Early detection of ovarian cancer: new technologies in pursuit of a disease that is neither common nor rare.
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Elimination of cancer in the 21st Century is likely to depend not only on more effective individualized treatment, but also upon earlier detection and prevention of different malignancies. Screening strategies for ovarian cancer have centered on the serum tumor marker CA 125, transvaginal sonography (TVS), or sequential use of the two modalities. A single determination of CA 125 is neither sufficiently sensitive nor specific to be used as an initial stage in screening. Specificity can be improved by monitoring CA 125 over time with an algorithm that estimates risk of ovarian cancer. Sensitivity of CA125 can be improved by use of multiple markers in combination. Gene expression array analysis, proteomics and lipomics are being utilized to identify markers that can be used in combination with CA 125 to detect >95% of early stage ovarian cancers. To maintain high specificity, values for different markers are being combined using novel approaches of neural network analysis and mixed multivariate analysis. Sequential use of multiple markers and TVS could provide a cost-effective strategy to detect a disease of intermediate prevalence. (+info)
Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects--a monozygotic twin study.
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Both genetic and environmental factors are involved in the etiology of obesity and the associated lipid disturbances. We determined whether acquired obesity is associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic (MZ) twins. 14 healthy MZ pairs discordant for obesity (10 to 25 kg weight difference) and ten weight concordant control pairs aged 24-27 years were identified from a large population-based study. Insulin sensitivity was assessed by the euglycemic clamp technique, and body composition by DEXA (% body fat) and by MRI (subcutaneous and intra-abdominal fat). Global characterization of lipid molecular species in serum was performed by a lipidomics strategy using liquid chromatography coupled to mass spectrometry. Obesity, independent of genetic influences, was primarily related to increases in lysophosphatidylcholines, lipids found in proinflammatory and proatherogenic conditions and to decreases in ether phospholipids, which are known to have antioxidant properties. These lipid changes were associated with insulin resistance, a pathogonomic characteristic of acquired obesity in these young adult twins. Our results show that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance. (+info)
Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling.
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Proteotoxic stress and cell lifespan control.
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Eukaryotic cells continuously integrate intrinsic and extrinsic signals to adapt to the environment. When exposed to stressful conditions, cells activate compartment-specific adaptive responses. If these are insufficient, apoptosis ensues as an organismal defense line. The mechanisms that sense stress and set the transition from adaptive to mal-adaptive responses, activating apoptotic programs, are the subject of intense studies, also for their potential impact in cancer and degenerative disorders. In the former case, one would aim at lowering the threshold, in the latter instead to increase it. Protein synthesis, consuming energy for anabolic processes as well as for byproducts disposal, can be a significant source of stress, particularly when difficult-to-fold proteins are produced. Recent work from our and other laboratories on the differentiation of antibody secreting cells, revealed a regulatory circuit that integrates protein synthesis, secretion and degradation (proteostasis), into cell lifespan determination. The apoptotic elimination - after an industrious, yet short lifetime - of terminal immune effectors is crucial to maintain immune homeostasis. Linking proteostasis to cell death, this paradigm might prove useful for biotechnological purposes, and the design of novel anti-cancer therapies. (+info)
Metabonomic analysis of exhaled breath condensate in adults by nuclear magnetic resonance spectroscopy.
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