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Biomedical subjects

A Silvani

Publications and source records attributed to A Silvani.

At least 55 records · Page 3Linked to original sources
PubMed1997

Advantage of treating anaplastic gliomas with aggressive protocol combining chemotherapy and radiotherapy.

We devised a treatment protocol for anaplastic gliomas consisting of:(a) chemotherapy prior to radiotherapy (b) a second chemotherapy regimen at tumor recurrence (c) repeated surgery whenever possible. 41 Anaplastic Astrocytoma (AA), 16 Anaplastic oligoastrocytoma (AOA) and 14 anaplastic oligodendroglioma (AOD) patients were treated. After surgery all patients received 5-6 cycles of carmustine+Cisplatinum chemotherapy. Radiotherapy was started during the last 2-3 cycles of chemotherapy. 17 patients (30.5%) were reoperated on at recurrence. All recurring patients underwent PVC chemotherapy. At this moment disease recurred in 56 patients. Median TTP was 24.5, 38.7 and 58.2 months for AA, AOA and AOD respectively. Median ST was 38.8, 71.8 and 73 months. In conclusion our sandwich protocol of prior chemotherapy, overlapping irradiation with second chemotherapy and, in favourable cases, a second surgical intervention, is of benefit in patients with anaplastic gliomas.

Adolescent↗
PubMed1997

Misdiagnosis of post-traumatic splenic rupture in a patient with acute cold agglutinin disease due to Mycoplasma infection.

We describe a case of cold agglutinin disease, secondary to Mycoplasma pneumoniae infection, which presented with anaemia and abdominal pains in apparent succession to a thoraco-abdominal trauma. An exploratory laparotomy, carried out because of suspected post-traumatic rupture of the spleen, was complicated by a transitory cardiorespiratory arrest. The subsequent and correct diagnosis of the mycoplasmal infection and the cold agglutinins led to specific and successful therapy. The previously unknown hypertrophic cardiomyopathy was a contributing factor to the cardiorespiratory arrest.

Anemia, Hemolytic, Autoimmune↗
PubMed1996

Interstitial chemotherapy with mitoxantrone in recurrent malignant glioma: preliminary data.

We undertook a phase I-II trail of loco-regional mitoxantrone in 12 patients affected by malignant gliomas. Mitoxantrone was delivered at tumor recurrence by Ommaya reservoir, with 2 cycles and a 1 month interval between each cycle, in conjunction with systemic chemotherapy (8 pts) or not (4 pts). Treatment tolerability was good, and 9 of the patients showed either response or stable disease at the end of the treatment schedule. Regardless of associated chemotherapy, time to further tumor progression was at 6 months. A combination of early systemic and loco-regional chemotherapy with surgery and radiotherapy seems worth while pursuing in the therapeutic approach to malignant gliomas.

Adult↗
PubMed1996

Intrathecal immunotherapy in CNS tumors disseminating via CSF: preliminary evaluation using different treatment schedules.

Eight patients affected by central nervous system tumours disseminating via cerebrospinal fluid received rIL-2 immunotherapy according to three different protocols involving intrathecal administration followed or not by systemic infusion. Immunological monitoring included serial evaluation of CSF leukocytes, CSF and peripheral blood CD3-CD56+ cells, and NK activity. The most marked rise in CSF leukocyte levels was induced by daily intrathecal rIL2 administration, which also induced increased PB NK activity. Systemic rIL2 infusion following intrathecal treatment maintained a high percentage of CSF CD3-CD56+ cells, but not CSF leukocytes at high levels. Clinical conditions improved after treatment in two patients, worsened in one and remained substantially unchanged in the remaining five. The side effects of intrathecal rIL2 treatment included fever, confusion, and seizures, and there were marked interindividual variations in the immunological response.

Adolescent↗
PubMed1996

Familial intracranial hypertension: a case report.

We report the cases of a father and his daughter developing idiopathic intracranial hypertension within a few months' of each other. A second daughter is affected by uveitis, while a third daughter presented an episode of visual loss of unknown nature.

Adolescent↗
PubMed1996

HOXB7 constitutively activates basic fibroblast growth factor in melanomas.

Homeobox (HOX) genes control axial specification during mammalian development and also regulate skin morphogenesis. Although selected HOX genes are variably expressed in leukemias and kidney and colon cancer cell lines, their relationship with the neoplastic phenotype remains unclear. In both normal development and neoplastic transformation, HOX target genes are largely unknown. We investigated the expression and function of HOXB cluster genes in human melanoma. The HOXB7 gene was constitutively expressed in all 25 melanoma cell lines and analyzed under both normal and serum-starved conditions, as well as in in vivo primary and metastatic melanoma cells; conversely, HOXB7 was expressed in proliferating but not quiescent normal melanocytes. Treatment of melanoma cell lines with antisense oligomers targeting HOXB7 mRNA markedly inhibited cell proliferation and specifically abolished expression of basic fibroblast growth factor (bFGF) mRNA. Band shift and cotransfection experiments showed that HOXB7 directly transactivates the hFGF gene through one out of five putative homeodomain binding sites present in its promoter. These novel findings indicate a key role for constitutive HOXB7 expression in melanoma cell proliferation via bFGF. The results also raise the possibility that growth factor genes are critical HOX target genes in other developmental and/or neoplastic cell systems.

Antisense Elements (Genetics)↗
PubMed1996

Prognostic value of some laboratory parameters in a group of intravenous drug users in the early stages of HIV infection.

During a 5 year follow-up we found significantly reduced survival for non-accidental deaths in 37 intravenous drug users (IVUDs) in the early stages of HIV infection when compared with 32 HIV-negative IVUDs (p = 0.017). Moreover, in HIV-positive subjects, survival was significantly reduced for those groups which at the beginning of the follow-up showed the following values: circulating CD4+ lymphocytes <250/mmc (p = 0.007), CD4+/CD8+ ratio < 0.5 (p = 0.027), serum albumin < 4.13 g/dl (p = 0.045), IgA > or = 2.5 g/l (p = 0.043), IgM < 1.8 g/L (p = 0.041) and platelet count < 130 x 1,000/mmc (p = 0.038). In HIV positive patients, the value of 250 units/mmc for the circulating CD4+ lymphocytes still remained the most predictive parameter of increased mortality for disease at 5 years, even following investigations conducted with other cut-offs. Relationships existing at the beginning of the follow-up between circulating CD4+ lymphocytes and other prognostic parameters suggest that IgA (r = -0.34; p = 0.04), serum albumin (r = 0.33; p = 0.05), and CD4+/CD8+ ratio (r = 0.72; p = 0.0001), but not IgM (r = 0.25; N.S.) and platelets (r = 0.07; N.S.), are dependent variables of shortened survival.

CD4 Lymphocyte Count↗
PubMed1995

Down-regulation of interleukin 6 receptor alpha chain in interleukin 6 transduced melanoma cells causes selective resistance to interleukin 6 but not to oncostatin M.

The cytokines interleukin 6 (IL-6) and oncostatin M are able to inhibit the growth of cell lines obtained from early but not advanced melanomas. Resistant cell lines have frequently been found to produce IL-6. Acquisition of IL-6 resistance and the relationship between resistance and endogenous IL-6 production are poorly defined phenomena. We have characterized a panel of melanoma cell lines for susceptibility to IL-6 and oncostatin M and have generated lines that acquired resistance to IL-6 by IL-6 cDNA transduction. These lines retained the previous oncostatin M sensitivity, suggesting that the alpha chain of IL-6 receptor (IL-6R alpha) is involved in the acquisition of resistance. In fact transduced cells lost the ability to bind 125I-IL-6 and to release soluble IL-6R alpha in culture. Moreover, addition of soluble recombinant IL-6R alpha were able to restore IL-6 sensitivity in association with IL-6 production. On the contrary, naturally IL-6 resistant melanoma cell lines were not inhibited by treatment with recombinant soluble IL-6R alpha in association with endogenously produced or recombinant IL-6. These results demonstrate that down-regulation of IL-6 receptor is only one of different mechanisms that are responsible of IL-6 resistance in melanoma cells.

Cell Division↗
PubMed1995

In vitro and in vivo stability and anti-tumour efficacy of an anti-EGFR/anti-CD3 F(ab')2 bispecific monoclonal antibody.

The in vitro and in vivo stability and anti-tumour efficacy of the anti-EGFR/anti-CD3 bispecific monoclonal antibody (biMAb), M26.1, were analysed. The interaction of the intact biMAb with Fc receptor I (Fc gamma RI) present on human leucocytes was not observed when the antibody was used as an F(ab')2 fragment. A CD8+ T-cell clone coated with M26.1 F(ab')2 was as effective as the intact biMAb in inducing IGROV1 target cell lysis when tested in a 51Cr-release assay. Variable levels of reduction of F(ab')2 to monovalent F(ab') were observed upon incubation with human ovarian cancer ascitic fluid (OCAF) or with human glioblastoma cavity fluid (GCF), but not with mouse or human sera. Activated lymphocytes coated with F(ab')2 and incubated in vitro with GCF or OCAF for 24 and 48 h respectively maintained their targeting. Thus, the F(ab')2, when present as a soluble molecule, but not when bound to T cells, might lose some functional activity as a consequence of partial reduction to F(ab'). In normal mice, M26.1 F(ab')2 retained full cytotoxic activity in the circulation, and clearance values were similar to those obtained with parental and other MAb F(ab')2. Treatment of IGROV1 tumour-bearing mice with activated human lymphocytes coated with the M26.1 F(ab')2 significantly prolonged survival of the animals compared with tumour-bearing untreated and control mice treated with lymphocytes or F(ab')2 alone. Together, these results suggest the clinical usefulness of bispecific M26.1 F(ab')2 as a targeting agent for local treatment of tumours such as glioma and ovarian cancers that express variable levels of epidermal growth factor receptor (EGFR).

Animals↗
PubMed1995

Modification of phlogosis indices in pneumonia during antibiotic therapy.

50 consecutive cases of pneumonia were treated using a standardized diagnostic-therapeutic protocol. The variations of the more common phlogosis indices (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], leucocytes) during the antibiotic therapy were evaluated, together with clinical progress. Comparative evaluations of the phlogosis indices were taken as well as the X-ray picture. The data analysed, according to the literature, showed a significantly faster and more widespread response to the therapy by the CRP, in respect to ESR and the leucocytes number. This data has been substantially confirmed even in individual groups into which the case study was subdivided. In the "compromised" (according to the British Thoracic Society) patients, the fall in the CRP level was not so early as in the "uncompromised" group. There did not seem to be however different behaviour of ESR and leucocytes between these two groups. Modifications in these two tests over time were rarely significant. An age equal to or greater than 70 appears the element which best defines the state of "compromised host". A comparison of the clinical progress with the variations of the tests of phlogosis and the radiographic tests confirms the usefulness of CRP as an early index of the clinical evolution and the lateness of X-ray tests.

Anti-Bacterial Agents↗
PubMed1994

Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes.

Human tumors can constitutively express cytokines and growth factors, but the extent of this expression has not been investigated. Using 44 different probes to cytokines, growth factors, and their receptors, we tested 21 melanoma and 5 melanocyte cultures for RNA transcript expression by reverse transcriptase-polymerase chain reaction. With 30 amplification cycles, expression of the cytokines interleukin (IL)-1 beta, IL-6, leukemia inhibitory factor (LIF), IL-7, gro alpha, IL-8 and the p35 chain of IL-12 was detected in more than 60% of melanomas. Concomitant receptors for IL-6 and IL-7 were also detected. IL-1 alpha, IL-5, Rantes, IL-10, interferon (IFN)-beta, tumor-necrosis factor (TNF)-alpha, G-colony-stimulating factor (CSF) and GM-CSF were expressed at lower levels. Melanocytes showed greatly reduced cytokine RNA transcripts, and only gro alpha was consistently detected. No expression of IL-2, IL-3, IL-4, IL-9, the p40 chain of IL-12, IFN-alpha or IFN-gamma RNA transcripts was detected in melanomas or melanocytes. The growth factors expressed by melanomas and, after further signal amplification, by melanocytes were transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), TGF-beta, endothelial-cell growth factor (ECGF), basic-fibroblast growth factor (bFGF), nerve growth factor (NGF) and steel. The receptors EGFR, FGFR, NGFRp70 and c-kit were also expressed by melanomas and melanocytes. These results point to new possible autocrine and paracrine pathways in melanoma biology.

Base Sequence↗
PubMed1994

Characterization of an established human, malignant, glioblastoma cell line (GBM) and its response to conventional drugs.

A cell line, GBM, was established from a human malignant glioblastoma and was characterized with particular reference to its response to conventional drugs. The GBM cell line exhibited a 73 +/- 7 h doubling time in monolayer cultures. Expression of glial fibrillary acidic and S-100 proteins was observed. Karyotype analysis of GBM cells at early passages revealed the presence of two near-triploid clones (A and B) with multiple chromosome rearrangements; a 100% frequency for clone B was observed in the established cell line. GBM cells had tumorigenic properties, since the s.c. injection of cultured cells into nude mice gave rise to slowly growing tumors. The morphology of GBM cells was retained during in vitro and in vivo passages, as judged by light microscopy. GBM cells were relatively resistant to most conventional drugs; among the tested drugs, only taxol exhibited a marked cytotoxic effect comparable to that found in cells of a different tumor type. GBM cells were found positive for the epidermal growth factor receptor, HER2-neu and P-glycoprotein by flow cytometry of cells labelled with monoclonal antibodies. In spite of the expression of relatively high gamma-glutamyltransferase activity, the intracellular glutathione level was comparable to that of other chemosensitive tumor cells. This glioblastoma cell line is a suitable model for the identification and preclinical studies of new agents and provides an additional system to explore the molecular basis of the intrinsic drug resistance of glioblastoma.

Animals↗
PubMed1994

Loco-regional immunotherapy with recombinant interleukin-2 and adherent lymphokine-activated killer cells (A-LAK) in recurrent glioblastoma patients.

Nine patients with recurrent glioblastoma were given autologous adherent lymphokine-activated killer (A-LAK) cells and interleukin-2 (IL-2) administered directly into the tumor cavity through an Ommaya tube placed during surgery/biopsy. The immunotherapy was well tolerated and the response rate was 33% (one complete response, two partial responses, four with stable disease and two with progressive disease). However, survival 18 months from initial diagnosis did not differ from that reported in the literature for patients treated conventionally. Serial determinations of IL-2 in the tumor cavity during the course of treatment revealed that IL-2 concentrations were sufficient to maintain lymphocyte activation. Since steroid medication was discontinued during treatment and A-LAK cells have greater antitumor activity than standard LAK cells, other factors are discussed that might explain the limited results.

Adult↗
PubMed1994

Successful adoptive immunotherapy with lymphokine-activated killer cells in the treatment of medulloblastoma disseminated via cerebrospinal fluid: case report.

We report the case of a girl who developed cerebellar medulloblastoma at the age of 12 years and in whom, 4 years after surgical removal and radiotherapy, neoplastic dissemination via the cerebrospinal fluid took place. After only partially effective systemic and intrathecal chemotherapy, an intrathecal administration of lymphokine-activated killer cells and recombinant interleukin-2 allowed complete clinical recovery persisting after a follow-up of 30 months.

Adult↗
PubMed1994

Immunological fluctuations during intrathecal immunotherapy in three patients affected by CNS tumours disseminating via CSF.

The immunological therapy of cancer has been proposed in a number of neoplasms (Borden, Sondel, 1989; Foon, 1989; Rosenberg, 1992) and has recently been adopted in the treatment of Central Nervous System (CNS) tumors in combination with conventional surgical and radiotherapeutical approach. In this context, loco-regional administration of immunomodulating agents (for instance in post-surgical cavity) allows to achieve much higher in situ concentrations than by systemic route. Since these treatments have potential adverse effects, careful assessment of clinical and immunological parameters in phase I trials is needed. CNS tumors disseminating via Cerebrospinal Fluid (CSF) pathways offer a stimulating opportunity for intrathecal immunotherapy. In this context, alpha-IFN and IL2 (alone or in combination with LAK cells) have been employed either loco-regionally or intrathecally (Merchant, Mc Vicar, Merchant & Young, 1992; Schiller, Hank, Storer, Borchert, Moore, Albertini, Bechhofer, Wesley, Brown, Bastin & Sondel, 1993). The rationale for the use of both these substances includes the known anti-tumor action of alpha-IFN (Mahaley, Urso, Whaley, Blue, Williams, Guaspari & Selker, 1985; Nagai, 1988) and the ability of r-IL2 to generate activated cells effective in lysing tumor cell targets (Hayes, Moore, Pierz, Chen, Da Rosso, Nirenberg & Allen, 1993). We treated 3 patients (2 affected by disseminating cerebellar medulloblastoma, 1 by disseminating thalamic glioblastoma) by intrathecal r-IL2 via recervoir. In the first 2 patients, this treatment was preceded by alpha-IFN (also intrathecally). Monitoring of immunological effects of the treatment schedule involved kinetics of CSF and serum TNF-alpha, IL2s and IL2R during the first day of r-IL2 treatment, as well as on day +2 and +4 of both r-IL2 cycles, and assessment of CSF cells, protein and CSF and PB NK cell activity and CD3-CD56+ cells during the course of all treatment cycles. We also assessed clinical and neuroradiological effects of immunotherapy.

Adult↗
PubMed1993

Lymphotoxin gene expression by melanocytes and melanoma cell lines and persistence of unspliced mRNA.

Human melanoma cell lines express many different cytokines [1], including lymphotoxin (LT), the production of which has been considered to be restricted to cells of the lymphocytic lineage in response to cell activation. LT expression by melanomas is constitutive and characterized by the presence of two mRNAs. In the present paper we report an analysis of the origin of the two LT-specific transcripts in four human melanoma cell lines at different stages of progression and in four melanocytic cell lines. Reverse transcription-polymerase chain reaction (RT-PCR) performed with primers lying in the first and fourth exons and hybridization with intron probes showed a spliced and a full-unspliced LT mRNA. This pattern was also displayed by one of four melanocyte cell lines. Western blot analysis indicated that LT RNA is properly translated to a 23-25 kDa protein and immunocytochemistry showed its localization within the cytoplasm and on the cell membrane.

Gene Expression↗