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AIM: A descriptive study was developed in an entire Argentine rural community considering breast cancer risk factors, preventive strategies and breast cancer incidence. PATIENTS AND METHODS: the study comprised of 83 women. A questionnaire of 34 items was employed; a mammogram and a breast ultrasound were performed. ANOVA and Pearson correlation were employed. RESULTS: Mean age was 54.5 years; 69% of women were postmenopausal; 96% had children; breastfeeding was X=10 months/child; Body Mass Index (BMI) was X=27.8 kg/m(2); 13% had first-degree relatives with breast cancer; 90% of women considered mammographic screening a necessary study. One woman had presented breast cancer. Argentine screening guidelines were not followed and an inverse relationship between education level and age of first mammogram was found (p<0.05). Mammographic and ultrasound studies did not reveal potential abnormalities. CONCLUSION: Peculiar social and cultural characteristics may be relevant to evaluate breast cancer risk factors in Argentina.
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Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , População Rural , Argentina/epidemiologia , Detecção Precoce de Câncer , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Incidência , Mamografia , Programas de Rastreamento , Fatores de RiscoRESUMO
AIM: Colorectal cancer (CRC) is one of the most prevalent malignancies in Argentina with 11,043 new cases and 6,596 deaths estimated to have occurred in 2008. The present study was developed to clarify the differential expression of MUC1, MUC2, sLex, and sLea in colorectal cancer patients and their relationship with survival and clinical and histological features. METHODS: Ninety primary tumor samples and 43 metastatic lymph nodes from CRC patients were studied; follow-up was documented. Twenty-six adenoma and 68 histological normal mucosa specimens were analyzed. An immunohistochemical approach was applied and statistical analysis was performed. RESULTS: In tumor samples, MUC1, sLea, and sLex were highly expressed (94%, 67%, and 91%, respectively); also, we found a significantly increased expression of the 3 antigens in primary tumors and metastatic lymph nodes compared with normal mucosa and adenomas. MUC2 was expressed in 52% of both normal mucosa and CRC samples; this reactivity significantly decreased in metastatic lymph nodes (p<0.05). A multiple comparison analysis showed that MUC1 and sLex discriminated among 3 groups: normal, adenoma, and CRC tissues. The increase of sLex expression showed an association with recurrence, and survival analysis showed that a high sLex staining was significantly associated with a poor survival. By multivariate analysis MUC1 inmunoreactivity correlated positively and significantly with tumor size, while MUC2 expression showed the opposite correlation. CONCLUSIONS: The correlation of sLex overexpression in primary tumors and metastatic lymph nodes, the discrimination among the normal, adenoma, and CRC groups based on sLex expression, as well as its association with recurrence and survival, all suggest a prognostic role of sLex in Argentinian CRC patients.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Fucosiltransferases/biossíntese , Antígenos CD15/biossíntese , Recidiva Local de Neoplasia/genética , Idoso , Idoso de 80 Anos ou mais , Argentina , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Fucosiltransferases/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Antígenos CD15/genética , Metástase Linfática/genética , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Mucina-1/biossíntese , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Análise de SobrevidaRESUMO
OBJECTIVE: In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis. RESULTS: All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased. CONCLUSION: Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer.
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The aim was to compare the expression of MUC1 and carbohydrate antigens in 124 tissue samples; 42 fibroadenoma (FA), 23 nonproliferative benign diseases (NPF), 25 usual epithelial hyperplasia (UEH), 7 atypical ductal hyperplasia (ADH), and 27 breast normal tissues. An immunohistochemical approach was adopted, using the following antibodies: reactive with MUC1 variable number of tandem repeats (C595, HMFG2, and SM3 monoclonal antibodies), anti-MUC1-cytoplasmic tail polyclonal antibody (CT33), and anti-carbohydrate antigens (sialyl Lewis x, Lewis x, Lewis y, Tn, and Thomsen-Friedenreich epitopes). Positive area of reaction, intensity, and pattern of expression were considered. A reactivity index was calculated as intensity (I) x 100+percentage of positive area (A). Statistical analysis comprised frequency analysis, P < 0.05, analysis of variance, and multiple correlation with principal component analysis. All samples expressed MUC1, detected by at least one anti-MUC1 antibody whereas Lewis x was the carbohydrate antigen most frequently found in all groups whereas variable number of tandem repeats MUC1 and Lewis x showed the highest correlation: 93% of normal samples, 62.5% of NPF, 87% of FA, 85% of UEH, and finally 80% of ADH. Although principal component analysis using reactivity indexes explained only 39% of data variability, normal samples appeared grouped and separated from benign breast diseases, which remained spread. Thomsen-Friedenreich was the only antigen that showed an increased tendency for positive expression and intensity from NPF through FA, UEH to ADH, whereas it was not detected in normals. With respect to the pattern of expression, an apical pattern was predominantly found in all the groups.
Assuntos
Antígenos Glicosídicos Associados a Tumores/análise , Neoplasias da Mama/diagnóstico , Mucina-1/análise , Anticorpos , Biomarcadores Tumorais/análise , Feminino , Humanos , Imuno-Histoquímica/métodos , Antígenos CD15/análise , Glândulas Mamárias Humanas/química , Análise de Componente PrincipalRESUMO
BACKGROUND: In 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
Assuntos
Complexo Antígeno-Anticorpo/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/imunologia , Imunidade Humoral , Antígenos do Grupo Sanguíneo de Lewis/sangue , Mucina-1/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo Antígeno-Anticorpo/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Western Blotting , Neoplasias da Mama/patologia , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Imunoprecipitação , Antígenos do Grupo Sanguíneo de Lewis/imunologia , Pessoa de Meia-Idade , Mucina-1/imunologia , Estadiamento de NeoplasiasRESUMO
An immunohistochemical analysis was employed to determine the expression of carbohydrate antigens associated to mucins in normal epithelia. Tissue samples were obtained as biopsies from normal breast (18), colon (35) and oral cavity mucosa (8). The following carbohydrate epitopes were studied: sialyl-Lewis x, Lewis x, Lewis y, Tn hapten, sialyl-Tn and Thomsen-Friedenreich antigen. Mucins were also studied employing antibodies against MUC1, MUC2, MUC4, MUC5AC, MUC6 and also normal colonic glycolipid. Statistical analysis was performed and Kendall correlations were obtained. Lewis x showed an apical pattern mainly at plasma membrane, although cytoplasmic staining was also found in most samples. TF, Tn and sTn haptens were detected in few specimens, while sLewis x was found in oral mucosa and breast tissue. Also, normal breast expressed MUC1 at a high percentage, whereas MUC4 was observed in a small number of samples. Colon specimens mainly expressed MUC2 and MUC1, while most oral mucosa samples expressed MUC4 and MUC1. A positive correlation between MUC1VNTR and TF epitope (r=0.396) was found in breast samples, while in colon specimens MUC2 and colonic glycolipid versus Lewis x were statistically significantly correlated (r=0.28 and r=0.29, respectively). As a conclusion, a defined carbohydrate epitope expression is not exclusive of normal tissue or a determined localization, and it is possible to assume that different glycoproteins and glycolipids may be carriers of carbohydrate antigens depending on the tissue localization considered.
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Mama/metabolismo , Colo/metabolismo , Antígenos CD15/metabolismo , Boca/metabolismo , Antígenos de Neoplasias/metabolismo , Biópsia , Mama/patologia , Membrana Celular/metabolismo , Membrana Celular/patologia , Colo/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Antígenos CD15/genética , Boca/patologia , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Mucina-1 , Mucina-2 , Mucina-4 , Mucinas/metabolismo , Mucosa/metabolismo , Mucosa/patologiaRESUMO
Tumor MUC1 expression as well as levels of MUC1, MUC1 circulating immune complexes (MUC1-CIC) and free antibodies against MUC1 (IgG and IgM-MUC1) were evaluated in 70 breast cancer patients with different stages of disease. Controls included: 135 serum samples from healthy women, normal mammary tissue samples (n = 7) and benign breast disease specimens (n = 6). In all assays, pre- and post-vaccination serum samples from breast cancer patients belonging to a vaccination protocol developed at the Memorial Sloan Kettering Cancer Center (New York, USA) were included as controls. Serum MUC1 was measured through Cancer Associated Serum Antigen test and CA15-3 test. Employing ELISA, MUC1-CIC-IgG/M were measured with either C595 or SM3 monoclonal antibodies (MAb) as catchers and also free antibodies against MUC1 (IgG and IgM) using 100mer peptide as catcher. Employing multivariate statistical analysis, results were correlated with age, tumor type, stage of disease and grade of differentiation. By quantitative immunohistochemistry using three anti-MUC1 core protein MAbs (C595, HMFG2 and SM3), tumor MUC1 was detected in 60/70 (86%) breast cancer specimens which reacted with at least one of these MAbs. High MUCI serum levels were detected in 14/67 (21%); IgG and IgM anti-MUC1 antibodies were found elevated in 32 and 14%, respectively, while IgG-MUC1-CIC-measured with C595 in 42% and IgM-MUC1-CIC in 54%; finally, SM3 was positive in 43 and 18%, respectively. Results of these studies demonstrate that in a group of breast cancer patients, MUC1 was detected both in tissue specimens as well as free in serum samples; furthermore, MUC1 can also circulate complexed with IgG and IgM antibodies; thus an accurate measurement should include free and complexed forms. On the other hand, immunohistochemical studies on breast cancer tissues may contribute to reveal different MUC1 glycoforms.
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Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Mucina-1/metabolismo , Neoplasias Ductais, Lobulares e Medulares/metabolismo , Adenocarcinoma/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo Antígeno-Anticorpo/imunologia , Antígenos de Neoplasias/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Neoplasias da Mama/sangue , Feminino , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Pessoa de Meia-Idade , Mucina-1/sangue , Mucina-1/imunologia , Neoplasias Ductais, Lobulares e Medulares/sangue , Distribuição TecidualRESUMO
Se determinó la actividad de arginasa hepática en Bufo arenarum adulto luego de la administración de 2,8 y 5,0 mg Cd/Kg p.c., inyectados por tercios a lo largo de 26 días. La actividad específica de la enzima en los sapos inyectadod con Cd se redujo 37-55 por ciento con respecto a los controles. La reducción de la actividad podría ser considerada como respuesta bioquímica a cantidades subletales de Cd en una de las principales enzimas del ciclo de la urea(AU)
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Animais , Adulto , Cádmio/administração & dosagem , Arginase/efeitos dos fármacos , Bufo arenarum , Fígado , Metais PesadosRESUMO
Se determinó la actividad de arginasa hepática en Bufo arenarum adulto luego de la administración de 2,8 y 5,0 mg Cd/Kg p.c., inyectados por tercios a lo largo de 26 días. La actividad específica de la enzima en los sapos inyectadod con Cd se redujo 37-55 por ciento con respecto a los controles. La reducción de la actividad podría ser considerada como respuesta bioquímica a cantidades subletales de Cd en una de las principales enzimas del ciclo de la urea
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Animais , Adulto , Arginase/efeitos dos fármacos , Bufo arenarum , Cádmio/administração & dosagem , Fígado , Metais PesadosRESUMO
The response to recombinant 10-KD heat shock protein (HSP of Mycobacterium leprae (rML10) was evaluated by indirect ELISA in sera from leprosy patients, household contacts, tuberculosis patients and healthy controls a leprosy-endemic area in tne North East of Argentina. Some technical parameters were a analyzed: within-assay and between-assay variability, dose-response curves and dectability indexed (specificity and sensitivity) of ELISA applied to measure anti-10kDa antibodies. High levels of these antibodies have already been reported in positive baciloscopy patients; herein we have also demonstrated that tuberculosis patients sera cross-react with this M. leprae antigen. This test seems to have a low sensificity for leporsy detection; it confirms that antibodies against highly conserved HSP antigens are important in the polycional response against mycobacterial epitopes in leprosy as well as in tuberculosis. (AU)
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Adulto , Pessoa de Meia-Idade , Idoso , Humanos , RESEARCH SUPPORT, NON-U.S. GOVT , Hanseníase/imunologia , Tuberculose/imunologia , Chaperonina 10/imunologia , Mycobacterium leprae/imunologia , Antígenos de Bactérias/imunologia , Anticorpos Antibacterianos/imunologia , Sensibilidade e Especificidade , Ensaio de Imunoadsorção Enzimática , Reações Cruzadas , Idoso de 80 Anos ou maisRESUMO
The response to recombinant 10-KD heat shock protein (HSP of Mycobacterium leprae (rML10) was evaluated by indirect ELISA in sera from leprosy patients, household contacts, tuberculosis patients and healthy controls a leprosy-endemic area in tne North East of Argentina. Some technical parameters were a analyzed: within-assay and between-assay variability, dose-response curves and dectability indexed (specificity and sensitivity) of ELISA applied to measure anti-10kDa antibodies. High levels of these antibodies have already been reported in positive baciloscopy patients; herein we have also demonstrated that tuberculosis patients sera cross-react with this M. leprae antigen. This test seems to have a low sensificity for leporsy detection; it confirms that antibodies against highly conserved HSP antigens are important in the polycional response against mycobacterial epitopes in leprosy as well as in tuberculosis.
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Adulto , Pessoa de Meia-Idade , Humanos , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Chaperonina 10/imunologia , Hanseníase/imunologia , Mycobacterium leprae/imunologia , Tuberculose/imunologia , Idoso de 80 Anos ou mais , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Sensibilidade e EspecificidadeRESUMO
Describe una técnica para realizar bioensayos de toxicidad con peces de la ictiofauna bonaerense como organismo prueba; dicho método se aplicó para evaluar la calidad del agua del río Reconquista y el impacto producido por pulsos simulados de contaminación por vertido de un metal pesado (Cadmio)
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Argentina , Bioensaio , Poluição de Rios , CádmioRESUMO
Se analiza el estado del agua del río Reconquista en base algunos parámetros indicadores de polución, integrando los valores monitoreados durante 24 meses. Se presenta los parámetros más representativos del estado de contaminación de las aguas determinados durante los meses de marzo, abril y mayo de 1994
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Argentina , Poluição da Água , Indicadores de ContaminaçãoRESUMO
Se describe una técnica para realizar bioensayos de toxicidad con peces de la ictiofauna bonaerense como organismo prueba; dicho método se aplicó para evaluar la calidad del agua del Río Reconquista y el impacto producido por pulsos simulados de contaminación por vertido de un metal pesado ; cadmio