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451.
Peretto C Biagi P Boschian G Broglio A De Stefani M Fasani L Fontana F Grifoni R Guerreschi A Iacopini A Minelli A Pala R Peresani M Radis G Ronchitelli A Sarti L Hohenstein UT Tozzi C 《Collegium antropologicum》2004,28(1):63-88
New researches have been performed on the analysis of some Italian dwelling structures dating from the Lower Paleolithic to Bronze Age. Different methods have been applied to each study according to the extensions of the areas explored. The following sites have been analyzed: Isernia La Pineta (Molise), Visogliano (Trieste) - Lower Paleolithic; Grotta del Cavallo (Lecce), Grotta Grande and Riparo del Molare (Salerno) - Middle Paleolithic; Grotta di Fumane (Verona), Riparo Tagliente (Verona), Grotta Continenza (Fucino L'Aquila), San Bartolomeo (Maiella Mountain, Abruzzo) - Upper Paleolithic; Mondeval de Sora (Belluno), Alpe Veglia (Verbania) and Grotta Edera (Aurisina, Trieste) -Mesolithic; Cala Giovanna Piano (Pianosa Island, Livorno), Contraguda (Perfugas, Sassari), Colle Santo Stefano (Fucino, L'Aquila), Catignano (Pescara), Settefonti (L'Aquila) - Neolithic; Castellaro Lagusello (Monzambano, Mantua) - Bronze Age. 相似文献
452.
Cardile V Renis M Scifo C Lombardo L Gulino R Mancari B Panico A 《The international journal of biochemistry & cell biology》2004,36(5):849-860
The aim of the present research was to determine whether the recently identified and characterized new fibrous amphibole fluoro-edenite may induce a cytopathic response in cultured cells. The final goal was to gain suggestions on the potentiality of fluoro-edenite to be harmful to human beings. Epidemiological studies, in fact, have shown an excess of developing mesothelioma among residents in Biancavilla, a town in eastern Sicily located in the Etna volcanic area. Therefore, we treated human lung fibroblasts, human lung alveolar epithelial cancer cell line A549 and monocyte-macrophage cell line J774 with fluoro-edenite or crocidolite; the latter used as a highly toxic amphibole asbestos reference. Our results show that fluoro-edenite may induce functional modifications and affects some biochemical parameters in tested cell cultures in a concentration and time dependent manner. However, the observed functional modifications induced by fluoro-edenite are generally less dramatic than those induced by crocidolite and more evident on human lung alveolar epithelial cancer cell line A549 with respect to those obtained on human lung fibroblasts or monocyte-macrophage cell line J774. The sequence of the damage is hypothesised to be as follows: at increasing fluoro-edenite concentrations, and/or treatment times, the increase in reactive oxygen species (ROS) production could trigger significant DNA damage in cell cultures, concomitantly with drop in cell metabolism and increase in lactic dehydrogenase release. In conclusion, according to our data, fluoro-edenite appears as a probable carcinogenic agent, responsible for the high incidence of malignant pleural mesothelioma in Biancavilla. 相似文献
453.
Barbieri L Brigotti M Perocco P Carnicelli D Ciani M Mercatali L Stirpe F 《FEBS letters》2003,538(1-3):178-182
It has been known that ribosome-inactivating proteins (RIPs) from plants damage ribosomes by removing adenine from a precise position of rRNA. Subsequently it was observed that all tested RIPs depurinate DNA, and some of them also non-ribosomal RNAs and poly(A), hence the denomination of adenine polynucleotide glycosylases was proposed. We report now that ricin, saporin-L2, saporin-S6, gelonin and momordin depurinate also poly(ADP-ribosyl)ated poly(ADP-ribose) polymerase (auto modified enzyme), an enzyme involved in DNA repair. We observed also that all RIPs but gelonin induce transformation of fibroblasts, possibly as a consequence of damage to DNA and of the altered DNA repair system. 相似文献
454.
455.
Guerrini M Agulles T Bisio A Hricovini M Lay L Naggi A Poletti L Sturiale L Torri G Casu B 《Biochemical and biophysical research communications》2002,292(1):222-230
The glycosaminoglycans heparin and heparan sulfate (HS) bind to fibroblast growth factor FGF1 and promote its dimerization, a proposed prerequisite for binding to a cellular receptor and triggering mitogenic signals. The problem of minimal structural requirements for heparin/HS sequences to bind FGF1 was approached by surface plasmon resonance (SPR), NMR spectroscopy, and MALDI mass spectrometry studies using the three synthetic tetrasaccharides GlcNSO(3)6OR-IdoA2SO(3)-GlcNSO(3)6OR'-IdoA2SO(3)OPr (AA, R = R' = SO(3); BA, R = H, R' = SO(3); BB, R = R' = H; Pr, propyl). AA and BA significantly interact with the protein, whereas BB is practically inactive. The NMR spectra show that, whereas the interaction of AA primarily involves the GlcNSO(3)6SO(3)IdoA2SO(3) disaccharide moiety at its nonreducing end, residues at both the nonreducing (NR) and reducing side (R) appear to be involved in the weaker complex of BA. Furthermore, MALDI experiments show that, in addition to 1:1 protein:tetrasaccharide complexes, AA and BA are able to form 2:1 complexes, indicating that heparin/HS-induced dimerization of FGF1 requires only one 6-OSO(3) group per tetrasaccharide. 相似文献
456.
Biological and pharmacological interactions of heparin and structurally related glycosaminoglycans (GAGs) such as heparan sulfate (HS) involve complex sequences of variously sulfated uronic acid and aminosugar residues. Due to their structural microheterogeneity, these sequences are usually characterized in statistical terms, by high-performance liquid chromatographic analysis of fragments obtained by enzymatic or chemical degradation. Nuclear magnetic resonance (NMR) spectroscopy is also currently used for structural characterization of GAGs. However, the use of monodimensional NMR analysis of complex GAGs is often limited by severe signal overlap that does not allow reliable quantitative measurements. Using magnetically equivalent signals, the higher resolution achieved by two-dimensional NMR methods could be also exploited for quantitative applications. In this work, heteronuclear single quantum coherence (HSQC) spectroscopy has been evaluated to determine variously substituted monosaccharide components of HS and HS mimics obtained by chemical modification of the Escherichia coli K5 polysaccharide (K5-PS) structurally related to the common biosynthetic precursor of heparin and HS. Heparin was used as a model for assessing the influence of 1H-13C spin-spin couplings on "volumes" of the corresponding signals. For major signals, the HSQC approach permitted quantification of additional structural features both in heparins and in a typical HS. The method was applied to profile the substitution patterns of K5-PS derivatives involving different degrees of N,O-sulfation and N-acetylation, including O-sulfated heparosans bearing free amino groups. 相似文献
457.
HER-2/neu evaluation by fluorescence in situ hybridization on destained cytologic smears from primary and metastatic breast cancer 总被引:2,自引:0,他引:2
OBJECTIVE: To evaluate HER-2/neu amplification by fluorescence in situ hybridization (FISH) (HER-2/neu by FISH) on archival cytologic smears stained with May-Grünwald-Giemsa (MGG) stain. STUDY DESIGN: Cytologic specimens from 69 breast cancer lesions (48 primary and 21 metastatic), stained with MGG stain for routine diagnostic cytology, were destained and subjected to HER-2/neu by FISH. Fifteen of the 69 samples were also evaluated by FISH on paired fresh smears. RESULTS: HER-2/neu by FISH was successfully assayed in 25 of the 48 primary tumors and in 15 of the 21 metastatic lesions, corresponding to an overall feasibility of 58%. These cases had been archived between 1 month and 10 years prior to FISH analysis. Eight of the 25 primary and 5 of the 15 metastatic tumors were amplified. In 15 of the 40 evaluable cases, HER-2/neu was also assessed on the corresponding fresh smears: 8 tumors were amplified and 7 unamplified on both destained MGG and fresh smears. CONCLUSION: HER-2/neu can be detected by FISH on routinely MGG-stained cytologic slides. This approach allows HER-2/neu evaluation whenever histologic sections or fresh cytologic material are not available. In these cases, HER-2/neu assessment on destained cytologic smears plays a role in the selection of targeted therapy. 相似文献
458.
Gionata De Vico Paola Maiolino Brunella Restucci Annamaria Passantino 《Theoretical biology forum》2005,98(2):279-296
Despite the ongoing search for "replacement" alternatives, animal models continue to play a crucial role in bio-medical research. However, both in vivo and in vitro models usually employed, such as rodents and/or cell lines, display intrinsic limits related to the specific characteristics of the biological systems used, whose management is very complex, and whose pathology, usually induced under artificial laboratory conditions, is frequently dissimilar to the studied human spontaneous disease. It has been suggested that carrying out clinical trials based on pre-clinical data obtained after a screening on animal models developing the neoplastic disease in a more similar way to human beings, as represented by spontaneous canine tumours, could accelerate the entry of new effective drugs into the clinical practice. In this paper the authors discuss the scientific foundation as well as the ethic and legal concerns related to the use of this "pet model" in comparative oncology, suggesting some "key words" as the necessary starting point for a correct approach to the matter. 相似文献
459.
Modulation of the heparanase-inhibiting activity of heparin through selective desulfation, graded N-acetylation, and glycol splitting 总被引:10,自引:0,他引:10
Naggi A Casu B Perez M Torri G Cassinelli G Penco S Pisano C Giannini G Ishai-Michaeli R Vlodavsky I 《The Journal of biological chemistry》2005,280(13):12103-12113
Heparanase is an endo-beta-glucuronidase that cleaves heparan sulfate (HS) chains of heparan sulfate proteoglycans on cell surfaces and in the extracellular matrix (ECM). Heparanase, overexpressed by most cancer cells, facilitates extravasation of blood-borne tumor cells and causes release of growth factors sequestered by HS chains, thus accelerating tumor growth and metastasis. Inhibition of heparanase with HS mimics is a promising target for a novel strategy in cancer therapy. In this study, in vitro inhibition of recombinant heparanase was determined for heparin derivatives differing in degrees of 2-O- and 6-O-sulfation, N-acetylation, and glycol splitting of nonsulfated uronic acid residues. The contemporaneous presence of sulfate groups at O-2 of IdoA and at O-6 of GlcN was found to be non-essential for effective inhibition of heparanase activity provided that one of the two positions retains a high degree of sulfation. N-Desulfation/ N-acetylation involved a marked decrease in the inhibitory activity for degrees of N-acetylation higher than 50%, suggesting that at least one NSO3 group per disaccharide unit is involved in interaction with the enzyme. On the other hand, glycol splitting of preexisting or of both preexisting and chemically generated nonsulfated uronic acids dramatically increased the heparanase-inhibiting activity irrespective of the degree of N-acetylation. Indeed N-acetylated heparins in their glycol-split forms inhibited heparanase as effectively as the corresponding N-sulfated derivatives. Whereas heparin and N-acetylheparins containing unmodified D-glucuronic acid residues inhibited heparanase by acting, at least in part, as substrates, their glycol-split derivatives were no more susceptible to cleavage by heparanase. Glycol-split N-acetylheparins did not release basic fibroblast growth factor from ECM and failed to stimulate its mitogenic activity. The combination of high inhibition of heparanase and low release/potentiation of ECM-bound growth factor indicates that N-acetylated, glycol-split heparins are potential antiangiogenic and antimetastatic agents that are more effective than their counterparts with unmodified backbones. 相似文献
460.
Innoceta A Galluzzi L Ruzzo A Andreoni F Chiarantini L Magnani M 《Molecular and cellular biochemistry》2002,231(1-2):173-177
Human monoblastoid cells (U937) grown in the presence of therapeutically relevant dideoxycytidine concentrations (0.1 M) become resistant to the drug thanks to an altered deoxycytidine kinase. In this paper we show that deoxycytidine kinase mRNA is significally reduced in drug-resistant U937 cells (U937-R) although the deoxycytidine kinase promoter is normal. A number of nucleotide deletions, insertions and substitutions was found in the coding region of deoxycytidine kinase gene. Several identified mutations result in truncated forms of the enzyme or in the introduction of stop codons: in one case a complete lack of exon 4 was found. Thus, the deoxycytidine kinase gene accumulates mutations at a very high rate, as already reported for other cytidine analogues (i.e. Ara C ) suggesting that the design of new antiviral or anticancer drugs of the cytidine family should take into account the potential development of cell resistance as a critical factor in drug failure. 相似文献