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R Benelli

Publications and source records attributed to R Benelli.

54 records · Page 3Linked to original sources
PubMed1994

Inhibition of AIDS-Kaposi's sarcoma cell induced endothelial cell invasion by TIMP-2 and a synthetic peptide from the metalloproteinase propeptide: implications for an anti-angiogenic therapy.

In the initial phases of angiogenesis, endothelial cells must degrade and cross the vessel basement membrane, as do tumor cells during invasion and metastasis formation. Various metalloproteinases have been implicated in tumor cell invasion, in particular MMP-2 (72 kDa collagenase IV, gelatinase A), which has been demonstrated to be associated with tumor metastasis formation. Supernatants from AIDS-Kaposi sarcoma (KS) cells induce normal endothelial cells to invade through a reconstituted basement membrane (Matrigel) in vitro, which correlates with the angiogenic potential of KS cells in vivo. Here we demonstrate that two specific inhibitors of MMP-2, TIMP-2 and a peptide from the MMP-2 propeptide region (peptide 74), inhibit endothelial cell invasion induced by AIDS-KS cell supernatants. Smooth muscle cells were much less sensitive to these inhibitors. These data suggest that MMP-2 activation is a key event in endothelial cell invasion, the initial phase of tumor-associated neoangiogenesis. Inhibition of this enzyme could be an effective treatment for KS and tumor-associated angiogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[Adenomatoid tumor of the epididymis].

Adenomatoid tumor of the epididymis is an uncommon lesion accounting for approximately 30% of all the paratesticular neoplasms. One case observed in this Urological Department is reported and a review of our series of paratesticular neoplasms treated in the last 10 years has been considered.

Epididymis↗
PubMed1994

Oncostatin M activates phosphatidylinositol-3-kinase in Kaposi's sarcoma cells.

Oncostatin M (OM) is a polypeptide cytokine that induces autocrine and paracrine effects on AIDS-Kaposi's sarcoma (KS) cells (Nair et al., Science, 255, 1430-1432, 1992; Miles et al., Science, 255, 1432-1434, 1992). The signalling pathways underlying this activation are largely unknown. We have found that OM binding to KS cell lines in vitro identifies a higher affinity binding site (Kd 10-20 pM) with a lower affinity (Kd 1.5 nM), high capacity binding site. The binding of OM to its receptor at the KS cell surface stimulates a rapid tyrosine phosphorylation of multiple proteins, including the p85 regulatory subunit of phosphatidylinositol-3-kinase (PI3K). In addition OM can stimulate the in vivo activation of PI3K and increases the PI3K activity in anti-phosphotyrosine and anti-src kinase family antibody directed immunoprecipitates. Genistein, an inhibitor of tyrosine kinases, inhibits the synthesis of phosphatidylinositol 3,4-biphosphate and the growth of KS cells. Finally, OM enhances tyrosine kinase activity in immune complex kinase assay performed with antibody anti-src kinase family. These data suggest that in KS cells OM can stimulate formation of tyrosine kinase co-ordinate signalling complexes, containing at least src kinase family and PI3K, which can drive the accumulation of the putative second-messengers D3-phosphorylated phosphoinositides.

Antineoplastic Agents↗
PubMed1986

Acetate in predilution in bicarbonate.

Acetate in predilution in bicarbonate dialysis with AN69 S. The purpose of this work was to assess whether bicarbonate dialysis, with infusion of acetate in predilution, using an AN69-S filter, offered some advantage over bicarbonate and acetate dialysis. In a period of 16 months we analysed 11 patients with this method, comparing them with one group of 7 patients in bicarbonate dialysis and another of 11 in acetate dialysis. The following parameters were investigated: acid-basic balance, HCT, weight and the intradialytic symptoms. There was some improvement in both objective and subjective parameters in patients treated by this method compared to patients in the control groups and the results were lasting.

Acetates↗
PubMedDate not supplied

KSHV sequences in biopsies and cultured spindle cells of epidemic, iatrogenic and Mediterranean forms of Kaposi's sarcoma.

The pathogenesis of Kaposi's sarcoma (KS) is still unclear, and several factors appear to be involved in the onset of the Kaposi's lesion. Epidemiological studies suggest that a common infective agent may contribute to KS. Sequences which appear to represent a new gammaherpesvirus, currently termed KSHV/HHV8, have recently been identified in KS. To further examine the relationship between this virus and KS, we obtained biopsy samples of KS lesions; these samples, the spindle cells cultured from these lesions and the PBMC of the same patients were tested for the presence of KSHV sequences by PCR. In addition, we tested several "late passage" KS spindle cell lines as well as control samples. The biopsy samples were from lesions of the following forms of KS: one sporadic KS, two epidemic KS and three iatrogenic KS, one of which was in the process of regressing after reduction of immunosuppressive therapy, and two that were at different stages (patch and nodular) from a single patient. The sporadic KS specimen was positive, as were the PBMCs from this patient, and cells grown from this biopsy appeared to contain KSHV viral sequences up to the fifth passage. Both epidemic KS biopsies were positive, but in these cases KSHV sequences were not detected in the cultured cells. The biopsy from the regressing iatrogenic KS lesion was negative, as were the cells cultured from this lesion. However, the PBMCs of this patient were weakly positive for KSHV at the time of biopsy, and PBMCs collected from this patient one month later were completely negative. The samples of both the patch and the nodular KS lesions obtained from another immunosuppressed patient showed amplifiable sequences of KSHV, but both the PBMCs of this patient and primary KS cell cultures from these biopsies were negative. Of the late-passage KS lines tested, only one, IST AIDS KS 12, was positive for KSHV. This line is derived from an early angiomatous-macula lesion. Taken together, these data suggest that an active KSHV infection is associated with KS and that elimination of KSHV from the lesion precedes regression of the lesion, strongly correlating KSHV with KS. In addition, early KS lesions may have a higher KSHV burden, or contain cells more susceptible to KSHV infection, further linking KSHV to KS.

Aged↗
PubMedDate not supplied

Establishment and characterization of two new Kaposi's sarcoma cell cultures from an AIDS and a non-AIDS patient.

We have established and characterized two new Kaposi's sarcoma (KS) cell lines derived from skin biopsies: AIDS-KSISTIV (from an AIDS-associated KS) and KSISTVIII (from a sporadic KS). AIDS-KSISTIV and KSISTVIII are composed mostly of spindle-shaped cells. They show similar patterns of immunohistochemical staining and are positive for smooth muscle (smooth muscle alpha-actin) and fibroblastoid (TE7) markers. Neither of these lines express the endothelial marker von Willebrand factor VIII. These immunohistochemical patterns are similar to numerous other KS lines that we and others have established. When seeded on a reconstituted basement membrane ("Matrigel"), AIDS-KSISTIV and KSISTVIII cells form branching colonies and invade into the Matrigel, as do other KS cultures that we have previously examined. This behaviour on Matrigel is similar to that of malignant sarcoma cells of different origin. The expression of vimentin and the morphology of the invasive colonies on Matrigel suggest that KS-derived cells are poorly differentiated mesenchymal cells. KS lesions are characterized by a conspicuous neovascularization, which appears to be derived from host cell recruitment. We tested the capability of the KS-cell supernatants to induce an angiogenic response in vitro. The new lines are able to stimulate human endothelial cell chemotaxis and invasion through Matrigel-coated filters. No differences in angiogenic potential in vitro were observed between the AIDS and the non-AIDS case, as we previously noted for other established cultures. Our new lines have the properties of true KS cells and confirm that KS spindle cells from HIV-positive or -negative patients have identical phenotypic and behavioural characteristics in vitro.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Antiangiogenic activity of chemopreventive drugs.

Tumors growing within the host form dynamic aberrant tissue that consists of host components, including the stroma, an expanding vasculature and often chronic inflammation, in addition to the tumor cells themselves. These host components can contribute to, rather than limit, tumor expansion, whereas deprivation of vessel formation has the potential to confine tumors in small, clinically silent foci. Therapeutic inhibition of vessel formation could be best suited to preventive strategies aimed at the suppression of angiogenesis in primary tumors in subjects at risk, or of micrometastases after surgical removal of a primary tumor. Our analysis of potential cancer chemopreventive molecules including N-acetylcysteine, green tea flavonoids and 4-hydroxyphenyl-retinamide has identified antiangiogenic activities that could account--at least in part--for the tumor prevention effects observed with these compounds. These drugs appear to target common mechanisms of tumor angiogenesis that may permit identification of critical targets for antiangiogenic therapy and antiangiogenic chemoprevention.

Acetylcysteine↗
PubMedDate not supplied

In vitro models of angiogenesis: the use of Matrigel.

Tumor-induced angiogenesis is a key event for neoplastic progression. In vitro assays are important for identification of potential angiogenic agents and rapid screening for pharmacological inhibitors. The increased interest in this field of study has generated several in vitro assays that recapitulate the steps of endothelial cell activation and differentiation. In this short report we emphasize the utility of Matrigel, a reconstituted basement membrane, to define two different steps in the angiogenic process: invasion in response to growth factors and organization of microvessels into a network with branching morphology on a Matrigel substrate.

Chemotaxis↗
PubMedDate not supplied

Inhibition of angiogenesis by type I interferons in models of Kaposi's sarcoma.

Kaposi's Sarcoma (KS) is a pathology which occurs with increased frequency and in a particularly aggressive form in AIDS patients. The HIV-1 Tat protein appears to be an important co-factor in the induction of the extensive neo-vascularization associated with AIDS-KS. Tat acts as a chemoattractant for endothelial cells in vitro, inducing both chemotactic and invasive responses. Several clinical trials have been performed testing the effectiveness of diverse biological agents in therapy of KS, among these the type I interferons. Type I IFNs have diverse biological functions besides their anti-viral activity, including anti-angiogenic properties. We have shown that IFN alpha and IFN beta are potent inhibitors of both primary and immortalized endothelial cell migration and morphogenesis in vitro as well as neo-angiogenesis induced by HIV-1 Tat in vivo. The inhibitory effect of IFN class I on HIV-Tat associated angiogenesis further supports its use as a therapy for epidemic Kaposi's sarcoma. The use of recombinant IFNs at the levels required to obtain a therapeutic effect are associated with side effects and toxicity, therefore we are now developing a gene therapy approach for constant and local delivery type I IFNs.

Angiogenesis Inhibitors↗
PubMedDate not supplied

[A new adjuvant therapy modality in the treatment of superficial bladder carcinoma. Study of feasibility of postoperative radiotherapy "flash"].

The Authors present the preliminary results of a feasibility study on the use of adjuvant radiotherapy (6 Gy single fraction, postoperatively, "flash") as a new treatment modality for superficial bladder cancer (Ta-T1, N0, M0, previously relapsed or not, G I-III). The rationale for this study derives mainly from the favourable results obtained with external beam radiotherapy, when applied before interstitial radiotherapy as a method to avoid scar relapses. Data regarding 55 cases treated with the "flash" are compared retrospectively with those regarding more than 100 cases treated with different types of "conventional" adjuvant therapy at the INRCA Center of Urology, during the last 3-4 years. The Authors stress the need for a prospective, randomized study of selected cases, to clarify if an adjuvant therapeutic modality is superior to the others. The radiotherapeutic option ("flash"), however, clearly produces less iatrogenic damage than the others, and is simpler and cheaper.

BCG Vaccine↗
PubMedDate not supplied

[Tumors of the excretory urinary tract in workers of the textile industry in the Prato area].

A hospital-based case-control study on bladder and lower urinary tract cancers was conducted in the Prato area, where the textile industry is the main manufacturing sector (about 50,000 employees). "Cases" were male subjects, aged over 15 years in whom urothelial cancer had been diagnosed in the period 1980-1985; controls (two for each case) were subjects of the same sex and age with other urological diseases or cancer of the prostate or testis. Cases and controls were interviewed via a questionnaire on occupational history and personal habits. A positive association was found for subjects who had worked in the textile industry (O.R. = 1.42; C.I. = 1.0-2.0). Analysis by job titles showed positive association for "rag selectors" (O.R. = 4.09; C.I. = 1.39-11.96), whereas no association was found for dyers (O.R. = 0.74; C.I. = 0.29-1.87).

Adolescent↗
PubMedDate not supplied

[Priapism. Etiopathogentic, clinical and therapeutic considerations].

The aetiopathogenesis and clinical picture of 3 cases of priapism are described, along with the treatment employed. The first patient suffered from thalassaemia minor, whereas in the second case priapism was a manifestation of aneurysm of the abdominal aorta perforated in the cava. In the last case, erection was a sequela of surgery for hydrocoele performed under peridural anaesthesia.

Adult↗