CINIBA
URI permanente para esta comunidad
Directora: Prof. Dra. Amada Segal Eiras.
Examinar
Examinando CINIBA por Autor "Croce, María Virginia"
Mostrando 1 - 7 de 7
Resultados por página
Opciones de ordenación
- Artículo
Acceso Abierto Breast cancer humoral immune response: involvement of Lewis y through the detection of circulating immune complexes and association with Mucin 1 (MUC1)(2009) Isla Larrain, Marina Teresita; Demichelis, Sandra O.; Crespo, Marina; Lacunza, Ezequiel; Barbera, Alberto; Creton, Aldo; Terrier, Francisco; Segal-Eiras, Amada; Croce, María VirginiaIn cancer patients, MUC1 glycoprotein may carry Lewis y which could be involved in immune response. Purposes: 1- to evaluate the presence of Lewis y and MUC1 in circulating immune complexes (Lewis y/CIC and MUC1/CIC, respectively) and their correlation; 2- to analyze the possible presence of Lewis y in carbohydrate chains of tumoral MUC1 glycoprotein and 3- to correlate serum and tissue parameters considered. Pretreatment serum and tissue breast samples from 76 adenocarcinoma, 34 benign and 36 normal specimens were analyzed. Anti-MUC1 and anti-Lewis y MAbs were employed. To detect Lewis y/CIC and MUC1/CIC, ELISA tests were developed; serum samples containing MUC1 were previously selected by Cancer Associated Serum Antigen (CASA). Immunoprecipitation (IP) was performed in 9 malignant, benign and normal samples and analyzed by SDS-PAGE and Western blot. Lewis y and MUC1 expression was studied by immunohistochemistry (IHC). Statistical analysis was performed employing principal component analysis (PCA), ANOVA, Tukey HSD, Chi square test and classical correlation (p < 0.05). By ELISA, Lewis y/IgM/CIC levels showed statistically significant differences between breast cancer versus benign and normal samples; mean +/- SD values expressed in OD units were: 0.525 +/- 0.304; 0.968 +/- 0.482 and 0.928 +/- 0.447, for breast cancer, benign disease and normal samples, respectively, p < 0.05. Lewis y/IgG/CIC did not show any statistically significant difference. MUC1/IgM/CIC correlated with Lewis y/IgM/CIC. By CASA, 9 samples with MUC1 values above the cut off were selected and IP was performed, followed by SDS-PAGE and Western blot; bands at 200 kDa were obtained with each MAb in all the samples. By IHC, with C14 MAb, 47.5%, 31% and 35% of malignant, benign and normal samples, respectively, showed positive reaction while all the samples were positive with anti-MUC1 MAb; in both cases, with a different pattern of expression between malignant and non malignant samples. Our findings support that in breast cancer there was a limited humoral immune response through Lewis y/IgM/CIC levels detection which correlated with MUC1/IgM/CIC. We also found that Lewis y might be part of circulating MUC1 glycoform structure and also that Lewis y/CIC did not correlate with Lewis y expression. - Informe de investigador
Acceso Abierto Informe científico de investigador: Croce, María Virginia (2012-2014)(2014) Croce, María VirginiaLa diseminación tumoral constituye un complejo proceso que comprende la invasión y la metástasis o diseminación a distancia. Esta secuencia se debe a múltiples factores que incluyen marcadores tumorales del proceso, los que podrían tener utilidad clínica para el seguimiento de los pacientes con cáncer. Durante el período informado se realizó un estudio comparado de la expresión de un conjunto de antígenos asociados a cáncer de mama en tumores primarios, metástatasis cutáneas y ganglios axilares comprometidos de la misma paciente. Se trató de establecer la existencia de una expresión diferencial de los antígenos asociados en los tres tipos de muestras analizadas. Es un tema de especial interés el determinar los factores implicados en la diseminación tumoral a determinados órganos. En el análisis que realizamos durante este período se incluyeron los ganglios y las metástasis en piel. El cáncer de mama es el tumor primario sólido que con más frecuencia da esta localización metastásica y no se conocen los mecanismos que están implicados en esta diseminación. - Informe de investigador
Acceso Abierto Informe científico de investigador: Croce, María Virginia (2014-2016)(2016) Croce, María VirginiaEl proceso de metástasis está regulado por el “cross-talk” entre las células neoplásicas y las del microambiente tumoral. Durante este período analizamos la identidad antigénica de las células neoplásicas en los tumores primarios y metástasis hallando diferentes subpoblaciones de células neoplásicas metastásicas que expresan MUC1, antígenos Lewis y romboides 2 justificando, al menos en parte, los posibles mecanismos de escape tumoral en relación al pronóstico de los pacientes. Se determinó la traslocación al núcleo de células neoplásicas de la fracción extramembranosa de MUC1, lo que sumaría otra vía de regulación de esta mucina a la diseminación. Asimismo, realizamos el análisis de la indoleamine-2,3-dioxygenase (IDO), molécula inmunosupresora, hallándola expresada por las células tumorales y demostrándose la asociación del gen de IDO con otros genes relacionados con la respuesta inmune y apoptosis. Se continuó con el estudio poblacional de factores de riesgo, incidencia y prevención del cáncer de mama y el desarrollo de modelos experimentales. - Informe de investigador
Acceso Abierto Informe científico de investigador: Croce, María Virginia (2016-2018)(2018) Croce, María VirginiaLa diseminación tumoral ocurre por la invasión de los capilares venosos y linfáticos con una primera estación en los ganglios linfáticos y posteriormente en órganos distantes. Durante este período se estudió la expresión de moléculas de adhesión implicadas en la diseminación tumoral en tumores primarios y ganglios linfáticos de cáncer de mama y colorrectal. Se estudió la presencia de vasos sanguíneos y linfáticos de neoformación observándose la invasión de células tumorales. Se analizó la preparación de nichos metastásicos mediante la determinación de la enzima indoleamine-2,3-dioxygenase (IDO), molécula inmunomoduladora, en carcinomas mamarios primarios y ganglios linfáticos pareados y se estudió el perfil de células linfoides en los ganglios comprometidos. Asimismo, se analizó la expresión de antígenos asociados a MUC1 y su valor pronóstico en pacientes con tumores epiteliales malignos de cabeza y cuello. Se continuó con el estudio poblacional de factores de riesgo, incidencia y prevención del cáncer de mama y el desarrollo de modelos experimentales. - Documento de conferencia
Acceso Abierto Metástasis cutáneas de cáncer de mama(2018) Croce, María Virginia; Castro Luna Berenguer, Ana María Del Carmen; Isla Larrain, Marina Teresita; Rabassa, Martín Enrique; Cabaleiro, P.; Zwenger, A. O.; Canzoneri, R.; Abba, Martín Carlos; Segal Eiras, AmadaEl objetivo de este estudio es identificar perfiles correspondientes a la metástasis cutánea en el cáncer de mama mediante el análisis de marcadores tumorales tales como MUC1 y antígenos carbohidratos asociados. - Artículo
Acceso Abierto MUCI expression and anti-MUCI serum immune response in head and neck squamous cell carcinoma (HNSCC): A multivariate analysis(2006) Pereyra, Adrián; Segal-Eiras, Amada; Croce, María Virginia; Rabassa, Martín EnriqueBackground: HNSCC progression to adjacent tissue and nodes may be mediated by altered glycoproteins and glycolipids such as MUC1 mucin. This report constitutes a detailed statistical study about MUC1 expression and anti-MUC1 immune responses in relation to different clinical and pathological parameters which may be useful to develop new anti HNSCC therapeutic strategies. Patients and methods: Fifty three pre treatment HNSCC patients were included: 26 (49.1%) bearing oral cavity tumors, 17 (32.1%) localized in the larynx and 10 (18.8%) in the pharynx. Three patients (5.7%) were at stage I, 5 (9.4%) stage II, 15 (28.3%) stage III and 30 (56.6%) at stage IV. MUC1 tumor expression was studied by immunohistochemistry employing two anti-MUC1 antibodies: CT33, anti cytoplasmic tail MUC1 polyclonal antibody (Ab) and C595 anti-peptidic core MUC1 monoclonal antibody. Serum levels of MUC1 and free anti-MUC1 antibodies were detected by ELISA and circulating immune complexes (CIC) by precipitation in polyethylene glycol (PEG) 3.5%; MUC1 isolation from circulating immune complexes was performed by protein A-sepharose CL-4B affinity chromatography followed by SDS-PAGE and Western blot. Statistical analysis consisted in Multivariate Principal Component Analysis (PCA); ANOVA test (Tukey's test) was employed to find differences among groups; nonparametrical correlations (Kendall's Tau) were applied when necessary. Statistical significance was set to p < 0.05 in all cases. Results: MUC1 cytoplasmic tail was detected in 40/50 (80%) and MUC1 protein core in 9/50 (18%) samples while serum MUC1 levels were elevated in 8/53 (15%) patients. A significant statistical correlation was found between MUC1 serum levels and anti-MUC1 IgG free antibodies, while a negative correlation between MUC1 serum levels and anti-MUC1 IgM free antibodies was found. Circulating immune complexes were elevated in 16/53 (30%) samples and were also statistically associated with advanced tumor stage. MUC1 was identified as an antigenic component of IgG circulating immune complexes. Moreover, poorly differentiated tumors were inversely correlated with tumor and serum MUC1 detection and positively correlated with node involvement and tumor mass. Conclusion: Possibly, tumor cells produce MUC1 mucin which is liberated to the circulation and captured by IgG antibodies forming MUC1-IgG-CIC. Another interesting conclusion is that poorly differentiated tumors are inversely correlated with tumor and serum MUC1 detection. - Artículo
Acceso Abierto Rhomboid domain containing 2 (RHBDD2): A novel cancer-related gene over-expressed in breast cancer(2009) Abba, Martín Carlos; Lacunza, Ezequiel; Nunez, M. I.; Colussi, Andrea G.; Isla Larrain, Marina Teresita; Segal Eiras, Amada; Croce, María Virginia; Aldaz, C. MarceloIn the course of breast cancer global gene expression studies, we identified an uncharacterized gene known as RHBDD2 (Rhomboid domain containing 2) to be markedly over-expressed in primary tumors from patients with recurrent disease. In this study, we identified RHBDD2 mRNA and protein expression significantly elevated in breast carcinomas compared with normal breast samples as analyzed by SAGE (n=46) and immunohistochemistry (n=213). Interestingly, specimens displaying RHBDD2 over-expression were predominantly advanced stage III breast carcinomas (p=0.001). Western-blot, RT-PCR and cDNA sequencing analyses allowed us to identify two RHBDD2 alternatively spliced mRNA isoforms expressed in breast cancer cell lines. We further investigated the occurrence and frequency of gene amplification and over-expression affecting RHBDD2 in 131 breast samples. RHBDD2 gene amplification was detected in 21% of 98 invasive breast carcinomas analyzed. However, no RHBDD2 amplification was detected in normal breast tissues (n=17) or breast benign lesions (n=16) (p=0.014). Interestingly, siRNA mediated silencing of RHBDD2 expression results in a decrease of MCF7 breast cancer cells proliferation compared with the corresponding controls (p=0.001). In addition, analysis of publicly available gene expression data showed a strong association between high RHBDD2 expression and decreased overall survival (p=0.0023), relapsefree survival (p= 0.0013), and metastasis-free interval (p=0.006) in patients with primary ERnegative breast carcinomas. In conclusion, our findings suggest that RHBDD2 over-expression behaves as an indicator of poor prognosis and may play a role facilitating breast cancer progression.