PubMed Health⌕ Search

Biomedical subjects

Mireia Castillo

Publications and source records attributed to Mireia Castillo.

12 recordsLinked to original sources
PubMed2006

TNF-alpha converting enzyme (TACE) protein expression in different clinical subtypes of multiple sclerosis.

Tumor necrosis factor (TNF)-alpha converting enzyme (TACE, also called ADAM17) is a key sheddase that releases TNF-alpha from its inactive cell-bound precursor. TACE protein expression levels in peripheral blood mononuclear cells were measured by Western blot analysis in 20 healthy controls and 80 multiple sclerosis (MS) patients before and after treatment with IFNbeta [20 patients with primary progressive (PP) MS, 20 patients with secondary progressive (SP) MS, and 40 patients with relapsing- remitting (RR) MS (20 patients during clinical remission and 20 patients in relapse)]. TNF-alpha serum levels were also measured by enzyme-linked immunoassay in the MS patients and healthy controls. TACE protein expression levels were lower in healthy controls and PPMS patients compared with SPMS patients and RRMS patient during clinical remission. No differences in TACE protein levels were observed between RRMS patients in relapse and during remission. TACE protein levels were increased in PPMS patients treated with IFNbeta. Serum TNF-alpha levels were higher in RRMS patients in relapse compared with RRMS patients during remission, and positive and negative correlations were found between TACE protein expression and serum TNF-alpha levels in RRMS patients during relapse and during remission respectively. These findings point to different regulatory mechanisms of the TACE-TNF-alpha pathway in the clinical MS subtypes and expand the role of TACE in MS pathogenesis.

ADAM Proteins↗
PubMed2005

Carcinosarcoma of the prostate: two cases with distinctive morphologic and immunohistochemical findings.

Carcinosarcomas (CS) of the prostate are very uncommon neoplasms defined by the admixture of malignant epithelial and mesenchymal components. We describe here two new examples of CS in two patients aged 66 and 77 years, the first without previous history of prostate adenocarcinoma and the second with a 5-year history of acinar type prostate adenocarcinoma. The diagnosis of CS was made on the cystoprostatectomy specimen in the first case and transurethral resection in the second case. Both biphasic tumours exhibited papillary areas of ductal differentiation and conventional adenocarcinoma in the epithelial component, as well as malignant fibrous histiocytoma and angiosarcomatous areas in the first case and solid, poorly differentiated epithelial areas with neuroendocrine features in the second case. Immunohistochemistry revealed over-expression of c-erb B2 in the papillary epithelial component of both cases, whereas the solid undifferentiated epithelial areas in the second patient expressed c-kit, CD10 and synaptophysin, thus conforming a very undifferentiated cell population. The angiosarcomatous component of the first case expressed CD31 and CD10. The clinical course of the cases was divergent; the first patient is free of disease after radical surgery and adjuvant therapy and the other died 5 months after the diagnosis of CS, having already developed liver metastases.

Aged↗
PubMed2005

Plasma osteopontin levels in multiple sclerosis.

Osteopontin (OPN) is a pleiotropic integrin binding protein with functions in cell-mediated immunity, inflammation, tissue repair, and cell survival. Recent studies have shown that OPN may play an important role in the pathogenesis of experimental autoimmune encephalomyelitis and multiple sclerosis (MS). Here, we investigated the plasma levels of OPN in 221 MS patients and 36 healthy controls using an enzyme-linked immunoassay. The MS group comprised of 71 patients with primary and transitional progressive MS (PP/TP-MS), 35 patients with secondary progressive MS (SPMS), and 115 patients with relapsing-remitting MS (RRMS)[46 patients during clinical remission, 26 patients during relapse, and 43 patients treated with interferon-beta (IFNbeta)]. Levels of OPN in plasma were elevated in SPMS patients compared with healthy controls, RRMS patients in remission, and PP/TP-MS patients. Patients with RRMS during relapse presented higher OPN levels than patients with RRMS during clinical remission. When MS patients were classified based on progression of neurological disability, an inverse relation between levels of OPN and disability progression was observed only in patients with relapsing MS. In RRMS patients receiving therapy with IFNbeta, OPN plasma levels were similar to RRMS patients during remission. These findings suggest that OPN is involved in both acute and chronic disease activity, thus expanding the role of OPN in MS pathogenesis suggested by previous studies. Furthermore, the different profiles of OPN levels found in acute relapses and chronic progression and its apparent lack of influence in primary progressive MS phenotypes raise interesting questions on the actual role of OPN in the pathogenesis of MS.

Adult↗
PubMed2005

Expression of membrane-bound mucins (MUC1 and MUC4) and secreted mucins (MUC2, MUC5AC, MUC5B, MUC6 and MUC7) in mucoepidermoid carcinomas of salivary glands.

Mucins are glycoproteins normally synthesized by a variety of secretory epithelial cells. The aim of this study was to investigate the expression of mucins (MUC1, MUC2, MUC4, MUC5AC, MUCB, MUC6, MUC7) in mucoepidermoid carcinomas, the most frequent malignant tumor of salivary glands. Forty mucoepidermoid carcinomas and twenty-two normal salivary glands were studied for these mucins by immunohistochemistry from formalin-fixed and paraffin-embedded material. Normal salivary glands frequently expressed MUC1 and MUC4, mainly in ductal cells; MUC5B and MUC7 stained mucous and serous acini respectively of submandibular and minor salivary glands; and MUC5AC and MUC2 were poorly detected in excretory ducts. All mucoepidermoid carcinomas expressed MUC1, and 38/40 tumors expressed MUC4. Both membrane-bound mucins stained membranes and cytoplasm of all cell types (epidermoid, intermediate, mucous, clear and columnar). MUC5AC and MUC5B stained glandular differentiated cells in most tumors (29/40 and 33/40 cases, respectively). MUC6 was positive in 13/40 tumors, and both MUC2 and MUC7 in only 2/40 tumors. The high expression of MUC1 was related to high histologic grades, high recurrence and metastasis rates and a shorter disease-free interval (P < 0.05). Conversely, MUC4 high expression was mainly related to low-grade tumors, lower recurrence rates and a longer disease-free interval (P < 0.05). In conclusion, mucoepidermoid carcinomas of salivary glands usually express MUC1, MUC4, MUC5AC and MUC5B; less frequently MUC6; and rarely MUC2 and MUC7. This mucin expression pattern can be useful for diagnostic purposes. Therefore, MUC1 expression is related to tumor progression and worse prognosis, whereas MUC4 expression is related to a better prognosis.

Adolescent↗
PubMed2005

Paraffin-embedded cell line microarray (PECLIMA): development and validation of a high-throughput method for antigen profiling of cell lines.

The introduction of high-throughput techniques is increasingly providing abundant information on molecular alterations requiring validation at the posttranscriptional level. Protein expression is now efficiently evaluated in large series of tumors included in tissue microarrays. We propose, describe and validate a technique to elaborate paraffin-embedded cell line microarrays (PECLIMA) from fixed cell cultures, which can be processed like standard surgical pathology biopsies prior to immunophenotyping. Our results show a reliable protein immunoexpression profiling in six widely used cell lines under different fixation conditions. This technique permits the simultaneous analysis of multiple antigens in multiple cell lines under different experimental conditions. Additional features of these arrays are long-term storage, their suitability for a variety of techniques including immunocytochemistry and in situ hybridization and their low cost.

Antigens, Neoplasm↗
PubMed2004

KIT expression in chromophobe renal cell carcinoma: comparative immunohistochemical analysis of KIT expression in different renal cell neoplasms.

The overexpression of c-Kit in chromophobe renal cell carcinoma (ChRCC) has been described by comparative gene expression analyses and has been proposed as a possible specific hallmark of this neoplasm. The aim of our study was to establish its immunohistochemical expression in a large series of ChRCC and to compare it with other renal neoplasms. In our study, immunohistochemical characterization of KIT was performed in 87 renal neoplasms including 25 cases of ChRCC, 13 cases of renal oncocytoma, and 39 renal cell carcinomas (21 cases of conventional RCC [CRCC], 8 cases of CRCC with granular cell differentiation, and 10 cases of papillary RCC [PRCC]). Eighty-eight percent ChRCC and 71% oncocytomas showed immunohistochemical expression of KIT, while the other types of RCC studied were all negative. The meaning of immunohistochemical expression of KIT in ChRCC and oncocytomas is still unknown, but its immunohistochemical staining appears to be useful in distinguishing ChRCC from PRCC, CRCC, and its granular cell variant. Moreover, our findings support current models that consider that there is a histopathogenic relationship between oncocytoma and ChRCC. Finally, it should be determined whether KIT plays a role in the tumorigenesis of ChRCC and oncocytoma and whether targeted therapy with STI-571, an inhibitor of KIT, could be effective in exceptional cases of ChRCC with metastatic extension or recurrence.

Biomarkers, Tumor↗
PubMed2004

C-kit expression in sarcomatoid renal cell carcinoma: potential therapy with imatinib.

PURPOSE: Sarcomatoid (S) renal cell carcinoma (RCC) is an uncommon subtype of RCC with a poor prognosis because of its local aggressiveness and high metastatic rate. Currently, there is no specific, effective treatment for it. A relatively nontoxic tyrosine kinase inhibitor, imatinib (STI-571) has been approved as a target therapy in neoplasms that express c-Kit. We investigated c-Kit expression in this type of tumor, which to our knowledge has not been previously described. MATERIALS AND METHODS: We reviewed 215 cases of RCC diagnosed at our department from 1995 to 2002. Of the cases 20 (9.3%) were SRCC. Formalin fixed, paraffin embedded material was available in 19 cases. We performed immunohistochemical staining against c-Kit using rabbit polyclonal antihuman antibody (CD117, Dako Corp., Carpinteria, California), diluted 1:100. Its expression was evaluated in the epithelial and the spindle components. RESULTS: Two of the 20 SRCC cases (10%) showed no epithelial differentiation. The epithelial component was conventional RCC in 10 cases (50%), papillary RCC in 5 (25%) and chromophobe RCC in 3 (15%). A total of 16 cases (80%) presented at an advanced stage at diagnosis, namely T3 or T4 and/or metastatic disease. Immunohistochemical study showed positivity in the epithelial component only in the 3 chromophobe SRCCs. The sarcomatoid component was positive for c-Kit in 18 cases (94.7%). CONCLUSIONS: High c-Kit expression in SRCC in our series and the existence of a target therapy, imatinib (STI-571), against cells that express this receptor open the possibility of using this treatment for these tumors, especially in cases of advanced disease.

Adult↗
PubMed2003

Routine use of immunophenotype by flow cytometry in tissues with suspected hematological malignancies.

BACKGROUND: Immunophenotype is an essential parameter in the diagnosis of hematological malignancies. Flow cytometry (FCM) is used in the analysis of bone marrow or peripheral blood samples but is less frequently used in the evaluation of tissue biopsies with suspected hematological malignancies. The aim of this study was to analyze the role of FCM in the diagnosis of biopsies from patients with a suspected hematological disorder. METHODS: A total of 422 consecutive biopsies were studied using standard morphology, immunohistochemistry (IHC), and FCM. Results of FCM were obtained in less than 3 h and were interpreted independently from morphology and IHC. RESULTS: A strong correlation between malignant disease and abnormal pattern of FCM was observed (218 of 250) with the exception of Hodgkin disease (P < 0.001). Overall, negative predictive value was 0.52 and positive predictive value was 1. Light chain restriction was observed in 182 of 201 B-cell lymphoma and in 0 of 142 non-B-cell disorders by FCM. In contrast, light chain pattern could only be evaluated in 38 of 91 cases by IHC. FCM allowed a rapid diagnosis of infrequent or high-grade malignancies such as histiocytic sarcoma or T-lymphoblastic lymphoma. The addition of FCM in the routine study of tissue biopsies facilitates the diagnosis of double pathology in five (1%) patients. CONCLUSIONS: FCM is a fast and reliable methodology for phenotyping tissue samples, which easily detects infrequent hematological malignancies, disease-specific phenotypes and clonality in B-cell lymphomas. Moreover, the simultaneous recognition of different cell populations allows the diagnosis of composite cell lymphomas, or double pathologies.

Biopsy↗
PubMed2003

Immunohistochemical expression of CK20, p53, and Ki-67 as objective markers of urothelial dysplasia.

Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Distinguishing CIS and dysplasia from reactive atypia is often difficult on the basis of histological features alone. Cytokeratin 20 (CK20), p53, and Ki-67 are related either to neoplastic change or prognosis in urothelial proliferations. The objective of the present study was to establish the immunohistochemical pattern of these three antibodies in urothelial dysplasia and CIS. Three groups of patients were evaluated: 40 nonneoplastic urothelial samples, 50 cases with histologically incontrovertible CIS, and 30 samples with nonconclusive atypical changes (atypia of unknown significance). Monoclonal antibodies (MoAb) against CK20, p53, and Ki-67 (MIB-1) were used on paraffin-embedded samples. Nonneoplastic urothelium showed no reactivity to CK20 except for umbrella cells; p53 and Ki-67 were negative or weakly positive in <10% of basal cells. In the CIS group, 42% showed positivity for all three MoAb; 44%, for two; and 14%, only for one. CK20 was positive through the full thickness of the urothelium in 72% of cases, p53 was positive in 80% of cases, and Ki-67, in 94% of cases. In the third group, the suspected dysplastic cells showed strong positivity in scattered cells through the epithelium in 75% of cases. Aberrant CK20 expression in urothelial cells plus overexpression of p53 and Ki-67 are indicators of dysplastic change in urothelial mucosa. Thus, immunohistochemistry is a useful tool to confirm the diagnosis of CIS and could be helpful to distinguish dysplastic changes from reactive atypia.

Antibodies, Monoclonal↗
PubMed2002

Parotid gland mucoepidermoid carcinoma in a 4-year-old child.

Salivary gland tumors account for less than 5% of the head and neck neoplasms. Among them, mucoepidermoid carcinoma is the most common malignant salivary gland tumor. About 45% of mucoepidermoid carcinomas occur in the parotid gland, and appear around the fifth decade of life, being unusual in children under 10 years. We report a case of a parotid mass arising in a 4-year-old female, who had no lateral adenopathy. After histological examination, the diagnosis was of a low-grade mucoepidermoid carcinoma of the parotid gland. Three years after surgery no recurrence was observed. As a conclusion, although rare, the presence of a parotid mass with progressive growth in children could correspond to a neoplasm.

Carcinoma, Mucoepidermoid↗