of BDNF, HIF-1?, VEGF-R2, Vimentin and E-Cadherin by immunofluorescence. The in vivo model consisted of 4T1 inoculation in Balb/c mice and tumor resection 2 weeks after and 6 h exposure to normoxia or hyperoxia (40%, 80% O2). We measured lung metastases and the same molecular markers, immediately and 4 weeks after surgery. The in vitro study showed that short-term hyperoxia exposure (80% O2) of TNBC cells increases ROS, increases BDNF expression and that promotes EMT and angiogenesis. The in vivo data indicates that perioperative hyperoxia enhances metastatic disease and this effect could be BDNF mediated.

SUBMITTER: Tiron A

PROVIDER: S-EPMC7140073 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression-Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study.

Tiron Adrian A Ristescu Irina I Postu Paula A PA Tiron Crina E CE Zugun-Eloae Florin F Grigoras Ioana I

Cancers 20200314 3

Perioperative factors promoting cancer recurrence and metastasis are under scrutiny. While oxygen toxicity is documented in several acute circumstances, its implication in tumor evolution is poorly understood. We investigated hyperoxia long-term effects on cancer progression and some underlying mechanisms using both in vitro and in vivo models of triple negative breast cancer (TNBC). We hypothesized that high oxygen exposure, even of short duration, may have long-term effects on cancer growth. C ...[more]

PMID: 32183322

Similar Datasets

Project description:Algae with potential biotechnological applications in different industries are commonly isolated from the environment in order to obtain pure (axenic) stocks that can be safely stored for long periods of time. To obtain axenic cultures, antibiotics are frequently employed, and cryopreservation is applied to preserve standing stocks. However, many of these now standard methods were developed using strains derived from pristine to near-pristine environments and cold to temperate regions. The potential effect of the said methods on the life cycle and biochemical profile of algae isolates from hyper-eutrophic and constant high-temperature tropical regions is not well understood. These effects could potentially render them unsuitable for their intended biotechnological application. In this study, we conducted a genetic characterization (18S rRNA) and evaluated the effect of purification (the use of the antibiotic chloramphenicol, CAP) and cryopreservation (dimethyl sulfoxide; DMSO-sucrose mix and glycerol) on the growth rate and lipid content of three new tropical freshwater algal isolates: Chorella sp. M2, Chlorella sp. M6, and Scenedesmus sp. R3, obtained from the Ecuadorian coast. The genetic and morphological characterization revealed a clear discrimination between these strains. All strains cultured with CAP exhibited a lower growth rate. Subsequent to cryopreservation, Chorella sp. M2, Chlorella sp. M6, and Scenedesmus sp. R3 presented no significant difference in growth rate between the cryopreservants. Further, a significantly higher lipid content was observed in the biomass cryopreserved with glycerol in relation to the DMSO-sucrose, with Chorella sp. M2 and Chlorella sp. M6 having twice as much as they had in the first treatment. These results highlight the relevance of selecting an appropriate method for storage, as the materials used can affect the biological performance of different tropical species, although it is still to be determined if the effects observed in this study are long lasting in subsequent cultures of these algae.

Project description:Streptococcus pneumoniae meningitis is a serious inflammatory disease of the central nervous system (CNS) and is associated with high morbidity and mortality rates. The inflammatory processes initiated by recognition of bacterial components contribute to apoptosis in the hippocampal dentate gyrus. Brain-derived neurotrophic factor (BDNF) has long been recommended for the treatment of CNS diseases due to its powerful neuro-survival properties, as well as its recently reported anti-inflammatory and anti-apoptotic effects in vitro and in vivo.In this study, we investigated the effects of BDNF-related signaling on the inflammatory response and hippocampal apoptosis in experimental models of pneumococcal meningitis. Pretreatment with exogenous BDNF or the tropomyosin-receptor kinase B (TrkB) inhibitor k252a was performed to assess the activation or inhibition of the BDNF/TrkB-signaling axis prior to intracisternal infection with live S. pneumoniae. At 24 h post-infection, rats were assessed for clinical severity and sacrificed to harvest the brains. Paraffin-embedded brain sections underwent hematoxylin and eosin staining to evaluate pathological severity, and cytokine and chemokine levels in the hippocampus and cortex were evaluated by enzyme-linked immunosorbent assay. Additionally, apoptotic neurons were detected in the hippocampal dentate gyrus by terminal deoxynucleotidyl transferase dUTP-nick-end labeling, key molecules associated with the related signaling pathway were analyzed by real-time polymerase chain reaction and western blot, and the DNA-binding activity of nuclear factor kappa B (NF-κB) was measured by electrophoretic mobility shift assay.Rats administered BDNF exhibited reduced clinical impairment, pathological severity, and hippocampal apoptosis. Furthermore, BDNF pretreatment suppressed the expression of inflammatory factors, including tumor necrosis factor α, interleukin (IL)-1β, and IL-6, and increased the expression of the anti-inflammatory factor IL-10. Moreover, BDNF pretreatment increased TrkB expression, activated downstream phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, and inhibited the myeloid differentiation primary response gene 88 (MyD88)/NF-κB-signaling pathway.These data suggested that BDNF administration exerted anti-inflammatory and anti-apoptotic effects on an experimental pneumococcal meningitis model via modulation of MyD88/NF-κB- and PI3K/AKT-signaling pathways. Our results indicated that treatment with exogenous BDNF might constitute a potential therapeutic strategy for the treatment of bacterial meningitis.

Dataset Information

Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression-Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study.

Publications

Long-Term Deleterious Effects of Short-term Hyperoxia on Cancer Progression-Is Brain-Derived Neurotrophic Factor an Important Mediator? An Experimental Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets