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Biomedical subjects

L Masiero

Publications and source records attributed to L Masiero.

25 records · Page 2Linked to original sources
PubMed1996

72-kilodalton type IV collagenase, type IV collagen, and Ki 67 antigen in serous tumors or the ovary: a clinicopathologic, immunohistochemical, and Serological study.

The immunohistochemical expression of 72-kDa type IV collagenase [matrix-metalloproteinase (MMP)-21], basement membrane component type IV collagen and proliferation-related antigen Ki 67 were investigated in 43 benign, borderline, and malignant serous tumors of the ovary. The results were compared with the histotypes of ovarian serous tumors and with their clinical behavior. Serum evaluation of MMP-2 was performed in 14 patients with cystadenocarcinoma and the data compared with that of a control group. The basement membrane (BM) was continuous in benign cystadenomas and in some borderline tumors, whereas it was discontinuous or absent in other borderline tumors, in borderline tumors with microinvasion, and cystadenocarcinomas. The percentage of MMP-2- and Ki 67-expressing cells increased from cystadenomas to borderline tumors, being the highest in malignant tumors; a frequent basal disposition of the MMP-2 cytoplasmic granules also was observed in cystadenocarcinomas. Statistical analysis demonstrated that MMP-2 expression was inversely related to BM integrity. Serum MMP-2 values did not differ from that of the control group. Cox regression analysis showed that tumor stage and grade were significant prognostic factors, whereas MMP-2 and Ki 67 immunohistochemical expression added no further significant information to the prognosis. The investigators conclude that the correlation between increasing MMP-2 expression and BM alteration gives support to the hypothesis of a direct role of the metalloproteinase in the process of destructive stromal invasion. MMP-2, type IV collagen, and Ki 67 immunodetection varied according to the histologic classification of ovarian serous tumors. However, neither these factors nor the serum evaluation of MMP-2 appear useful as prognostic predictors in this series.

Antibodies, Monoclonal↗
PubMed1995

Synthesis and refolding of human TIMP-2 from E. coli, with specific activity for MMP-2.

Tissue inhibitors of metalloproteinase (TIMPs) are inhibitory counterparts of collagenases, containing 12 cysteine residues paired to six internal disulphide bridges. TIMP-2, an inhibitory protein of 72 kDa gelatinase/type IV collagenase (MMP-2), was expressed in Escherichia coli as a fusion protein with a 34 amino acid NH2-linked tail containing six consecutive histidine residues. The protein was purified in a single-step using an ion metal affinity column (IMAC) in denaturing conditions. The immobilized fusion TIMP-2 protein was refolded at a high concentration in the column, producing about 5 mg of protein per litre of bacterial cells. It shows specific binding and inhibitory activity against MMP-2, but has no effect against 92 and 45 kDa gelatinases.

Amino Acid Sequence↗
PubMed1994

HIV-1 modulates the expression of gelatinase A and B in monocytic cells.

The levels of mRNA of both gelatinases A and B were dramatically decreased in HIV-infected cells, when compared to uninfected cells. The expression of gelatinase A in HIV-infected cells was selectively increased by tumor necrosis factor (TNF alpha) while the expression of gelatinase B was not affected. In contrast, in uninfected cells TNF alpha down regulated gelatinase B mRNA level, without affecting the gelatinase A. N-acethylcysteine (NAC) increased the levels of mRNA of both gelatinases. The conditioned media from HIV-infected and uninfected cells had comparable level of secreted gelatinase A protein. These data suggest that in monocytic cells different regulatory pathways control gelatinases A and B and that HIV could modulate in vivo the expression of these proteolytic enzymes, critically involved in regulation of invasion of basement membrane.

Cell Line↗
PubMed1992

Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy.

Cancer cells elaborate metalloproteinases which may play a role in invasion and metastasis. The serum level of the M(r) 72,000 type IV collagenase (MMP-2) was measured in 87 lung cancer patients. Stage IV cancer levels were significantly elevated (P less than 0.0001) compared to normal sera. A significant difference (P less than 0.01) was found between enzyme levels in the presence versus the absence of distant metastasis. For 29 patients treated with combination chemotherapy, a positive relationship was noted between response failure and elevated enzyme levels. Serum metalloproteinase levels may provide information relevant to prognosis as well as treatment decisions.

Biomarkers, Tumor↗
PubMedDate not supplied

Tissue and serum metalloproteinase (MMP-2) expression in advanced ovarian serous cystoadenocarcinomas: clinical and prognostic implications.

OBJECTIVE: The object of this study was to analyse the tissue and serum metalloproteinase (MMP-2), an enzyme which degrades the basement membrane collagen type IV, as a potential marker useful in prognostic evaluation and clinical monitoring of the follow-up, in patients with advanced ovarian serous cystadenocarcinoma. MATERIALS AND METHODS: Tissue MMP-2 expression was determined in 21 FIGO stage III ovarian serous cystadenocarcinomas treated with primary surgery and adjuvant chemotherapy, and compared to 10 cystadenomas used as controls. Retrospective analysis of clinical data allowed the comparison of accepted prognostic factors to tissue MMP-2 expression for impact on disease-free survival. In fourteen out of 21 patients, serum MMP-2 levels were also analysed. RESULTS: Compared to cystadenomas, the tissue MMP-2 expression was significantly (P < 0.001) higher in serous cystadenocarcinomas. A significant relationship was observed between tissue MMP-2 and disease-free survival (P = 0.0003), independently of tumor architectural grade, lymph nodal status and residual disease after debulking surgery. Recurrence risk in patients whose carcinomas had a tissue MMP-2 > or = 29% was significantly higher than that in patients whose carcinomas demonstrated lower tissue MMP-2 expression (P = 0.004). Serum MMP-2 levels correlated with tissue staining, and also expressed a significant relationship with disease-free survival (P = 0.002). CONCLUSIONS: Tissue MMP-2 seems to be a prognostic indicator in patients with FIGO stage III ovarian serous cystadenocarcinoma, significantly correlated with recurrence risk and apparently independent of tumor architectural grade, lymph nodal status, and residual disease after debulking surgery. An interesting relationship was observed between tissue staining and MMP-2 serum levels.

Basement Membrane↗
PubMedDate not supplied

The role of calcium in the regulation of invasion and angiogenesis.

The complex process of invasion and metastasis is now being dissected at the level of cell-cell and cell-substratum signaling. New tools are being developed to facilitate these studies. These tools include mechanisms for the investigation of cellular actions, such as the identification of agents that can be used to examine the signaling pathways involved in adhesion, proteolysis, motility, and angiogenesis. We have demonstrated that CAI, carboxyamido-triazole, selectively inhibits calcium uptake, stimulated or basal, and thereby modulates the elements involved in invasion and angiogenesis. Through modulation of cellular calcium balance, CAI secondarily inhibits calcium-dependent signaling pathways, such as release of second messengers, protein phosphorylation and gene transcription. We have demonstrated that CAI treatment resulted in inhibition of endothelial cell adhesion, migration, expression of proteolytic enzymes, and vessel formation in vitro and in vivo. The process of endothelial cell adhesion and spreading on extracellular matrix substrata results in an increase in intracellular calcium that can be inhibited by CAI exposure. Furthermore, endothelial cell adhesion and spreading on type IV collagen stimulates the secondary signaling events of tyrosine phosphorylation of focal adhesion kinase (pp125FAK) and autophosphorylation of pp125FAK. CAI treatment of the endothelial cells inhibited cell spreading, and both the induction of pp125FAK phosphorylation and the phosphorylation of exogenous substrates by pp125FAK kinase. These data indicate that regulation of cellular events key in the process of angiogenesis may be modulated by intracellular calcium balance thereby creating a new therapeutic target for anticancer research. CAI is in phase I clinical trial for patients with advanced cancers, yielding plasma concentrations in the in vitro anti-angiogenic range.

Calcium↗