74 research outputs found

    Low PCA3 expression is a marker of poor differentiation in localized prostate tumors: exploratory analysis from 12,076 patients

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    Contains fulltext : 177804.pdf (publisher's version ) (Open Access)BACKGROUND: Prostate cancer antigen 3 (PCA3) is a prostate cancer diagnostic biomarker that has been clinically validated. The limitations of the diagnostic role of PCA3 in initial biopsy and the prognostic role are not well established. Here, we elucidate the limitations of tissue PCA3 to predict high grade tumors in initial biopsy. RESULTS: PCA3 has a bimodal distribution in both biopsy and radical prostatectomy (RP) tissues, where low PCA3 expression was significantly associated with high grade disease (p/=8) with 55% sensitivity and high false negative rates; 42% of high Gleason (>/=8) samples had low PCA3. In RP, low PCA3 is associated with adverse pathological features, clinical recurrence outcome and greater probability of metastatic progression (p<0.001). MATERIALS AND METHODS: A total of 1,694 expression profiles from biopsy and 10,382 from RP patients with high risk tumors were obtained from the Decipher Genomic Resource Information Database (GRIDTM)prostate cancer database. The primary clinical endpoint was distant metastasis-free survival for RP and high Gleason grade for biopsy. Logistic regression analyses and Cox proportional hazards models were used to evaluate the association of PCA3 with clinical variables and risk of metastasis. CONCLUSIONS: There is high prevalence of high grade tumors with low PCA3 expression in the biopsy setting. Therefore, urologists should be warned that using PCA3 as stand-alone test may lead to high rate of under-diagnosis of high grade disease in initial biopsy setting

    (Sub)mm Interferometry Applications in Star Formation Research

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    This contribution gives an overview about various applications of (sub)mm interferometry in star formation research. The topics covered are molecular outflows, accretion disks, fragmentation and chemical properties of low- and high-mass star-forming regions. A short outlook on the capabilities of ALMA is given as well.Comment: 20 pages, 7 figures, in proceedings to "2nd European School on Jets from Young Star: High Angular Resolution Observations". A high-resolution version of the paper can be found at http://www.mpia.de/homes/beuther/papers.htm

    Observational diagnostics of gas in protoplanetary disks

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    Protoplanetary disks are composed primarily of gas (99% of the mass). Nevertheless, relatively few observational constraints exist for the gas in disks. In this review, I discuss several observational diagnostics in the UV, optical, near-IR, mid-IR, and (sub)-mm wavelengths that have been employed to study the gas in the disks of young stellar objects. I concentrate in diagnostics that probe the inner 20 AU of the disk, the region where planets are expected to form. I discuss the potential and limitations of each gas tracer and present prospects for future research.Comment: Review written for the proceedings of the conference "Origin and Evolution of Planets 2008", Ascona, Switzerland, June 29 - July 4, 2008. Date manuscript: October 2008. 17 Pages, 6 graphics, 134 reference

    High-fat diet fuels prostate cancer progression by rewiring the metabolome and amplifying the MYC program

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    Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet

    Massive Star Formation

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    This chapter reviews progress in the field of massive star formation. It focuses on evidence for accretion and current models that invoke high accretion rates. In particular it is noted that high accretion rates will cause the massive young stellar object to have a radius much larger than its eventual main sequence radius throughout much of the accretion phase. This results in low effective temperatures which may provide the explanation as to why luminous young stellar objects do not ionized their surroundings to form ultra-compact H II regions. The transition to the ultra-compact H II region phase would then be associated with the termination of the high accretion rate phase. Objects thought to be in a transition phase are discussed and diagnostic diagrams to distinguish between massive young stellar objects and ultra-compact H II regions in terms of line widths and radio luminosity are presented.Comment: 21 pages, 6 figures, chapter in Diffuse Matter from Star Forming Regions to Active Galaxies - A Volume Honouring John Dyson, Edited by T.W. Hartquist, J. M. Pittard, and S. A. E. G. Falle. Series: Astrophysics and Space Science Proceedings. Springer Dordrecht, 2007, p.6

    The Cancer Genome Atlas Comprehensive Molecular Characterization of Renal Cell Carcinoma

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    Renal cell carcinoma(RCC) is not a single disease, but several histologically defined cancers with different genetic drivers, clinical courses, and therapeutic responses. The current study evaluated 843 RCC from the three major histologic subtypes, including 488 clear cell RCC, 274 papillary RCC, and 81 chromophobe RCC. Comprehensive genomic and phenotypic analysis of the RCC subtypes reveals distinctive features of each subtype that provide the foundation for the development of subtype-specific therapeutic and management strategies for patients affected with these cancers. Somatic alteration of BAP1, PBRM1, and PTEN and altered metabolic pathways correlated with subtype-specific decreased survival, while CDKN2A alteration, increased DNA hypermethylation, and increases in the immune-related Th2 gene expression signature correlated with decreased survival within all major histologic subtypes. CIMP-RCC demonstrated an increased immune signature, and a uniform and distinct metabolic expression pattern identified a subset of metabolically divergent (MD) ChRCC that associated with extremely poor survival

    Space as a Tool for Astrobiology: Review and Recommendations for Experimentations in Earth Orbit and Beyond

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