p53 protein expression in basal cell carcinomas.
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Biomedical subjects
Publications and source records attributed to M Cristofolini.
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Increases in cutaneous malignant melanoma (CMM) incidence and mortality rates have occurred in the last decades in virtually all white populations, more markedly in those which permanently (immigrants) or temporarily (tourists/vacationers) reside in very sunny areas distant from their original living environment. The strong relationship between sex and site of CMM in these upward trends (ie trunk in males, lower limbs and, more recently, trunk as well in females) points to intense intermittent ultraviolet light exposure as the cause of the CMM epidemic. In Europe the highest rates of melanoma are seen in Denmark, The Netherlands, the United Kingdom, Ireland and Germany, where many individuals have light complexion with tendency to burn. Increases of 2 to 7% per year in mortality rates appeared earlier in these countries, but were subsequently seen also in relatively low-risk areas such as southern European countries. The interpretation of data from case-control studies is, however, hampered by the difficulties in quantifying retrospectively CMM risk correlates (ie host factors, sun exposure, clothing habits, sunburns etc) in various periods during the life span.
Malignant blue nevus is a rare melanotic tumor of the skin arising from a pre-existing blue nevus. To date only few cases have been reported. The diagnosis of malignant blue nevus is frequently difficult. Generally accepted criteria do exist, but their application may be controversial. The present paper reports four new cases of malignant blue nevus with follow-up of 3-5 years. Our present data, along with those of the literature, suggest that malignant blue nevus may be more aggressive than generally thought.
New bioisoters of psoralen, obtained by replacing carbon 8 of the central benzene ring with a nitrogen, were studied from the photochemical, photobiological and phototherapeutic points of view. In particular, 4,4'-, 4',5'-dimetyl, 4,4',5'-trimethyl and 3,4,4',5'-tetramethylazapsoralen were studied. The crystal and molecular structure of 4,4',5'-trimethylazapsoralen, obtained by X ray diffraction, was also reported. Like psoralen, these compounds form a molecular complex with DNA, undergoing intercalation inside the double helix of the macromolecule. When irridiated with long ultraviolet light (365 nm), the intercalated drug photoconjugates covalently to the macromolecule, forming mono- and diadducts. The photobinding rate show the following order of magnitude: 4,4',5'-trimetylazapsoralen (4,4',5'-TMAP) = 3,4,4',5'-tetramethylazapsoralen (3,4,4',5'-TMAP) greater than 4',5'-dimethylazapsoralen (4',5'-DMAP) = 4,4'-dimethylazapsoralen (4,4'-DMAP). The DNA photobinding rate of 8-methoxypsoralen (8-MOP), taken as reference compound, is similar to that of the two dimetylazapsoralens but lower than tri- and tetramethyl derivatives. The ability of azapsoralens to form cross-links in DNA is lower than that of 8-MOP. However, capacity to induce cross-links does not parallel the DNA photobinding rate; it is higher for trimethyl derivate and lower for tetramethylazapsoralen. Azapsoralens show evident antiproliferative activity. The trimethyl derivative is the most active, followed by tetrametyl, both these compounds showing activity slightly higher than that of 8-MOP. The two dimethylderivatives are less active. The mautagenic activity of azapsoralens on E. coli WP2 TM6 is lower than that of 8-MOP in the same conditions. The new compounds do not show any skin phototoxicity on guinea pig skin. On the basis of its DNA photobinding, antiproliferative activity, mutagenicity and lack of skin phototoxicity, 4,4',5'-TMAP was chosen for clinical evaluation. Clinical results obtained by topical treatment of psoriatic plaques reveal evident therapeutic effectiveness and clearing is between good and moderate, although 8-MOP, used as reference compound, is more effective.
The monofunctional furocoumarins, the 6-methylangelicins, were tested for their antiproliferative activity with various animal models and for genotoxicity in micro-organisms and in mammalian cells. The most active compound was 6,4,4'-trimethylangelicin, which showed a high antiproliferative effect and reduced genotoxicity in comparison with 8-methoxypsoralen (8-MOP). Some of these compounds were also tested clinically by topical application on 17 patients with psoriasis. They appeared to be more active than 8-MOP in clearing psoriasis without inducing skin phototoxicity. The methylangelicins also caused skin pigmentation.
The relationship between cutaneous malignant melanoma (CMM) and the colour of skin, hair and eyes, the extent of sun exposure and reaction to it, education, and the occurrence of skin neoplasms in patients and their families was evaluated in a case-control study of 103 cases of CMM and 205 control subjects hospitalized for acute conditions other than malignant or hormonal disease. A significantly higher risk was associated with fair skin as compared to dark/medium skin (RR = 4.0; 95% CI: 1.5-10.5) and positive family history for CMM (RR = 8.1; 95% CI: 1.0-200.9). CMM seemed to occur more frequently, but not significantly so, in individuals with brown or blond hair, higher education and clinically diagnosed dysplastic naevi. Outdoor occupation and heavy sun exposure in the last 20 years seemed to increase the risk of CMM in sun-exposed sites but to be negatively associated with CMM in normally unexposed sites.
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The diagnosis and removal of precursor and early lesions is the only method to improve the prognosis and survival rate in malignant melanomas of the skin since the aetiology of the disease is unknown and treatment ineffective when the neoplasm is diagnosed at an advanced stage. A campaign for the prevention and early diagnosis of melanoma is based on the health education of the entire population with the distribution of illustrative material that by teaching people to examine their skin will show up suspicious pigmentary lesions that can be examined and removed by the dermatologist. Thin melanoma is always curable when removed and constitutes the basic tumour to be described to the public as it is easily identified and has constant, typical features. Among the precursors the most interesting lesions is the sporadic or familial dysplastic nevus despite the controversy over its pathogenic significance and morphological aspect. The other pigmentary neoplasias (congenital and acquired nevus) only must to be removed when they present changes resembling thin melanoma.
The authors report the results obtained treating 39 subjects affected from psoriasis with hydropinic therapy and thermal balneo-therapy, using the thermal water of Comano. At the end of the treatment the results were rather bad with an inclusive reduction of 8.5% of the lesions as regards the initial data, but after 3-6 months an average per cent reduction of the lesions about 50% and in some cases quite a total regression of the psoriasis has been noted. No kind of collateral effects has been noted.
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A case of angiosarcoma involving primarily the gingiva in an 86-year-old woman is reported. The neoplasm was strongly positive for factor VIII-related antigen, negative for cytokeratins, and positive for vimentin, confirming the vascular nature of the tumor. The patient died from heart failure 1 month after surgical excision of the lesion without clinical evidence of metastasis.
Aspiration biopsy cytology is an accurate, safe, innocuous alternative to excisional biopsy in diagnosing the nature of concomitant superficial nodules or lymphadenopathy in patients with known cutaneous malignancy. In patients with penile cancer, aspiration biopsy cytology may avoid the morbidity (30-50%) and mortality (3%) of groin dissection staging. A positive aspirate is conclusive of Stage III tumor and, in patients with occult nodal metastases, may lead to early curative lymphadenectomy. In the present study of 28 patients with known cutaneous malignant melanoma, the aspiration biopsy cytology of 31 superficial nodules resulted in a cytologic diagnosis of metastasis in 29 nodules from 26 patients. In the management of patients with known melanoma, the positive cytology of superficial nodules is conclusive of metastatic disease and requires an accurate radiologic study to establish or exclude disseminated disease. Surgical removal of a metastatic superficial nodule is indicated when the lesion is considered localized disease and the patient, having been accurately examined, is determined to be apparently free of disease in other sites and organs. When systemic diffuse melanoma is found, the excision of metastatic superficial nodules is unnecessary. Positive aspiration cytology may avoid risk from ill-judged surgical procedures and indicate appropriate palliative treatment of the disease.
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Four patients with keratoacanthomas 2 to 3 cm in size were treated with etretinate. All the patients demonstrated early response and complete regression of the lesions. Follow-up (of 24 months in one case) did not reveal any recurrence.
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Large geographic and ethnic variations in incidence and mortality rates of cutaneous malignant melanoma (CMM) suggest inverse correlations with the degree of skin pigmentation and latitude. Increases in CMM incidence and mortality rates have occurred in virtually all white populations, more markedly in those that permanently (immigrants) or temporarily (tourists/vacationers) reside in very sunny areas outside their primitive living environment. The interpretation of data from case-control studies is, however, hampered by the difficulties in quantifying retrospectively, but reliably, CMM risk correlates (e.g., host factors, sun exposure, clothing habits, sunburns) in various periods during the life span. There is, thus, a need for large prospective studies on the development of CMM and naevi, ideally in different contexts as concerns host factors, sun exposure, and other life-style habits within and across different populations.