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Biomedical subjects

X Matias-Guiu

Publications and source records attributed to X Matias-Guiu.

At least 19 recordsLinked to original sources
PubMed2005

Tumour necrosis factor alpha in fat redistribution syndromes associated with combination antiretroviral therapy in HIV-1-infected patients: potential role in subcutaneous adipocyte apoptosis.

BACKGROUND: The pathogenesis of fat redistribution syndromes (FRS) observed in the setting of highly active antiretroviral therapy (HAART) for the treatment of HIV-1-infection remains elusive. A dysregulation of the tumour necrosis factor alpha (TNF-alpha) system occurs in HIV-infected patients with FRS. MATERIALS AND METHODS: The study looked at both the in vivo and in vitro relationship between TNF-alpha and the degree of subcutaneous adipocyte apoptosis in 60 HIV-1-infected patients on HAART with FRS, another 60 HIV-1-infected patients on HAART without FRS and 60 uninfected control patients. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP (deoxyuridine 5'-triphosphate)-digoxigenin Nick End Labelling (TUNEL) method. Soluble receptors of TNF-alpha were determined by the sandwich enzyme immunoassay technique. The in vitro viability was assessed by staining with 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and apoptosis by TUNEL. RESULTS: HIV-1-infected patients with FRS had significantly higher degrees of subcutaneous adipocyte apoptosis than those without FRS (P = 0.0001) and uninfected controls (P < 0.0001). There was a statistically significant association between serum levels of soluble TNF-alpha receptors #1 and #2 and the degree of subcutaneous adipocyte apoptosis in patients with and without FRS (P < 0.0001 for both receptors). In vitro, the addition of TNF-alpha (10 ng mL(-1)) to an adipocyte culture embedded with indinavir, either alone or in clinically relevant combinations with stavudine (d4T) and lamivudine (3TC), significantly decreased adipocyte viability (P = 0.0001) and increased adipocyte apoptosis (P < 0.0001) with respect to that observed with the addition of antiretrovirals alone. CONCLUSIONS: TNF-alpha plays a significant role in subcutaneous adipocyte apoptosis, which occurs in the setting of FRS in HIV-1-infected patients on highly active antiretroviral therapy.

3T3 Cells↗
PubMed2004

Kikuchi's disease (necrotizing lymphadenitis) with cutaneous involvement associated with subacute cutaneous lupus erythematosus.

Necrotizing histiocytic lymphadenopathy (Kikuchi's disease) is a rarely observed clinical entity characterized by fever, and solitary or multiple lymphadenopathy predominantly in the posterior cervical region. Kikuchi's disease has been reported to precede, coexist with or follow the diagnosis of systemic lupus erythematosus. In only rare instances has its association with cutaneous lupus erythematosus without systemic involvement been reported. We report a 45-year-old woman who presented characteristic systemic and cutaneous manifestations of Kikuchi's disease. Several months later, after sun exposure, she developed lesions of subacute cutaneous lupus erythematosus. The American Rheumatism Association criteria for systemic lupus erythematosus were not fulfilled. The possible pathogenic relationships between the two processes are discussed.

Female↗
PubMed2001

Microsatellite instability, MLH-1 promoter hypermethylation, and frameshift mutations at coding mononucleotide repeat microsatellites in ovarian tumors.

BACKGROUND: Microsatellite instability (MI) is frequent in endometrial carcinomas (ECs), but its occurrence in ovarian tumors is uncertain. Microsatellite instability positive ECs frequently are associated with frameshift mutations in coding mononucleotide tracts in IGFIIR, BAX, hMSH6, and hMSH3. METHODS: DNA from 52 consecutive patients with ovarian tumors (10 benign, 7 borderline, and 35 malignant) was obtained from neoplastic and normal tissue. After preliminary results, the series was expanded by including 41 additional, previously selected, endometrioid and clear cell carcinomas. Microsatellite instability analysis was assessed by evaluating three (CA)n dinucleotide repeats (D2S123, D5S346, D17S250) and two mononucleotide tracts (BAT 25 and BAT 26). Frameshift mutations at coding mononucleotide repeats (IGFIIR, TGF beta II, BAX, hMSH6, and hMSH3) were investigated by single-strand conformation polymorphism analysis and DNA sequencing. MLH-1 methylation was assessed by methylation specific PCR. RESULTS: Microsatellite instability was identified in only 2 of the 52 (3.8%) tumors of the initial series (1 endometrioid and 1 clear cell carcinoma). After expanding the initial series of 15 endometrioid and clear cell carcinomas with 41 additional endometrioid and clear cell carcinomas, MI was found in 7 of the total series of 56 endometrioid and clear cell carcinomas (12.5%). Frameshift mutations in coding mononucleotide tracts were detected in BAX (6 of 7), IGFIIR (1 of 7), and MSH3 (2 of 7). MLH-1 promoter hypermethylation was identified in three of six MI positive tumors. CONCLUSIONS: Microsatellite instability was infrequent in this series of ovarian tumors, and it was limited to endometrioid and clear cell carcinomas. Like EC, many ovarian carcinomas with MI follow the same process of MLH-1 promoter methylation and accumulation of mutations in coding mononucleotide tracts.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Microglandular adenosis of the breast in a BRCA1 mutation carrier: radiological features.

Microglandular adenosis is a very uncommon benign proliferative disorder of the breast that may mimic tubular carcinoma radiologically and pathologically. We describe the radiological features of this rare condition in a patient with BRCA 1 mutation. To our knowledge, this is the first case of microglandular adenosis reported in the radiology literature. The relationship between microglandular adenosis and malignancy and the association between BRCA 1 and proliferative benign disorders are also discussed.

Adult↗
PubMed2001

Loss of heterozygosity on chromosome 13q12-q14, BRCA-2 mutations and lack of BRCA-2 promoter hypermethylation in sporadic epithelial ovarian tumors.

BACKGROUND: BRCA-1 and BRCA-2 are tumor suppressor genes in familial breast-ovarian carcinoma syndrome. BRCA-1 is also a tumor suppressor gene in sporadic ovarian carcinomas. However, the role of BRCA-2 in sporadic ovarian tumors remains unclear. METHODS: DNA from 52 patients with clinically apparent sporadic ovarian tumors was extracted from blood and from fresh-frozen tumor tissue and normal tissue (10 benign, 7 borderline, and 35 malignant). Loss of heterozygosity (LOH) was analyzed in six microsatellite loci on chromosome 13q. BRCA-2 mutations were detected by single-strand conformation polymorphism analysis and the protein truncation test. BRCA-2 promoter methylation was evaluated by methylation specific polymerase chain reaction analysis. RESULTS: LOH on chromosome 13q12-q14 was identified in 16 tumors (30.8%): Fifteen of these tumors were carcinomas (15 of 35 tumors; 42.8%) and one was a borderline tumor. LOH was frequent in carcinomas with serous differentiation (12 of 16 tumors; 75%). LOH on chromosome 13q12-q14 coexisted with LOH on chromosome 17q in 10 carcinomas. BRCA-2 methylation was not detected in any tumor. BRCA-2 mutations were found in three tumors (one somatic nonsense and two germline frameshift). BRCA-2 fulfilled the two hits for a tumor suppressor gene in these three tumors; in one of them, a BRCA-1 tumor suppressor role had been demonstrated previously. CONCLUSIONS: The results suggest that BRCA-1 and BRCA-2 may act synergically in sporadic ovarian carcinomas with serous differentiation. The demonstration of BRCA-2 germline mutations in patients with ovarian carcinoma with LOH on chromosome 13q12-q14 and lack of a remarkable family history of cancer suggest that the proportion of ovarian carcinomas that result from hereditary predisposition may be higher than previously estimated.

BRCA2 Protein↗
PubMed2001

p14ARF silencing by promoter hypermethylation mediates abnormal intracellular localization of MDM2.

The INK4a/ARF locus encodes two distinct tumor suppressors, p16INK4a and p14ARF. Although the contribution of p16INK4a to human tumorigenesis through point mutation, deletion, and hypermethylation has been widely documented, little is known about specific p14ARF lesions and their consequences. Recent data indicate that p14ARF suffers inactivation by promoter hypermethylation in colorectal cancer cells. Because it is known that p14ARF prevents MDM2 nucleocytoplasmic shuttling and thus stabilizes p53 by attenuating MDM2-mediated degradation, we studied the relationship of p14ARF epigenetic silencing to the expression and localization of MDM2 and p53. Cancer cell lines with an unmethylated p14ARF promoter showed strong nuclear expression of MDM2, whereas in a colorectal cell line with p14ARF hypermethylation-associated inactivation, MDM2 protein was also seen in the cytosol. Treatment with the demethylating agent 5-aza-2'-deoxycytidine was able to reinternalize MDM2 to the nucleus, and p53 expression was restored. No apparent changes in retinoblastoma localization were observed. We also studied the profile of p14ARF promoter hypermethylation in an extensive collection of 559 human primary tumors of different cell types, observing that in colorectal, gastric, renal, esophageal, and endometrial neoplasms and gliomas, aberrant methylation of p14ARF was a relatively common epigenetic event. MDM2 expression patterns revealed that lack of p14ARF promoter hypermethylation was associated with tumors showing exclusive nuclear MDM2 staining, whereas MDM2 cytosolic staining was frequently observed in neoplasms with aberrant p14ARF methylation. Taken together, these data support that epigenetic silencing of p14ARF by promoter hypermethylation is a key mechanism in the disturbance of the MDM2 nuclear localization in human cancer.

DNA Methylation↗
PubMed2001

Postirradiation multiple minute digitate porokeratosis.

BACKGROUND: Development of multiple minute digitate hyperkeratoses (MMDH) after irradiation has been reported previously. The keratotic lesions in these cases were confined within the irradiation field, and histopathological examination disclosed a focal column of parakeratosis (cornoid lamella) arising from an epidermis devoid of granular layer. OBJECTIVE: We describe a 78-year-old woman who developed multiple, discrete, tiny, filiform, keratotic papules on the anterior aspect of the right chest wall, 13 months after postmastectomy cobalt irradiation therapy for mammary infiltrating ductal carcinoma. CONCLUSION: Postirradiation MMDH represents a peculiar radiation-induced disorder that we believe should be distinguished from other cases of MMDH and included within the spectrum of porokeratosis.

Aged↗
PubMed2001

K-ras mutations in endometrial carcinomas with microsatellite instability.

K-ras mutations are known to occur in hyperplasias and carcinomas of the endometrium. No clear correlation has been found yet between K-ras mutations and microsatellite instability (MI) in these lesions. Fifty-eight endometrial carcinomas (ECs) and 22 endometrial hyperplasias (EHs) were analysed for K-ras mutation by single-strand conformational polymorphism analysis (SSCP), restriction analysis, and DNA sequencing. MI status had been established previously at five dinucleotide loci and was reconfirmed with markers BAT-25 and BAT-26 by SSCP. K-ras mutations were detected in 11 ECs (18.9%). All 11 tumours were endometrioid carcinomas. K-ras mutations were more frequent in MI-positive (6/14, 42.8%) than in MI-negative tumours (5/44, 11.3%) (p=0.017). Methylation-related transitions were detected in five of the six MI-positive tumours but in only one of the five MI-negative carcinomas. K-ras mutation was identified in only one atypical EH (1/22, 4.5%); in this case, the EH co-existed with EC and both lesions exhibited MI. The results support a close relationship between K-ras mutations and the phenomenon of MI in endometrial carcinomas. The frequent occurrence of methylation-related transitions in these tumours may indicate a cause-effect relationship with the altered methylation status which has been described in association with MI.

Carcinoma↗
PubMed2001

Abnormalities of the E-cadherin/catenin adhesion complex in classical papillary thyroid carcinoma and in its diffuse sclerosing variant.

The cadherin/catenin complex regulates cellular adhesion and motility and is believed to function as an invasion suppressor system. Several studies have identified alterations in the expression profiles of those molecules in different histotypes of thyroid carcinoma. The diffuse sclerosing variant (DSV) of papillary thyroid carcinoma (PTC) is a rare, highly invasive variant of PTC in which an impairment of cell-cell adhesion may play a major role. In an attempt to progress in the understanding of the clinicopathological features of DSV, this study examined eight cases of DSV, 18 cases of classical PTC and a control group of normal thyroid by immunohistochemistry (E-, P- and N-cadherins and beta-, gamma- and alpha-catenins). The E-cadherin gene was also studied by polymerase chain reaction/single strand conformation polymorphism (PCR/SSCP) and methylation-specific PCR (MSP). In contrast to classical PTC, which showed heterogeneous loss of E-cadherin expression, in almost every case of DSV a pronounced reduction was observed in its membranous expression, accompanied by a relocation to the cytoplasm. Inactivation of the E-cadherin/catenin complex appears to occur in DSV via two different pathways: E-cadherin alteration either through mutation (one out of the eight cases) or through methylation of the E-cadherin gene promoter (three out of five cases); and beta- and/or gamma-catenin alterations (three of the eight cases). Methylation of the E-cadherin gene promoter, abnormalities of E-cadherin expression and alterations of gamma-catenin were also detected in classical PTC. In DSV, as in classical PTC, there is neo-expression of P-cadherin in areas of squamous metaplasia and no N-cadherin expression. In conclusion, abnormalities of the E-cadherin/catenin complex appear to be more pronounced in DSV than in classical PTC. It remains to be shown whether or not such differences are associated with the more aggressive behaviour of DSV compared with classical PTC.

Cadherins↗
PubMed2001

Beta- and gamma-catenin expression in endometrial carcinoma. Relationship with clinicopathological features and microsatellite instability.

The activation of the adenomatous polyposis coli (APC)/beta-catenin/T-cell factor (Tcf) pathway due to beta-catenin gene mutation has been recently implicated in the development of some endometrial carcinomas. beta- and gamma-catenin are structurally and functionally related molecules that participate in cell adhesion and signal transduction. Nuclear accumulation of beta- and gamma-catenin have been related to the activation of the APC/beta-catenin/Tcf pathway. In this study, we investigate the immunohistochemical expression pattern (nuclear vs membranous) of beta- and gamma-catenin in 40 endometrial carcinomas and their correlation with clinicopathological features and microsatellite instability (MI) status. MI was detected at three or more loci in 12 tumors: 11 were endometrioid and one was non-endometrioid. Nuclear catenin expression was found in 13 carcinomas: ten carcinomas had nuclear beta-catenin expression and three carcinomas had nuclear gamma-catenin expression. The nuclear catenin expression pattern significantly correlated with the histological type, International Federation of Gynecology and Obstetrics (FIGO) grade, and the presence of a second neoplasm. Nuclear catenin expression was always observed in low-grade endometrioid carcinomas; it was also more frequently associated with a second carcinoma. No correlation was observed between the catenin expression pattern and the level of myometrial infiltration, stage, associated endometrial hyperplasia, the existence of a source of estrogenic stimulation, and MI. However, four of 13 endometrioid carcinomas in this series had both catenin nuclear expression and MI. These data suggest that at least two different neoplastic pathways can lead to endometrial carcinomas with an endometrioid phenotype. In one, MI would be a key event, while in the other, the APC/beta-catenin/Tcf signaling pathways could be activated. Probably, in some cases, both pathways could simultaneously occur.

Carcinoma, Endometrioid↗
PubMed2001

Hypertrichosis lanuginosa acquisita preceding extraskeletal Ewing's sarcoma.

A 62-year-old woman with acquired hypertrichosis lanuginosa as a paraneoplastic presenting sign of an extraskeletal Ewing's sarcoma is described. Despite initial comprehensive screening to rule out an associated malignancy, a definitive diagnosis of sarcoma was established only 1 year after the onset of the cutaneous symptoms. To the best of our knowledge, this is the first report of hypertrichosis lanuginosa acquisita associated with a soft tissue sarcoma. Our observation expands the spectrum of malignancies associated with this uncommon paraneoplastic disorder.

Female↗
PubMed2001

Molecular pathology of endometrial hyperplasia and carcinoma.

Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas beta-catenin mutations do not seem to be associated with such a phenomenon.

Cytoskeletal Proteins↗
PubMed2001

Solitary fibrous tumor of the thyroid gland: report of seven cases.

Solitary fibrous tumor is a soft tissue neoplasm initially described in the pleura but subsequently reported in a wide variety of locations. The clinical behavior is usually benign, but the existence of aggressive cases has been documented both in the pleura and in extrapleural sites. In this report clinical and pathologic features of seven solitary fibrous tumors of the thyroid gland are presented. Patients' ages ranged from 43 to 64 years (mean 52 years), and tumor sizes varied from 2 to 6 cm. Grossly, the tumors were white-tan and well circumscribed. Microscopically, there was a variegated, wavy, storiform, hemangiopericytic or desmoid-like arrangement of spindle cells. Trapped thyroid follicles within the tumor and peripheral jagged tumor infiltration among follicles were common. There was immunohistochemical reactivity for CD34, CD99, and bcl-2, and ultrastructural analysis of one tumor was consistent with a fibroblastic lineage. The differential diagnosis included other benign and malignant mesenchymal tumors of the thyroid, spindle cell follicular adenoma, Riedel's thyroiditis, the spindle cell, and paucicellular variants of anaplastic carcinoma, papillary thyroid carcinoma with exuberant nodular fasciitis-like stroma, and the spindle epithelial tumor with thymus-like differentiation. The cumulative data of 13 cases (comprised of the seven present cases and the six previously reported) suggest a benign clinical behavior for thyroid SFT.

12E7 Antigen↗
PubMed2001

Loss of heterozygosity at the RB-1 locus and pRB immunostaining in epithelial ovarian tumors: a molecular, immunohistochemical, and clinicopathologic study.

Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia. The frequency of loss of heterozygosity (LOH) at the RB-1 locus on chromosome 13q14 was studied in a series of 51 epithelial ovarian tumors (10 benign, 7 borderline, and 34 malignant). LOH was scored by the absence or reduction of the signal to < 50% of one of the alleles in tumor DNA compared with normal DNA. LOH results were correlated with retinoblastoma protein (pRB) immunostaining. LOH at the RB-1 locus was observed in 9 tumors (17.6%), specifically in 1 of 7 borderline tumors and 8 of 34 ovarian carcinomas (23.5%). Among the malignant tumors, LOH occurred more frequently in carcinomas with serous differentiation (7/23; 30%). A heterogeneous (10% to 70% cells) or diffuse (> 70% cells) pRB immunostaining was less frequent in benign (1/10; 10%) and borderline (2/7; 28%) tumors than in ovarian carcinomas (15/34; 44%), an observation that correlated with the higher proliferative index in carcinomas than in benign and borderline tumors. However, lack or only focal (< 10% cells) pRB immunostaining occurred in the vast majority of tumors with LOH at the RB-1 locus (7/9; 77%), a finding that may suggest a tumor suppressor role for RB-1 in these tumors. The results suggest that RB-1 may play a role in a subset of ovarian carcinomas, particularly those exhibiting serous differentiation.

Adenocarcinoma, Clear Cell↗
PubMed2001

Paucicellular variant of anaplastic thyroid carcinoma: report of two cases.

The paucicellular variant of anaplastic carcinoma is an infrequent type of thyroid tumor. It was described as a tumor characterized by very low cellularity and prominent fibrosis, probably secondary to extensive infarction. These features could lead to an erroneous diagnosis of Riedel's thyroiditis. In this paper, we report the clinical and pathological features of two new cases of this unusual entity. Tumor cells were negative for thyroglobulin immunostaining and positive for keratins and p53. Although the number of reported cases is small, the cumulative data on these two cases and the previously reported ones lead us to suggest that the paucicellular variant may occur in younger patients than the conventional anaplastic thyroid carcinoma and that the tumor may be associated with a less aggressive tendency to local progression and metastasis.

Aged↗
PubMed2000

Frameshift mutations at coding mononucleotide repeat microsatellites in endometrial carcinoma with microsatellite instability.

BACKGROUND: Microsatellite instability (MI) is a frequent occurrence in endometrioid carcinoma of the endometrium (EC). Several genes known to contain mononucleotide short tracts in their coding sequences (TGF-beta RII, IGFIIR, BAX, hMSH6, and hMSH3) are likely targets for mutations in these tumors. METHODS: DNA from 24 patients with EC and MI was extracted from blood and from fresh-frozen and paraffin embedded tumor tissue. Seven of these patients were found to have metastatic spread to paraaortic lymph nodes. DNA also was studied from 10 patients with EC without MI. RESULTS: Frameshift mutations at coding mononucleotide repeats were detected by single strand conformation polymorphism analysis and DNA sequencing. Frameshift mutations were detected more frequently in BAX (11 of 24 MI positive (+) tumors; 45.8%) than in TGF-beta RII (0 of 24 tumors; 0%), IGFIIR (3 of 24 tumors; 12.5%), hMSH3 (6 of 24 tumors; 25%), or hMSH6 (0 of 24 tumors; 0%). The mutations frequently were distributed heterogeneously throughout the tumors. Overall, frameshift mutations at 1 or more of these mononucleotide repeat microsatellites were found in 17 of 24 MI+ tumors (70.8%) but in none of the 10 MI negative neoplasms. In the seven EC patients with lymph node metastases, mutations in IGFRII were found more commonly in those with metastatic (three of seven patients) rather than primary (one of seven) tumors. CONCLUSIONS: The results of the current study confirm that BAX is an important target gene in ECs with MI. The frequent detection of IGFRII frameshift mutations in lymph node metastases suggest that IGFRII may play a role in tumor progression in these patients.

Endometrial Neoplasms↗
PubMed2000

Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors.

BACKGROUND: Inherited mutations in the BRCA1 gene may be responsible for almost half of inherited breast carcinomas. However, somatic (acquired) mutations in BRCA1 have not been reported, despite frequent loss of heterozygosity (LOH or loss of one copy of the gene) at the BRCA1 locus and loss of BRCA1 protein in tumors. To address whether BRCA1 may be inactivated by pathways other than mutations in sporadic tumors, we analyzed the role of hypermethylation of the gene's promoter region. METHODS: Methylation patterns in the BRCA1 promoter were assessed in breast cancer cell lines, xenografts, and 215 primary breast and ovarian carcinomas by methylation-specific polymerase chain reaction (PCR). BRCA1 RNA expression was determined in cell lines and seven xenografts by reverse transcription-PCR. P values are two-sided. RESULTS: The BRCA1 promoter was found to be unmethylated in all normal tissues and cancer cell lines tested. However, BRCA1 promoter hypermethylation was present in two breast cancer xenografts, both of which had loss of the BRCA1 transcript. BRCA1 promoter hypermethylation was present in 11 (13%) of 84 unselected primary breast carcinomas. BRCA1 methylation was strikingly associated with the medullary (67% methylated; P =.0002 versus ductal) and mucinous (55% methylated; P =.0033 versus ductal) subtypes, which are overrepresented in BRCA1 families. In a second series of 66 ductal breast tumors informative for LOH, nine (20%) of 45 tumors with LOH had BRCA1 hypermethylation, while one (5%) of 21 without LOH was methylated (P =.15). In ovarian neoplasms, BRCA1 methylation was found only in tumors with LOH, four (31%) of 13 versus none of 18 without LOH (P =.02). The BRCA1 promoter was unmethylated in other tumor types. CONCLUSION: Silencing of the BRCA1 gene by promoter hypermethylation occurs in primary breast and ovarian carcinomas, especially in the presence of LOH and in specific histopathologic subgroups. These findings support a role for this tumor suppressor gene in sporadic breast and ovarian tumorigenesis.

Breast Neoplasms↗