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Alberghina L.,University of Milan Bicocca | Gaglio D.,University of Milan Bicocca | Gaglio D.,CNR Institute of Molecular Bioimaging and Physiology
Cell Death and Disease | Year: 2014

Glutamine utilization promotes enhanced growth of cancer cells. We propose a new concept map of cancer metabolism in which mitochondrial NADH and NADPH, in the presence of a dysfunctional electron transfer chain, promote reductive carboxylation from glutamine. We also discuss why nicotinamide nucleotide transhydrogenase (NNT) is required in vivo for glutamine utilization by reductive carboxylation. Moreover, NADPH, generated by both the pentose phosphate pathway and the cancer-specific serine glycolytic diversion, appears to sustain glutamine utilization for amino-acid synthesis, lipid synthesis, and for ROS quenching. The fact that the supply of NAD+ precursors reduces tumor aggressiveness suggests experimental approaches to clarify the role of the NADH-driven redox network in cancer. © 2014 Macmillan Publishers Limited All rights reserved.

Cerretelli P.,CNR Institute of Molecular Bioimaging and Physiology | Gelfi C.,University of Milan
European Journal of Applied Physiology | Year: 2011

An holistic approach for interpreting classical data on the adaptation of the animal and, particularly, of the human body to hypoxic stress was promoted by the discovery of HIF-1, the "master regulator" of cell hypoxic signaling. Mitochondrial production of ROS stabilizes the O2- regulated HIF-1α subunit of the HIF-1 dimer promoting transaction functions in a large number of potential target genes, activating transcription of sequences into RNA and, eventually, protein production. The aim of the present preliminary study is to assess whether adaptive changes in oxygen sensing and metabolic signaling, particularly in the control of energy turnover known to occur in cultured cells exposed to hypoxia, are detectable also in the muscles of animals and man. For the present analysis, data obtained from the proteome of the rat gastrocnemius and of the vastus lateralis muscle of humans together with functional measurements were compared with homologous data from hypoxic cultured cells. In particular, the following variables were assessed: (1) the role of stress response proteins in the maintenance of ROS homeostasis, (2) the activity of the PDK1 gene on the shunting of pyruvate away from the TCA cycle in rodents and in humans, (3) the COX-4/COX-2 ratio in hypoxic rodents, (4) the overall efficiency of oxidative phosphorylation in humans during exercise in hypoxia, (5) some features of muscle mitochondrial autophagy in humans undergoing subchronic and chronic altitude exposure. Despite the limited number of observations and the differences in the experimental approach, some initial interesting results were obtained encouraging to pursue this innovative effort. © 2010 Springer-Verlag.

Camici P.G.,San Raffaele Scientific Institute | D'Amati G.,University of Rome La Sapienza | Rimoldi O.,CNR Institute of Molecular Bioimaging and Physiology
Nature Reviews Cardiology | Year: 2015

Obstructive disease of the epicardial coronary arteries was recognized as the cause of angina pectoris >2 centuries ago, and sudden thrombotic occlusion of an epicardial coronary artery has been established as the cause of acute myocardial infarction for >100 years. In the past 2 decades, dysfunction of the coronary microvasculature emerged as an additional mechanism of myocardial ischaemia that bears important prognostic implications. The coronary microvasculature (vessels <300 μm in diameter) cannot be directly imaged in vivo, but a number of invasive and noninvasive techniques, each with relative advantages and pitfalls, can be used to assess parameters that depend directly on coronary microvascular function. These methods include invasive or noninvasive measurement of Doppler-derived coronary blood flow velocity reserve, assessment of myocardial blood flow and flow reserve using noninvasive imaging, and calculation of microcirculatory resistance indexes during coronary catheterization. These advanced techniques for assessment of the coronary microvasculature have provided novel insights into the pathophysiological role of coronary microvascular dysfunction in the development of myocardial ischaemia in different clinical conditions. © 2015 Macmillan Publishers Limited.

Cerretelli P.,CNR Institute of Molecular Bioimaging and Physiology
Extreme Physiology and Medicine | Year: 2013

This article is an autobiographical account of my career as a human physiologist. I have spent 55 years traversing mountains, continents, seas, and skies, carrying out research in the laboratories of several international institutions as well as in the field. My scientific roots, approach to the mountains and altitude populations, both in Europe and in Asia, together with an account of my experimental studies at altitude, including extreme conditions, shall be presented together with pertinent occasional reflections of a personal nature. © 2013 Cerretelli; licensee BioMed Central Ltd.

Scalco E.,CNR Institute of Molecular Bioimaging and Physiology | Fiorino C.,San Raffaele Scientific Institute | Cattaneo G.M.,San Raffaele Scientific Institute | Sanguineti G.,Johns Hopkins University | Rizzo G.,CNR Institute of Molecular Bioimaging and Physiology
Radiotherapy and Oncology | Year: 2013

Background and purpose During radiotherapy (RT) for head-and-neck cancer, parotid glands undergo significant anatomic, functional and structural changes which could characterize pre-clinical signs of an increased risk of xerostomia. Texture analysis is proposed to assess structural changes of parotids induced by RT, and to investigate whether early variations of textural parameters (such as mean intensity and fractal dimension) can predict parotid shrinkage at the end of treatment. Material and methods Textural parameters and volumes of 42 parotids from 21 patients treated with intensity-modulated RT for nasopharyngeal cancer were extracted from CT images. To individuate which parameters changed during RT, a Wilcoxon signed-rank test between textural indices (first and second RT week; first and last RT week) was performed. Discriminant analysis was applied to variations of these parameters in the first two weeks of RT to assess their power in predicting parotid shrinkage at the end of RT. Results A significant decrease in mean intensity (1.7 HU and 3.8 HU after the second and last weeks, respectively) and fractal dimension (0.016 and 0.021) was found. Discriminant analysis, based on volume and fractal dimension, was able to predict the final parotid shrinkage (accuracy of 71.4%). Conclusion Textural features could be used in combination with volume to characterize structural modifications on parotid glands and to predict parotid shrinkage at the end of RT. © 2013 Elsevier Ireland Ltd. All rights reserved.

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