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I Fonseca

Publications and source records attributed to I Fonseca.

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

Laminin and collagen IV in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: an immunohistochemical study.

Laminin and collagen have been studied in several tumor types and their immunomorphological expression correlated with tumor morphogenesis, local invasiveness, and metastatic behavior. In a series of 53 cases of pleomorphic adenomas (PA) and 16 cases of carcinomas ex-pleomorphic adenoma (Ca ex-PA), we investigated by immunohistochemistry the distribution pattern of laminin (lam) and collagen IV (col IV) at the basement membrane (BM) and the interstitial compartments, and their potential relationship with the metastatic behavior of Ca ex-PA. At the BM compartment, lam and col IV were expressed in 37 and 41 of all cases, respectively. In PA, there were lam and col IV around cell aggregates in 47.2% and 56.6% of the cases, respectively, and around isolated cells in 30.2% and 26.4%, respectively. In Ca ex-PA cases, both antigens were expressed in 56.3% and in 18.8% of the cases around cell aggregates and isolated cells, respectively. At the interstitial compartment, the fibro-hyaline matrix contained few lam in PA (19.2%) in contrast to Ca ex-PA (75%), including the benign areas of the neoplasms (90%), being the difference statistically significant (P < .001). In the Ca ex-PA group, a statistically significant difference was found on col IV deposits around tumor cell aggregates between metastasizing and nonmetastasizing neoplasms (P < .001). These findings support that laminin and collagen IV are involved in the process of malignant transformation of pleomorphic adenomas and their biological progression.

Adenoma, Pleomorphic↗
PubMed1998

A refined localization of two deleted regions in chromosome 6q associated with salivary gland carcinomas.

Deletions within chromosome 6 (6q25 to 6qter) are the most consistent structural change observed in salivary gland carcinomas. To better define the location of these deletions we investigated loss of heterozygosity (LOH) for 23 polymorphic markers within 19 salivary gland carcinomas covering several histological subtypes. LOH was observed in 47% of tumors, confirming previous reports that such losses are frequent and occur in almost all histological subtypes of tumors. The highest frequency of LOH was found at, or distal to, D6S437. Seven tumors had allelic losses for D6S297 and/or D6S37. A second peak of loss was also observed at D6S262 and D6S32. In some tumors we observed LOH in one or the other of these two regions. In other tumors we observed loss of both regions with retention of intervening loci. These data suggest that two small deletions commonly occur, one between D6S262 and D6S32 (estimated to cover less than 1.5 Mb) and another between D6S297 and D6S446 (estimated to cover approximately 2 Mb). These results extend previous studies by sublocalizing the regions of LOH and suggest that inactivation of one or more tumor suppressor genes located in these regions may be an important step in salivary gland carcinogenesis.

Blotting, Southern↗
PubMed1997

Cell proliferation in salivary gland adenocarcinomas with myoepithelial participation. A study of 78 cases.

We used three markers of cell proliferation mitotic counts, mitotic index and expression of proliferating cell nuclear antigen--to assess the proliferative activity of a series of 78 low-grade salivary adenocarcinomas with myoepithelial participation classified according to: their histological type, the predominant architectural type, and the predominant cytological type. The series included adenoid cystic carcinomas (40), epithelial-myoepithelial carcinomas (19), polymorphous low-grade adenocarcinomas (12) and basal cell adenocarcinomas (7). The proliferation indicators were found to be similar in the first three groups, being significantly lower than in the last. Tumours formed by basal cells had statistically significant higher mitotic indexes than those predominantly composed of clear cells of myoepithelial type and ductal cells. Tubular tumours, irrespective of the histological classification of the neoplasm, had proliferation indexes similar to those found in cribriform neoplasms. Solid tumours, whether formed by ductal or clear myoepithelial-type cells, had higher indexes than the neoplasms with differentiated (cribriform and tubular) patterns. The highest mean values for every proliferation indicator used were found in tumours with solid organization that were predominantly formed by basal cells. These results agree with the hypothesis that cell proliferation is inversely related to neoplastic differentiation. The identification of the prevalent cell phenotype and architecture may extend our knowledge from adenoid cystic carcinoma, whose solid variant carries a worse prognosis, and supports that the usual classification of this group of salivary adenocarcinomas would benefit to be complemented with information on tumour architecture and cellular composition.

Adenocarcinoma↗
PubMed1997

Cytogenetic characterisation of Warthin's tumour.

Warthin's tumour is a peculiar subtype of monomorphic adenomas of the salivary glands, frequently cystic, and that characteristically associates an epithelial glandular cell component to a dense lymphoid infiltrate. Short-term cultures from 12 Warthin's tumours of salivary glands, including 5 previously reported cases were successfully karyotyped and clonal numerical and/or structural changes were detected in 7 of them (58%). 3 cases showed numerical abnormalities with loss of chromosomes Y (2 cases) and X (1 case). The remaining 4 abnormal cases presented the following structural changes: complex translocation t(11;19;16)(q21;p12;p13.3); reciprocal translocations t(6;8)(p23;q22) and t(6;15)(p21;q15) (2 cases); and 1p22, 3p26, 11p13 changes. In 1 case, clonal numerical deviations (+ 7 and -Y) were concurrent with the structural rearrangement t(6;8). Two of these aberrations are suggested to be Warthin's tumour-associated: 11q;19p translocation has already been described in 3 cases, and structural rearrangements of 6p23 have also been reported in another case. Our study extends the cytogenetic information about Warthin's tumour and identifies two recurrent abnormalities --6p rearrangements and t(11;19)--specific for this salivary neoplasm.

Adenolymphoma↗
PubMed1997

Therapy of post-renal transplantation hyperlipidaemia: comparative study with simvastatin and fish oil.

BACKGROUND: Recipients of renal transplantation (RT) exhibit disturbances of serum lipids and apoproteins that may contribute to their cardiovascular morbidity and mortality. In our renal transplant department the hypercholesterolaemia prevalence at the first and fifth year of RT is 70.0% and 81.2%, respectively. Lipid-lowering therapy has been utilized in many Transplant Units. The aim of our study was to evaluate post-RT hyperlipidaemia control with simvastatin or fish oil. METHODS: Forty-three RT patients (26 men and 17 women) with persistent hypercholesterolaemia and stable graft function which were resistant to a lipid-lowering diet (American Heart Association Step Two) were randomized into two groups and treated for 3 months with simvastatin (S) (10mg/day; n = 25) and fish oil (F) (6 g/day; n = 18). Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), lipoprotein a (Lp(a)), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were monitored and at the study baseline they were similar between the two groups. RESULTS: No side effects were detected after 3 months of therapy. In group S, the concentrations of TC (271 +/- 46 mg% vs 228 +/- 49 mg%; P < 0.001), TG (180 +/- 78 vs 134 +/- 45; P < 0.01), LDL-C (177 +/- 40 vs 144 +/- 43; P < 0.01) and Apo B (96 +/- 18 vs 82 +/- 16; P < 0.001) were significantly reduced, and Apo A1 concentration had increased (135 +/- 24 vs 149 +/- 30; P < 0.01). In group F, the concentrations of TC (266 +/- 25 vs 240 +/- 31; P < 0.001), TG (203 +/- 105 vs 156 +/- 72; P = 0.02) and HDL-C (63 +/- 15 vs 53 +/- 12; P < 0.01) were significantly reduced. CONCLUSIONS: We concluded that low-dose simvastatin and fish oil are both effective and safe in correcting post-RT hyperlipidaemia. Further prospective studies with larger follow-up are needed to clarify whether this therapy has an impact on cardiovascular morbidity and mortality in RT patients.

Adult↗
PubMed1997

Immunoexpression of c-erbB-2 and p53 in benign and malignant salivary neoplasms with myoepithelial differentiation.

AIM: To evaluate whether the immunoexpression of c-erbB-2 and p53 is involved in the pathogenesis and progression of salivary tumours with myoepithelial differentiation. METHODS: 233 tumours from 211 patients were studied. These included 76 primary and 24 recurrent adenocarcinomas (polymorphous low grade adenocarcinoma, 13; epithelial-myoepithelial carcinoma, 19; adenoid cystic carcinoma, 56; and basal cell adenocarcinoma, 12) and 133 pleomorphic adenomas and myoepitheliomas, 96 being primary and the remaining recurrent tumours. All cases were formalin fixed and paraffin wax embedded. A StrepABC peroxidase method and polyclonal c-erbB-2 and p53 specific antisera were used. RESULTS: Cell membrane staining of c-erbB-2 was not found in any benign or malignant tumour. There was p53 protein accumulation in one primary and one recurrent pleomorphic adenoma and in 10 adenocarcinomas (polymorphous low grade adenocarcinoma, one; epithelial-myoepithelial carcinoma, one; adenoid cystic carcinoma, five; and basal cell adenocarcinoma, three), three of them being recurrences. CONCLUSIONS: The c-erbB-2 and p53 proteins are not involved in the pathogenesis of pleomorphic adenoma and myoepithelioma and do not constitute biomarkers in assessing the risk of recurrence. c-erbB-2 is not involved in the genesis of low grade salivary neoplasia with myoepithelial differentiation. The percentage of this type of neoplasia with p53 accumulation is low (10%) and does not appear to be related to tumour recurrence.

Adenocarcinoma↗
PubMed1996

Malignant salivary gland neoplasms: a cytogenetic study of 19 cases.

A group of 19 malignant salivary gland neoplasms of various histological types (mucoepidermoid carcinoma, acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, myoepithelial carcinoma, basal cell adenocarcinoma, carcinoma ex-pleomorphic adenoma, ductal carcinoma, adenocarcinoma not otherwise specified and undifferentiated carcinoma) were cytogenetically investigated. Previous karyotypic information revealed deletion of the long arm of chromosome 6, loss of chromosome Y and the gain of chromosome 8 as the most recurrent deviations found in these neoplasms. Clonal chromosome aberrations were detected in 11 cases of this series. In 7 of them there were only numerical deviations (gain of chromosomes 2, 7, 8, 10 and X and loss of chromosomes 18, 21 and Y) without concomitant structural anomalies. Structural rearrangements such as t(2;7), t(6;16), t(6;9) and t(1;1) translocations were found in two mucoepidermoid carcinomas, one adenoid cystic carcinoma and one ductal carcinoma, respectively. The wide spectrum of changes found in this group of neoplasms may reflect the diversity in their histogenesis and differentiation phenotypes.

Adolescent↗
PubMed1996

Prognostic significance of biomarkers (c-erbB-2, p53, proliferating cell nuclear antigen, and DNA content) in salivary duct carcinoma.

Salivary duct carcinoma (SDC), a rare neoplasm of the major salivary glands, is a high-grade carcinoma with a predilection for elderly men. The authors investigated the prognostic role of p53, c-erbB2, proliferating cell nuclear antigen (PCNA), and DNA flow cytometry in a pathobiological evaluation of a cohort of 30 patients with these neoplasms. The patient group comprised 24 men and 6 women, with ages ranging from 22 to 87 years (mean = 61 years). Twenty-eight tumors were located in the parotid gland and two in the submandibular gland. Tumor size ranged from 1.0 to 8.0 cm (mean = 3.48 cm). Regional metastases were found in 73.3% (22 patients), systemic metastases in 43.3% (13 patients), and recurrences in 8 (26.6%) patients. DNA aneuploidy was found in 18 tumors (58.0%) and DNA diploidy in 12 (42%), with proliferative fractions ranging from 8.60% to 15.5 (mean = 10.6%). p53 protein nuclear immunostaining was positive in 56.6% and c-erbB2 overexpression was observed in 63% of the tumors. PCNA positivity ranged from 16.5% to 91.0%, with a mean of 49.5%. p53 immunopositivity, DNA aneuploidy, high growth, and proliferative fractions by PCNA and flow cytometry did not correlate with patient outcome. These results indicate that tumor size (P = .05), distant metastasis (P = .006), and C-erbB2 amplification (P = .04) are independent prognostic parameters in patients with salivary duct carcinoma.

Adult↗
PubMed1996

Immunohistochemical study of c-erbB-2 expression in carcinoma ex-pleomorphic adenoma.

A series of 19 cases of carcinoma ex-pleomorphic adenoma was studied for the immuno-expression of c-erbB-2 oncoprotein. Twelve tumours showed a malignant component with only one histological type; in the remaining seven there was co-existence of areas of various carcinoma types, adenocarcinoma NOS being the most frequent. Membranous c-erbB-2 reactivity was found in 21.1% of the cases, all corresponding to high-grade adenocarcinomatous areas. The low-grade carcinoma types that formed the malignant mixed tumours components were negative. Benign pleomorphic adenoma areas, either adjacent or intermingled with carcinomatous areas, were also consistently negative, proving that c-erbB-2 accumulation is associated with the acquisition of the malignant phenotype. The finding of a preferential association between c-erbB-2 overexpression and high-grade malignant mixed tumour may indicate prognostic implications for the oncogene protein and may also be indicative of its specific relationship with the putative pathway of malignant transformation in pleomorphic adenomas.

Adenocarcinoma↗
PubMed1996

Basal cell adenocarcinoma of minor salivary and seromucous glands of the head and neck region.

Basal cell adenocarcinoma of salivary glands is an uncommon and recently described entity occurring almost exclusively at the major salivary glands. This report provides an overview of the clinicopathologic profile of this neoplasm by including the personal experience on the clinical features, microscopic and ultrastructural characteristics, proliferation activity, and DNA tumor patterns of 12 lesions occurring at the minor salivary glands of the head and neck region, where basal cell adenocarcinoma is probably an underecognized entity, previously reported under different designations. Basal cell adenocarcinoma predominates at the seventh decade without sex preference. The tumors affecting the minor salivary glands occur most frequently at the oral cavity (jugal mucosa, palate) and the upper respiratory tract. The prevalent histologic tumor pattern is represented by solid neoplastic aggregates with a peripheral cell palisading arrangement frequently delineated by basement membrane-like material. The neoplastic clusters are formed by two cell populations: the small dark cell type (that predominates) and a large cell type. Necrosis, either of the comedo or the apoptotic type, is a frequent finding. Perineural growth occurs in 50% of the cases and vascular permeation in 25%. Immunohistochemistry identifies a dual differentiation with a reactivity pattern indicative of ductal epithelial and myoepithelial differentiation, which can be confirmed by electron microscopy. The differential diagnosis of the neoplasm includes its benign counterpart, the basal cell adenoma, solid variant of adenoid cystic carcinoma, undifferentiated carcinoma, and basaloid squamous carcinoma. The tumors recur more frequently than lesions originating in major salivary glands. Mortality is associated with the anatomic site of the lesion, advanced stage, residual neoplasia at surgery, and tumor recurrence. The importance of recognizing basal cell adenocarcinoma outside major salivary glands is related to the clinical behavior of the neoplasm that seems to be less indolent than that of tumors arising in major salivary glands.

Adenocarcinoma↗
PubMed1995

Synthesis, structure, and pharmacological evaluation of the stereoisomers of furnidipine.

The synthesis and pharmacological activities of the four stereoisomers of methyl tetrahydrofuran-2-ylmethyl 2,6-dimethyl-4-(2'-nitrophenyl)-1,4-dihydropyridine-3,5- dicarboxylate(furnidipine) are reported. The four isomers were synthesized by a modified Hantzsch synthesis by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 3-aminocrotonate and methyl 2-[(2'-nitrophenyl)methylene]acetoacetate or, alternatively, by reaction of (-)- or (+)-tetrahydrofuran-2-ylmethyl 2-[(2'-nitrophenyl)methylene]acetoacetate and methyl 3-aminocrotonate. The 1:1 diastereomeric mixtures thus obtained were separated by chromatography, using poly(D-phenylglycine) as the chiral stationary phase. The enantiomeric purity of the stereoisomers was determined by a high-performance liquid chromatography-chiral stationary phase technique (HPLC-CSP). Attempts to obtain crystals of a single stereoisomer failed in different solvents, while methanol crystallization of the product obtained from (+/-)-tetrahydrofuran-2-ylmethyl 2-[(2'-nitrophenyl)methylene]acetoacetate and methyl 3-aminocrotonate yielded good-quality crystals of the most insoluble racemate which proved to be a mixture of the (SS)/(RR) enantiomers by X-ray crystallography. Conformational analysis of the stereoisomers, assuming rotation of the aryl substituent and ester groups, shows small energy differences (about 4 kcal.mol-1) between the most and the least favorable conformations. Binding studies were performed using [3H]isradipine as a reference ligand. The results showed stereospecificity of the furnidipine isomers in brain, ileum, and cardiac tissues, the (SS)- and (SR)-isomers clearly being more potent than their (RR)- and (RS)-enantiomers. The (SS)- and (SR)-isomers were also more selective on cerebral tissue when compared with ileal and cardiac preparations.

Animals↗
PubMed1995

Synthesis and structural, conformational, biochemical, and pharmacological study of new compounds derived from tropane-3-spiro-4'(5')-imidazoline as potential 5-HT3 receptor antagonists.

A series of tropane-3-spiro-4'(5')-imidazolines was synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 2'-(1H-indol-3-yl)tropane-3-spiro-4'(5')-imidazoline hydrochloride 5(6)f was determined by X-ray diffraction. In CD3OD solution, compounds 5(6)a-f display the same preferred conformation. The pyrrolidine and piperidine rings adopt an envelope conformation flattened at N8 and a distorted chair conformation puckered at N8 and flattened at C3, respectively, with the N-substituent in the equatorial position with respect to the piperidine ring. This conformation is similar to that observed for compound 5(6)f in the solid state. From binding studies on the compounds synthesized, compound 5(6)d demonstrated the ability to efficiently displace the binding of [3H]GR65630 to bovine brain area postrema membranes to an extent comparable to MDL 72222. In the von Bezold-Jarisch reflex, compound 5(6)d was equipotent with metoclopramide. It is, therefore, likely that the imidazoline ring may provide a useful bioisosteric replacement for the carbonyl group in 5-HT3 antagonists.

Animals↗
PubMed1995

Benign salivary gland tumors: a cytogenetic study of 21 cases.

Cytogenic findings of 21 benign salivary gland tumors, including 14 pleomorphic adenomas, 5 Warthin's tumors, 1 myoepithelioma, and 1 cystadenoma, are reported. The present study confirms that pleomorphic adenomas characteristically have highly specific rearrangements involving only a few chromosome regions (3p21, 8q12 and 12q13-15) which suggests their specific role in the mixed tumor genesis. Warthin's tumors also show non-random numerical and structural alterations that were concurrent in one of the cases studied. To our knowledge no cytogenetic data are available in myoepitheliomas and cystadenomas. The former reveals a normal karyotype and the latter shows only clonal numerical alterations (gain of chromosomes 2 and 18).

Adenolymphoma↗
PubMed1994

Simple mucin-type carbohydrate antigens (T, Tn and sialosyl-Tn) in mucoepidermoid carcinoma of the salivary glands.

Thirty-two cases of mucoepidermoid carcinoma of the salivary glands were studied in order to characterize the expression of simple mucin-type carbohydrate antigens T, Tn and sialosyl-Tn and to evaluate its implication for tumour histogenesis. Monoclonal antibodies of known specificity were used on formalin-fixed, paraffin-embedded tissue, and the expression of these antigens was studied in each of the three cell types (mucous, intermediate and squamous) as well as in the secretory content of neoplastic lumina. Aberrant glycosylation of simple-mucin type antigens was found in all cell types, as compared with that of normal excretory duct cells of the salivary glands. The more 'primitive' antigens Tn and sialosyl-Tn were present in a high percentage of epidermoid and intermediate cells. Mucous cells and the intraluminal secretory content also expressed Tn in 57.7% of the cases. This contrasts with the absence of secretion of these simple mucin type carbohydrates by normal salivary gland cells. Mucin-producing cells did not express T antigen but only sialosyl-T, in contrast to 57.1% and 56.3% respectively of the epidermoid and intermediate cell types. T and sialosyl-T were also found in the secretory products of the neoplastic lumina in 11.5% and 53.6% of the cases, respectively. The distinctive glycosylation pattern between mucin-producing cells on the one hand and intermediate and squamous cells on the other does not contradict the common origin of the three cell types from the reserve cell of the salivary excretory duct, but favours the proposition that intermediate cells constitute a step in the differentiation pathway of epidermoid, but not of mucin-producing, cells.

Adolescent↗
PubMed1993

Synthesis and structural, biochemical, and pharmacological study of 3 beta-acyloxy-3 alpha-methoxycarbonyltropane derivatives.

A series of 3 beta-acyloxy-3 alpha-methoxycarbonyltropanes were synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of 3 alpha-methoxycarbonyl-3 beta-pyridincarbonyloxytropane (5d) was determined by X-ray diffraction. In CDCl3 solution, compounds 5a-f display the same preferred conformation. The pyrrolidine and piperidine rings adopt an envelope conformation flattened at N-8 and a distorted chair conformation puckered at N-8 and flattened at C3, respectively, with the N-substituent in the equatorial position with respect to the piperidine ring. The pharmacological profile of one of these compounds makes it an adequate candidate for the design of novel GABAB antagonist agents.

Animals↗