She is the coauthor of several published papers involving
hypoxic cell sensitization from that research project.
Not exact matches
These «aggregates» can comprise hundreds of thousands of
cells, be up to 2 mm in diameter and be eight times more resistant to chemotherapy drugs — firstly because
hypoxic conditions are created inside the aggregates and secondly because these tumour
cells reduce growth and are therefore less sensitive.
«We would hope to create little protein factories in the tumour
cell that are only switched on when the
cells are
hypoxic,» says Kingsman.
Professor Ali Tavassoli, who led the study with colleague Dr. Ishna Mistry, explains: «In an effort to better understand the role of HIF - 1 in cancer, and to demonstrate the potential for inhibiting this protein in cancer therapy, we engineered a human
cell line with an additional genetic circuit that produces the HIF - 1 inhibiting molecule when placed in a
hypoxic environment.
Cadherin - 22 is located on
cell surfaces, allowing
hypoxic cancer
cells to stick together and migrate collectively as a group, said Uniacke.
In an earlier article, Jenkins showed that females with severe
hypoxic ischemic injury benefit from a combination treatment of hypothermia and NAC, which provides the rate - limiting amino acid for the primary anti-oxidant in all
cells.
Interestingly, Rho kinase inhibition under
hypoxic conditions produced a more effective increase in chondrocyte - specific gene expression and synthesis of extracellular matrix components by HCS - 2 / 8
cells.
They play a pivotal role in regulating synaptic transmission, modulating excitotoxicity responsible for much of the neuronal damage caused by
hypoxic insult in the brain [37], and are expressed in retinal photoreceptors, horizontal
cells, and bipolar
cells as well as the amacrine and ganglion
cells of the inner retina [38 — 41].
In normoxic
cells, the transcription factor HIF - 1α is degraded by the action of E3 ubiquitin ligase on the oxygen - dependent degradation domain (ODD) of HIF - 1α; however HIF - 1α is stabilized and therefore, accumulates in
hypoxic cancer
cells.
Progenitor
cell trafficking is regulated by
hypoxic gradients through HIF - 1 induction of SDF - 1.
Embryonic endothelial progenitor
cells armed with a suicide gene target
hypoxic lung metastases after intravenous delivery.
Expression of angiopoietin - 1 in
hypoxic pericytes: regulation by hypoxia - inducible factor - 2alpha and participation in endothelial
cell migration and tube formation.
During tumor development, rapid expansion of cancer
cells creates a
hypoxic microenvironment that is followed by periods of reoxygenation to promote tumor progression.
Guava ViaCount Reagent (Millipore Corporation) was used to determine the viability and
cell numbers after each
hypoxic cycle.
Cells were collected from either the media (floating subpopulation) or the adherent subpopulation after each
hypoxic cycle and dissociated into single -
cell suspension by trypsin / EDTA (trypsin / ethylenediaminetetraacetic acid).
Melanocytes have the capacity to respond to a diverse number of extracellular signals, including UVR, endocrine signaling cascades that occur during pregnancy, micro-environments of the stem
cell hair bulge vs. differentiated hair follicle niches, and
hypoxic conditions found in metastatic melanoma tumors.
Support to date for the existence of an
hypoxic niche in marrow blood stem
cells came from indirect evidence such as expression of the hypoxia protein Hif - 1 and related genes and staining with surrogate markers of hypoxia.
Similar to Tam, gefitinib blocked the
hypoxic effect in ER - α — positive primary samples and
cell lines but had no effect on ER - α — negative primary samples or
cell lines (Fig. 2C).
Hypoxic effect on adherent holoclone culture (C) and percentage ALDH1 - positive
cells (D).
No significant differences were seen between the normoxic and
hypoxic anoikis - resistant populations collected from MCF7
cells and a single significant gene change (PIP) was seen in T47D (Table 1) suggesting that the CSC - enriched population remains virtually unchanged following
hypoxic culture and the increase in MFC, HFC, and tumor initiating
cells is, therefore, due to expansion of the population, perhaps by increased symmetric self - renewal of the CSC or de-differentiation of early progenitor
cells, rather than simply the acquisition of anoikis resistance in non-CSC.
ERK1 / 2 inhibition increases antiestrogen treatment efficacy by interfering with hypoxia - induced downregulation of ERalpha: a combination therapy potentially targeting
hypoxic and dormant tumor
cells
Recent reports show increased CSC activity following
hypoxic exposure in breast cancer
cell lines (18 — 20), but no reports have studied this rare population in primary human breast cancer samples.
These data support the hypothesis that ER - α plays an important role in the
hypoxic CSC response in ER - α — positive
cells and that signaling through this pathway is responsible, at least in part, for the increase in CSC.
There may be a certain level of complexity in elucidating the mechanisms involved in this negative response as we have shown that the response can be easily altered with expression of either ER - α or N1 - ICD, and this suggests that the intrinsic
hypoxic response of these
cells can be overcome quite simply.
Putative model of breast cancer
cell hierarchy and the
hypoxic effect.
We measured the expression of ALDH1 in
cell lines following normoxic and
hypoxic culture and, in support of the MFC and HFC data shown above, show increased ALDH1 - positive
cell number in ER - α — positive lines and a contrasting decrease in ER - α — negative lines (Fig. 1D).
To mimic the in vitro
hypoxic response in vivo, we developed a xenograft model based on the hypothesis that with increasing xenograft sizes, there will be a parallel increase in hypoxia due to rapid
cell proliferation and restricted blood supply to the xenograft
cells.
Dormant tumor
cells in a
hypoxic bone marrow niche (19) will be enriched for CSC in ER - α — positive breast cancer but depleted in ER - α — negative cancers profoundly influencing the capacity for late disease recurrence.
They found that exosomes derived from older children's
cells were only reparative if they were subjected to
hypoxic conditions (lack of oxygen), while exosomes from newborns»
cells improved rats» cardiac function with or without hypoxia.
Tam significantly reduced the
hypoxic - MFC increase in all ER - α — positive
cells tested, although in 2 of 6 primary cases, the MFC remained significantly raised compared with control (Fig. 2B).
NSCs localize to infiltrative tumor
cells and
hypoxic tumor regions, which are inaccessible to intravenously administered drugs [7].
Inhibition of ER - α blocked the
hypoxic CSC response in all ER - α — positive
cells, supporting the role of estrogen signaling in the
hypoxic response.
N1 - ICD was increased in all ER - α — positive primary
cells and lines following
hypoxic culture (Fig. 3A).
Hypoxic Induction of Vasorin Regulates Notch1 Turnover to Maintain Glioma Stem - Like
Cells.
Cancer stem
cells (CSCs) in the
hypoxic BM regions are blamed for the incurability of MM, because CSCs are often resistant to drugs currently used against BM cancers (including proteasome inhibitors and immunomodulatory agents).
In 1924, the Nobel Laureate Otto Heinrich Warburg, determined that cancer
cells have a dependency on glucose for growth and metastastic processes under
hypoxic (low oxygen conditions), using glycolysis
(a) The oxidative catabolism of free fatty acids and amino acids (via the Respiratory Chain and Citric Acid Cycle) might be inhibited in
hypoxic cancer
cells via the judicious use of agents which inhibit their availability, i.e., partially inhibit hepatic fatty acid synthesis and keep plasma amino acid levels within the normal range, thus decreasing ATP production;
Hypoxic ischemic encephalopathy (HIE) is a condition which causes the newborn baby's brain
cells to die due to lack of oxygen supply, causing permanent brain damage.