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Biomedical subjects

B Giannotti

Publications and source records attributed to B Giannotti.

At least 55 records · Page 3Linked to original sources
PubMed1994

Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma.

PURPOSE: Some phase II studies have suggested that the combination of interferons (IFNs) with dacarbazine (DTIC) in the treatment of malignant melanoma (MM) increases the antitumor activity of DTIC alone. In an attempt to confirm this hypothesis, a randomized study was performed with the further intent of observing whether low doses of recombinant interferon alfa-2a (rIFN alpha 2a) could be as effective as intermediate doses. PATIENTS AND METHODS: Two hundred sixty-six patients were randomized onto three different treatment arms: DTIC 800 mg/m2 intravenously (IV) days 1 and 21; DTIC plus rIFN alpha 2a 9 mIU intramuscularly (IM) daily; and DTIC plus rIFN alpha 2a 3 mIU IM three times per week. Major prognostic factors were well balanced among the three arms. Chemotherapy was administered for a maximum of eight cycles. After 6 months of therapy, rIFN alpha 2a was continued until disease progression at 3 mIU three times per week in responding patients who had received the combined treatment. RESULTS: The percentage of objective responses did not differ among the three groups (20%, 28%, and 23%, respectively), although a significant prolongation of response duration was observed when rIFN alpha 2a was added to DTIC (2.6 v 8.4 v 5.5 months, respectively). However, this improvement in response duration did not translate into an amelioration of overall survival. The addition of rIFN alpha 2a led to the onset of flu-like syndrome, but in no case was it necessary to withdraw the treatment program and no toxic deaths or life-threatening toxicities were reported. CONCLUSION: In this study, rIFN alpha 2a significantly prolonged response duration, whereas no effects on response rate and survival were observed; rIFN alpha 2a 3 mIU appeared to be equally effective and better tolerated than 9 mIU.

Adult↗
PubMed1994

Topical corticosteroids and unwanted local effects. Improving the benefit/risk ratio.

The main goal of pharmacological research in the field of topical corticosteroids (TCs) is to dissociate efficacy and adverse effects as much as possible. The optimal use of TCs, i.e. the careful evaluation of the benefit/risk ratio, depends on: (i) the chemical structure of the TC; (ii) the type of vehicle; (iii) the mode of application; and (iv) the features of the skin to be treated. The recent availability of TCs characterised by a good dissociation between efficacy and adverse effects makes the classic and widely used classification system of TCs based upon potency out of date. Indeed, TCs with increasing potency have been characterised up to now, as a rule, by an increasing risk of adverse effects. Therefore, a classification system taking into major account the benefit/risk ratio seems particularly needed for clinical use in dermatology.

Administration, Topical↗
PubMed1994

Dendritic cells in T- and B-cell proliferation in the skin.

In lymphoproliferative diseases of the skin, DC have a key role in T- and B-cell homing. Furthermore, DC alterations may have a pathogenic role in the natural history of specific disorders, either in the neoplastic lymphoid cell progression or in antitumoral lymphocyte reaction. Finally, the morphoantigenic and topographic features of DC may have diagnostic and histogenetic relevance in specific conditions. In CTCL, dermal CD1a+ DC ("indeterminate cells") seem to play a significant role in the neoplastic progression of MF, whereas the possible pathogenetic role of specific alterations of epidermal LC is yet to be proven. Recently, a possible implication of DD (resident, perivascular factor XIIIa+/CD1a- DC) in the pathogenesis of MF has been also suggested. The presence and possible significance of DC in CTCL non-MF are presently poorly studied. At present, DC number, distribution, and phenotype seem possibly useful in the differential diagnosis between CTCL and pseudo-CTCL, but this hypothesis has to be adequately confirmed. CBCL has been recently proposed as a unique type of clinically low-grade lymphoma, namely, skin-associated lymphoid tissue (SALT)-related B-cell lymphoma. Both SALT- and mucosa-associated lymphoid tissue (MALT)-related B-cell lymphoma share with a peculiar nodal lymphoma of follicle mantle origin (parafollicular-monocytoid lymphoma) the nonaggressive clinical behavior and the uniform phenotype (CD5-, CD10-) and genotype (lack of bcl-2 gene rearrangement) of neoplastic B cells, despite the wide variability of cytomorphologic appearances. The putative origin of CBCL is further supported by the typical CD14-, nerve growth factor receptor (NGFr)+ immunophenotype of DRC. Moreover, the immunophenotype and architectural fashion of DRC are interesting clues to the differentiation between neoplastic and true reactive folliclelike nodules and may be of help in the differential diagnosis between CBCL and B-cell pseudolymphoma as well as in the correct interpretation of lesions showing monoclonal proliferations of B cells accompanied by polyclonal follicular reactions.

B-Lymphocytes↗
PubMed1993

Adhesion molecule profile and malignancy of melanocytic lesions.

The ability of melanoma cells to metastasize is largely dependent upon cell surface molecules that mediate cell-matrix and cell-cell interactions. Our aim was to investigate the expression of such molecules (adhesion molecules) on tissue sections of a series of melanocytic lesions in different stages of tumour progression. Four common naevi, four congenital naevi, four dysplastic naevi, three Spitz naevi, 20 primary melanomas and 15 metastatic melanomas were tested with an alkaline phosphatase/anti-alkaline phosphatase technique and a panel of monoclonal antibodies directed toward different alpha subunits of VLA receptors, beta 1, VNR-alpha and beta 3 subunit, and CD44 hyaluronate receptor. Only metastatic melanomas expressed the alpha 4 subunit, and only thick primary melanomas and metastases expressed the beta 3 subunit. The alpha 6/beta 1 chain was expressed at significantly higher levels on benign lesions, and a trend towards increased expression of alpha 2 and alpha 3 subunits was found in malignant versus benign lesions. Our results show that the pattern of integrin expression changes in melanocytic lesions along with malignant transformation.

Antibodies, Monoclonal↗
PubMed1992

Topical corticosteroids. Which drug and when?

A number of factors have to be taken into account when dealing with the treatment of skin diseases with topical corticosteroids, including disease type and phase, potency of the drug, safety, site to be treated, age of the patient, and drug formulation. Concerning the specific indications for topical corticosteroid treatment, we can distinguish skin diseases in which: (a) topical corticosteroids are the treatment of choice; (b) topical corticosteroids are useful as alternative and/or adjuvant treatment; (c) the proposed use of topical corticosteroids has to be confirmed as useful; and (d) topical corticosteroids can be used as a symptomatic treatment. Within these groups, the treatment schedule has to be adjusted according to the above mentioned general factors.

Administration, Topical↗
PubMed1991

Melanocytic naevi: clinical features and correlation with the phenotype in healthy young males in Italy.

Six-hundred and fifteen young healthy Italian males were examined for the number, localization and clinical features of melanocytic naevi. The data were correlated with the phenotype and skin type of the subjects. Eighty-eight per cent had melanocytic naevi, 7% congenital naevi and 21.3% atypical naevi with a diameter greater than 5 mm and indistinct or irregular borders and were variable in colour. Of the sample only 2.43% had more than 30 naevi. Those subjects with blond or red hair, fair skin, blue or green eyes and with a skin type of I and II had higher numbers of naevi which were more often atypical than those subjects with dark hair, brown eyes and who were skin types III-V.

Adolescent↗
PubMed1991

Immunohistochemical evidence of skin immune system involvement in vulvar lichen sclerosus et atrophicus.

Biopsies taken from vulvar lesions in 12 women affected by vulvar lichen sclerosus et atrophicus (LSA) have been processed for immunohistological study. Activated (HLA-Dr+) T cells, associated with CD1a+ accessory cells, were found in the dermis in all cases, with architectural patterns varying in relation to the histological phase (early, well developed, old) of the lesion. Interestingly, the number of epidermal CD1a+ Langerhans cells (LCs) was increased in all cases, without any correlation with the amount of the dermal infiltrate and with the histological phase of the lesions. In fact, also in old lesions the number of epidermal CD1a+ LCs was increased, and the sparse dermal lymphoid cells showed a persistent HLA-Dr antigen expression. These data, indicating the persistent activation of epidermal antigen-presenting cells and lymphoid cells in all the evolutive phases of vulvar LSA, suggest a possible involvement of the skin immune system in the pathogenesis of LSA.

Adolescent↗
PubMed1990

Phase II study of interferon alpha-2a and dacarbazine in advanced melanoma.

Based on the report of some activity of combination therapy with dacarbazine (DTIC) and interferon alpha-2a (rIFN alpha-2a) in disseminated melanoma, we conducted a phase II study to determine the feasibility and efficacy in a large series of patients. DTIC was administered in 79 patients at the dose of 800 mg/m2 every 3 weeks and rIFN alpha-2a was given daily at the dose of 9 X 10(6) IU for the first 10 weeks and three times a week thereafter. Among the 75 evaluable patients, 25% achieved an objective response, with 8% complete and 17% partial remissions. The regression occurred within a mean time of 1.9 +/- 1.03 months from starting therapy and the mean duration of response was 8.2 +/- 4.2 months. The major side effects were vomiting, anorexia, fever, fatigue, and myalgia. There was one death related to sepsis after myelosuppression. In the other patients bone marrow and liver toxicities were not remarkable. Our data reveal that a combination regimen of rIFN alpha-2a with a cytotoxic agent has some therapeutic activity in the management of advanced malignant melanoma.

Adolescent↗
PubMed1990

Ki67 antigen expression correlates with tumor progression and HLA-DR antigen expression in melanocytic lesions.

Advanced steps of tumor progression are generally characterized by an increased growth fraction within the neoplastic cell population. The presence of a relevant growth fraction is also related to widely accepted prognostic parameters in some human malignancies. Our aims were to evaluate the presence of a growth fraction with Ki67 monoclonal antibody (MoAb), and to correlate it with tumor progression and HLA-DR antigen expression in 88 melanocytic lesions. The lesions were 19 acquired melanocytic nevi, 58 primary melanomas [divided into 26 superficial spreading melanomas (SSM), 24 superficial spreading melanomas with nodular areas (SS + NM), and five nodular melanomas (NM)], and 11 metastases from malignant melanomas. Ki67 MoAb stained 16%, 19%, 71%, 100%, and 82% of nevi, SSM, SS + NM, NM, and metastases, respectively. Among primary melanomas, Ki67 MoAb stained 12%, 28%, 50%, and 70% of tumors less than 0.75, 0.75-1.49, 1.5-2.9, and greater than or equal to 3 mm thick, respectively. A concordant reactivity pattern for Ki67 and HLA-DR antigens was found in 72% of lesions (p less than 0.0001). We have shown that a representative growth fraction (ie, Ki67 reactivity) is present in melanocytic lesions only in advanced steps of tumor progression and correlates with HLA-DR antigen expression. Despite the different biologic values of Ki67 and HLA-DR antigens, we suggest the joint evaluation of both antigens as a useful marker of aggressive behavior in melanoma.

Antibodies, Monoclonal↗
PubMed1990

Langerhans cells and mycosis fungoides--a critical overview of their pathogenic role in the disease.

Skin biopsies from seven patients with mycosis fungoides in various clinical stages (patches, plaques, nodules) were studied immunohistochemically and ultrastructurally, with the aim of investigating and quantifying the distribution of Langerhans cells and their relationships to mycosis cells. Our findings have revealed that in patches and plaques both Langerhans cells and mycosis cells were numerous in the epidermis. Notwithstanding this, in all the specimens examined, only one Langerhans cell forming close contact with a mycosis cell was detected. In the nodules, Langerhans cells and mycosis cells were sparse in the epidermis and no contacts were seen between them. Moreover, in all the patients studied, only a single Langerhans cell was found in the dermal infiltrate without any closely related mycosis cells. Conversely, numerous interdigitating cells have been found in the dermis of patches and plaques, often tightly adhering to mycosis cells. In the nodule, a few scattered interdigitating cells were seen, but often these had close contacts with neoplastic lymphoid cells. These findings indicate that close apposition between Langerhans cells and mycosis cells, which led previous authors to hypothesize a persistent stimulatory action of Langerhans cells on T lymphocytes, eventually leading to the malignant transformation of the latter, is unusual in mycosis fungoides. Therefore, if such a pathogenic role may be attributed to accessory cells in mycosis fungoides it is more probably exerted by dermal interdigitating cells and not by Langerhans cells, as previously proposed.

Humans↗
PubMed1990

HLA-DR and 96-K antigens and intratumoral lymphocytic infiltrate in primary cutaneous melanoma as markers of tumor progression.

It was recently demonstrated that HLA-DR antigens in primary melanomas are correlated with 96-K antigen expression and with the presence of an intratumoral lymphocytic infiltrate (ILI). As HLA-DR antigens are known to be associated with advanced phases of tumor progression in melanocytic lesions, we investigated whether primary melanomas in different progression phases could be distinguished on the basis of the expression of HLA-DR and 96-K antigens and of the presence of an ILI. A concordant presence of the two antigens and of an ILI was frequent both in vertical growth pattern melanomas and in melanomas thicker than 1 mm. On the contrary, both antigens and the ILI were frequently absent both in thin melanomas (less than 1 mm) and in radial growth pattern melanomas. These observations suggest that a joint study of HLA-DR and 96-K antigens and of the ILI is useful to define the phase of progression of primary melanomas.

Antibodies, Monoclonal↗