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Example sentences for: refractory
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Malignant tumor cells frequently show deregulation and hyperactivation of signalling pathways, one of which is represented by the TGFβ signal transduction pathway [ 1 ] . TGFβ has been shown to potently inhibit proliferation of most epithelial, endothelial and hematopoietic cells [ 2 ] . However, during tumor progression malignant cells may become refractory to TGFβ-mediated cell cycle arrest.
It is widely agreed, even though this is controversial too, that in patients with advanced cancer and other terminal diseases the provision of sedation leading to unconsciousness sometimes can be a necessary therapeutic procedure of last resort for symptom relief [ 1 ] . In the final stages of life, symptoms may remain refractory.
Though we could not make a clear differentiation between primary (when patients want to be sedated approaching the moment of death) and secondary sedation (when sedation results as a "side-effect" in otherwise refractory symptom control [ 46 ] , it must be clear to all, that the intention of sedation in the terminal and final phase is not a concealed form of euthanasia [ 47 ] . Under ethical aspects the requests for sedation to reduce consciousness to a state of unawareness need an individual and balanced approach, especially when the wish for sedation is not connected with the intolerability of physical or psychological distress This makes it necessary to discuss the problem of "terminal sedation" like other forms of therapeutic and existential support with patients and family members at an early stage in palliative care.
If tails are amputated during this refractory period, genes that are normally expressed during the early stages of tadpole tail regeneration, such as BMP4, Msx1 , and Notch-1 , are not expressed.
Dysfunction of voltage dependent anion channel opening, ADP/ATP exchange, the electron transport chain, oxidative phosphorylation, and calcium buffering through the action of this family of proteins have been reported [ 6 7 8 ] . While early defects in the electron transport chain can be reversed by addition of exogenous cytochrome c, the damage eventually becomes refractory to cytochrome c addition [ 8 ] . This finding suggests that pro-death Bcl-2 proteins can damage mitochondrial function independent of cytochrome c loss.
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