M R Tosi

National Institute of Molecular Genetics (INGM), Milano, Lombardy, Italy

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Publications (43)77.66 Total impact

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    ABSTRACT: Gastric cancer is the second most common cancer worldwide. The involvement of reactive oxygen species (ROS) in the pathogenesis of gastric malignancies is well known. Many human tumours have shown significant changes in the activity and expression of superoxide dismutase (SOD), which might be correlated with clinical-pathological parameters for the prognosis of human carcinoma. The aim of this study is the detection of MnSOD and CuZnSOD activity and their expression in gastric adenocarcinoma and healthy tissues. Gastric samples (adenocarcinoma and healthy tissues) harvested during endoscopy or resected during surgery were used to determine MnSOD and CuZnSOD activity and expression by spectrophotometric and Western blotting assays. The total SOD activity was significantly higher (p<0.05) in healthy mucosa with respect to gastric adenocarcinomas. No differences were found in MnSOD activity and, on the contrary, CuZnSOD activity was significantly lower (p<0.001) in cancer samples with respect to normal mucosa. The rate of MnSOD/CuZnSOD activity in adenocarcinoma was over ninefold higher than that registered in healthy tissues (p<0.05). Moreover, in adenocarcinoma MnSOD activity represented the 83% of total SOD with respect to healthy tissues where the ratio was 52% (p<0.001). On the contrary, in cancer tissues, CuZnSOD activity accounted for only 17% of the total SOD (p<0.001 if compared with the values recorded in normal mucosa). After immunoblotting, MnSOD was more expressed in adenocarcinoma with respect to normal mucosa (p<0.001), while CuZnSOD was similarly expressed in adenocarcinoma and healthy tissues. The SOD activity assay might provide a specific and sensitive method of analysis that allows the differentiation of healthy tissue from tumour tissue. The MnSOD to CuZnSOD activity ratio, and the ratio between these two isoforms and total SOD, presented in this preliminary study might be considered in the identification of cancerous from healthy control tissue.
    Biomarkers 10/2008; 11(6):574-84. · 1.88 Impact Factor
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    ABSTRACT: The metabolic profile and morphologic aspects of normal and pathologic human gastric mucosa were studied. The aim of the present research was the application of ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) to the human gastric tissue to get information on the molecular steps involved in gastric carcinogenesis and the identification of biochemical markers useful for the development of in vivo MRS methodologies to diagnose gastric pathologies in clinical situations. Twelve normal subjects, five with autoimmune atrophic gastritis, five with Helicobacter pylori infection, and five with adenocarcinoma were examined. Ten biopsies were taken during endoscopy from each patient. Specimens from carcinoma were also obtained during gastrectomy. Of the 10 biopsies, 4 were used for histologic evaluation, 4 were fixed in glutaraldehyde and processed for transmission and scanning electron microscopy, and 2 were immersed in liquid nitrogen and stored at -85 degrees C for monodimensional and bidimensional ex vivo HR-MAS MRS analysis. Ex vivo HR-MAS MRS identified glycine, alanine, free choline, and triglycerides as possible molecular markers related to the human gastric mucosa differentiation toward preneoplastic and neoplastic conditions. Ultrastructural studies of autoimmune atrophic gastritis and gastric adenocarcinoma revealed lipid accumulations intracellularly and extracellularly associated with a severe prenecrotic hypoxia and mitochondria degeneration. This is the first report of synergic applications of ex vivo HR-MAS MRS and electron microscopy in studying the human gastric mucosa differentiation. This research provides useful information about some molecular steps involved in gastric carcinogenesis. The biochemical data obtained on gastric pathologic tissue could represent the basis for clinical applications of in vivo MRS.
    Cancer Epidemiology Biomarkers &amp Prevention 07/2008; 17(6):1386-95. · 4.56 Impact Factor
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    ABSTRACT: We report on the magnetic resonance spectroscopy (MRS) characterisation of different human meningiomas. Three histological subtypes of meningiomas (meningothelial, fibrous and oncocytic) were analysed both through in vivo and ex vivo MRS experiments. The ex vivo high-resolution magic angle spinning (HR-MAS) investigations, permitting an accurate description of the metabolic profile, are very helpful for the assignment of the resonances in vivo of human meningiomas and for the validation of the quantification procedure of in vivo MR spectra. By using one- and two-dimensional experiments, we were able to identify several metabolites in different histological subtypes of meningiomas. Our spectroscopic data confirmed the presence of the typical metabolites of these benign neoplasms and, at the same time, that meningomas with different morphological characteristics have different metabolic profiles, particularly regarding macromolecules and lipids. The ex vivo spectra allowed a better understanding and interpretation of the in vivo MR spectra, showing that the HR-MAS MRS technique could be a complementary method to strongly support the in vivo MR spectroscopy and increase its clinical potentiality.
    International Journal of Molecular Medicine 12/2006; 18(5):859-69. · 1.96 Impact Factor
  • Analytical Biochemistry 11/2006; 357(1):150-2. · 2.58 Impact Factor
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    ABSTRACT: The HR-MAS is an ideal technique for the investigation of intact tissue specimens (10–50 mg) and permits the obtainment of spectra with a resolution comparable to that observed in solution in a time that does not exceed a half of an hour for a routine analysis. The potentialities of HR-MAS NMR spectroscopy in the identification of the metabolites characterizing the healthy gastric mucosa are here presented. The direct inspection of the 1D 1H NMR spectra enables only few metabolites to be confidently assigned, and the use of selected 2D experiments strongly amplify the analytical effectiveness of the technique. © 2006 Wiley Periodicals, Inc. Concepts Magn Reson Part A 28A: 430–443, 2006
    Concepts in Magnetic Resonance Part A 10/2006; 28A(6):430 - 443. · 1.24 Impact Factor
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    ABSTRACT: The present study reports the characteristics of the biochemical profile of human gastric adenocarcinoma in comparison with that of healthy gastric mucosa, using ex vivo HR-MAS Magnetic Resonance Spectroscopy. Healthy human mucosa is mainly characterized by the presence of small metabolites (more than 50 identified) and macromolecules, whereas the adenocarcinoma spectra are dominated by the presence of signals due to triglycerides, whose content on the contrary is very low in healthy gastric mucosa. The use of spin-echo experiments enable us to detect some metabolites in the unhealthy tissues and to determine their variation with respect to the healthy ones. We have observed that the Cho:ChoCC ratio changes from 20:80 in the healthy tissues to 80:20 in the neoplastic gastric mucosa.
    Oncology Reports 10/2006; 16(3):543-53. · 2.30 Impact Factor
  • Digestive and Liver Disease - DIG LIVER DIS. 01/2006; 38.
  • Digestive and Liver Disease - DIG LIVER DIS. 01/2006; 38.
  • Vitaliano Tugnoli, Maria Raffaella Tosi
    Clinica Chimica Acta 11/2005; 360(1-2):208-10. · 2.85 Impact Factor
  • Maria R Tosi, Vitaliano Tugnoli
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    ABSTRACT: Cholesteryl esters, formed by the esterification of cholesterol with long-chain fatty acids, on one hand, are the means by which cholesterol is transported through the blood by lipoproteins, on the other, the way cholesterol itself can be accumulated in the cells. Therefore, these important molecules play an active part in metabolic pathways that form the basis of cholesterol trafficking and homeostasis. The role of different regulatory mechanisms in cholesterol homeostasis in physiologic and neoplastic conditions with emphasis on intracellular content of cholesteryl esters is here reviewed. Numerous studies carried out on tumor cell lines, experimental tumors, and human tumors have shown an abnormal cholesterol metabolism that is reflected by an increase in intracellular cholesteryl esters due to an alteration in all the mechanisms that form the basis of regulation, in particular: cholesterol de novo biosynthesis; uptake of exogenous cholesterol LDL receptor mediated; cholesterol esterification mediated by the ACAT activity; cholesterol efflux HDL receptor mediated. The most recent analytic-spectroscopic applications that permit cholesteryl ester determination on tumor lipidic extracts and directly in vivo are also reported. This review gives an overview of cholesterol homeostasis in physiological and pathological conditions where cholesteryl esters are over-expressed.
    Clinica Chimica Acta 10/2005; 359(1-2):27-45. · 2.85 Impact Factor
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    ABSTRACT: The present case report was aimed at identifying the molecular profile characteristic of a primitive neuro-ectodermal tumor (PNET) in a 3-year-old child affected by a lesion localized in the cerebellar region. The histological diagnosis was medulloblastoma. In vivo single voxel 1H magnetic resonance spectroscopy (MRS) shows high specificity in detecting the main metabolic alterations in the primitive cerebellar lesion; a very high amount of the choline-containing compounds and very low level of creatine derivatives and N-acetylaspartate. Ex vivo high resolution magic angle spinning (HR-MAS) 1H magnetic resonance spectroscopy, performed at 9.4 Tesla on the neoplastic specimen collected during surgery, allows for the unambiguous identification of several metabolites giving a more in-depth evaluation of the metabolic pattern of the lesion. The ex vivo HR-MAS MR spectra show that the spectral detail is much higher than that obtained in vivo and that, for example, myo-inositol, taurine and phosphorylethanolamine contribute to the in vivo signal at 3.2 ppm, usually attributed to choline-containing compounds. In addition, the spectroscopic data appear to correlate with some morphological features of the medulloblastoma. Consequently, the present study shows that ex vivo HR-MAS 1H MRS is able to strongly improve the clinical possibility of in vivo MRS and can be used in conjunction with in vivo spectroscopy for clinical purposes.
    International Journal of Molecular Medicine 09/2005; 16(2):301-7. · 1.96 Impact Factor
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    ABSTRACT: Raman spectra were obtained directly in a non-destructive and non-invasive way from the biomaterials PMMA [poly(methyl methacrylate)], HDPE (high-density polyethylene), α-Al2O3 (alumina) and HA (hydroxyapatite) constituting the components (bone cement, acetabular cup, ball and stem coated with ceramic) of a hip prosthesis. The aim was to give an objective contribution at a molecular level to predict their biocompatibility. In particular, Raman spectra of explanted PMMA bone cements do not show the 1640 cm−1 band due to the stretching mode of CC unsaturated centres. Moreover, conformational changes of PMMA following the implant appear in the spectra in the range 1100-500 cm−1, where conformational marker bands at 985, 968, 601 and 565 cm−1 are present. The limited number of HDPE explanted acetabular cups did not allow unequivocal Raman results to be obtained by means of band deconvolution in the region between 1500 and 1000 cm−1, regarding the changes in the crystalline, amorphous and interfacial contents of the acetabular cup surfaces following the implant. α-Al2O3 proved to be a ceramic with good biocompatibility as a biomaterial constituting a hip prosthesis. As regards the stem coating, Raman and Fourier transform IR spectra of HA pre-coating and HA coating on metal implants show spectroscopic modifications due to structural and chemical changes with formation of other calcium phosphates. The development of new bioactive coatings containing precursors of bone growth and able to promote osteogenesis is outlined.
    Journal of Raman Spectroscopy 04/2005; 25(1):109 - 114. · 2.68 Impact Factor
  • Vitaliano Tugnoli, Andrea Trinchero, Maria Raffaella Tosi
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    ABSTRACT: The assumption that kidney tumors are characterized by high lipid content has directed our research towards the evaluation and comparison of lipids in healthy and neoplastic human renal tissues. This research appears to have marked importance owing to the role of lipids in cancer cell biochemistry. Nuclear Magnetic Resonance spectroscopy and chromatographic methods allow the full description of the lipidic profile typical of intact medulla, intact cortex, clear-cell renal carcinomas, chromophobe-cell renal carcinomas, oncocytomas and two samples of medulla infiltrated by a nephrocarcinoma. Significant differences among healthy, benign and malignant tissues were shown, and the results were discussed in relation to the different roles of each lipidic component and compared with the literature data.
    The Italian journal of biochemistry 01/2005; 53(4):169-82.
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    ABSTRACT: The present study was aimed at identifying the molecular profile characteristic of the healthy human gastric mucosa. Ex vivo HR-MAS magnetic resonance spectroscopy performed at 9.4 Tesla (400.13 MHz for (1)H) on gastric specimens collected during endoscopy, permits the identification of more than forty species giving a detailed picture of the biochemical pattern of the gastric tissues. These preliminary data will be used for a comparison with gastric preneoplastic and neoplastic situations. Moreover, the full knowledge of the biochemical pattern of the healthy gastric tissues is the necessary presupposition for the application of magnetic resonance spectroscopy directly in vivo.
    International Journal of Molecular Medicine 01/2005; 14(6):1065-71. · 1.96 Impact Factor
  • V Tugnoli, A Poerio, M R Tosi
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    ABSTRACT: This study presents a multinuclear (1H, 13C and 31P) magnetic resonance spectroscopy characterization of the total lipid fraction extracted from different regions of a human kidney affected by a clear cell renal carcinoma. It was thus possible to demonstrate that cholesteryl esters and phosphatidylcholine are markers of the tumor infiltration, histologically confirmed, in the kidney medulla. The tumor tissue contains twice the amount of phosphatidylcholine compared to normal cortex. The results appear relevant in light of new clinical applications based on the biochemical composition of human tissues.
    Oncology Reports 09/2004; 12(2):353-6. · 2.30 Impact Factor
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    ABSTRACT: We report on the characterization of the lipid obtained from cortical and medullary normal human kidney tissue, benign renal neoplasms (oncocytoma) and 2 different types of malignant renal neoplasms (chromophobic cell carcinoma and clear cell carcinoma). The total lipid fractions were analyzed by 13C magnetic resonance spectroscopy and thin-layer chromatography, whereas the composition of the total fatty acids and the content of total cholesterol were determined by gas chromatography. alpha-Tocopherol was detected and quantified by high-performance liquid chromatography. The spectroscopic and chromatographic analysis revealed significant differences in the renal tissues examined. It was confirmed that cholesteryl esters (mainly oleate) are typical of clear cell renal carcinomas. Their potential role as prognostic and diagnostic factors is discussed, with particular emphasis on its capability to indicate the tumor diffusion in healthy renal parenchyma. alpha-Tocopherol is prevalent in clear cell carcinoma and it is present in nearly the same low amounts in cortex, medulla and chromophobic cell renal carcinoma. Q10 coenzyme and dolichols were detected by thin-layer chromatography and they are present in significant amounts in the cortex and the benign oncocytoma. Great variations were found in the distribution of saturated and unsaturated fatty acids, especially in the docosapentaenoic, docosahexaenoic and arachidonic acids and the corresponding omega-6/omega-3 fatty acids ratio.
    International Journal of Molecular Medicine 08/2004; 14(1):93-100. · 1.96 Impact Factor
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    ABSTRACT: 1H and 13C NMR spectroscopy was used to evaluate the degree of unsaturation and the cholesterol/cholesteryl ester ratio on the total lipid fractions obtained from human renal and cerebral tissues. The unsaturated/saturated fatty acid ratio was determined in the 13C NMR spectra from the ratio of the integrated areas of the resonances at 14.13 and 14.17 ppm assigned to the terminal methyl groups of saturated and unsaturated FA, respectively, and is validated by the traditional but time consuming gas-chromatographic analysis. Cholesteryl esters are easily discriminated in the total lipid fraction extracted from human tissues by means of the well-resolved component at 0.99 ppm (1H NMR spectra) of the resonance at about 1.00 ppm generally assigned to free cholesterol. The role of NMR spectroscopy in the study of lipidic biochemistry of human tissues is confirmed.
    The Italian journal of biochemistry 01/2004; 52(4):141-4.
  • M R Tosi, A Reggiani, V Tugnoli
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    ABSTRACT: Lipids extracted from three human renal neoplasms have been characterized by means of 13C magnetic resonance spectroscopy. The presence of free cholesterol, high levels of unsatured fatty acids, and phosphatidylcholine, and a very high fatty acids/cholesterol ratio makes the lipid profile of a rare chromophobe cell carcinoma very similar to that of an oncocytoma. On the contrary, clear cell carcinomas are mainly characterized by the presence of almost fully esterified cholesterol and by a markedly lower level of unsatured fatty acids. Since chromophobic cell carcinomas have a more favourable prognosis than clear cell carcinomas, their analogy in the lipid composition with a benign renal neoplasm could have a clinical significance. In particular, our report suggests that cholesteryl esters and high levels of unsatured fatty acids could be a marker of a poor (clear cell carcinomas) or a good (chromophobic cell carcinomas) prognosis, respectively. More in depth studies are required of the molecular composition of the neoplastic pathologies that add new knowledge, with potential clinical implications.
    International Journal of Molecular Medicine 08/2003; 12(1):99-102. · 1.96 Impact Factor
  • Vitaliano Tugnoli, Maria Raffaella Tosi
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    ABSTRACT: In vivo and in vitro Magnetic Resonance Spectroscopy is useful for monitoring changes in intracellular metabolites of human cerebral and renal tissues. Healthy and tumoral tissues of different histologic types have been characterized from a biochemical point of view. In vitro molecular characterization is performed on both the aqueous and lipid extracts of surgically removed tissue biopsies, after in vivo MRS, yielding a full picture of tissue biochemistry. Biochemical markers of healthy brain and kidney and of their relative neoplastic lesions have been disclosed. Moreover, some biochemical features can differentiate neoplasm within the same histological type. Ex vivo MRS also gives molecular information related to necrotic phenomena in glial tumors. MRS finding paralleled histologic data and new knowledge about the molecular base of proliferative neoplastic phenomena can be obtained.
    The Italian journal of biochemistry 07/2003; 52(2):80-6.
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    ABSTRACT: Cholesteryl esters (CholE) were detected in human malignant neoplasms by means of in vitro nuclear magnetic resonance spectroscopy. Spectroscopic analysis of the total lipid extracts obtained from cerebral tumors revealed appreciable amount of esterified cholesterol in high grade gliomas such as glioblastomas and anaplastic oligodendrogliomas, characterized by prominent neovascularity. The finding that no CholE were detected in the healthy brain and in low grade and benign tumors supports a possible correlation between this class of lipids and histological vascular proliferation. Compared with high grade gliomas, renal cell carcinomas show higher levels of CholE, absent in the healthy renal parenchyma and in benign oncocytomas. In nefro-carcinomas, cytoplasmic lipid inclusions and prominent vascularization contribute to the increased levels of CholE present mainly as oleate. CholE are discussed as potential biochemical markers of cancer and as a target for new therapeutic strategies.
    International Journal of Molecular Medicine 02/2003; 11(1):95-8. · 1.96 Impact Factor