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- Labbé, David P., et al.
(författare)
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TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:22, s. 7072-7083
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient's progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches.
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| 2. |
- Santoni, Gregory W., et al.
(författare)
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Mass fluxes and isofluxes of methane (ch4) at a new hampshire fen measured by a continuous wave quantum cascade laser spectrometer
- 2012
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Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117, s. D10301-
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a mid-infrared continuous-wave quantum cascade laser direct-absorption spectrometer (QCLS) capable of high frequency (>= 1 Hz) measurements of (CH4)-C-12 and (CH4)-C-13 isotopologues of methane (CH4) with in situ 1-s RMS delta C-13(CH4) precision of 1.5 parts per thousand and Allan-minimum precision of 0.2 parts per thousand. We deployed this QCLS in a well-studied New Hampshire fen to compare measurements of CH4 isoflux by eddy covariance (EC) to Keeling regressions of data from automated flux chamber sampling. Mean CH4 fluxes of 6.5 +/- 0.7 mg CH4 m(-2) hr(-1) over two days of EC sampling in July, 2009 were indistinguishable from mean autochamber CH4 fluxes (6.6 +/- 0.8 mgCH(4) m(-2) hr(-1)) over the same period. Mean delta C-13(CH4) composition of emitted CH4 calculated using EC isoflux methods was -71 +/- 8 parts per thousand (95% C.I.) while Keeling regressions of 332 chamber closing events over 8 days yielded a corresponding value of -64.5 +/- 0.8 parts per thousand Ebullitive fluxes, representing similar to 10% of total CH4 fluxes at this site, were on average 1.2 parts per thousand enriched in C-13 compared to diffusive fluxes. CH4 isoflux time series have the potential to improve process-based understanding of methanogenesis, fully characterize source isotopic distributions, and serve as additional constraints for both regional and global CH4 modeling analysis.
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