Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultrahigh- performance liquid chromatography-mass spectrometry. The correlation between metabolites and clinical parameters was studied, and metabolites with differential abundance in PCa urinary EVs were detected and mapped into cellular pathways. We detected 248 metabolites belonging to different chemical families including amino acids and various lipid species. Among these metabolites, 76 exhibited significant differential abundance between PCa and BPH. Interestingly, urine EVs recapitulated many of the metabolic alterations reported in PCa, including phosphathidylcholines, acyl carnitines, citrate and kynurenine. Importantly, we found elevated levels of the steroid hormone, 3beta-hydroxyandros-5-en-17-one-3-sulphate (dehydroepiandrosterone sulphate) in PCa urinary EVs, in line with the potential elevation of androgen synthesis in this type of cancer. This work supports urinary EVs as a non-invasive source to infer metabolic changes in PCa.Urine contains extracellular vesicles (EVs) that concentrate molecules and protect them from degradation. Thus, isolation and characterisation of urinary EVs could increase the efficiency of biomarker discovery. We have previously identified proteins and RNAs with differential abundance in urinary EVs from prostate cancer (PCa) patients compared to benign prostate hyperplasia (BPH). Here, we focused on the analysis of the metabolites contained in urinary EVs collected from patients with PCa and BPH. Targeted metabolomics analysis of EVs was performed by ultrahigh- performance liquid chromatography-mass spectrometry. The correlation between metabolites and clinical parameters was studied, and metabolites with differential abundance in PCa urinary EVs were detected and mapped into cellular pathways. We detected 248 metabolites belonging to different chemical families including amino acids and various lipid species. Among these metabolites, 76 exhibited significant differential abundance between PCa and BPH. Interestingly, urine EVs recapitulated many of the metabolic alterations reported in PCa, including phosphathidylcholines, acyl carnitines, citrate and kynurenine. Importantly, we found elevated levels of the steroid hormone, 3beta-hydroxyandros-5-en-17-one-3-sulphate (dehydroepiandrosterone sulphate) in PCa urinary EVs, in line with the potential elevation of androgen synthesis in this type of cancer. This work supports urinary EVs as a non-invasive source to infer metabolic changes in PCa

¿Por qué y cómo tener en cuenta al cannabis en nuestros pacientes fumadores?

El Proyecto ÉVICT (Evictproject.org), a raíz del aumento de consumo de cannabis en población juvenil española, ha estudiado su asociación con el tabaco, concluyendo que el consumo conjunto de tabaco y cannabis: tiene una influencia en el proceso de aprender a fumar, pues el inicio puede ser conjunto y con influencia bidireccional; tiene una influencia en el desarrollo de dependencia pues su interacción es relevante para el desarrollo de este trastorno, y tiene una influencia en la toxicidad, pues probablemente, el fumar tabaco y cannabis genera mayores problemas que fumar solo una de las 2. Y, por tanto, el equipo EVICT emite unas consideraciones en prevención: diferenciar uso medicinal y recreativo; comunicar que fumar cannabis no es terapéutico ni inocuo, y puede ayudar a generar dependencia de nicotina o, menos frecuentemente, al propio cannabis. Consideraciones en abordaje y tratamiento: en personas que consumen tabaco/cannabis debemos plantear como primera opción el cese de las 2 sustancias. Consideraciones en reducción de daños: a quienes solo consumen productos de tabaco/cannabis, los programas serían más aplicables a aquella cuyo consumo se considere más problemático

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator 1α (PGC1α) suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is downregulated in prostate cancer and associated with disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1α activates an oestrogen-related receptor alpha (ERRα)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1α–ERRα pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment

Microsoft Word - pxflshading.–

Abstract Over the years, there have been two main branches of computer graphics image-synthesis research; one focused on interactivity, the other on image quality. Procedural shading is a powerful tool, commonly used for creating high-quality images and production animation. A key aspect of most procedural shading is the use of a shading language, which allows a high-level description of the color and shading of each surface. However, shading languages have been beyond the capabilities of the interactive graphics hardware community. We have created a parallel graphics multicomputer, PixelFlow, that can render images at 30 frames per second using a shading language. This is the first system to be able to support a shading language in real-time. In this paper, we describe some of the techniques that make this possible. CR Categories and Subject INTRODUCTION We have created a SIMD graphics multicomputer, PixelFlow, which supports procedural shading using a shading language. Even a small (single chassis) PixelFlow system is capable of rendering scenes with procedural shading at 30 frames per second or more. In procedural shading, a user (someone other than a system designer) creates a short procedure, called a shader, to determine the final color for each point on a surface. The shader is respon- † Now at Silicon Graphics, Inc., 2011 N. Shoreline Blvd., M/S #590, Mountain View, CA 94043 (email: [email protected]) ‡ UNC Department of Computer Science, Sitterson Hall, CB #3175, Chapel Hill, NC 27599 (email: [email protected]) sible for color variations across the surface and the interaction of light with the surface. Shaders can use an assortment of input appearance parameters, usually including the surface normal, texture coordinates, texture maps, light direction and colors. Procedural shading is quite popular in the production industry where it is commonly used for rendering in feature films and commercials. The best known examples of this have been rendered using Pixar's PhotoRealistic RenderMan softwar