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Biomedical subjects

L Del Vecchio

Publications and source records attributed to L Del Vecchio.

At least 19 recordsLinked to original sources
PubMed2003

Immunophenotypic analysis of human gingival fibroblasts and its regulation by Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF).

BACKGROUND: The aim of the present study was to perform an immunophenotypic analysis of human gingival fibroblast cells and its eventual modulation by Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF). METHODS: Gingival fibroblasts were derived from gingival biopsy of 15 healthy subjects. The presence of fibroblast cells in culture and the absence of epithelial cells was performed with fluorescence microscopy using vimentin and cytokeratin markers, respectively. Molecular expression of gingival fibroblast cell membrane was carried out with monoclonal antibodies by flow cytometry analysis. Human recombinant GM-CSF at the concentration of 200 ng/ml was used for the in vitro stimulation of gingival fibroblasts. Statistical analysis was performed using the Student "t"-test. RESULTS: Human gingival fibroblasts express a wide surface molecular panel including mainly CD59, CD99, CD9, CD95, CD55, CD63, CD26, CD117, CD71 and CD86. The GM-CSF seems to regulate the CD49B expression positively and the CD40 and CD103 expression negatively. CONCLUSIONS: Results show that GM-CSF is able to modulate the in vitro expression of some membrane molecules of gingival fibroblasts and therefore it may regulate, in vivo, peculiar specific biological functions of gingival tissue.

Antigens, CD↗
PubMed2002

Rituximab: a useful drug for a repeatedly relapsed hairy cell leukemia patient.

We describe a case of complete response in a patient with hairy cell leukemia, relapsed after treatment with interferon-alpha, 2'-deoxycoformicin, and 2-chlorodeoxyadenosine, and then successfully treated with rituximab. A fourfold reduction of leukemic cells was observed concomitantly with restoration of normal blood count and differential.

Adult↗
PubMed2001

Endoglin: An accessory component of the TGF-beta-binding receptor-complex with diagnostic, prognostic, and bioimmunotherapeutic potential in human malignancies.

Endoglin (CD105) is a cell membrane glycoprotein over-expressed on highly proliferating endothelial cells in culture, and on endothelial cells of angiogenetic blood vessels within benign and malignant tissues. CD105 binds several factors of the Transforming Growth Factor (TGF)-beta superfamily, and its over-expression modulates cellular responses to TGF-beta1. The complex of experimental findings accumulated in the last few years strongly indicate that CD105 is a powerful marker of angiogenesis, and that it might play a critical role in the pathogenesis of vascular diseases and in tumor progression. In this paper, we will review the structural, biological and functional features of CD105, as well as its distribution within normal and neoplastic tissues, emphasizing its foreseeable role as a molecular target for new diagnostic and bioimmunotherapeutic approaches in human malignancies.

Animals↗
PubMed2001

Characterization of two novel cell lines, DERL-2 (CD56+/CD3+/Tcry5+) and DERL-7 (CD56+/CD3-/TCRgammadelta-), derived from a single patient with CD56+ non-Hodgkin's lymphoma.

Two novel IL2-dependent cell lines, DERL-2 and DERL-7, were established from a patient with hepatosplenic gammadelta T cell lymphoma. This patient presented, at diagnosis, two discrete populations of CD56+ cells, one TCRgammadelta+, the second lacking T cell-restricted antigens. The cell lines derived displayed features corresponding to the two cellular components of the disease: DERL-2 was CD56+/CD3+/TcRgammadelta+ while DERL-7 was CD56+/CD3-/TcRgammadelta-. Along with CD56, the two cell lines shared the expression of CD7, CD2, CD158b and CD117. Karyotype analysis showed that both cell lines were near-diploid, with iso-7q and loss of one chromosome 10. In addition, DERL-2 showed 5q+ in all metaphases analyzed, while DERL-7 revealed loss of one chromosome 4. Genotypically, both cell lines shared the same STR pattern at nine loci and demonstrated an identical rearranged pattern of the T cell receptor genes beta, gamma and delta, with respect to the original tumor cells. These data indicated that both cell lines and the original neoplastic populations were T cell-derived and arose from a common ancestor. Among a large panel of cytokines tested, only SCF was able to substitute IL2 in supporting cell proliferation. Moreover, SCF and IL2 acted synergistically, dramatically enhancing cell growth. These cell lines may represent a model to further analyze the overlap area between T and NK cell malignancies, and may provide new information about the synergistic action of IL2 and SCF on normal and neoplastic T/NK cells.

Adult↗
PubMed2001

Dialysis: its role in optimizing recombinant erythropoietin treatment.

Although iron deficiency is probably the most important factor affecting response to recombinant erythropoietin (Epo, epoetin), other factors are of significance, including dialysis adequacy. Additionally, water treatment and distribution, sterilizants and the quality of the dialysate in terms of trace elements (particularly chloramine) are of importance in relation to erythropoiesis inhibition. Microbiological or pyrogenic contamination can cause or aggravate anaemia in haemodialysis patients, and the impact of enhanced production of cytokines should be taken into consideration. By removing small and (possibly) medium/large molecules, adequate dialysis is of paramount importance in correcting anaemia and optimizing epoetin therapy. The biocompatibility of dialysis membranes and flux are other important factors. As yet unknown uraemic toxins may suppress erythropoiesis and contribute towards the development of anaemia. It is reasonable to hypothesize that, because anaemia improves after the start of dialysis with cellulose membranes, low molecular weight erythropoiesis inhibitors are involved, as well as medium/large molecular weight inhibitors, which are removed by more permeable membranes. However, in highly selected, adequately dialysed patients without iron or vitamin depletion, the effects of dialysis membrane type on haematological parameters and epoetin efficacy are smaller than might be expected from the results of uncontrolled studies. Improvement in anaemia has been observed using on-line haemofiltration, haemodiafiltration, and sterile dialysate. The results of prospective, randomized trials examining the impact of these factors on anaemia and the effectiveness of epoetin treatment are eagerly awaited.

Anemia↗
PubMed2000

Glycosyl phosphatidylinositol (GPI)-anchored molecules and the pathogenesis of paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by the expansion of one or more clones of stem cells producing progeny of mature blood cells deficient in the plasma membrane expression of all glycosyl phosphatidylinositol (GPI)-anchored proteins (AP). This is due to somatic mutations in the X-linked gene PIGA, encoding one of the several enzymes required for GPI anchor biosynthesis. More than 20 GPI-APs are variously expressed on hematological cells. GPI-APs may function as enzymes, receptors, complement regulatory proteins or adhesion molecules; they are often involved in signal transduction. The absence of GPI-APs may well explain the main clinical findings of PNH, i.e., hemolysis and thrombosis in the venous system. Other aspects of PNH pathophysiology such as various degrees of bone marrow failure and the dominance of the PNH clone may also be linked to the biology and function of GPI-APs. Results of in vitro and in vivo experiments on embryoid bodies and mice chimeric for nonfunctional Piga have recently demonstrated that Piga inactivation confers no intrinsic advantage to the affected hematopoietic clone under physiological conditions; thus additional factors are required to allow for the expansion of the mutated cells. A close association between PNH and aplastic anemia suggests that immune system mediated bone marrow failure creates and maintains the conditions for the expansion of GPI-AP deficient cells. In this scenario, a PIGA mutation would render GPI-AP deficient cells resistant to the cytotoxic autoimmune attack, enabling them to emerge. Even though the 'survival advantage' hypothesis may explain all the various aspects of this intriguing disease, a formal proof of this theory is still lacking.

Animals↗
PubMed2000

Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic leukemia cells by NF-kappa B/Rel- specific decoy oligodeoxynucleotides.

The activity of NF-kappa B/Rel nuclear factors is known to inhibit apoptosis in various cell types. We investigated whether the subtraction of NF-kappa B/Rel activity influenced the response of 11 AML (M1, M2 and M4) patients' cells to AraC. To this end we used a phosphorothioate double-stranded decoy oligodeoxynucleotide (ODN) carrying the NF-kappa B/Rel- consensus sequence. Cell incubation with this ODN, but not its mutated (scrambled) form used as a control, resulted in abating the NF-kappa B/Rel nuclear levels in these cells, as verified by electrophoretic mobility shift assay (EMSA) of cells' nuclear extracts. We incubated the leukemic cells with AraC (32 or 1 microM), in either the absence or presence of the decoy or the scrambled ODN, and analyzed cell apoptosis. The spontaneous cell apoptosis detectable in the absence of AraC (<25%) was not modulated by the oligonucleotide presence in cell cultures. On the other hand, in 10 of the 11 samples tested, the decoy kappa B, but not the scrambled ODN significantly (P < 0.01 in a Student's t test) enhanced cell apoptotic response to AraC. Such an effect was particularly remarkable at low AraC doses (1 microM). These findings indicate that NF-kappa B/Rel activity influences response to AraC in human primary myeloblastic cells, and suggests that the inhibition of NF-kappa B/Rel factors can improve the effect of chemotherapy in AML. Gene Therapy (2000) 7, 1234-1237.

Antimetabolites, Antineoplastic↗
PubMed2000

Spurious estimations of sodium removal during CAPD when [Na](+) is measured by Na electrode methodology.

BACKGROUND: The aim of this study was to investigate the effect of pH and glucose concentration on sodium removal and the dialysate and plasma sodium ratio (D/PNa) as measured by means of a flame photometer (NaF) or direct ion-selective electrode (NaE) in continuous ambulatory peritoneal dialysis (CAPD). METHODS: In vitro, glucose concentration, pH, NaF, and NaE were measured in fresh peritoneal dialysis solutions (PDSs) before and after the addition of glucose or KOH. In vivo, 66 four-hour peritoneal equilibration tests were performed in 35 patients on CAPD using a low pH PDS with a glucose concentration of 3.86%. RESULTS: In vitro, NaF and NaE were significantly influenced by the glucose concentration and pH of the PDS. In vivo, in fresh PDS, there was a significant difference between the NaF and NaE results; the respective median values were 132.1 (interquartile range 129.3 to 137.5) versus 138.0 (134.4 to 141.5) mmol/L (P < 0.0001). The D/PNa ratio calculated by NaE was significantly lower than that calculated by NaF (0.88 +/- 0.03 vs. 0.91 +/- 0.04 and 0. 90 +/- 0.03 vs. 0.94 +/- 0.04 at 60 and 240 min, respectively, P < 0.0001), whereas there was no significant difference between the NaE and NaF values after correction for plasma water and a Donnan factor of 0.96 (0.88 +/- 0.03 vs. 0.88 +/- 0.04 and 0.90 +/- 0.03 vs. 0.91 +/- 0.04, P < 0.3473). Sodium removal was significantly lower when calculated as NaE than when calculated as NaF (43.9 +/- 32.7 vs. 61.0 +/- 32.2 mmol, P < 0.0001). CONCLUSIONS: The fresh PDS sodium concentration can be corrected using a glucose concentration-related factor. The D/PNa ratio calculated as NaE or NaF is not different after correction for plasma water and a Donnan factor of 0.96. Sodium removal must be measured by means of NaF rather than NaE. This could have an important clinical impact.

Adult↗
PubMed2000

CD56 expression is an indicator of poor clinical outcome in patients with acute promyelocytic leukemia treated with simultaneous all-trans-retinoic acid and chemotherapy.

PURPOSE: Preliminary reports suggest that leukemic cell expression of CD56, a neural cell adhesion molecule, is associated with adverse clinical outcome in either acute myeloid leukemia with t(8;21) or acute promyelocytic leukemia (APL). We investigated the prognostic relevance of CD56 in a series of patients with APL who were treated homogeneously with all-trans-retinoic acid (ATRA) and chemotherapy. PATIENTS AND METHODS: Clinicobiologic presenting features and therapeutic results were analyzed in a series of 100 patients with genetically proven APL who were treated, according to the example of the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto multicenter trial, with ATRA plus idarubicin (AIDA) and for whom data on CD56 expression were available at diagnosis. RESULTS: Fifteen patients (15%) showed expression of CD56 in greater than or equal to 20% blasts at diagnosis and were considered as CD56(+). No differences were found regarding age, sex, WBC and platelet counts, incidence of coagulopathy, hemoglobin and fibrinogen levels, promyelocytic leukemia/retinoic acid receptor (PML/RAR) alpha fusion type, or complete remission (CR) rate in the comparison of the CD56(+) and CD56(-) populations. Conversely, compared with patients who were CD56(-), patients with CD56(+) APL had shorter CR duration (P =.04) and overall survival (P =.002). In the multivariate analysis, CD56 positivity and initial WBC count greater than 10 x 10(9) cells/L retained statistical significance in overall survival (P =.04 and P =.02, respectively). CONCLUSION: The expression of CD56 is significantly associated with inferior CR duration and survival in patients with APL who were treated with modern frontline treatment that included ATRA and simultaneous chemotherapy. Combined with other well-established prognostic factors such as WBC count, CD56 expression at diagnosis might be used to build prognostic scores for risk-adapted therapy in APL.

Adolescent↗
PubMed2000

Coexistence of two distinct cell populations (CD56(+)TcRgammadelta(+) and CD56(+)TcRgammadelta(-)) in a case of aggressive CD56(+) lymphoma/leukemia.

BACKGROUND AND OBJECTIVE: Large granular lymphocytes derive from two major lineages: one expressing the CD3 surface antigen (T-lymphocytes), and the other lacking this marker (NK-cells). Although developmental overlaps between natural killer cells and T-cells have been described, malignancies derived from these two cell types are considered as distinct lymphoid disorders. DESIGN AND METHODS: We report the case of a 30-year old man affected by a lymphoma/leukemia syndrome presenting with hepatosplenic lymphoma which rapidly transformed into aggressive NK-leukemia. Extensive flow cytometry studies and molecular analysis were repeated during the course of the disease, and showed an unexpected changing pattern. RESULTS: At diagnosis, flow cytometry analysis showed the co-existence of two cell populations, one CD56(+), CD3(+), TcRgd(+), and the other CD56(+), CD3(-) and TcRgd(-). Molecular analysis showed that the TcR genes had the same clonally rearranged pattern involving b, g and d genes in both populations. At disease relapse and during the terminal refractory phase, only CD3(-) cells were present. INTERPRETATION AND CONCLUSIONS: This is an unusual case of CD56(+) aggressive lymphoma/leukemia characterized by the clonal expansion of two phenotypically different cell populations, variably balanced during the course of the disease. The presence of the same TcR genomic rearrangement suggests the origin from a common progenitor able to differentiate along both T- and NK-pathways.

Adult↗
PubMed2000

The role of underlying nephropathy in the progression of renal disease.

BACKGROUND: Disease-specific pathogenic mechanisms may be major determinants of the spontaneous rate of progression of chronic renal failure (CRF). To clarify the role of different underlying renal diseases, we examined the rate of CRF progression in 886 patients with chronic nephropathies. METHODS: Secondary analysis of two multicenter, prospective randomized trials: the Northern Italian Cooperative study (NIC) and the AIPRI study (ACE-Inhibition in Progressive Renal Insufficiency). Univariate and multivariate analyses of variance were used to select the covariates possibly related to CRF progression (estimated by means of the slope of the reciprocal of SCr against time), focusing on the contributory role of primary renal diseases. RESULTS: The overall rate of CRF progression was relatively low but there was a considerable difference in the slopes relating to the underlying nephropathy (particularly evident in the patients with chronic glomerulonephritis (CGN)). The median rate of CRF progression in both studies was more rapid in patients with polycystic kidney disease (PKD) and CGN than in those with other nephropathies. Multivariate analysis showed PKD as an independent predictor of the CRF progression rate only in the NIC Study (P < 0.0015); the selected variables in both studies predicted a variation of only 15-18% in the CRF progression rate. CONCLUSION: The underlying renal disease certainly plays a role in the natural history of CRF, but the variability of the CRF progression rates related to different renal diseases and between individuals with the same diagnosis underlines the need for caution in evaluating risk factors and predicting single patient outcomes.

Adult↗
PubMed1999

In vitro exposure of acute promyelocytic leukemia cells to arsenic trioxide (As2O3) induces the solitary expression of CD66c (NCA-50/90), a member of the CEA family.

Arsenic trioxide (As2O3) is a useful drug for the treatment of acute promyelocytic leukemia (APL), acting through a complex mechanism involving the induction of apoptosis. We investigated by flow cytometry whether in vitro treatment of APL leukemic cells with As2O3 determined specific surface membrane changes. Twelve APL bone marrow aspirates were analyzed following 7 days of in vitro treatment with As2O3 (0.25, 0.5 and 2.5 microM) with regard to the expression of a series of differentiation antigens. Twelve acute myeloid leukemia (AML) samples of non-APL morphotype were analyzed as controls. Exposure of APL as well as non-APL samples to any concentration of As2O3 did not affect the expression of beta2 integrins (CD11a and CD11b), CD45 isoforms (RA, RB and R0), CD44/H-CAM, CD33 and the CEA-related antigen family members CD66ade and CD66b, thus failing to disclose any maturating effect. Of interest, in all APL samples (but not in AML) every tested dose of As2O3 determined a dramatic upregulation of CD66c display; intermediate concentration (0.5 microM) of As2O3 increased the median percentage of CD66c+ cells from 5% in control cultures (25th-75th percentile 2-12%) to 80% in drug-exposed cultures (25th-75th percentile 58-90%) (P<0.001). The induction of solitary expression of CD66c is a new finding which demonstrates As2O3 capability of generating phenotypic changes absolutely restricted to APL cells Moreover, these results provide experimental basis for considering the involvement of the newly described CD66 signalling pathway in As2O3-driven programmed cell death.

Antigens, CD↗
PubMed1999

Long-lasting decrease of marrow and circulating long-term culture initiating cells after allogeneic bone marrow transplant.

We investigated bone marrow (BM) and circulating (PB) hematopoietic progenitor cells in 37 normal donors and in 25 patients 1 to 8 years after successful allogeneic bone marrow transplant. At the time of testing, transplanted patients had normal blood counts and bone marrow cellularity. By flow cytometry, BM CD34+ cells were found to be three- to four-fold decreased in transplanted patients compared to normal donors, while the number of PB CD34+ cells was the same as in normal donors. Using a methylcellulose colony assay, primary BM colony-forming cells (CFU-GM) were decreased 2.1-fold, whereas PB CFU-GM were only marginally decreased. In a long-term culture initiating cell (LTC-IC) assay, an eight-fold decrease of early progenitor cells was observed in the marrow of transplanted patients compared to normal donors, and a five-fold decrease was documented in peripheral blood. We found that the BM LTC-IC cell number correlated with concurrently determined BM CD34+ cells and committed progenitor cell number (measured as CFU-GM) and with PB LTC-IC number, but not with PB CFU-GM and CD34+ cells. We conclude that marrow and circulating early stem cell compartments, as measured by the LTC-IC assay, are greatly and permanently depressed following bone marrow transplant. The correlation between BM and PB LTC-IC indicates that the enumeration of circulating LTC-IC can be used as a measure of the stem cell compartment in the bone marrow after transplant. It seems that the deficiency of the most immature progenitor cells persists forever after successful bone marrow transplant; this means that a complete hematopoietic reconstitution can be sustained by a reduced stem cell pool.

Adolescent↗
PubMed1999

Complete remission in acute myeloid leukaemia with t(8;21) following treatment with G-CSF: flow cytometric analysis of in vivo and in vitro effects on cell maturation.

A 75-year-old patient diagnosed as having acute myeloid leukaemia with t(8;21) received G-CSF alone as induction therapy. Complete remission was achieved following 2 weeks of treatment. Flow cytometric analysis, performed by CD45 technique modified by the introduction of preliminary gating with LDS-751, confirmed the disappearance of blast cells along with myeloid maturation. Finally, in vitro studies demonstrated that G-CSF, as compared to other differentiation inducers, was able to induce a striking effect toward neutrophilic differentiation.

Acute Disease↗