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Massimo Libra

Publications and source records attributed to Massimo Libra.

35 records · Page 2Linked to original sources
PubMed2005

Plasma levels and zymographic activities of matrix metalloproteinases 2 and 9 in type II diabetics with peripheral arterial disease.

Deregulation of matrix metalloproteinases (MMPs) is an important factor contributing to the development of vascular lesions. Plasma levels and zymographic activities of MMP-2 and MMP-9 were investigated in type II diabetics with (n = 51) or without (n = 42) peripheral artery disease (PAD) and in normal volunteers (n = 23). Plasma MMP-2 levels were higher in type II diabetics with (p < 0.01) or without (p > 0.05) PAD in comparison with normal volunteers. Similarly, type II diabetics with (p < 0.0001) or without (p > 0.05) PAD had higher plasma MMP-9 levels than normal volunteers. Plasma zymographic activities of both MMP-2 and MMP-9 were positively correlated with their plasma levels. Plasma MMP-2 zymographic activity was higher in type II diabetics with PAD than type II diabetics without PAD (p > 0.05). Plasma MMP-9 zymographic activity was higher in type II diabetics with (p < 0.0001) or without (p < 0.0001) PAD in comparision with normal volunteers. Together, these results indicate that increased plasma levels and zymographic activities of MMP-2 and MMP-9 may contribute to PAD in type II diabetics. In particular, plasma MMP-9 may be a useful marker for the development of vascular disease in type II diabetics.

Aged↗
PubMed2005

Aggressive forms of non-Hodgkin's lymphoma in two patients bearing coinfection of Epstein-Barr and hepatitis C viruses.

Although epidemiologic and experimental data suggest an etiopathogenetic role for both hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection in development of B-cell non-Hodgkin's lymphoma (NHL), potential interactions between EBV and HCV during progression of B-cell NHL have not yet been fully investigated. In the present study, tumor biopsy specimens from patients with both B-cell NHL and chronic HCV infection (HCV(+)) were analyzed for the presence of EBV-encoded RNA (EBER) by in situ hybridization (ISH). VH and VL gene segments were amplified from tumor biopsy specimen DNA by PCR. EBV infection (EBV(+)) was detected in tumors from 2 of 31 (6%) HCV(+) B-cell NHL patients. Clinical histories of these two EBV(+)/HCV(+) B-cell NHL patients indicated a particularly aggressive course of disease. Chemotherapy failed to induce long lasting remission for either of these EBV(+)/HCV(+) B-cell NHL patients. Amplification of CDR3 of the Ig heavy chain gene from DNA isolated from each EBV(+)/HCV(+) B-cell NHL indicated the presence of monoclonal B-cell expansion. Rearrangement of Ig genes in neoplastic B-cell clones from both EBV(+)/HCV(+) patients was similar to that previously reported for EBV(-)/HCV(+) B-cell NHL patients. Additionally, neoplastic B-cell clones from these two EBV(+)/HCV(+) B-cell NHL patients did not exhibit intraclonal variation. Previous studies have demonstrated that intraclonal variation is common among neoplastic B-cell clones from EBV(-)/HCV(+) patients. EBV infection may have prevented evolution of variant neoplastic B-cell clones by suppressing antibody affinity maturation. Together, these data suggest that EBV infection may cooperate with HCV infection during progression of B-cell NHL in immunocompetent individuals. Such an interaction may accelerate the course of disease in B-cell NHL patients.

Aged↗
PubMed2005

Bovine seminal ribonuclease is cytotoxic for both malignant and normal telomerase-positive cells.

Bovine seminal-ribonuclease (BS-RNase) is a member of the 'ribonucleases with special biological actions' family since it possesses specific anti-tumour, anti-spermatogenic and embryotoxic activities and exerts an immunosuppressive effect on T lymphocytes. In previous studies it was demonstrated that BS-RNase induced apoptosis in proliferating, malignant and normal cells and that telomerase activity loss also caused apoptotic death in neoplastic cells. Since an obvious relationship between cell proliferation and telomerase activity exists, the aim of this work was to study if the pro-apoptotic cytotoxic action exerted by BS-RNase on proliferating malignant cells (HT29) and proliferating normal cells (PHA-stimulated lymphocytes) could be linked to a possible BS-RNase effect on telomerase activity. In BS-RNase-treated HT29 cells (Na-butyrate-differentiated or not) and human lymphocytes (proliferating or not), we investigated cell vitality (MTT method) and morphology (SEM), BS-RNase localization (immunofluorescence), telomerase activity (TRAP-ELISA method), hTR mRNA expression (RT-PCR), and hTERT levels (western blot). While no BS-RNase effect was detectable on not proliferating cells, a clear relationship was noticed between the diminished number of vital elements of both proliferating cell populations after treatment (48 h and 72 h for HT29 and PHA-stimulated lymphocytes, respectively) with 50 microg/ml BS-RNase and the decrease of their telomerase activity. At the same time, we found that hTR levels, the RNA subunit of telomerase, in proliferation-inhibited BS-RNase-treated cells were diminished. Moreover, by immunofluorescence technique, we detected BS-RNase in the HT29 cell nucleolus after 3-h treatment. Therefore, as hTR has been recently proven to co-fractionate with nucleoli, we hypothesize that a BS-RNase direct action on the telomerase hTR subunit could be a possible mechanism of action by which BS-RNase exerts its pro-apoptotic effects only on proliferating cells.

Animals↗
PubMed2004

Thymidylate synthetase mRNA levels are increased in liver metastases of colorectal cancer patients resistant to fluoropyrimidine-based chemotherapy.

BACKGROUND: Fluoropyrimidines such as 5-fluorouracil (5-FU) and 5-fluoro-2'deoxyuridine (FUDR) are among the most effective chemotherapeutic agents for treatment of metastatic colorectal cancer (CRC). Increased expression of thymidylate synthetase (TS) in CRC metastases has been proposed to be an important mechanism of resistance to fluoropyrimidine-based chemotherapy. METHODS: The present study investigated whether TS mRNA levels in liver metastases of 20 CRC patients before treatment with FUDR by hepatic arterial infusion (HAI) correlated with frequency of clinical response or survival duration. RESULTS: Median survival duration of patients with TS mRNA levels above and below the median was 15 and 18 months, respectively (p > 0.05). Clinical response was achieved in 40% of patients with low TS mRNA levels, but in only 20% of patients with high TS mRNA levels (p = 0.01). TS mRNA levels were also measured for liver metastases of 7 of the patients that did not achieve a clinical response. A statistically significant increase in expression of TS mRNA was observed for liver metastases resistant to chemotherapy (21 +/- 14) in comparison to liver metastases of the same patients before chemotherapy (8 +/- 4) (p = 0.03). CONCLUSION: This is the first report to demonstrate increased TS expression in liver metastases from CRC patients resistant to fluoropyrimidine based chemotherapy. These findings are consistent with previous studies indicating that increased TS expression is associated with resistance to fluoropyrimidine-based chemotherapy.

Adult↗
PubMed2004

Second primary lymphoma or recurrence: a dilemma solved by VDJ rearrangement analysis.

A lymphoma patient in remission that develops a second lymphoma is frequently assumed to have had a relapse of the original lymphoma. However, the second lymphoma may instead be a new lymphoma with a different clonal origin. Comparison of histological characteristics alone is insufficient in many cases to distinguish new lymphomas from recurrent lymphomas. In contrast, clonal origins of B-cell lymphomas can be reliably compared by VDJ rearrangement analysis of B-cell IgH genes. Simultaneous lymphomas have similarly been analyzed by this technique to determine whether or not both tumors share a common clonal origin. Application of VDJ rearrangement analysis in clinical research has been important for characterizing mechanisms of lymphoma development. Furthermore, this technique has the potential to improve treatment of lymphoma patients because management of recurrent lymphomas differs from that of new lymphomas.

Gene Rearrangement, B-Lymphocyte, Heavy Chain↗
PubMed2004

Detection of bcl-2 rearrangement in mucosa-associated lymphoid tissue lymphomas from patients with hepatitis C virus infection.

It has been shown that t(14;18)(q32;q21) involving fusion of IGH with MALT1 occurs frequently in mucosa-associated lymphoid tissue (MALT) lymphomas. Results of the present study indicate that the classical form of t(14;18)(q32;q21) involving fusion of IGH with bcl-2 can be detectable in a subset of MALT lymphomas in patients with hepatitis C virus (HCV) infection.

Adult↗
PubMed2003

Methylenetetrahydrofolate reductase 677 C-->T polymorphism and risk of proximal colon cancer in north Italy.

PURPOSE: Gene silencing by hypermethylation plays an important role in proximal colon carcinogenesis. Conversely, DNA hypomethylation has been associated with distal colon cancer (CLC). Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of 5',10'-methylenetetrahydrofolate to 5'-methyl tetrahydrofolate, which serves as methyl donor in the remethylation of homocysteine to methionine. A common MTHFR 677 C-->T polymorphism is characterized by reduced catalytic activity, which affects methionine synthesis and DNA methylation. The aim of the study was to investigate the role of MTHFR 677 C-->T gene polymorphism in the tumorigenesis of proximal and distal CLC in a monoinstitutional group of patients in North Italy. EXPERIMENTAL DESIGN: One-hundred thirty four consecutive proximal and 142 consecutive distal CLC patients, and 279 control subjects without cancer were genotyped for MTHFR using PCR-restriction fragment-length polymorphism analysis. RESULTS: The prevalence of the 677 TT genotype was significantly (P = 0.005) lower in patients with proximal tumors (10 of 134, 7%) than in subjects with distal tumors (28 of 142, 20%). Case/control approach indicated that individuals homozygous for the 677 TT allele had a significantly reduced risk (2.8-fold) (adjusted odds ratio, 0.36; 95% confidence intervals, 0.14-0.91) of developing proximal CLC compared with those harboring the wild-type or heterozygous genotype (677 CC or 677 CT). No significant association between CLC risk and TT genotype was observed in patients with distal tumors (odds ratio, 1.01; 95% confidence interval, 0.48-2.14). CONCLUSIONS: Our findings support a role for MTHFR 677 TT genotype in reducing proximal CLC risk in North Italy.

Alleles↗
PubMed2003

All trans retinoic acid sensitizes colon cancer cells to hyperthermia cytotoxic effects.

The effects of all trans retinoic acid and hyperthermia were studied in the human colon adenocarcinoma cell line HT29. Cell cytotoxicity after exposure to ATRA or heat-shock, alone or in association, was evaluated by the MTT assay while cell surface and ultrastructure modifications and actin fibre assembly changes were investigated by electron microscopy and by the FITC-phalloidin method. Apoptosis was evaluated by flow cytofluorimetry and electron microscopy. Reverse transcriptase-polymerase chain reaction was employed to study mRNA expression of genes involved in apoptosis, differentiation and growth arrest. Joint treatments were more effective in reducing the vital cell yield, being this effect only partially due to apoptosis. A marked up-regulation of the cyclin-dependent kinase inhibitor p21WAF1/Cip1 expression, not followed by any differentiation process, was responsible for growth arrest. Modulation of Hsp-70 expression, involved in cell response to treatments, was considered. Our results demonstrate that cell treatment with ATRA followed by heat-shock may elicit useful effects to treat tumours, which are responsive to retinoids, as well as those malignant cells which may be constitutively thermotolerant.

Actins↗
PubMed2002

Expression of cyclin-dependent kinase inhibitor p27(Kip1) in AIDS-related diffuse large-cell lymphomas is associated with Epstein-Barr virus-encoded latent membrane protein 1.

Knowledge of the role of cell-cycle regulators in the pathogenesis of acquired immune deficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHLs) is scarce. Here we analyzed 86 systemic AIDS-NHLs and 20 AIDS-primary central nervous system lymphomas for expression of p27(Kip1), a negative regulator of cell-cycle progression belonging to the Kip family of cyclin-dependent kinase inhibitors. In parallel, we investigated the relationship between p27(Kip1), the lymphoma proliferation index, Epstein-Barr virus status, expression of cellular cyclin D3 and cyclin D1, and B-cell differentiation stage. We report that AIDS-immunoblastic lymphomas (AIDS-IBLs), either systemic or primarily localized to the central nervous system, consistently express p27(Kip1) protein (19 of 24 and 10 of 14, respectively) despite the high proliferative rate of the lymphoma clone, suggesting a failure of p27(Kip1) to inhibit the cell cycle in AIDS-IBL. Conversely, the remaining systemic AIDS-NHLs and AIDS-primary central nervous system lymphomas preferentially fail to express p27(Kip1). Expression of p27(Kip1) in Epstein-Barr virus-positive AIDS-NHLs generally associates with latent membrane protein 1 (LMP1) expression and is related to a late stage of B-cell differentiation, characterized by the BCL-6-/MUM1+/syn-1+/- phenotypic profile, whereas it seems to be unrelated to the expression of cellular cyclins. In B cells in vitro, induction of LMP-1 expression under the control of inducible promoters up-regulates expression of p27(Kip1), thus providing a putative mechanistic explanation for the association between LMP1 and p27(Kip1) observed in vivo. Overall, these data show that AIDS-IBL pathogenesis is characterized by loss of the inverse relationship between p27(Kip1) positivity and tumor growth fraction that is otherwise generally observed in normal lymphoid tissues and in most other types of NHLs.

Arabidopsis Proteins↗
PubMed2002

Differentiation between non-Hodgkin's lymphoma recurrence and second primary lymphoma by VDJ rearrangement analysis.

Relapses in non-Hodgkin's lymphomas (NHL) could be due to the reappearance of the initial neoplasm or new primary tumours. Discrimination between the two events would allow a more targeted therapeutic approach. VDJ rearrangement was used as marker of clonality in metachronous biopsy specimens from 10 patients with relapsed B-NHL. Complimentary determining region 3 was amplified and sequenced. D-JH was identical in eight matched primary/secondary tumours, confirming the diagnosis of recurrence. In contrast, primary and secondary tumours in two patients were of different clonal origin. Our data indicate that VDJ analysis is a fundamental tool for identification of relapses in NHL.

Adult↗
PubMedDate not supplied

D1S80 VNTR locus genotypes in a population of Southeastern Sicily: distribution and genetic disequilibrium.

Locus D1S80 is one of the best-known polymorphic loci, showing a variable number of tandem repeats. This article presents the results on D1S80 allele distributions in a sample of 324 unrelated Sicilian individuals, collected and analyzed in two distinct laboratory centers. Although, as expected, the two most frequent alleles were those with 18 and 24 repeat units, the population sample from southeastern Sicily showed a relatively low frequency of allele 29 (2.9%) and allele 31 (3.4%) and a relatively high frequency of allele 25 (6.0%), allele 30 (1.9%), and allele 32 (1.5%) in comparison with other populations. Statistical analysis performed by the five alleles model provided evidence that the population did not follow the Hardy-Weinberg equilibrium expectations (observed heterozygosity 70.99% vs. expected heterozygosity 76.31%). The calculated F (fixation index), as a measure of heterozygote deficiency or excess, was positive for four allele groups and negative for one allele group. This finding was consistent with a substantial diversity of human ethnic groups when tested with VNTR systems and might represent a genuine inconsistency, not due to a methodological bias. This scenario deserves further investigation, i.e., by performing a short tandem repeat (STR) units analysis on a greater number of loci in the same population sample.

Adolescent↗
PubMedDate not supplied

Lack of HCV infection in malignant cells refutes the hypothesis of a direct transforming action of the virus in the pathogenesis of HCV-associated B-cell NHLs.

AIMS AND BACKGROUND: Preliminary evidence suggests that hepatitis C virus (HCV) might play a pathogenetic role in autoimmune-related, non-malignant B-cell lymphoproliferation, as well as in a subset of B-cell non-Hodgkin's lymphomas (NHLs). With regard to the mechanism(s) by which HCV might favor B-cell expansion and malignant transformation, most data support an indirect pathogenetic role of the virus as an exogenous trigger. A direct oncogenetic role of HCV by direct cell infection and deregulation has only been hypothesized on the basis of the lymphotropism of the virus. METHODS: In this study we investigated the possible HCV infection of NHL B cells by means of sensitive and quantitative polymerase chain reaction (PCR) on affinity-purified neoplastic cells, and by HCV-specific immunohistochemistry and in situ hybridization. RESULTS: HCV infection of neoplastic B cells was documented in only three cases, namely the low-grade B-cell NHLs that arose in the course of mixed cryoglobulinemia syndrome (MC). HCV infection, below one viral genome per cell, was detectable only by PCR. All the remaining low-grade (one case) and high-grade B-cell NHLs (two cases) were HCV uninfected. Previous immunoglobulin gene analyses were consistent with an antigen-driven B-cell lymphoproliferation in the studied cases. CONCLUSIONS: Overall, our data are consistent with an indirect oncogenetic role of HCV in B-cell lymphomagenesis as an exogenous trigger. Infection of B cells by HCV appears possible in some NHL subsets, but the implications remain unknown.

Aged↗
PubMedDate not supplied

Cisplatin may be a valid alternative approach in ovarian carcinoma with carboplatin hypersensitivity. Report of three cases.

Platinum-based therapy is considered the standard treatment for patients with advanced ovarian cancer. Carboplatin has a more favorable toxicity profile than cisplatin; however, hypersensitivity reactions to carboplatin have been reported occasionally. We reviewed 112 cases of ovarian cancer treated with carboplatin at our institute to identify the hypersensitivity reactions to this chemotherapeutic agent. Hypersensitivity reactions were documented in nine cases (8%). No deaths occurred, but the reactions were judged severe in three of the 112 patients (2.6%). In our own experience with patients showing idiosyncrasy to carboplatin we observed successful resolution after retreatment with cisplatin. Since patients who relapse after initial treatment with carboplatin often respond to it a second time, it is important to continue this treatment.

Adenocarcinoma↗
PubMedDate not supplied

Long-term survival in patients with metastatic renal cell carcinoma treated with continuous intravenous infusion of recombinant interleukin-2: the experience of a single institution.

AIM AND BACKGROUND: Metastatic renal cell carcinoma is one of the few tumors for which a clear benefit of immunotherapy has been demonstrated. The aim of this study was to evaluate the long-term survival of patients with metastatic renal cell carcinoma, along with response rate and other prognostic and predictive factors. PATIENTS AND METHODS: Between July 1989 and May 1995, 56 patients with metastatic renal cell carcinoma were treated in a single institution with high-dose recombinant interleukin-2 in continuous infusion. Survival was measured by the Kaplan and Meier method. Prognostic factors were assessed by univariate and multivariate analyses of survival (Cox proportional hazard ratio model). RESULTS: Of 56 patients, 15 had objective responses (26.8%), 16 stable disease (28.6%), 18 disease progressions (32.1%), and 7 (12.5%) were not valuable for response. Median overall survival was 20 months, and probability of 2- and 5-year survival was 41% and 21%, respectively. At multivariate analysis, the increased risk of death for: performance status > or = 2 vs 0 (HR = 6.20), stable disease (HR = 1.87), disease progression (HR = 10.61) vs partial or complete remission, and for hypotension and oliguria toxicity, G3 + G4 vs G1 + G2 (HR = 2.19). CONCLUSIONS: Our study confirms the activity of IL-2 based immunotherapy in renal cell carcinoma. Moreover, ECOG performance status, clinical response, hypotension and oliguria toxicity resulted as independent survival prognostic factors.

Aged↗