Emerging field of metabolomics: big promise for cancer biomarker identification and drug discovery.

The success of forensic investigations involving fatalities very often depends on the establishment of the correct timeline of events. Currently used methods for estimating the postmortem interval (PMI) are mostly dependent on the professional and tacit experience of the investigator, and often with poor reliability in the absence of robust biological markers. The aim of this study was to investigate the potential of metabolomic approaches to highlight molecular markers for PMI. Rat and human muscle tissues, collected at various times postmortem, were analyzed using an untargeted metabolomics approach. Levels of certain metabolites (skatole, xanthine, n-acetylneuraminate, 1-methylnicotinamide, choline phosphate, and uracil) as well as most proteinogenic amino acids increased steadily postmortem. Threonine, tyrosine, and lysine show the most predictable evolution over the postmortem period, and may thus have potential for possible PMI markers in the future. This study demonstrates how a biomarker discovery approach can be extended to forensic investigations using untargeted metabolomics.

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Postmortomics: The Potential of Untargeted Metabolomics to Highlight Markers for Time Since Death

Alterations in lipid metabolism in cancer cells impact cell structure, signaling, and energy metabolism, making lipid metabolism a potential diagnostic marker and therapeutic target. In this study, we combined PET, desorption electrospray ionization-mass spectrometry (DESI-MS), nonimaging MS, and transcriptomic analyses to interrogate changes in lipid metabolism in a transgenic zebrafish model of oncogenic RAS-driven melanocyte neoplasia progression. Exogenous fatty acid uptake was detected in melanoma tumor nodules by PET using the palmitic acid surrogate tracer 14(R,S)-18F-fluoro-6-thia-heptadecanoic acid ([18F]-FTHA), consistent with upregulation of genes associated with fatty acid uptake found through microarray analysis. DESI-MS imaging revealed that FTHA uptake in tumors was heterogeneous. Transcriptome and lipidome analyses further highlighted dysregulation of glycerophospholipid pathways in melanoma tumor nodules, including increased abundance of phosphatidyl ethanolamine and phosphatidyl choline species, corroborated by DESI-MS, which again revealed heterogeneous phospholipid composition in tumors. Overexpression of the gene encoding lipoprotein lipase (LPL), which was upregulated in zebrafish melanocyte tumor nodules and expressed in the majority of human melanomas, accelerated progression of oncogenic RAS-driven melanocyte neoplasia in zebrafish. Depletion or antagonism of LPL suppressed human melanoma cell growth; this required simultaneous fatty acid synthase (FASN) inhibition when FASN expression was also elevated. Collectively, our findings implicate fatty acid acquisition as a possible therapeutic target in melanoma, and the methods we developed for monitoring fatty acid uptake have potential for diagnosis, patient stratification, and monitoring pharmacologic response. SIGNIFICANCE: These findings demonstrate the translational potential of monitoring fatty acid uptake and identify lipoprotein lipase as a potential therapeutic target in melanoma.

/pdf/enhanced-fatty-acid-scavenging-and-glycerophospholipid-ul5yh52odg.pdf

Enhanced Fatty Acid Scavenging and Glycerophospholipid Metabolism Accompany Melanocyte Neoplasia Progression in Zebrafish.

Transplantable murine melanomas are well-established models for the study of experimental cancer therapies. The aim of this study was to explore the behaviour of four different B16 murine melanoma cell sublines after inoculation into C57BL/6J mice; and, more specifically to analyse skin changes, with respect to two specific parameters: clinical (tumour volume, melanin amount, erythema) and histological (H & E, S100, VEGF expression). Both non-invasive and invasive analysis showed that B164A5 is the most aggressive melanoma cell line for C57BL/6J's skin, followed by B16F10 and then by diminished aggressive growth pattern by the B16GMCSF and B16FLT3 cell lines.

Behaviour of four different B16 murine melanoma cell sublines: C57BL/6J skin

http://www.funcmetabol.com/NFUpload/nfupload_down.php?tmp_name=20150326140421.2390.4.0&name=1.J+of+proteoimc+%3F%3F%3F%3F+2015-1.pdf

Dihydrolipoyl dehydrogenase as a potential UVB target in skin epidermis; using an integrated approach of label-free quantitative proteomics and targeted metabolite analysis

Prognostic relationship of metabolic profile obtained of melanoma B16F10.

https://www.clinicsjournal.com/wp-content/uploads/articles_xml/1807-5932-clin-75-e1768/1807-5932-clin-75-e1768.pdf

Response to fatigue observed through magnetic resonance imaging on the quadriceps muscle in postmenopausal women

Programa de Grado en Ciencia del Movimiento Humano, Facultad de Ciencias de la Salud (FACIS) Universidad Metodista de Piracicaba São Paulo, Brasil Instituto de Ortopedia y Traumatología, Facultad de Medicina, Universidad de São Paulo, Laboratorio de Kinesiología, São Paulo, Brasil Departmento de Radiología, Universidad de São Paulo, São Paulo, Brasil Facultad Adventista Hortolandia, Hortolandia, São Paulo, Brasil Grupo Universitario Laureate de Anhembi, São Paulo, Brasil Facultades Metropolitanas Unidas Grupo FMU-Laureate, São Paulo, Brasil

Thiago Antonio Fedele

Papers

Prognostic relationship of metabolic profile obtained of melanoma B16F10.

Response to fatigue observed through magnetic resonance imaging on the quadriceps muscle in postmenopausal women

La Respuesta Morfológica y de Rendimiento en el Entrenamiento de Pilates en Mujeres Activas