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Biomedical subjects

A Sacchi

Publications and source records attributed to A Sacchi.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Exogenous wt-p53 protein is active in transformed cells but not in their non-transformed counterparts: implications for cancer gene therapy without tumor targeting.

BACKGROUND: Expression of exogenous wild-type p53 (wt-p53) protein in tumor cells can suppress the transformed phenotype whereas it does not apparently induce detrimental effects in non-transformed cells. This observation may provide a molecular basis for p53-mediated gene therapy of p53-sensitive cancers without the need for tumor targeting. METHODS: To understand the molecular mechanisms responsible for this different behavior in tumor versus normal cells, biochemical and functional analyses of exogenous wt-p53 protein were performed on non-transformed C2C12 myoblasts and their transformed counterparts, the C2-ras cells. RESULTS: The exogenous wt-p53 protein, which induced persistent growth arrest only in transformed C2-ras cells, was shown to be significantly more stable in transformed than in non-transformed cells. This different stability was due to different p53 proteolytic degradation. Moreover, constitutively, exogenous wt-p53 protein was found to be transcriptionally active only in C2-ras cells but it could also be activated in C2C12 cells by genotoxic damage. CONCLUSIONS: Non-transformed C2C12 cells present regulatory system(s) which control the expression and the activity of exogenously expressed wt-p53 protein probably through degradation and maintenance in a latent form. This regulatory system is lost/inactivated upon transformation.

Adenoviridae↗
PubMedDate not supplied

Changes of phenotypic characteristics of variants derived from Lewis lung carcinoma during long-term in vitro growth.

Two cultured cell clones derived from Lewis lung carcinoma (3LL), which have been shown to differ in their metastatic potential, were studied for their phenotypic stability in vitro. Several growth properties (lag-phase duration, doubling time, saturation density, cell shedding, plating efficiency) have been monitored for more than three years. The ability to induce primary tumors and metastasis, together with the response of cultured cells to adriamycin and bleomycin, have also been evaluated over the same period. The results show that the pattern of metastatic heterogeneity of the two clones is maintained during the serial passages in vitro, although the most actively metastatic clone (C108) displayed a reduced lung colony-forming ability at late passages. Furthermore, both clones exhibited an increasing sensitivity to adriamycin, while no changes were observed in the response to bleomycin. The present data suggest a phenotypic instability of tumor clones adapted to tissue culture conditions and, in particular, that the inherent chemosensitivity of tumor cells may change during long-term culture.

Animals↗
PubMedDate not supplied

Stimulation of tumor cell growth in vitro by a monoclonal antibody to a tumor specific protein (TSP-180) present on the cell surface of 3LL cells.

Proliferation capacity and MHC class I antigen expression of two Lewis lung carcinoma (3LL) metastatic variants (C87, BC215) grown under defined experimental conditions (serum-free defined medium or 10 per cent serum) have been studied following exposure to MoAb 135-13C which recognizes on these cells a tumor surface protein of 180,000 daltons (TSP-180). The results of this study indicate that the high metastatic clone (C87) binds higher amounts of MoAb to TSP-180 and Db antigens than does the low metastatic one (BC215), while both clones express very low amounts of Kb antigens. 3LL clones grown in 10 per cent serum or adapted in serum-free, defined medium show the same metastatic phenotype and MHC class I antigen expression, but when grown in defined medium exhibit increased capacity to bind MoAb 135-13C. However, the relative binding rate of 3LL clones grown in 10 per cent serum or in defined medium is unchanged: the high metastatic clone always showing higher capacity to bind MoAb to TSP-180. Furthermore, comparison of EGF binding sites on the cell surface of 3LL clones, grown in different culture conditions, demonstrates that the C87 clone binds higher amounts of labelled EGF and that this amount increases in serum-free defined medium, exactly as reported for TSP-180. In addition, competition experiments demonstrated that MoAb 135-13C does not compete for EGF binding sites on 3LL cell surface. Studies on cell proliferation following exposure to MoAb 135-13C, revealed that the low metastatic clone (BC215) is more actively stimulated than the high metastatic one. Moreover, similar data were obtained after exposure of 3LL clones to physiological amounts of different growth factors (i.e. EGF, MSA, insulin). Analysis of MHC class I antigen expression following exposure to MoAb 135-13C indicated that MoAb 135-13C induces on the cell surface of the C87 clone a transient low modulation of Db antigens. These results suggest that 3LL cells endowed with lower metastatic potential are more dependent on the microenvironmental conditions than the high metastasizing ones, and that MoAb 135-13C binding to 3LL cell surface stimulates proliferation as reported for several known growth factors.

Animals↗
PubMedDate not supplied

[A case of maxillary metastasis from breast cancer].

The literature data relating to the jaws as a metastasis site are examined, along with the basic criteria and main symptomatological pictures observed. A personal and relatively unusual instance of metasis to the upper jaw from breast cancer is presented. The features that led to diagnosis are discussed. Reference is made to the reported theories that justify the rarity of metastasis from breast cancer to the maxillofacial bones.

Adult↗
PubMedDate not supplied

[The use of a bactericidal substance as medication in the indirect capping of healthy dentin].

An association of trimethoprim and sulphamethoxazol (Bactrim, Roche) was employed in the indirect capping of healthy teeth in the dog. Tetracycline labelling showed dentinogenesis in these teeth and comparison was made with the controls, A quantitative and qualitative change in dentinogenesis was noted below the control cavities. This alteration was less marked in Bactrim-treated teeth. It is deduced, therefore, that the operations involved in the preparation and filling of cavities in healthy teeth leads to pulp damage that can be partly prevented by using a bactericide.

Animals↗
PubMedDate not supplied

Activation of p53/p21waf1 pathway is associated with senescence during v-Ha-ras transformation of immortal C2C12 myoblasts.

It has recently been shown that tumor cells can retain the ability to undergo senescence, while the capacity of bypassing senescence has been associated with tumor progression. In this report, we showed that v-Ha-ras-mediated transformation of already immortal C2C12 myoblasts can be associated with senesence, in a low amount during in vitro passages and, to a higher extent, affer cellular stress (cell culture alkalinkation), or DNA damage (doxorubicin treatment). The capacity to undergo replicative senescence is associated with a strong increase of wt-p53 transcriptional activity and p21WAF1 up-regulation. These biochemical activities are down-modulated in the cells that evade the massive replicative senescence after stressing stimuli. Altogether, these findings show that active ras can cause senescence during the transformation of already immortal cells in associaton with p53/p21WAF1 pathway activation and support the hypothesis that p53/p21WAF1 functional activity is important in maintaining the integrity of the senescence pathway during cellular transformation.

Animals↗
PubMedDate not supplied

In vitro antioxidant and in vivo photoprotective effects of a lyophilized extract of Capparis spinosa L buds.

The aim of the present study was to evaluate the in vitro antioxidant and in vivo photoprotective activities of a lyophilized extract of Capparis spinosa L. (LECS) obtained by methanolic extraction from the flowering buds of this plant. For the in vitro experiments, LECS was tested employing three different models: (a). bleaching of the stable 1,1-diphenyl-2-picrylhydrazyl radical (DPPH test); (b). peroxidation, induced by the water-soluble radical initiator 2,2'-azobis(2-amidinopropane) hydrochloride, of mixed dipalmitoylphosphatidylcholine/linoleic acid unilamellar vesicles (LUVs) (LP-LUV test); and (c). UV-induced peroxidation of phosphatidylcholine multilamellar vesicles (UV-IP test). The in vivo antioxidant/radical scavenger activity was assessed by determining the ability of topically applied LECS to reduce UVB-induced skin erythema in healthy human volunteers. From the results obtained in in vitro and in vivo tests, LECS showed a significant antioxidant effect. Furthermore, by chromatographic fractionation and spectroscopic methods, we identified the major constituents of LECS, and particularly some flavonols (kaempferol and quercetin derivatives) and hydroxycinnamic acids (caffeic acid, ferulic acid, p-cumaric acid, and cinnamic acid).

Adult↗
PubMedDate not supplied

[Differential diagnosis of hematoma, pulsating hematoma and pseudoaneurysm of the femoral artery using color Doppler].

Color Doppler and Duplex Doppler US were employed on 4 patients with clinically suspected pseudoaneurysms as a complication of femoral artery puncture after cardiac catheterization. Pseudoaneurysms were identified with Color Doppler US and their typical appearance was confirmed. The grey-scale findings did not allow an adequate differentiation between hematoma and pulsed hematoma without fibrous encapsulation: only Color Doppler US easily detected the track between damaged artery and blood collection and allowed a sample to be obtained for pulsed Doppler examination. Color Doppler US allowed an accurate and non-invasive diagnosis of groin masses after femoral artery catheterization.

Aneurysm↗
PubMedDate not supplied

Metastatic phenotype: growth factor dependence and integrin expression.

Homogeneous subpopulations, which are endowed with low or high metastatic potential, were selected from Lewis lung carcinoma (3LL) in an attempt to correlate metastatic phenotype with specific properties of tumor cells. Since the growth of malignant cells at secondary sites could depend on their ability to respond to microenvironments, the growth factor dependence of 3LL variants has been studied. The ability of variant lines to grow in monolayer and in soft agar cultures, either in the presence or absence of different growth factors or serum, was analyzed and correlated with their metastatic potential. The reported results demonstrate that tumor cells expressing higher metastatic potential also exhibit higher capacity to grow and proliferate in all the culture conditions tested, independently of the addition of exogenous growth factors or serum. Moreover, since highly metastasizing cells express a significant amount of TGF-beta 1 mRNA, a pattern of autocrine growth is postulated for 3LL metastatic cells. One relevant aspect of the phenotype of transformed cells is their reduced adhesion to solid substrates; this phenomenon is thought to reflect the invasive and metastatic potential of tumor cells. Since the adhesion of the cells to substrata is mediated by molecules of the extracellular matrix, the expression of extracellular matrix receptors (integrins) was studied on 3LL metastatic variants. In particular, through immunochemical and biochemical studies we investigated the expression of the laminin receptor(alpha 6/beta 1) and of a novel receptor (integrin: alpha 6/beta 4), of unknown function. The receptors were quantitated on the cell surface of 3LL variants by the use of specific monoclonal antibodies which recognize, respectively, different epitopes of alpha 6, beta 4 or beta 1 subunits. Results demonstrate that the novel integrin alpha 6/beta 4, is specifically expressed in highly metastasizing 3LL cells, whereas the laminin receptor alpha 6/beta 1 is expressed in all 3LL variants. In conclusion, data presented demonstrate that 3LL cells endowed with higher metastatic potential are more independent of the microenvironmental conditions in that they possess a higher autocrine capacity than the lower metastasizing ones, and could acquire higher capacity to invade through the expression on their cell surface of specific receptors for cell adhesion (the novel integrin, defined as alpha 6/beta 4).

Animals↗