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Vitaliano Tugnoli

Associate Professor

Department of Biomedical and Neuromotor Sciences

Academic discipline: BIO/10 Biochemistry

Curriculum vitae

Dr. Vitaliano Tugnoli was graduated with honors from the University of Bologna in 1981 with a degree in Pharmacology. Since 1/4/2000, he has been a researcher in the Faculty of Medicine and Surgery, within the Department of Biochemistry. Dr.Tugnoli is teacher of Chemistry and Propaedeutic Biochemistry in several courses in the Faculty of Medicine and Surgery and in the PhD in Biochemistry. Dr. Tugnoli published 129 original article papers and its research activities primarily involve the application of the Nuclear Magnetic Resonance Spectroscopy (MRS) in vitro, ex vivo and in vivo in the study of the metabolic processes which characterize human healthy and neoplastic tissues. Cerebral and renal tissues have already been studied, and their relative neoplasms of various histological types and grading of malignancy. The use of the MRS to study tissues in vitro is an important and necessary biochemical prerequisite for more comprehensive understanding of its uses in vivo. Within this scientific context, Dr. Tugnoli's activities concern the three areas of application of the MRS in the biomedical field: MR spectroscopy in vivo, applied directly on the patient, consisting of a combination of Magnetic Resonance Imaging (MRI) to define the volume of interest of the examined organ, and spectroscopy for the identification of the metabolites contained therein; ex vivo MRS, performed on an intact biopsy of tissues; and, MRS spectroscopy in vitro, using either aqueous extracts or lipid fractions of the aforementioned tissues, removed surgically, which had been studied in vivo. The first part of the research involves healthy and neoplastic human cerebral tissues. The use of a molecular investigation technique such as MRS has permitted a comparative biochemical description of human cerebral tissue, between functional and neoplastic. Thus, it has become possible, using MRS, to identify, in vitro, biochemical markers of healthy cerebral tissue, and of tumors of varying histological types and grading. The study conducted on healthy cerebral tissue produced the following results: the MR spectroscopy in vivo as well as another one in vitro have identified in N-acetyl-aspartate (NAA) an amino acid marker of correct neuronal functioning; it has been found near compounds containing choline (ChoCC) and creatine (Cr) in virtually equal concentrations; the absence of resonance attributable to the presence of mobile lipids in the spectrum, both in vivo and ex vivo has also been noted. In neoplastic tissues we have also found: a drastic reduction, to the point of disappearance of signals relating to NAA, due to neuronal loss in the neoplastic lesion, confirming that this amino acid is a neuronal marker; a marked increase in the ratio of choline to creatine; an appreciable increase in compounds containing choline, which is involved in the synthesis of cellular membranes, due to the proliferation of neoplastic cells, and we have correlated this with a histo-pathological parameter (Ki67). Diverse areas within a single neoplasm, characterized by higher values of Ki67, have shown higher values of the ratio ChoCC/Cr. This correlation may be of great significance if one considers the fact that information regarding Ki67 can only be obtained by way of an invasive biopsy, while the choline/creatine ration can be determined non-invasively in vivo; the presence, within the spectrum in vivo and ex vivo, of resonance attributable to mobile lipids that originate as a consequence of the disintegration of the cellular membrane due to necrotic processes. The mobile lipid-necrosis correlation permits direct identification of a neoplastic lesion at a high level of malignancy. Mobile lipids detected via spectroscopy in vivo in patients with brain tumors assume a strong clinical significance, indicating an unfavorable prognosis. Oligodendroglioma (WHO grade II) and anaplastic oligodendroglioma (WHO grade IV) demonstrate a choline/creatine ratio markedly higher in the latter case, which accords with a more pronounced cellular proliferation (higher Ki67) in the higher-level lesion. MRN in vitro of lipid extracts shows a higher relative concentration of phosphatidyl-choline of similar malignant neoplasms; moreover, MRS in vitro of lipid extracts evidences the presence of non-free, but esterified, cholesterol in tumors of a high malignancy level. We interpreted the presence of esterified cholesterol (absent in healthy tissues, and in low-grade neoplasms) by way of the rich vascularization of these neoplasms, and the neoplastic cellular proliferation. Also studied were functional and neoplastic human renal tissue. The scope of the research is to execute a biochemical map of healthy kidneys, of malignant renal neoplasms (nefrocarcinomas with clear, chromophile and chromophobic cells), and of benign renal neoplasms (oncocytomas), in order to individualize their characteristic biochemical markers. Principal results obtained thus far: the healthy renal parenchyma, rich in osmolytes, which are distributed among the cortical and medullar components. These metabolites maintain a normal osmotic balance within the renal cell; all of these osmolytes drop drastically or disappear in nefrocarcinomas with clear cells, and can therefore be considered markers of the correct functioning of the kidney. It must be emphasized how the resonance of all these osmolytes is clearly visible with MRS in vivo, thereby enabling its use as a monitor. Oncocytomas, benign low-grade neoplasm, appear to show an intermediate metabolic pattern between that of a healthy tissue and of a clear-celled malignant nefrocarcinoma. Similarly, when present in highly malignant cerebral tumors (but not in healthy parenchyma or benign oncocytomas), the esters of cholesterol in lipid extracts of clear-celled nefrocarcinomas can serve as a marker of the vascular proliferation of the neoplastic lesion, in accordance with a histopathological diagnosis. This correlation may be of great importance if one considers that for a highly-vascularized renal tumor, the development of metastases is highly probable. In addition, the elevated level of cholesterol esters in clear-celled nefrocarcinomas offers consistent confirmation of their involvement in neoplastic cellular proliferation. In fact, it has been recently reported that this class of lipids was linked to the velocity growth of various lines of neoplastic cells, and in various experimental tumors. In this regard, it is very interesting to note the case of a chromophobic nefrocarcinoma which, similarly to healthy tissue and benign oncocytomas, does not contain esterified cholesterol. This neoplasm, in effect, while malignant, is not richly vascularized, and has a more positive long-term prognosis than a clear-celled nefrocarcinoma. A more recent line of research refers to the application of MRS conducted ex vivo by way of HR-MAS (High Resolution Magic Angle Spinning) performed on human adenocarcinomas of the gastrointestinal tract. This technique, performed directly on biopsied tissues using a probe that rotates the sample to the so-called magic angle makes it possible to view high-resolution spectra of an intact tissue, without any treatment. The possibility of using the most modern bi-dimensional techniques (COSY, TOCSY, J-resolved, etc.) allows unambiguous identification of tissue metabolites, furnishing the metaboloma of the tissue sample examined.It is thus possible to provide a complete description of a functional or neoplastic tissue from the point of view of its biochemical composition, permitting the identification of biochemical markers of great diagnostic and/or prognostic importance.

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