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M Modesti

Publications and source records attributed to M Modesti.

At least 19 recordsLinked to original sources
PubMed2005

Reinforcing effect of organo-modified layered silicates in high-density polyethylene.

This study focuses on the understanding of the reinforcing effect given by organo-modified layered silicates to a high-density polyethylene and the influence on the crystallization properties of this polymer. The addition of organo-modified clay to high-density polyethylene resulted in an evident increase in the tensile and flexural Young's modulus of the material with respect to unfilled polymer. The morphology, crystallinity, and thermo-oxidative stability of such nanocomposites were investigated using X-ray diffraction, transmission electron microscopy, differential scanning calorimetry, and oxidation induction time test. The materials obtained show tactoid as well as intercalated and exfoliated structures with different dominant states depending on the loading level and process conditions. It was observed that organic ions not only change mixing behavior but also influence material properties, including the degree of crystallinity and the stability to the thermo-oxidative phenomena.

Aluminum Silicates↗
PubMed2005

Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells.

Autocrine and paracrine mechanisms modulate the synthesis and secretion of extracellular matrix (ECM); moreover, each component of the ECM is capable of modulating the synthesis and release of other ECM molecules. Therefore, the synthesis of ECM glycoprotein fibronectin and laminin was studied in the human breast cancer cell lines MCF7 and MDA MB 23, plated on different ECM. Our results showed that the cells plated on a fibronectin substrate increased laminin synthesis: this event correlated with an increase in alpha2 and alpha3 integrin subunits. Staurosporine-induced apoptosis was then analyzed in the cell lines plated on different ECM. Staurosporine treatment determined the apoptosis of 35 and 33% respectively of MDA MB 231 and MCF7; these values increased to 60 and 64% in cells plated on laminin, to 48 and 63% in cells plated on fibronectin and to 64 and 69% in cells plated on matrigel. Moreover, staurosporine treatment decreased bcl-2 expression in the cells plated on fibronectin and laminin. Yet, staurosporine treatment determined PARP cleavage and PARP partial disappearance when the cells were plated on matrigel. Finally, a partial loss of function mutant Ras protein that activated only Raf pathway, was expressed in MCF7, in order to identify whether the increase of apoptosis induced by extracellular matrix involved the Raf/MAP kinase pathway. The increase of apoptosis of the cells plated on matrigel suggested that the activation of the Raf pathway is probably involved in the decrease of survival on matrigel. These data demonstrate that the modification of ECM modulates the apoptotic process of breast cancer cells and suggest that it is worthwhile to dissect the role of ECM in the control of apoptotic process.

Apoptosis↗
PubMed2004

[The breast phyllodes tumor: surgical therapy following histological transformation. Case report].

The Authors report a clinical case of mammary phyllodes tumor recurrence; characterized by the histological transformation of the recurrence respect to primary tumor. PT are 0.3-1% of all mammary neoplasia. They are classified with Tavassoli's criteria (1999). The surgical treatment of PT is the wide excision (WE). Local recurrences are detected in about 20% of patients undergone to surgery. Surgical therapy of recurrences depends on the histological grade of primary lesion. Authors believe it is necessary to perform simple mastectomy when high grade PT recurrences are detected and when histological transformation of the lesion changes from low grade to high grade.

Breast Neoplasms↗
PubMed2001

DNA repair: spot(light)s on chromatin.

Chromatin modifications regulate many nuclear processes. Recent studies on the phosphorylation of a histone 2A variant have revealed that this chromatin modification is a general and evolutionarily conserved cellular response to DNA double-strand breaks.

Animals↗
PubMed2001

DNA-binding and strand-annealing activities of human Mre11: implications for its roles in DNA double-strand break repair pathways.

DNA double-strand breaks (DSBs) in eukaryotic cells can be repaired by non-homologous end-joining or homologous recombination. The complex containing the Mre11, Rad50 and Nbs1 proteins has been implicated in both DSB repair pathways, even though they are mechanistically different. To get a better understanding of the properties of the human Mre11 (hMre11) protein, we investigated some of its biochemical activities. We found that hMre11 binds both double- and single-stranded (ss)DNA, with a preference for ssDNA. hMre11 does not require DNA ends for efficient binding. Interestingly, hMre11 mediates the annealing of complementary ssDNA molecules. In contrast to the annealing activity of the homologous recombination protein hRad52, the activity of hMre11 is abrogated by the ssDNA binding protein hRPA. We discuss the possible implications of the results for the role(s) of hMre11 in both DSB repair pathways.

Animals↗
PubMed2001

Changes in the expression of surface receptors on lymphocyte subsets in the elderly: quantitative flow cytometric analysis.

The immunophenotype of circulating lymphocytes, including the intensity expression of surface receptors, changes with ageing. Until now, no results of systematic studies on age-dependent changes with respect to the expression of the major lymphocyte surface receptors in healthy elderly subjects have been reported. In order to identify age-related changes in both representation and immunophenotype of lymphocyte populations, we investigated, by means of triple-color whole-blood immunostaining and quantitative flow cytometry, the percent values and the absolute numbers, as well as the levels of surface antigen expression or antigen molecules per cell (ABC values x 10(3)), of different peripheral blood lymphocyte subsets from 23 healthy elderly subjects and 13 young donors. Naive (CD45RA+CD3+) T cells, total B cells, and CD5+ B lymphocytes are decreased (22%, 6%, 0.8% vs. 30%, 12%, 1.4%, respectively), whereas activated (HLA-DR+CD3+) and memory (CD45RO+CD3+) T cells, CD3+CD7- T lymphocytes, and lymphocytes expressing the NK marker CD56 are expanded in the elderly (2%, 53%, 13%, 6% vs. 0.8%, 45%, 8%, 8%, respectively). Moreover, T lymphocytes from elderly individuals express lower CD3 (61 +/- 10) compared to young (69 +/- 10). Considering the different T-cell populations, CD3 antigen is respectively decreased on CD45RO+ T cells (55 +/- 14 vs. 66 +/- 14) and up-regulated on CD56+ T lymphocytes (62 +/- 21 vs. 45 +/- 20). Increased CD8 expression characterizes CD3+CD7- lymphocytes (70 +/- 34 vs. 44 +/- 17) while HLA-DR on activated T cells is lower in old (39 +/- 7) than young (46 +/- 9) donors. CD7 is down-regulated both in T (22 +/- 3 vs. 28 +/- 3) and NK (48 +/- 18 vs. 71 +/- 18) cells, whereas CD2 expression, unchanged on NK cells, is up-regulated on T lymphocytes (54 +/- 10 vs. 41 +/- 8). Age-related changes in B-cell antigen expressions were also found: CD20 is increased (124 +/- 23 vs. 105 +/- 16) whereas, despite the unchanged CD5 expression of T cells, CD5 intensity on the B-cell subset co-expressing this antigen is higher in old (49 +/- 37) than in young (22 +/- 4) people. The observed changes in the expression of functionally important cellular receptors can contribute to the remodeling of immune function characteristic of the elderly. Moreover, since quantitative flow cytometry is becoming widely employed in clinical practice, our results also contribute to the assessment of specific age-dependent antigen expression changes to be considered for diagnostic approaches in the elderly.

Adult↗
PubMed2001

Immunosenescence and infectious diseases.

Infectious diseases are major causes, with malignancies, of morbidity and mortality in the elderly. Increased susceptibility to infections may result from underlying dysfunction of an aged immune system; moreover, inappropriate immunologic functions associated with aging can determine an insufficient response to vaccines. Impairments of cellular, humoral and innate immunity in the elderly, contributing to increased incidence of infectious diseases, are discussed in this review.

Aging↗
PubMed2000

Adhesion molecules on peripheral blood lymphocyte subpopulations in the elderly.

Adhesion molecules, such as CD49d, CD50 and CD62L, have important roles in many adhesive interactions involving cells of the immune system. Since it has been shown that many immunological alterations are present in aged subjects, we studied, by means of triple colour whole blood immunostaining and multiparametric flow cytometry, the expression and intensity level (MFI) of these molecules on peripheral blood lymphocyte subpopulations from 23 healthy elderly subjects and 13 young controls. In the elderly a decrease in total peripheral blood lymphocytes bearing CD62L antigen was observed (39 +/- 13% vs 63 +/- 6% and 745 +/- 312/mm3 vs 1,393 +/- 407/mm3; p<0.001), whereas the numbers of lymphocytes expressing CD49d and CD50 antigens were comparable in aged and young subjects. In addition, CD50 and CD62L MFI values on total peripheral blood lymphocytes were higher in elderly than in young subjects (5.23 +/- 1.03 vs 4.18 +/- 0.44, p = 0.001 and 2.60 +/- 0.35 vs 2.21 +/- 0.40, p = 0.005 respectively) while the intensity expression of CD49d was unchanged. The percentages and absolute numbers of T and B lymphocytes expressing CD62L were decreased in elderly compared to young subjects (CD62L+CD3+: 43 +/- 15% vs 66 +/- 9% and 581 +/- 257/mm3 vs 1,028 +/- 418/mm3, p<0.001; CD62L+CD19+: 78 +/- 12% vs 90 +/- 4%, p < 0.005 and 103 +/- 64/mm3 vs 207 +/- 98, p < 0.001). A decrease in the proportion of CD62L bearing NK cells was also observed in the elderly (25 +/- 14% vs 46 +/- 24%, p<0.005), although their absolute number was unchanged. No significant differences were detected in the proportion of T, B and NK lymphocytes expressing CD49d and CD50 antigens and only the absolute numbers of B cells expressing these adhesion molecules were lower in elderly (CD49d+CD19+: 121 +/- 71/mm3 and CD50+CD19+: 107 +/- 73/mm3) compared to young donors (CD49d+CD19+: 248 +/- 112/mm3 and CD50+CD19+: 235 +/- 120/mm3, p < 0.001). Moreover, the intensity of adhesion molecule expression was differentially modulated in the elderly depending on the specific lymphocyte cell population considered. The densities of CD49d, CD50 and CD62L antigens on B and NK lymphocytes from the two age groups were not different; on the contrary, T lymphocytes from elderly donors exhibited increased CD49d (1.69 +/- 0.09 vs 1.62 +/- 0.07, p < 0.05), CD50 (4.98 +/- 1.16 vs 3.77 +/- 0.46, p < 0.001) and CD62L (2.26 +/- 0.38 vs 1.99 +/- 0.37, p < 0.05) MFI values compared to young donors.

Adult↗
PubMed2000

Crystal structure of the Xrcc4 DNA repair protein and implications for end joining.

XRCC4 is essential for carrying out non-homologous DNA end joining (NHEJ) in all eukaryotes and, in particular, V(D)J recombination in vertebrates. Xrcc4 protein forms a complex with DNA ligase IV that rejoins two DNA ends in the last step of V(D)J recombination and NHEJ to repair double strand breaks. XRCC4-defective cells are extremely sensitive to ionizing radiation, and disruption of the XRCC4 gene results in embryonic lethality in mice. Here we report the crystal structure of a functional fragment of Xrcc4 at 2.7 A resolution. Xrcc4 protein forms a strikingly elongated dumb-bell-like tetramer. Each of the N-terminal globular head domains consists of a beta-sandwich and a potentially DNA-binding helix- turn-helix motif. The C-terminal stalk comprising a single alpha-helix >120 A in length is partly incorporated into a four-helix bundle in the Xrcc4 tetramer and partly involved in interacting with ligase IV. The Xrcc4 structure suggests a possible mode of coupling ligase IV association with DNA binding for effective ligation of DNA ends.

Amino Acid Sequence↗
PubMed2000

Coagulation and cancer: implications for diagnosis and management.

Coagulation disorders are a common problem in neoplastic patients and many factors contribute to increase the risk of thromboembolic events in these patients. An hypercoagulable state is induced by malignant cells interacting directly with hemostatic system and activating the coagulation cascade. More sensitive tests to assess an hypercoagulable state in cancer patients have been developed; even though these tests are always altered in cancer patients, none of them possess a clinical significance in terms of predictive value for the occurence of thromboembolism and disease prognosis in the individual patient. The most frequent thromboembolic complications in cancer patients are deep vein thrombosis of the lower extremities and pulmonary embolism; therefore, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura or haemolytic uremic syndrome are special manifestations of neoplastic disease. Diagnosis of idiopathic deep vein thrombosis, in the absence of other risk factors, could indicate the presence of occult malignant disease; however, the need for an extensive work-up to detect malignancy is still controversial. Neoplastic patients showing a thromboembolic event should be treated with unfractioned heparin or, alternatively, with low molecular weight heparins. In order to prevent recurrence, the administration of heparin should be associated and followed by an oral anticoagulant drug. In recent years new approaches in anti-aggregation therapy have been studied, such as COX-inhibitors, cicaprost and ReoPro; further studies are needed to determine the usefulness of these molecules in treatment of malignancies.

Antineoplastic Agents↗
PubMed2000

CD50 and CD62L adhesion receptor expression on naive (CD45RA+) and memory (CD45RO+) T lymphocytes in the elderly.

A complex reshaping characterizes cellular immunity in the elderly. In particular, the hallmark of the "senescence" of the T cell compartment is a decrease in the proportion of CD45RA+ naive T lymphocytes concomitantly with an expansion of CD45RO+ memory T cells. However, in addition to age-dependent changes in their representation, phenotypical and functional anomalies also characterize naive and memory T cell populations in the elderly. Since cell adhesion molecules (CAMs) are multifunctional receptors which play important roles not only in cell-to-cell and cell-to-matrix interactions but also in signal transduction and cell activation, we analysed, by means of a three-colour flow cytometry method, the proportion, absolute number and density expression or mean fluorescence intensity (MFI) of CD50 (ICAM-3) and CD62L (L-selectin homing receptor) adhesion receptors on CD45RA+ and CD45RO+ peripheral blood CD3+ T cell subsets from 10 healthy elderly subjects and 10 young controls. Our aim was to investigate age-dependent changes in the expression pattern of these CAMs on naive and memory lymphocytes which might contribute to the remodelling of the immune system in the elderly. We considered the mean values +/- standard deviations of the percentage, absolute number and MFI of positive cells. The percentage of naive T cells expressing CD50 was not significantly modified in aged (94.8 +/- 5.0%) compared to young individuals (97.8 +/- 3.2%). On the contrary, the percentage of memory T cells exhibiting CD50 was lower in elderly than young donors (92.0 +/- 6.4 vs. 98.3 +/- 2.2%; p < 0.01). The percentage of naive T cells expressing CD62L was decreased in the elderly donors (53.3 +/- 18.8 vs. 80.8 +/- 11.0%; p < 0.001), whereas the proportion of CD62L+ memory T lymphocytes was substantially comparable between the two age groups (63.5 +/- 15.7 vs. 54.7 +/- 12.3%). The absolute number per mm(3) of CD50+ naive T cells from aged individuals was decreased (251.9 +/- 141.9 vs. 621.8 +/- 238.0/mm(3); p < 0.001), whereas memory peripheral blood T lymphocytes expressing CD50 were substantially unchanged (863.8 +/- 260.9 vs. 802.7 +/- 139.6/mm(3)). On the contrary, the absolute numbers per mm(3) of naive and memory peripheral blood T lymphocytes exhibiting CD62L were respectively decreased (190.8 +/- 133.4/mm(3)) and increased (515.1 +/- 146.8/mm(3)) in elderly donors compared to young controls (601.3 +/- 129.1 and 351.8 +/- 195.0/mm(3); p < 0.001 and p < 0.05, respectively). Finally, CD50 MFI values of naive as well as memory T cell subpopulations from aged subjects were increased compared to young donors (14.0 +/- 2.0 vs. 9.8 +/- 1.2 and 14.0 +/- 2.0 vs. 11.6 +/- 1.3; p < 0.001 and p < 0.01, respectively). CD62L was also overexpressed in both naive (8.4 +/- 1.6 vs. 6.7 +/- 1.4; p < 0.05) and memory (10.3 +/- 2.5 vs. 5.4 +/- 1.1; p < 0.001) T subsets in the elderly. CD50 and CD62L upregulation could be interpreted as a compensatory mechanism for a decreased responsiveness and a greater requirement for activation signals rather than an age-related anomaly.

Adult↗
PubMed2000

[Blood coagulation changes and neoplastic pathology].

Cancer patients show an increased susceptibility to develop thromboembolic diseases, suggesting that disorders of coagulation are very common in this pathology. Tumor cells possess the capacity to interact with the hemostatic system, activating the coagulation cascade and stimulating the prothrombotic properties of other blood cell components; the same events while inducing a hypercoagulable state, also contribute to the processes of tumor growth, neoangiogenesis and metastatic formation. Multiple risk factors associated with malignant disease contribute to the hypercoagulability state: stasis induced by prolonged bed rest, vascular invasion by the tumor and iatrogenic complications including the use of central vein catheters and chemotherapy. Several tests have been developed to assess the hypercoagulable state, however their clinical significance still needs to be defined, especially in terms of their predictive value for thrombosis. Clinical manifestations vary from localized deep venous thrombosis (DVT) or pulmonary embolism, more generally associated with solid tumors, to disseminated intravascular coagulation, frequent in hematologic malignancies and metastatic cancer. Diagnosis of idiopathic DVT, in the absence of other risk factors, could indicate the presence of occult cancer, but the usefulness of an extensive work-up to detect malignancy in terms of cost to benefit ratio still has to be demonstrated. Patients with cancer and thromboembolism must be treated with anticoagulant therapy; a large number of studies have shown that either low molecular weight heparins or standard unfractionated heparin for the treatment of acute deep vein thrombosis in hospitalized patients are equally safe and effective; however, the first treatment has been reported to be associated with a lower mortality. After an episode of thrombosis the patients should be protected by a long term course of oral anticoagulation, remaining high the risk of recurrence for as long as the cancer is active.

Blood Coagulation↗
PubMed1999

DNA binding of Xrcc4 protein is associated with V(D)J recombination but not with stimulation of DNA ligase IV activity.

Mammalian cells are protected from the effects of DNA double-strand breaks by end-joining repair. Cells lacking the Xrcc4 protein are hypersensitive to agents that induce DNA double-strand breaks, and are unable to complete V(D)J recombination. The residual repair of broken DNA ends in XRCC4-deficient cells requires short sequence homologies, thus possibly implicating Xrcc4 in end alignment. We show that Xrcc4 binds DNA, and prefers DNA with nicks or broken ends. Xrcc4 also binds to DNA ligase IV and enhances its joining activity. This stimulatory effect is shown to occur at the adenylation of the enzyme. DNA binding of Xrcc4 is correlated with its complementation of the V(D)J recombination defects in XRCC4-deficient cells, but is not required for stimulation of DNA ligase IV. Thus, the ability of Xrcc4 to bind to DNA suggests functions independent of DNA ligase IV.

Animals↗
PubMed1999

[The intracystic concentration of MCA in the fluid from large breast cysts].

75 patients with breast gross cystic disease and no cancer have been included in the study. For each patients serous and intracystic concentrations of MCA have been measured. The aim of the study is to assess whether if a relation between intracystic concentration of the marker and resistance and capability of cellular reproduction exists (confirmed by the release of the cyst). The analysis of intracystic values shows that synthesis of MCA is an intrinsic peculiarity of cytologic kind. It is apparently independent from inflammatory or hemorrhagic contemporary processes.

Adult↗
PubMed1999

Analysis of mammary carcinoma onset and progression in HER-2/neu oncogene transgenic mice reveals a lobular origin.

Morphologic examinations of mammary neoplasias arising in BALB/c (H-2d) mice carrying the activated rat HER-2/neu oncogene (BALB-NeuT), and in FVB (H-2q) mice bearing the wild-type proto-oncogene (FVB-NeuN), indicate that both conditions result in a very human-like lobular carcinoma of alveolar type, whose histotype is the result of the preferential expression of HER-2/neu products in the epithelium of lobular ducts and lobules. Detailed analysis of tumor progression indicates that transition from lobular hyperplasia to overt carcinoma is associated with a high epithelial proliferation rate, as assessed by anti-proliferating cell nuclear antigen immunostaining, and coincides with the activation and maximal extension of tumor angiogenic process as assessed by microvessel count (anti-CD31), anti-beta3 integrin, and anti-laminin immunostaining. Neovascularization is accompanied by vascular endothelial cell growth factor and basic fibroblast growth factor production by hyperplastic epithelial cells. By contrast with the BALB-NeuT tumors, E-cadherin expression is almost nonexistent in those arising in FVB-NeuN mice and this may explain their high metastatic potential. Despite their different kinetics, however, the lung metastases observed in both strains are histologically similar and resemble the primary tumor. Both strains can thus be proposed as models for "in vivo" investigation of the origin and progression of the alveolar type of lobular mammary carcinoma and the testing of new therapeutic approaches.

Animals↗
PubMed1998

99mTc MIBI prone scintimammography in patients with suspicious breast cancer: relationship with mammography and tumor size.

99mTc MIBI prone scintimammography (PSM) is reported to be a specific examination in order to assess the nature of breast lesions. Fifty-three patients whose mammography was stratified according to the breast imaging reporting and data system (BI-RADS), the five category classification of mammography approved by the American college of radiology, were studied with prone scintimammography, with the aim of assessing the accuracy of this exam and its usefulness in clinical practice. Thirty-five out of forty-one patients with BI-RADS category V (high probability of cancer) showed cancer at histology. Thirty-one of them had positive PSM. Three out of the six patients with mammo-graphic features of category IV indicated malignancy. PSM was positive in all of them and negative in the three benign lesions. One of the five patients with category III mammography showed cancer and positive PSM. The PSM was negative in 12/13 patients with benign patology (specificity 92.3%). When the cancers were stratified for T-category significant differences were found between the sensitivity for tumors larger or smaller than 1 cm. The sensitivity was 50% for the cancers smaller than 1 cm and 96.9% for those larger than 1 cm. PSM is a very specific method to determine the nature of breast lesions. Its sensitivity is also high but has to be improved when tumors smaller than 1 cm have to be detected. From a clinical point of view PSM can at the moment be considered as an accurate method for the study of borderline lesions of IV and also of III BI-RADS category. In this case a positive PSM indicates an impact in clinical decision making.

Breast Diseases↗