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T Lotti

Publications and source records attributed to T Lotti.

At least 37 records · Page 2Linked to original sources
PubMed1999

Role of neoadjuvant treatment in clinically confined prostate cancer. Takeda NHT Italian Group.

OBJECTIVE: This prospective, randomized, multicenter comparative trial studied the effect of neoadjuvant hormonal treatment (NHT) prior to radical, prostatectomy. METHODS: Histopathologic tissue specimens were obtained from 91 consecutive patients (aged 60-70 years) who underwent a radical prostatectomy for stage B prostate adenocarcinoma. The patients had received NHT for three months. Specimens were compared with those from 48 age-matched control patients who underwent similar surgery for stage B disease without receiving preoperative therapy. RESULTS: Treated tumors with an acinar pattern were distinguishable from the untreated tumors by neoplastic acini that appeared shrunken and areas of individual infiltrating tumor cells separated by an abundant interglandular connective tissue. The epithelial tumor cells had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation and pyknosis, cytoplasmic clearing, and enlargement by coalescence of vacuoles and rupture of cell membranes. No mitotic figures were seen in any treated tumors. CONCLUSIONS: Preliminary results show a benefit for patients receiving NHT in regard to the histologic indicators that we evaluated.

Adenocarcinoma↗
PubMed1999

Changes in tissue transglutaminase activity and expression during retinoic acid-induced growth arrest and apoptosis in primary cultures of human epithelial prostate cells.

We treated primary epithelial cells from human normal prostate (NEPC) and prostate cancer (CEPC) with all-trans-retinoic acid (RA) to study whether it regulates the activity of tissue transglutaminase (tTGase), an enzyme that accumulates in cells undergoing apoptosis. tTGase activity was assessed by [14C]spermidine incorporation; tTGase, P53, Bcl-2, and p21 protein levels were evaluated by Western blotting; and RA receptors (RAR alpha, -beta, and -gamma), tTGase, retinol-binding protein (RBP), and cellular RBP type I transcripts were determined by semiquantitative RT-PCR. After 72-96 h of 10(-6) mol/L RA treatment, cell growth inhibition and apoptosis were associated with increased tTGase activity in both NEPC and CEPC, and with increased tTGase protein and messenger ribonucleic acid levels only in NEPC. Moreover, RA down-regulated RAR alpha and -beta and increased RBP messenger ribonucleic acid levels in NEPC, whereas it increased RAR beta gene expression and decreased Bcl-2 protein levels in CEPC. Our results suggest that RA induces tTGase gene expression and enzyme activity in normal prostate cells, and that RA-regulated pathways are impaired in cancer cells. Moreover, down-regulation of Bcl-2 protein and up-regulation of RAR beta suggest that retinoid may act on the genetic defect responsible for prostate cancer progression.

Apoptosis↗
PubMed1999

Oxidative stress in Systemic Sclerosis.

In 63 patients affected by Systemic Sclerosis (SSc) (limited subset: 40; diffuse subset: 23; early: 30; advanced: 33) the peroxidation product diene-conjugates (DC) and antibodies against oxidised low density lipoproteins (Ab oxLDL) were tested in serum by a spectrophotometer (absorbance 234 mn) and by a standard ELISA respectively. The data were compared with those obtained by 21 healthy subjects. DC was significantly higher in patients (73.3 +/- 37.2 microM/l; p < 0.0001) than in controls (48.4 +/- 16.7) as well as in the limited (80 +/- 48.8; p < 0.05) than in the diffuse subset (64.5 +/- 36.4); and in early (84.1 +/- 31.4; p < 0.05) than in advanced stage of the disease (67.9 +/- 42.5). The levels of Ab oxLDL were significantly higher in SSc patients (309.5 +/- 367.2 mU/ml; p < 0.0001) in all its subsets (limited: 351.9 +/- 351.1, p < 0.0001; diffuse: 207.7 +/- 316.1, p < 0.05; early: 428.9 +/- 417.1, p < 0.001; advanced: 302.7 +/- 89.9, p < 0.0001) than in controls (89.3 +/- 29.1). These antibodies levels were higher in limited subset than in diffuse (p < 0.05) and in early SSc than in advanced SSc (p < 0.05). The highest values of parameters of oxidative stress are found in the early stages, when the episodes of reperfusion after ischemic episodes (Raynaud's phenomenon) are very frequent. Moreover, the damage is higher in the early stages of SSc, with intact microvessels, than in late stages, when microvessels are very reduced in number, destroyed by the worsening of the disease. These data show that the respiratory burst deduced by the lipoperoxidation is higher in SSc than in controls, and may be an important pathogenetic factors involved in tissue changes in SSc.

Antibodies↗
PubMed1998

Circulating Vdelta1+ T cells are activated and accumulate in the skin of systemic sclerosis patients.

OBJECTIVE: An increased percentage of Vdelta1+/gamma/delta T cells has been detected both in the peripheral blood and bronchoalveolar lavage fluid of patients with systemic sclerosis (SSc). This study evaluated the subset distribution, activation status, and expression of cellular adhesion molecules, such as intercellular adhesion molecule 1 (CD54), very late activation antigen alpha4 (CD49d), and lymphocyte function-associated antigen 1alpha (CD11a), on circulating gamma/delta T cells, as well as their presence in the skin of SSc patients. METHODS: We studied 12 patients with SSc and 16 healthy volunteer donors. The distribution, activation status, and expression of cellular adhesion molecules were studied by flow cytometry; their presence in SSc patient skin was evaluated by immunohistochemistry. RESULTS: We found that the percentages and absolute numbers of peripheral blood gamma/delta T cells, CD16, CD8, CD45RO, CD25, HLA-DR, CD54, and CD11a coexpression did not differ significantly from those of the controls. CD49d gamma/delta T cells were significantly increased in SSc patients (2.3%) compared with controls (0.5%). A marked increase in the ratio of Vdelta1+ cells to gamma/delta cells was observed in the patients (72%) compared with the controls (31%). The Vdelta1+ subset showed a significant expression of both HLA-DR (83% of total Vdelta1+ cells) and CD49d (90% of total Vdelta1+ cells) compared with the controls (20.5% and 60%, respectively). In the skin, the absolute numbers of gamma/delta T cells were found in striking amounts in perivascular areas, particularly in the early edematous phase of SSc (22.58 in patients and 0 in controls); the majority of gamma/delta T cells were Vdelta1+ (19 in patients and 0 in controls). In the advanced phase of SSc, Vdelta1+ T cells were also increased compared with controls (3.5 versus 0). CONCLUSION: Our results show that Vdelta1+ T cells express both adhesion molecules and activation markers, and strongly support gamma/delta T cell homing to sites of inflammation. The increase in the Vdelta1 subset suggests a selective V gene subset expansion.

Adult↗
PubMed1998

Cutaneous small-vessel vasculitis.

Cutaneous small-vessel vasculitis (CSVV) refers to a group of disorders usually characterized by palpable purpura; it is caused by leukocytoclastic vasculitis of postcapillary venules. CSVV can be idiopathic or can be associated with a drug, infection, or underlying systemic disease. Initially, the pathogenesis of CSVV is immune complex related, but in its later stages different pathogenetic mechanisms may intensify the reaction and lymphocytes may predominate in the infiltrate. Cure requires elimination of the cause (ie, drugs, chemicals, infections, food allergens) when possible, as well as therapy with nonsteroidal antiinflammatory agents, corticosteroids, dapsone, potassium iodide, fibrinolytic agents, aminocaproic acid, immunosuppressive agents (ie, cyclophosphamide, azathioprine, methotrexate, cyclosporine) or even monoclonal antibodies, depending on disease severity.

Aminocaproates↗
PubMed1998

Leuprorelin 1-month depot as neoadjuvant therapy for prostate cancer. Takeda NHT Italian Group.

In the last few years, the role of neoadjuvant hormonal treatment (NHT) prior to radical prostatectomy has been largely debated and investigated in randomized multicenter trials as well as in large single-institution studies. We have initiated a prospective randomized comparative trial with parallel groups in patients with clinically limited disease to contribute to the clarification of the possible role of NHT; to evaluate the efficacy of NHT with leuprolide plus cyproterone acetate in 'maintaining' the stage of the disease; to reduce the percentage of pathological overstaging, and mainly to accurately assess the pathological modifications induced by NHT. The present paper is an interim report of the results.

Adenocarcinoma↗
PubMed1998

Neuropeptides: role in inflammatory skin diseases.

The cutaneous nervous system recently has been demonstrated to interact with multiple target cells in the skin and to mediate actions important in inflammatory conditions. Neuropeptides released by cutaneous neurons such as substance P (SP), vasointenstinal peptide (VIP), calcitonine gene regulated peptide (CGRP), proopiomelancortin (POMC) peptides and others modulate the function of immunocompetent and inflammatory cells as well as epithelial and endothelial cells. They have been found to function as mediators of cell proliferation, cytokine and growth factor production as well as adhesion molecule and cell surface receptor expression. In addition many cells including keratinocytes, fibroblasts, endothelial cells and inflammatory cells have been shown to release several neuropeptides and they express their corresponding receptors. These findings indicate that neuropeptides participate in the complex network of mediators that regulate cutaneous inflammation, hyperproliferation and wound healing.

Humans↗
PubMed1997

Different expression patterns of somatostatin receptor subtypes in cultured epithelial cells from human normal prostate and prostate cancer.

The transcripts of five SRIH receptor subtypes (SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5) were investigated by RT-PCR in epithelial cells (EC) and stromal cells (SC) from primary cultures of five normal human prostates and six prostate cancers. Primary cultures of prostate EC were established in serum-free keratynocyte medium with 5% FCS, epidermal growth factor, and bovine pituitary extract; SC were cultured in MEM with 10% FCS. Total RNA was extracted from EC and SC using a modified guanidine thiocyanate method. RT-PCR was performed after deoxyribonuclease treatment, using SSTR1-, SSTR2-, SSTR3-, SSTR4-, and SSTR5-specific-primers and adding glyceraldehyde-3-phosphate dehydrogenase-specific primers as internal control. A PCR product of the expected size of 334 bp, corresponding to SSTR1, was expressed only in EC from prostate cancer, whereas the expected 461-bp product of SSTR2 was found only in EC from normal prostate. SSTR3 messenger RNA was undetectable in normal and cancer EC, whereas SSTR4 and SSTR5 were present in both cell types. SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5 messenger RNAs were not expressed in SC from both normal and cancer prostates. The RT-PCR method clearly demonstrated SSTRs' expression in the human prostate EC in vitro with differences between normal and tumoral samples. Our results may explain the ineffectiveness of some SSTR2 selective SRIH analogues in the treatment of prostate cancer and suggest that the absence of SSTR2 could represent a growth advantage in prostate cancer.

Aged↗
PubMed1996

Alopecia areata: immunohistochemistry and ultrastructure of infiltrate and identification of adhesion molecule receptors.

BACKGROUND: Alopecia areata (AA) is a noncicatricial alopecia with still unknown pathogenesis, but increasing evidence suggests that an immunologic process might be responsible for the disease. MATERIALS AND METHODS: Nineteen patients with AA were studied with ten of them in the progressive phase of the disease and nine in the stabilized phase. Biopsies of both affected and unaffected skin were taken. For immunohistochemistry, monoclonal antibodies directed against CD3, CD4, CD8, CD10a, CD36, and HLA-DR antigens, were used, as well as antibodies directed against adhesion molecules ICAM-1, ELAM-1 and LFA-1. For electron microscopy (EM), specimens were fixed in glutaraldehyde-sodium cacodylate buffer, post-fixed in osmium tetroxide, and stained with uranyl acetate. For statistical analysis, sections from involved and uninvolved skin of each patient for each antibody, the sign test, Fisher's F-test, and the Tukey-Kramer test were used. RESULTS: There was a rich infiltrate of CD4+ cells and CD1a+ cells, particularly in the perivascular zone of both unaffected and affected skin (here in the perivascular and in the peribulbar zone) in the progressive phase of AA. In the stabilized phase the infiltrate was scant, both in unaffected and affected skin and limited to the peribulbar area. Receptors of adhesion molecules (ICAM-2, ELAM-1, LFA-1) were strongly expressed, mainly at the microvascular level in both unaffected and affected skin in the progressive phase, but were only weakly or not at all expressed in the stabilized phase, again in unaffected and affected skin. Ultrastructural data confirmed the immunohistochemical findings and showed close contacts between infiltrating lymphocytes and Langerhans'-lineage cells mainly in the progressive phase. CONCLUSIONS: Our results suggest that: 1) an immunologic process, apparently carried out by CD4+ lymphocytes and by dendritic CD1a+ and CD36+ cells, may play a key role at least in the early phase of the disease involving primarily microvessels and later on the bulbar area; 2) the expression of adhesion molecule receptors is involved at the beginning of the disease by mediating the adherence of leukocytes to endothelial cells and subsequent trafficking into the dermis.

Adolescent↗
PubMed1996

Itch and pain.

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Antipruritics↗
PubMed1996

Cyclosporine A inhibits tPA mRNA transcription in A431 cell line.

Cyclosporine A (CyA), a well established treatment of psoriasis, is a highly lipophilic cyclic undecapeptide mainly used for its immunosuppressive properties and exerting a wide spectrum of biological activities including fungicidal antiproliferative and anti-inflammatory effects. Plasminogen activators (PA), urokinase (UK, M(r) 55,000) and tissue type plasminogen activators (tPA, M(r) 74,000), physiologically catalyze the conversion of the plasminogen to the wide spectrum proteinase plasmin. UK and tPA are involved in cell growth, differentiation and migration. It has recently been shown that psoriatic epidermis is provided with abnormal tPA-dependent PA activity and that in lesional epidermis elevated tPA mRNA levels are present. It has been suggested that the tPA-dependent PA activity is a marker of disease activity and is reversible with different topical and systemic treatments. In this preliminary study we investigate the effect of CyA on the tPA mRNA transcription on A431 keratinocytes cell line. Subconfluent A431 cell cultures have been treated with CyA at in vivo relevant concentrations (10, 7.5, 5 micrograms/ml) for 48 h. Northern blot analysis of total RNA extracted from cultured A431 cell line has been performed for detecting tPA mRNA. mRNA for tPA has been detected in the control samples whereas an evident decrease of tPA mRNA expression has been detected in the CyA-treated samples. These data suggest that CyA could have an effect in clearing psoriatic lesions also modulating the abnormal plasminogen activation i.e. tPA-dependent serinoproteinase activity.

Cyclosporine↗