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Id: lil-785729
Autor: Okcelik, Sezgin; Soydan, Hasan; Ates, Ferhat; Berber, Ufuk; Saygin, Hasan; Sönmez, Güner; Karademir, Kenan.
Título: Evaluation of PCA3 and multiparametric MRI's: collective benefits before deciding initial prostate biopsy for patients with PSA level between 3-10ng/mL
Fonte: Int. braz. j. urol;42(3):449-455tab, graf.
Idioma: en.
Resumo: ABSTRACT Objective To analyze the contribution of multiparametric MRI and PCA3 assay, pre- decision of initial biopsy in PSA level between 3-10 ng/mL patients with normal digital rectal examination(DRE). Materials and Methods PSA level 3-10 ng/mL ,patients, with normal DRE results and no previous prostate biopsy history, were included in this study. Each patient underwent multiparametric MRI one week before biopsy. Urine sample taking for PCA3 examination preceded the biopsy. Systematic and targeted biopsies were conducted. Patients with high PSA levels were seperated into two groups as: high PCA3 scored and low PCA3 scored. Then each group was divided into two sub-groups as: MRI lesion positive and negative. Tumor incidence, positive predictive values(PPV) and negative predictive values(NPV) were calculated. Results 53 patients were included between February 2013 and March 2014.Mean age 61.22 ± 1.06. Mean PSA value 5.13 ± 0.19 ng / mL. Mean PCA3 score 98.01 ± 23.13 and mean prostate size was 48.96 ± 2.67 grams. Fourty nine patients had both PCA3 score and multiparametric MRI. The PCA3’s PPV value was 58.33%. If multiparametric MRI lesions are added to high PCA3 scores , the PPV appears to elevate to 91.66%. NPV of PCA3 was 96%. NPV was 95% when there was no lesion in the multiparametric MRI with low PCA3 scores. Sensitivity was 91.66% , specificity was 95% respectively. Conclusion Adding multimetric MRI can also support biopsy decision for patients with high PCA3 value. When PCA3 value is low, patients can be survailled without any need to take a MRI.
Descritores: Próstata/patologia
Neoplasias da Próstata/patologia
Neoplasias da Próstata/diagnóstico por imagem
Imageamento por Ressonância Magnética
Antígeno Prostático Específico/sangue
Antígenos de Neoplasias/urina
-Tamanho do Órgão
Próstata/diagnóstico por imagem
Neoplasias da Próstata/urina
Valores de Referência
Biópsia
Valor Preditivo dos Testes
Estudos Prospectivos
Reprodutibilidade dos Testes
Fatores Etários
Medição de Risco
Exame Retal Digital/métodos
Gradação de Tumores
Tomada de Decisão Clínica
Pessoa de Meia-Idade
Limites: Humanos
Masculino
Responsável: BR1.1 - BIREME


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Id: biblio-954061
Autor: Cao, Dalong; Gu, Chengyuan; Ye, Dingwei; Dai, Bo; Zhu, Yao.
Título: PCA3 rs544190G>A and prostate cancer risk in an eastern Chinese population
Fonte: Int. braz. j. urol;44(3):500-505, May-June 2018. tab.
Idioma: en.
Projeto: National Natural Science Foundation of China.
Resumo: ABSTRACT Background: The association of prostate cancer antigen 3 (PCA3) polymorphism (SNP, rs544190G>A) with metastatic prostate cancer in European descent has been reported. Our aim of the current study was to re-validate the effect of PCA3 polymorphism on prostate cancer risk in an Eastern Chinese population and then estimate possible genetic discrepancies among population. Materials and Methods: Taqman assay was employed to determine genotype of SNP rs544190 in 1015 ethnic Han Chinese patients with prostate cancer and 1032 cancer-free controls. Simultaneously, odds ratios (OR) and 95% confidence intervals (95%CI) for risk relationship were calculated by logistic regression models. Results: The statistically significant relationship between PCA3 rs544190G>A and higher prostate cancer risk was not found. Stratification analysis revealed that there was no remarkable association of rs544190 variant AG/AA genotype with prostate cancer risk in every subgroup, except for patients with Gleason score ≤7(3+4). Conclusion: Although the results demonstrated that SNP rs544190 was not involved in prostate cancer risk in Eastern Chinese descent, unlike in European population, these might have clinical implications on prostate cancer heterogeneity around the World. To validate these findings, well-designed studies with different ethnic populations are warranted.
Descritores: Neoplasias da Próstata/genética
Medição de Risco/métodos
Polimorfismo de Nucleotídeo Único/genética
Grupo com Ancestrais do Continente Asiático/genética
Antígenos de Neoplasias/genética
-Neoplasias da Próstata/etnologia
Neoplasias da Próstata/patologia
Fumar/efeitos adversos
Estudos de Casos e Controles
Expressão Gênica
Modelos Logísticos
China
Fatores de Risco
Estudos de Associação Genética
Gradação de Tumores
Genótipo
Estadiamento de Neoplasias
Limites: Humanos
Masculino
Idoso
Responsável: BR1.1 - BIREME


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Id: biblio-952824
Autor: Barros, Luciana; Pretti, Marco Antonio; Chicaybam, Leonardo; Abdo, Luiza; Boroni, Mariana; Bonamino, Martin Hernán.
Título: Immunological-based approaches for cancer therapy
Fonte: Clinics;73(supl.1):e429s, 2018. graf.
Idioma: en.
Resumo: The immunologic landscape of tumors has been continuously unveiled, providing a new look at the interactions between cancer cells and the immune system. Emerging tumor cells are constantly eliminated by the immune system, but some cells establish a long-term equilibrium phase leading to tumor immunoediting and, eventually, evasion. During this process, tumor cells tend to acquire more mutations. Bearing a high mutation burden leads to a greater number of neoantigens with the potential to initiate an immune response. Although many tumors evoke an immune response, tumor clearance by the immune system does not occur due to a suppressive tumor microenvironment. The mechanisms by which tumors achieve the ability to evade immunologic control vary. Understanding these differences is crucial for the improvement and application of new immune-based therapies. Much effort has been placed in developing in silico algorithms to predict tumor immunogenicity and to characterize the microenvironment via high-throughput sequencing and gene expression techniques. Each sequencing source, transcriptomics, and genomics yields a distinct level of data, helping to elucidate the tumor-based immune responses and guiding the fine-tuning of current and upcoming immune-based therapies. In this review, we explore some of the immunological concepts behind the new immunotherapies and the bioinformatic tools to study the immunological aspects of tumors, focusing on neoantigen determination and microenvironment deconvolution. We further discuss the immune-based therapies already in clinical use, those underway for future clinical application, the next steps in immunotherapy, and how the characterization of the tumor immune contexture can impact therapies aiming to promote or unleash immune-based tumor elimination.
Descritores: Imunoterapia/métodos
Neoplasias/imunologia
Neoplasias/terapia
-Terapia Genética
Transformação Celular Neoplásica
Terapia Combinada
Evasão Tumoral/imunologia
Vacinas Anticâncer/uso terapêutico
Microambiente Tumoral/imunologia
Mutação
Antígenos de Neoplasias/análise
Neoplasias/genética
Limites: Humanos
Tipo de Publ: Revisão
Responsável: BR1.1 - BIREME


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Id: biblio-1012322
Autor: Suyama, Taisuke; Kanbe, Shigeki; Maegawa, Masanobu; Shimizu, Hirofumi; Nakajima, Koichi.
Título: Prognostic significance of inflammation-based prognostic scoring in patients with upper urinary tract urothelial carcinoma
Fonte: Int. braz. j. urol;45(3):541-548, May-June 2019. tab, graf.
Idioma: en.
Resumo: ABSTRACT Objectives: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. Patients and methods: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. Results: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a significant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. Conclusion: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.
Descritores: Prognóstico
Carcinoma/sangue
Neoplasias Urológicas/sangue
-Valores de Referência
Proteína C-Reativa/análise
Albumina Sérica/análise
Carcinoma/patologia
Biomarcadores Tumorais/sangue
Modelos de Riscos Proporcionais
Reprodutibilidade dos Testes
Estudos Retrospectivos
Sensibilidade e Especificidade
Neoplasias Urológicas/patologia
Estatísticas não Paramétricas
Urotélio/patologia
Queratina-19/sangue
Estimativa de Kaplan-Meier
Pessoa de Meia-Idade
Antígenos de Neoplasias/sangue
Limites: Humanos
Masculino
Feminino
Idoso
Idoso de 80 Anos ou mais
Responsável: BR1.1 - BIREME


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Id: biblio-1001831
Autor: Eder-Czembirek, Christina; Moser, Doris; Holawe, Simone; Brodowicz, Thomas; Ries, Jutta; Sulzbacher, Irene; Selzer, Edgar.
Título: Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries
Fonte: Clinics;74:e701, 2019. tab, graf.
Idioma: en.
Resumo: OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.
Descritores: Neoplasias Ósseas/terapia
Osteossarcoma/terapia
-Prognóstico
Áustria/epidemiologia
Neoplasias Ósseas/mortalidade
Neoplasias Ósseas/patologia
Imuno-Histoquímica
Biomarcadores/análise
Osteossarcoma/mortalidade
Osteossarcoma/patologia
Taxa de Sobrevida
Estudos Retrospectivos
Anticorpos Monoclonais/análise
Antígenos de Neoplasias/análise
Limites: Humanos
Masculino
Feminino
Adulto
Pessoa de Meia-Idade
Idoso
Idoso de 80 Anos ou mais
Tipo de Publ: Estudo Comparativo
Responsável: BR1.1 - BIREME


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Id: biblio-1134242
Autor: Qin, Zhiqiang; Yao, Jianxiang; Xu, Luwei; Xu, Zheng; Ge, Yuzheng; Zhou, Liuhua; Zhao, Feng; Jia, Ruipeng.
Título: Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis
Fonte: Int. braz. j. urol;46(5):691-704, Sept.-Oct. 2020. tab, graf.
Idioma: en.
Resumo: ABSTRACT Background: The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. Materials and Methods: A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR−), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. Results: With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR−, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. Conclusions: The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.
Descritores: Neoplasias da Próstata/diagnóstico
-Biomarcadores Tumorais
Razão de Chances
Curva ROC
Sensibilidade e Especificidade
Antígenos de Neoplasias
Limites: Humanos
Masculino
Tipo de Publ: Metanálise
Revisão Sistemática
Responsável: BR1.1 - BIREME


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Id: lil-731287
Autor: Val, Luciane Ferreira do; Nichiata, Lucia Yasuko Izumi.
Título: Comprehensiveness and programmatic vulnerability to stds/hiv/aids in primary care / La integralidad y vulnerabilidad programática de las ets/vih/sida en la atención básica / A integralidade e a vulnerabilidade programática às DST/HIV/AIDS na Atenção Básica
Fonte: Rev. Esc. Enferm. USP;48(spe):145-151, 08/2014. tab.
Idioma: en.
Projeto: FAPESP.
Resumo: 


This study aimed to identify programmatic vulnerability to STDs/HIV/AIDS in primary health centers (PHCs). This is a descrip - tive and quantitative study carried out in the city of São Paulo. An online survey was applied (FormSUS platform), involving administrators from 442 PHCs in the city, with responses received from 328 of them (74.2%), of which 53.6% were nurses. At - tention was raised in relation to program - matic vulnerability in the PHCs regarding certain items of infrastructure, prevention, treatment, prenatal care and integration among services on STDs/HIV/AIDS care. It was concluded that in order to reach comprehensiveness of actions for HIV/ AIDS in primary health care, it is necessary to consider programmatic vulnerability, in addition to more investment and reor - ganization of services in a dialogue with the stakeholders (users, multidisciplinary teams, and managers, among others).


.

Objetivo Fue identificar la vulnerabilidad programática de las Unidades Básicas de Salud con la atención a las ETS/VIH/SIDA. Método Es un estudio descriptivo con un abordaje cuantitativo llevado a cabo en el Municipio de San Pablo. Fue utilizado un formulario online (el FormSUS) con los gerentes de las 442 Unidades Básicas de Salud del Municipio de San Pablo. Participaran en el estudio 74.2% de los gerentes, estos 53.6% eran enfermeros. Resultados Se destaca la vulnerabilidad programática de las Unidades Básicas de Salud en relación a algunos elementos de la infraestructura, acciones de prevención, tratamiento, prenatal y la integración entre los servicios en la atención a las ETS/VIH/SIDA. Conclusión La construcción de tales marcadores constituye un instrumento, presentado en otro artículo, el cual puede ayudar a apoyar la captura de vulnerabilidades de las mujeres en relación a las ETS/VIH en el contexto de los servicios de Atención Primaria de Salud. Los marcadores constituyen importante herramienta para operacionalizar el concepto de vulnerabilidad en la Atención Primaria. Además, promueven procesos de trabajo inter e multidisciplinar e inter e multisectorial. La propuesta de un instrumento basado en dichos marcadores puede apoyar la captura de la vulnerabilidad de las mujeres en relación a las ETS/VIH. .

Objetivo Identificar a vulnerabilidade programática às DST/HIV/aids na Atenção Básica para o enfrentamento do HIV/Aids. Método Estudo descritivo, com abordagem quantitativa, realizado no Município de São Paulo (MSP). Utilizou-se formulário online (FormSUS), com gerentes das 442 Unidades Básicas de Saúde (UBS) do MSP. Participaram do estudo 74,2% gerentes, dos quais 53,6% eram enfermeiros. Resultados Destaca-se a vulnerabilidade programática nas UBS com relação a alguns itens de infraestrutura, ações de prevenção, de tratamento, no pré-natal e de integração entre os serviços na atenção às DST/HIV/aids. Conclusão Para a efetivação da integralidade no enfrentamento do HIV/aids na Atenção Básica é necessário atentar para a vulnerabilidade programática, além de mais investimentos e reorganização dos serviços, num diálogo com os atores sociais envolvidos (usuários, equipe multiprofissional, gerentes, gestores, entre outros).


 .
Descritores: Anticorpos Monoclonais/genética
Anticorpos Antineoplásicos/genética
Região Variável de Imunoglobulina/genética
-Especificidade de Anticorpos
Antígenos de Neoplasias
Neoplasias Colorretais/imunologia
Fixadores
Biblioteca de Peptídeos
Neoplasias Gástricas/imunologia
Células Tumorais Cultivadas
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: lil-107153
Autor: Alcántara Ascón, René Augusto.
Título: Cáncer embrionario de ovario / Embryonary neoplasms of the ovary
Fonte: Ginecol. & obstet;37(11):57-62, 1991. tab.
Idioma: es.
Resumo: De 1965 al 1990 se estudian 33 casos de cáncer embrionario de ovario en los hospitales Belén y Regional de Trujillo, con la finalidad de determinar su incidencia y complicaciones. Este grupo de tumores representó el 17.6 por ciento de todas las neoplasias ováricas malignas, siendo el disgerminoma el tumor más frecuentemente encontrado (16 casos). Se apreció un predominio en las pacientes menores de 30 años (29 casos), que acudieron por dolor y tumoración abdominal (33 casos), presentando 25 de ellas un tiempo de evolución menor de 7 meses. Asimismo, 23 llegaron en estadíos III y IV. Todas fueron operadas a excepción de una que falleció el día de su ingreso al Hospital. La complicación más frecuente fué la anemia (15 casos), habiéndose registrado un caso con perforación de colon. Fueron derivadas al INEN 25 pacientes, 6 no regresaron a su control y 2 fallecieron víctimas de la enfermedad
Descritores: Neoplasias Embrionárias de Células Germinativas/classificação
Neoplasias Embrionárias de Células Germinativas/diagnóstico
-Peru
Teratoma/diagnóstico
Teratoma/terapia
Disgerminoma/diagnóstico
Disgerminoma/tratamento farmacológico
Disgerminoma/terapia
Antígenos de Neoplasias
Tipo de Publ: Revisão
Responsável: PE1.1 - Oficina Universitária de Biblioteca


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Id: lil-121533
Autor: Morales Guzmán-Barrón, Rosanna; Cano Pérez, Roque; Mendoza Pérez, Germán; Pow-Sang, Mariella.
Título: Comparación entre antígeno prostático específico y gammmagrafía ósea en el diagnóstico de metástasis en pacientes operados por cáncer de prostata. Reporte Preliminar. / Comparison of Prostate-specific antigen and bone scintigraphyin in metastasis diagnosis in patients after radical prostatectomy
Fonte: Acta cancerol;23(1):3-6, mar. 1993. ilus, tab.
Idioma: es.
Resumo: Para comparar el valor del antígeno prostático específico (APE) con los resultados de la gammagrafía ósea se estudiaron 25 pacientes portadores de adenocarcinoma de próstata que llenaban los siguientes requisitos: 1. confirmación anátomo-patológica del diagnóstico;2. tratados con criterio curativo mediante prostatectomía radical hasta tres meses antes de la gammagrafía; 3. Una gammagrafía ósea y dosaje de APE con un mes de diferencia entre ambos. Catorce casos fueron normales pr ambas técnicas. Los once casos restantes correspondieron a metástasis según la gammagrafía ósea, teniendo 5 de ellos dosajes de APE dentro de límites normales. Alplicando a los resultados el coeficiente de rangos de Spearman se detuvo rs = 1,92, con alfa =0,01, con lo cual se rechaza Ho y se acepta que ambas técnicas son comparables
Descritores: Cintilografia
Neoplasias dos Genitais Masculinos/complicações
Antígenos de Neoplasias
-Neoplasias da Próstata/complicações
Cintilografia
Limites: Humanos
Masculino
Pessoa de Meia-Idade
Tipo de Publ: Estudo Comparativo
Responsável: PE1.1 - Oficina Universitária de Biblioteca


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Id: lil-553355
Autor: Bettoni, Fabiana.
Título: Utilização dos dados de seqüências expressas na identificação e caracterização de novos antígenos tumorais Cancer/Testi / Utilization of the expressed sequences data to the identification and characterization of new Cancer/Testis antigens.
Fonte: São Paulo; s.n; 2007. 125 p. ilus, tab.
Idioma: pt.
Tese: Apresentada a Fundação Antônio Prudente para obtenção do grau de Doutor.
Resumo: Os antígenos Cancer/Testis (CTs) são um subgrupo de antígenos tumorais com expressão restrita a testículo normal e diferentes tipos de tumores. Estes antígenos são capazes de induzir resposta imune humoral e celular em pacientes com câncer e, devido ao seu restrito padrão de expressão, são considerados candidatos ideais para o desenvolvimento de vacinas e imunização passiva. Neste trabalho, uma estratégia computacional baseada em dados de expressão provenientes de seqüências expressas (ESTs) foi utilizada para a identificação de novos antígenos CT. Seqüências expressas (mRNA e ESTs) foram alinhadas a seqüência genômica humana permitindo o agrupamento de seqüências expressas derivadas de um mesmo gene. ... Com base nesta análise, foram identificados cinco candidatos a antígenos CT freqüentemente em diferentes tipos de tumores. ... Anticorpos anti-CT101 [transcrito correspondente ao gene PASD1 (PAS domain containing protein 1)] foram encontrados em 41% das amostras de plasma de pacientes com câncer de útero e em 43,3% dos indivíduos sadios. A freqüência de anticorpos anti-CT802 [transcrito correspondente ao gene ASZ1 ou GASZ (Germ cell-specific ankyrin, SAM and basic leucine zipper domain containing protein 1)] observada nas amostras de plasma de pacientes com câncer de útero foi de 22,7% enquanto dentre os indivíduos sadios a freqüência foi de 6,7%. Já a freqüência de anticorpos anti-CT809, correspondente ao gene FAM46D (Family with sequence similarity 46, member D), foi de 7,7% nos pacientes com câncer de próstata e 6,7% nos indivíduos sadios. Além disso, utilizamos a técnica de RACE para caracterizar os candidatos CT704 e CT1001 que não apresentavam seqüência completa de mRNA disponível em banco de dados públicos. Em conjunto esses resultados demonstram que a estratégia in silico utilizada neste trabalho foi eficiente na identificação de 5 antígenos CTs sendo que para 3 destes foi possível detectar resposta imune humoral em pacientes com câncer.

Cancer/testis (CT) antigens are a subgroup of tumor antigens with a restricted expression in normal testis and in different types of tumors. These antigens are capable of eliciting humoral and cellular immune response in cancer patients and due to their restricted expression pattem they are considered promising candidates for the development of vaccines and passive immunotherapy. In this work, a computational approach based on expression data from expressed sequence tags (ESTs) was used to identify novel CT antigens. Expressed sequences (mRNA ans ESTs) were aligned against the human genome sequence, allowing the clustering of the sequences derived from a same gene. Considering the tissue origin of the expressed sequences corresponding to each gene it was possible to define an in silico expression pattem and to select novel CT antigen candidates. A total of 1255 candidate genes represented by spliced ESTs derived from testis and/or tumoral cDNA libraries were identified and 93 of them were selected for experimental validation of their expression pattem. The experimental validation of the expression pattem was carried out by RT-PCR in 21 normal tissues, 17 tumor cell lines and 160 samples deri ved from 9 different types of tumors. Based on this analysis we were able to identify five CT antigens candidates frequently expressed in different types of tumors. Candidate CT 1 O 1 was expressed in 41% o f tumor samples and the highest frequency of expression was observed in glioblastomas (70% ). Candidate CT704 was expressed in 65% of tumor samples with a high expression frequency among lung tumors (93%). Candidate CT802 was expressed in 20% of tumor samples with higher expression in uterus tumors (50%). Candidate CT809 was expressed in 24% of tumor samples and was predominantly expressed in lung tumors (50%). Candidate CT1001 was expressed in 18% of the tumor samples being more frequently expressed in gastric tumors (33.3%). Candidates CT101, CT802 and CT809 for which a full-length sequence were already available in public databases were selected to evaluate the presence o f hum oral immune response in cancer patients. The respective recombinant proteins were expressed in a bacterial system and were used in immunoblotting assays. Anti-CT101 antibodies [transcript corresponding to PASD1 gene (PAS domain containing protein 1)] were observed in 41% of plasma samples from patients with uterus tumor and in 43.3% of plasma from healthy individuais. The frequency of anti-CT802 antibodies [transcript corresponding to ASZ1 or GASZ gene (Germ cell-specific ankyrin, SAM and basic leucine zipper domain containing protein 1)] observed in plasma samples from patients with uterus tumor was 22.7% while among healthy individuais the frequency was 6.7%. Finally, the frequency of anti-CT809 antibodies, that corresponds to FAM46D gene (Family with sequence similarity 46, member D) was 7.7% among patients with lung tumors and 6.7% among healthy individuais. Moreover, we performed RACE experiments to characterize candidates CT704 and CT1001 that did not present a full-length mRNA sequence available in public databases. Taken together, these results showed that the in silico strategy used in this work was efficient in the identification of 5 CT antigens and for 3 of them it was possible to detect humoral immune response in cancer patients (AU)
Descritores: Antígenos de Neoplasias
Biologia Computacional
Etiquetas de Sequências Expressas
Imunoterapia
RNA Mensageiro
Limites: Humanos
Responsável: BR30.1 - Biblioteca
BR30.1



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