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M Scotti

Publications and source records attributed to M Scotti.

At least 19 recordsLinked to original sources
PubMed2004

Gene expression profiles of epithelial cells microscopically isolated from a breast-invasive ductal carcinoma and a nodal metastasis.

Expression profiles of breast carcinomas are difficult to interpret when they are obtained from tissue in toto, which may contain a large proportion of non-cancer cells. To avoid this problem, we microscopically isolated cells from a primary invasive ductal carcinoma of the breast and from an axillary node harboring a metastatic breast carcinoma, to obtain pure populations of carcinoma cells ( approximately 500) and used them for serial analysis of gene expression. The expression profiles generated from both populations of cells were compared with the profile of a disease-free mammary epithelium. We showed that the expression profiles obtained are exclusive of carcinoma cells with no contribution of non-epithelial cells. From a total of 16,939 unique tags analyzed, we detected 559 statistically significant changes in gene expression; some of these genes have not been previously associated with breast cancer. We observed that many of the down-regulated genes are the same in both cancers, whereas the up-regulated genes are completely different, suggesting that the down-regulation of a set of genes may be the basic mechanism of cancer formation, while the up-regulation may characterize and possibly control the state of evolution of individual cancers. The results obtained may help in characterizing the neoplastic process of breast cancer.

Breast↗
PubMed2004

Association of rat8 with Fyn protein kinase via lipid rafts is required for rat mammary cell differentiation in vitro.

We previously identified rat8 in the pathway involved in epithelial cell differentiation that occurs in the rat mammary gland at pregnancy when tubules and alveoli are formed. rat8, which encodes an IFN-inducible membrane protein, is the rat homologue of the mouse gene fragilis. By differential detergent extraction and isopycnic sucrose density gradients, we show that rat8 protein is associated to lipid membrane domains together with Lyn and Fyn, members of the Src tyrosine kinase family. We also show that recruitment of rat8 to lipid membrane domains is a necessary step in mammary epithelial cell differentiation. Immunoprecipitation analysis, performed with an anti-Fyn protein antibody, shows that rat8 was present in the Fyn immunoprecipitate. Antisense oligonucleotides, used to inhibit Fyn protein expression, block mammary cell differentiation. Taken together, these results suggest that the functional interaction, via lipid membrane domains, of rat8 and Fyn proteins is required for mammary cell differentiation. Therefore, rat8, like fragilis, may be involved in developmental decisions and the demarcation of a subset of cells in the mammary gland that cause epithelial cells to develop into a network of tubuloalveolar structures involved in secretion.

Animals↗
PubMed2004

Immunodeficiency in different histotypes of radically operable gastrointestinal cancers.

Cell-mediated immunodeficiency, with Total and T lymphocytes count decrease, is well established in cancer patients and it predicts a poor prognosis and poor survival rates. Furthermore, major surgery induces a transient immunodeficiency, too. Nevertheless, cell-mediated immunity in pancreatic cancer, which has a very poor prognosis, has not been completely outlined. Aim of this study is to evaluate the cell-mediated IL-2 dependent immune status in operable pancreatic cancer patients and to compare it with other gastrointestinal tumors. One hundred and twenty-one cancer patients (22 pancreatic, 48 gastric and 51 colorectal), with a median age of 66 years (range 42-83), 55 males and 66 females, were enrolled. Total lymphocyte count and lymphocytes subset (T helper count - CD4+) were assessed preoperatively and on the 14th and 50th postoperative day. Results obtained were compared between the groups and related to nodal involvement (N0 versus N+). Colorectal and gastric cancer patients showed quantitative lymphocyte deficiency at baseline in 29% and 41% of cases, respectively. Fourteen days after surgery values below normal range were found in 44% and 54% (Total) and 53% and 67% (T helper), respectively. Recovery of postoperative surgery-related lymphocytopenia occurred late only in patients with normal count at baseline. According to regional nodal involvement (pN0/N+) T helper deficiency was significantly more frequent in patients with nodal involvement than in patients without. In pancreatic cancer, percentage of immunodepressed patients at baseline was higher compared to the other two groups (71%). Lymphocyte count was significantly different between pancreatic and gastric/colorectal cancer, reaching a statistical significance at baseline and on the 14th and 50th postoperative day. No differences of T helper deficiency were noted according to nodal involvement (N0 versus N+) neither at baseline nor in the postoperative period. In conclusion, the degree of immunosuppression varies among different tumor types: since initial stages of disease, immunodepression was significantly greater in pancreatic cancer which should be considered always a systemic disease even in early stages and indipendently from the nodal involvement and from tumor load.

Adenocarcinoma↗
PubMed2003

Alteration of hypothalamus-pituitary-adrenal gland axis in colorectal cancer patients. Preliminary report.

AIM: In advanced cancer patients a cell-mediated immunological impairment, both at baseline and during postoperative period, is often found and is associated with poor prognosis. Cortisol is strictly involved in the response to major surgical stress, is an immunosuppressor and causes a redistribution of immunological population cells in different tissues. The aim of the study was to verify serum levels and circadian rhythm of cortisol in patients with colorectal cancer at baseline before surgery and in the postoperative period, and relate it to the immune status. METHODS: In 21 patients with colorectal cancer undergoing surgery we evaluated the assessment of total lymphocytes, CD4+, cortisolemia, circadian rhythm of cortisol (11 p.m. and 8 a.m.) at baseline and in 3(rd) and 7(th) postoperative days. RESULTS: Increase of cortisolemia, as decrease of total and CD4+ lymphocytes in the postoperative period versus baseline was statistically significant. Patients with an altered circadian rhythm were 47% and 36% at 3rd and 7th postoperative days, respectively. At baseline 19% of patients had an altered cortisol circadian rhythm and it was more frequent in patients with nodal involvement (p<0.05) and with metastasis (p<0.01). No relations between lymphocytopenia and alteration of cortisolemia and cortisol circadian rhythm were found, either at baseline or postoperatively (p<0.05). CONCLUSION: Lymphocytopenia in cancer patients seems not to be associated with cortisol level and circadian rhythm alteration, either at baseline or after surgical stress. An impairment of circadian rhythm of cortisol was found at baseline in 19% of patients. It was significantly associated with the presence of metastatic disease.

Adenocarcinoma↗
PubMed2001

Characterization of mec1 kinase-deficient mutants and of new hypomorphic mec1 alleles impairing subsets of the DNA damage response pathway.

DNA damage checkpoints lead to the inhibition of cell cycle progression following DNA damage. The Saccharomyces cerevisiae Mec1 checkpoint protein, a phosphatidylinositol kinase-related protein, is required for transient cell cycle arrest in response to DNA damage or DNA replication defects. We show that mec1 kinase-deficient (mec1kd) mutants are indistinguishable from mec1Delta cells, indicating that the Mec1 conserved kinase domain is required for all known Mec1 functions, including cell viability and proper DNA damage response. Mec1kd variants maintain the ability to physically interact with both Ddc2 and wild-type Mec1 and cause dominant checkpoint defects when overproduced in MEC1 cells, impairing the ability of cells to slow down S phase entry and progression after DNA damage in G(1) or during S phase. Conversely, an excess of Mec1kd in MEC1 cells does not abrogate the G(2)/M checkpoint, suggesting that Mec1 functions required for response to aberrant DNA structures during specific cell cycle stages can be separable. In agreement with this hypothesis, we describe two new hypomorphic mec1 mutants that are completely defective in the G(1)/S and intra-S DNA damage checkpoints but properly delay nuclear division after UV irradiation in G(2). The finding that these mutants, although indistinguishable from mec1Delta cells with respect to the ability to replicate a damaged DNA template, do not lose viability after UV light and methyl methanesulfonate treatment suggests that checkpoint impairments do not necessarily result in hypersensitivity to DNA-damaging agents.

Alleles↗
PubMed1991

[Diagnostic and therapeutic strategy in extrahepatic biliary lithiasis. Our experience].

The paper describes the Authors' personal experience in the diagnosis and treatment of extrahepatic biliary lithiasis in 166 patients admitted to the Surgical Division of the International Evangelical Hospital. The basic tests for a correct diagnostic strategy are echotomography and ERCP in cases of jaundice and/or dilatation of the biliary tract with negative echographic results for lithiasis of the choledochus. The indications for surgery are also discussed and the new possibilities of pre- and post-operative PSTE are also taken into account.

Adult↗
PubMed1991

Wide spectrum detection of precarcinogens in short-term bioassays by simultaneous superinduction of multiple forms of cytochrome P450 isoenzymes.

The use of Aroclor 1254 to induce S9 liver fractions is a standard method for conducting short-term genotoxicity assays. An alternative induction procedure, using beta-naphthoflavone (beta-NF), as a safe (non-carcinogenic) substitute for polychlorinated biphenyls, combined with sodium phenobarbital (PB), was found to be equally effective. The aim of this work is to realize a novel schedule of induction for the preparation of metabolizing systems containing a wider spectrum of induced cytochrome P450s. Five inducers of different 'classes' such as PB (class IIB P450s), beta-NF (IA), isosafrol (IA2), ethanol (IIE1) and pregnenolone 16 alpha-carbonitrile (IIIA) were injected daily both separately (to achieve maximal monooxygenase induction) in male and female mice. Induction was monitored using specific P450-linked activities. In the optimal schedule for complete induction, the various monooxygenases were greater (2- to 4-fold) than those achieved by the classical schedule. More than a 14-fold increase of total P450 and 3.3-fold increase of NADPH-cytochrome (P450) c-reductase activity, over those uninduced, account for the above increase. For example, there was a marked increase in the deethylation of ethoxyresorufin (37-fold) compared to the uninduced mice that was considerably higher than classical induction (8-fold over uninduced). On the contrary, phase II reactions i.e. epoxide hydrolase, glutathione S-transferase, glutathione S-epoxide transferase and UDP-glucuronosyl transferase, examined to compare the phase I/phase II ratios in the traditional and proposed procedures, were increased to a lesser extent (2-fold over uninduced). No significant sex differences were seen. Five precarcinogens specifically metabolized by each of the induced P450s elicited a higher mutagenicity response in the presence of superinduced fractions with respect to the classical one, when tested on Salmonella typhimurium (cyclophosphamide, benzo[alpha]pyrene, 2-naphthylamine and dimethylnitrosamine) or Saccharomyces cerevisiae D7 strain (diethylstilbestrol). These novel metabolizing biosystems, with an enhanced spectrum of induced P450s and oxidative/post-oxidative reaction rates, are recommended for detecting unknown xenobiotics in genotoxicity studies.

Animals↗
PubMed1991

[Prenatal diagnosis of a case of obstruction of the uretero-pelvic junction].

The Authors report a case of bilateral ureteropelvic junction obstruction in a pregnant woman at to 20th week of gestation. The pathology arose suddenly during the second trimester. An anhydramnios was picant and the enlarged kidneys filled the entire fetal abdomen. The woman decided for abortion. The Authors describe the etiopathology and management of this disease.

Abnormalities, Multiple↗
PubMed1990

Dimethylsulfoxide as modifier of the organospecific mutagenicity of metronidazole in mice.

Mutagenicity and carcinogenicity of metronidazole (MT) are imputable to the formation of toxic intermediates, which include radical forms derived from the nitroreductive process. Since dimethylsulfoxide (DMSO), the "universal" solvent, can quench free radicals in vitro, it was suggested that DMSO might protect by scavenging free radical generation in vivo. This study wanted to evaluate if DMSO (given concomitantly or prophylactically) protects against the organospecific mutagenicity of MT in vivo by means of the intrasanguineous host-mediated assay. DMSO used as solvent showed a 20%-30% reduction in the mutation frequencies by MT. Prophylactic administration of DMSO for 3 d caused a suppression of the organospecific mutagenicity. However, some increases in the spontaneous mutation frequency and enhancement of MT mutagenicity in kidney were observed. The protective effect was paralleled by a decrease in NADPH cytochrome c (P450) reductase in liver, kidney, and to a lesser extent in lung microsomes from pretreated mice. Inhibition of mutagenic activity might be related to scavenging of radical species as supported by the lack of tissue specificity and no appreciable changes in specific enzyme activity. However, changes in reductase content in prophylactically pretreated mice can affect the quantitative biotransformation of MT to the proximal mutagen contributing to the observed suppression in mutation frequencies.

Animals↗
PubMed1990

Strategies for optimization of short-term genotoxicity tests: the synergistic effect of NADPH and NADH on P450 function in processing pre-mutagens.

The synergistic effect of NADPH and NADH on P450 functions upon pre-mutagens requiring metabolism during the incubation conditions used in the liver microsomal assay (LMA) was studied. The mean specific activity (Asp) during 1 h of pre-incubation (LMA) of some microsomal mono-oxygenases (i.e. ethylmorphine N-demethylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase) examined with S9 fractions from sodium phenobarbital and beta-naphthoflavone pre-treated mice, was doubled when both NADPH and NADH were present. In contrast, when lipid peroxidation was used as the main enzymatic inactivation index, there was no appreciable change. In agreement with biochemical data, in vitro DNA binding of the pre-mutagenic agent [14C]-1,1,1,2-tetrachloroethane ([14C]TTCE), mediated by mouse hepatic enzymes, showed a significant enhancement (4.4-fold) of specific activity in the presence of both pyridine nucleotides. Mutagenesis experiments using TTCE in the diploid D7 strain of Saccharomyces cerevisiae (from stationary growth phase) as a biological test system, showed a significant enhancement of mitotic gene conversion and reverse point mutation frequencies when using NADPH plus NADH in the medium. Conversely, no positive results without NADH were seen. These findings lead us to suggest the routine use of both NADPH and NADH in order to increase the 'sensitivity' of in vitro mutagenicity screens.

Animals↗
PubMed1989

[Hartmann's operation in complicated lesions of the sigmoid and rectum].

A personal series of 49 Hartmann's operations carried out in the period 1975-1986 for complicated rectal-sigmoid lesions, 43 for cancer and 6 for diverticular sigmoiditis, are reported. Fully 45 of these patients (92%) were operated on in emergency conditions and the choice of the operation was imposed by the gravity of the lesions observed. In the light of this series and a review of the literature, it is maintained that the operation still has a place in complicated rectal-sigmoid lesions, especially under emergency conditions and in patients at risk for age and general conditions, it being very well tolerated and consenting recanalisation if necessary.

Aged↗
PubMed1989

[Effect of somatostatin and salmon calcitonin on carcinoid syndrome. A clinical case].

In carcinoid syndrome, calcitonin administration proved to have an effective action in reducing symptomatology. During the perioperative period, treatment with somatostatin, thanks to the ease of administration of the drug and the reductive action of gastroenteric secretion, demonstrated its usefulness in countering the action of serotonin. In the present case, the data reported in the most recent literature on the use of the two drugs in the carcinoid syndrome are confirmed.

Aged↗
PubMed1988

Organospecific activation of azathioprine in mice: role of liver metabolism in mutation induction.

The organ-specific mutagenicity of azathioprine was examined by means of the intrasanguineous host-mediated assay in mice, combined with the D7 strain of Saccharomyces cerevisiae. To assay for changes in the frequency of mitotic gene conversion, mitotic crossing-over and point reverse mutation frequency, a single i.p. dose of azathioprine was administered. Kidney-mediated mutagenicity was significantly enhanced. The ability of liver, kidney and lung S9 fractions (from Na-phenobarbital + beta-naphthoflavone induced mice) to activate azathioprine into genotoxic intermediates was also evaluated in vitro by incubating organ homogenates with S. cerevisiae cells as a target organism. Organ-specific activation was demonstrated only in the liver. The relative role of liver metabolism in the induction of mutations and tumor induction was investigated in in vivo experiments with partially hepatectomized mice. The data demonstrated that liver affects both kidney- and lung-mediated mutagenicity and indicated that hepatic metabolism can contribute mutagenic metabolites for cancer initiation by azathioprine.

Animals↗
PubMed1987

Mutagenicity studies on thymomodulin.

Thymomodulin (Leucotrofina), an orally administrable thymic derivative endowed with interesting immunomodulating and myelomodulating properties, was tested for mutagenicity by means of the following in vitro and in vivo tests: mutagenesis on S. typhimurium with and without metabolic activation system (S-9), gene conversion on S. cerevisiae D 7 with and without metabolic activation, urinary assay in the mouse with and without metabolic activation, urinary assay in the mouse with S. cerevisiae D 7, host mediated assay in the mouse with S. cerevisiae and DNA repair test with and without metabolic activation. On the basis of the results obtained thymomodulin proved to be free of mutagenic activity.

Animals↗