ORCID Profile
0000-0002-2173-2513
Current Organisation
Malaghan Institute of Medical Research
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Publisher: Wiley
Date: 23-12-2008
Abstract: The past decade has seen the emergence of a new mechanistic paradigm of cancer therapeutics. Not only have mitochondria taken centre stage as key cellular organelles mediating intrinsic pathways of cell death by apoptosis, but nonapoptotic pathways have also been shown to involve mitochondrial mechanisms. Both pathways of cell death involve permeabilization of mitochondrial membranes, but the exact nature of the molecular complexes involved at the inner mitochondrial membrane (IMM) and outer mitochondrial membrane (OMM) remains uncertain in the light of recent gene knockout studies. Consequently, the boundary between mitochondrially-mediated apoptotic and nonapoptotic cell death is controversial. Here, we discuss the nature of the pore complexes involved in permeabilization of the IMM and OMM. Several compounds that interact directly with components of these pore complexes and have been shown to exhibit anticancer activity are discussed while other compounds appear to act indirectly through stress-related pathways.
Publisher: Elsevier BV
Date: 02-2008
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 16-06-2009
Publisher: Oxford University Press (OUP)
Date: 19-10-2011
DOI: 10.1189/JLB.0710417
Abstract: This research investigated the level of glycolytic metabolism in leukemic blasts as a prognostic marker in AML. Using an in vitro dye-reduction assay, we determined the level of glycolytic metabolism in 26 BM s les taken from 23 adult patients with newly diagnosed (n=19) or relapsed (n=4) AML, and AML blasts stratified into two distinct cohorts of moderate (& %) or high (& %) levels of glycolytic metabolism. All s les taken at relapse were moderately glycolytic. However, nine of the 19 s les taken at diagnosis were highly glycolytic, and 10 were moderately glycolytic. Three patients had paired s les taken at diagnosis and relapse, and the glycolytic metabolism of these s les did not alter between the two time-points. The level of glycolytic metabolism did not correlate with the percentage of marrow blasts, patient age, or CG/molecular risk group. Highly glycolytic AML blasts were more resistant to apoptosis induced by ATRA and/or ATO in vitro, suggesting potential resistance to induction chemotherapy, as has been observed in solid tumors. Despite this, high levels of glycolytic metabolism at diagnosis were predictive of a significantly improved duration of CR1 and OS following AML remission induction chemotherapy. In conclusion, we found that the extent of myeloblast glycolysis may be an effective and easily applied method to determine the pretreatment prognosis of AML.
Location: Netherlands
No related grants have been discovered for Patries Herst.