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1.
J. coloproctol. (Rio J., Impr.) ; 42(2): 120-125, Apr.-June 2022. tab, ilus
Artigo em Inglês | LILACS | ID: biblio-1394416

RESUMO

Background: Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide, and is one of the major health problems in Asia, Africa, Europe, and America. The tumor antigens recently are of interesting indicators as diagnostic and prognostic tools, The aim of the present study is to detect the expression levels of carbonic anhydrase IX (CA9), the Wilms tumor gene (WT1), and the preferentially expressed antigen in melanoma (PRAME) in the peripheral blood of CRC patients in comparison with healthy controls. Methods: A prospective case-control study of CRC patients was conducted. We included 25 newly-diagnosed CRC eligible patients and obtained peripheral blood samples of them as well as 10 blood samples from the control group. All samples were then submitted to deoxyribonucleic acid (DNA) extraction and a molecular study through real-time polymerase chain reaction (PCR). Results: The CRC group consisted of 15 (60%) female and 10 (40%) male patients with a mean age of 50.52 ± 9.8 years, while the control group included 4 (40%) female and 6 (60%) male patients with a mean age of 47.7 ± 7.9 years. The CRC group, 24 (96%) of patient samples were CA9-positive with strong statistically significant differences (p < 0.00001; sensitivity: 96%; specificity: 90%). Regarding the WT1 gene, there were 11 (44%) positive samples in the CRC group, with no statistically significant differences (p = 0.055; sensitivity: 44%; specificity: 90%). The PRAME gene was positive in 9 (36%) samples in the CRC group, with no statistically significant differences (p = 0.357; sensitivity: 36%; specificity: 80%. Among CA9 (24 patients; 96%) of patients with CRC expressed positive results, in WT1 11(91.6%) CRC patients expressed gene, and in PRAME gene, 9 patients with CRC (81.8%) expressed positive results. Conclusion: Overexpression of the CA9 gene in CRC of high sensitivity and specificity to be used as a tool to discriminate CRC from benign associate with high accuracy compare to WT1 and PRAME genes. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Neoplasias Colorretais/diagnóstico , Biomarcadores Tumorais , Proteínas WT1/genética , Anidrase Carbônica IX/genética , Antígenos de Neoplasias/genética , Prognóstico , Estudos de Casos e Controles , Expressão Gênica , Estudos Prospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
2.
Int. j. morphol ; 39(5): 1509-1515, oct. 2021. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1385480

RESUMO

SUMMARY: Immunohistochemistry allows in situ detection of cell and extracellular components through specific antibodies. The objective was to compare the immunohistochemical expression patterns of the S-100, HMB-45 and MART-1 proteins for differential diagnosis of malignant melanoma and melanocytic nevus in human skin biopsies. Thirty-nine biopsies of human tissue were used. They were divided into two groups: 19 in malignant melanoma and 20 in melanocytic nevi. Next, the samples were fixed with paraformaldehyde and processed following the protocol for inclusion. Then, immunohistochemical staining was performed. Finally, the histological and qualitative analysis of the samples was carried out. S-100, HMB-45, and MART-1 markers showed positive immunoreaction in melanoma biopsies. HMB-45 marker was generally present with weaker expression than S-100 and MART-1 in melanocytic nevus biopsies. No expression pattern was observed which specifically associates one or more markers with some types of histopathological diagnosis. Immunohistochemistry is fundamental in differential diagnosis of melanomas and melanocytic nevi. However, there is no antibody or set of antibodies which allows unequivocal diagnosis between melanoma and nevus. It is therefore necessary to analyze with care the expression pattern and location of the lesion using standard morphological characteristics.


RESUMEN: La inmunohistoquímica permite la detección in situ de componentes celulares y extracelulares a través de anticuerpos específicos. El objetivo de nuestro estudio fue comparar los patrones de expresión inmunohistoquímica de las proteínas S-100, HMB-45 y MART-1 para el diagnóstico diferencial de melanoma maligno y nevo melanocítico en biopsias de piel humana. Se utilizaron treinta y nueve biopsias de tejido humano, las que fueron divididas en dos grupos: 19 en melanoma maligno y 20 en nevos melanocíticos. A continuación, las muestras se fijaron con paraformaldehído y se procesaron siguiendo el protocolo convencional para su inclusión. Luego, se realizó la tinción inmunohistoquímica. Finalmente, se realizó el análisis histológico y cualitativo de las muestras. Los marcadores S-100, HMB- 45 y MART-1 mostraron inmunorreacción positiva en biopsias de melanoma. El marcador HMB-45 estuvo generalmente presente con una expresión más débil que S-100 y MART-1 en biopsias de nevo melanocítico. No se observó ningún patrón de expresión que asocie específicamente uno o más marcadores con algunos tipos de diagnóstico histopatológico. La inmunohistoquímica es fundamental en el diagnóstico diferencial de melanomas y nevos melanocíticos. Sin embargo, no existe ningún anticuerpo o panel de anticuerpos que permita un diagnóstico inequívoco entre el melanoma y el nevo. Por tanto, es necesario analizar con cuidado el patrón de expresión y la localización de la lesión utilizando características morfológicas estándar.


Assuntos
Humanos , Neoplasias Cutâneas/diagnóstico , Melanoma/diagnóstico , Nevo/diagnóstico , Neoplasias Cutâneas/patologia , Imuno-Histoquímica , Proteínas S100 , Biomarcadores Tumorais , Diagnóstico Diferencial , Antígeno MART-1 , Melanoma/patologia , Complexo Antígeno-Anticorpo , Antígenos de Neoplasias , Nevo/patologia
3.
J. appl. oral sci ; 29: e20210374, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1350894

RESUMO

Abstract Background: Squamous cell carcinoma antigen (SCCA) is used as a prognostic marker for recurrence of squamous cell carcinoma in various sites, including head and neck. Studies suggest that its high serum levels are correlated to some clinical features, such as nodal metastasis. However, it is still unknown if high SCCA in patients with SCCA tissue expression in tumor cells are related to peripheral T-lymphocytes. Therefore, we did this study to evaluate SCCA expression in squamous cell carcinoma and verrucous carcinoma and to compare it with normal oral mucosa, also investigating the correlation between serum-based and tissue-based antigen levels. Methodology: In this study, the immunohistochemistry (IHC) technique was used to determine the SCCA1 expression pattern in 81 specimens divided into 3 groups, including oral squamous cell carcinoma, verrucous carcinoma, and normal oral mucosa. Serum-based and tissue-based antigen levels of 20 oral squamous cell carcinoma cases were compared by the western blot assay. SCCA expression was also evaluated and compared in both tumor cells and peripheral T-lymphocytes by the immunofluorescence assay. Results: Our results showed that the SCCA levels in SCC specimens were significantly lower than in verrucous carcinoma and normal and hyperplastic oral mucosa specimens. We found no correlation between the IHC expression of SCCA and serum levels. SCCA was well expressed in both tumor cells and peripheral T-lymphocytes. Conclusion: Decreasing SCCA in SCC specimens suggested that SCC tumor cells may affect more than the serum levels of SCCA in some patients. In addition, expression of SCCA in peripheral T-lymphocytes showed that both tumor cells and T-lymphocytes may cause serum SCCA.


Assuntos
Humanos , Neoplasias Bucais , Carcinoma de Células Escamosas , Carcinoma Verrucoso , Neoplasias de Cabeça e Pescoço , Linfócitos T , Biomarcadores Tumorais , Serpinas , Carcinoma de Células Escamosas de Cabeça e Pescoço , Mucosa Bucal , Antígenos de Neoplasias
4.
Int. braz. j. urol ; 46(5): 691-704, Sept.-Oct. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1134242

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.


Assuntos
Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Biomarcadores Tumorais , Razão de Chances , Curva ROC , Sensibilidade e Especificidade , Antígenos de Neoplasias
5.
Gac. méd. Méx ; 156(3): 229-236, may.-jun. 2020. graf
Artigo em Inglês, Espanhol | LILACS | ID: biblio-1249899

RESUMO

Resumen Los anticuerpos terapéuticos son proteínas recombinantes empleadas en el tratamiento del cáncer. Existe una nueva generación de anticuerpos monoclonales con actividad contra las células cancerosas, conocidos como anticuerpos conjugados a fármacos. Estas moléculas están integradas por tres elementos: un anticuerpo monoclonal, un fármaco citotóxico con alta potencia y un enlazador químico que los une. El anticuerpo reconoce antígenos tumorales, por lo que permite la entrega dirigida del agente citotóxico hacia las células cancerosas. Tras el reconocimiento de su antígeno, el anticuerpo conjugado a fármaco es endocitado por las células blanco, donde se induce la degradación lisosomal de la fracción proteica y se libera el fármaco citotóxico. En el presente artículo se revisan las características generales de los anticuerpos conjugados a fármacos y se describe la evidencia clínica de la eficacia y seguridad de los primeros cuatro aprobados por las agencias reguladoras de Estados Unidos y Europa.


Abstract Therapeutic antibodies are recombinant proteins used in the treatment of cancer. There is a new generation of monoclonal antibodies with activity against cancer cells, known as antibody-drug conjugates. These molecules are made up of three elements: a monoclonal antibody, a highly potent cytotoxic drug, and a chemical linker that binds them together. The antibody recognizes tumor antigens, thereby allowing targeted delivery of the cytotoxic agent to cancer cells. After recognizing its antigen, the antibody-drug conjugate is endocytosed by the target cells, where the protein fraction is degradated into lysosomes, releasing the cytotoxic drug. This article reviews antibody-drug conjugates general characteristics and describes the clinical evidence of efficacy and safety of the first four approved by regulatory agencies in the United States and Europe.


Assuntos
Humanos , Imunoconjugados/administração & dosagem , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Biotecnologia , Imunoconjugados/efeitos adversos , Imunoconjugados/farmacologia , Antígenos de Neoplasias/imunologia , Neoplasias/imunologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia
6.
Int. braz. j. urol ; 45(3): 541-548, May-June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1012322

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.


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , 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
7.
Clinics ; 74: e701, 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1001831

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.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , 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
8.
Int. braz. j. urol ; 44(3): 500-505, May-June 2018. tab
Artigo em Inglês | LILACS | ID: biblio-954061

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.


Assuntos
Humanos , Masculino , Idoso , Neoplasias da Próstata/genética , Medição de Risco/métodos , Polimorfismo de Nucleotídeo Único/genética , Povo 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
10.
J. venom. anim. toxins incl. trop. dis ; 24: 1-7, 2018. graf, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1484749

RESUMO

Background Cnidarian venoms and extracts have shown a broad variety of biological activities including cytotoxic, antibacterial and antitumoral effects. Most of these studied extracts were obtained from sea anemones or jellyfish. The present study aimed to determine the toxic activity and assess the antitumor and antiparasitic potential of Palythoa caribaeorum venom by evaluating its in vitro toxicity on several models including human tumor cell lines and against the parasite Giardia intestinalis. Methods The presence of cytolysins and vasoconstrictor activity of P. caribaeorum venom were determined by hemolysis, PLA2 and isolated rat aortic ring assays, respectively. The cytotoxic effect was tested on HCT-15 (human colorectal adenocarcinoma), MCF-7 (human mammary adenocarcinoma), K562 (human chronic myelogenous leukemia), U251 (human glyoblastoma), PC-3 (human prostatic adenocarcinoma) and SKLU-1 (human lung adenocarcinoma). An in vivo toxicity assay was performed with crickets and the antiparasitic assay was performed against G. intestinalis at 24 h of incubation. Results P. caribaeorum venom produced hemolytic and PLA2 activity and showed specific cytotoxicity against U251 and SKLU-1 cell lines, with approximately 50% growing inhibition. The venom was toxic to insects and showed activity against G. intestinalis in a dose-dependent manner by possibly altering its membrane osmotic equilibrium. Conclusion These results suggest that P. caribaeorum venom contains compounds with potential therapeutic value against microorganisms and cancer.


Assuntos
Animais , Antígenos de Neoplasias/análise , Antígenos de Protozoários/análise , Citotoxinas/análise , Venenos de Cnidários/efeitos adversos , Venenos de Cnidários/toxicidade , Venenos de Cnidários/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais
11.
Clinics ; 73(supl.1): e429s, 2018. graf
Artigo em Inglês | LILACS | ID: biblio-952824

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.


Assuntos
Humanos , 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
12.
Medicina (B.Aires) ; 76(5): 307-314, Oct. 2016. ilus
Artigo em Espanhol | LILACS | ID: biblio-841598

RESUMO

En los últimos años la inmunoterapia ha revolucionado el tratamiento de pacientes con cáncer avanzado. El mayor conocimiento de la biología tumoral y de la inmunología ha permitido desarrollar tratamientos racionales manipulando el sistema inmunitario con importante impacto clínico. Entre otras estrategias de inmunoterapia contra el cáncer se ha explorado el uso de vacunas terapéuticas basadas en células dendríticas (CD). Las CD son células de origen hematopoyético, que expresan constitutivamente moléculas presentadoras de antígeno, y son funcionalmente las inductoras más potentes de la activación y proliferación de linfocitos T a los que presentan antígenos. Los linfocitos T CD8+ proliferan y adquieren capacidad citotóxica cuando reconocen su antígeno específico presentado en la superficie de CD, aunque solo algunos tipos de CD pueden presentar antígenos internalizados desde el exterior celular a precursores de linfocitos T citotóxicos (a esta función se la llama presentación cruzada). Explotar la inducción de una respuesta inmunitaria adaptativa eficaz se considera una buena opción por su especificidad y prolongada duración de la respuesta. Las CD, gracias a su particular capacidad de presentación antigénica y de estimulación linfocitaria, son capaces de revertir la respuesta inmunitaria antitumoral deficiente que presentan algunos pacientes con cáncer. Las CD se pueden obtener a partir de distintas fuentes, empleando diversos protocolos para generar diferenciación y maduración, y se administran por diversas vías como son subcutánea, intravenosa o intranodal. La gran variedad de protocolos en los que se aplican las CD explica los resultados clínicos tan heterogéneos que se han comunicado hasta la fecha.


In recent years immunotherapy has revolutionized the treatment of patients with advanced cancer. The increased knowledge in the tumor immune-biology has allowed developing rational treatments by manipulation of the immune system with significant clinical impact. This rapid development has significantly changed the prognosis of many tumors without treatment options up to date. Other strategies have explored the use of therapeutic vaccines based on dendritic cells (DC) by inducing antitumor immunity. DC are cells of hematopoietic origin, constitutively expressing molecules capable to present antigens, that are functionally the most potent inducers of the activation and proliferation of antigen specific T lymphocytes. The CD8+ T cells proliferate and acquire cytotoxic capacity after recognizing their specific antigen presented on the surface of DC, although only some types of DC can present antigens internalized from outside the cell to precursors of cytotoxic T lymphocytes (this function is called cross-presentation) requiring translocation mechanisms of complex antigens. The induction of an effective adaptive immune response is considered a good option given its specificity, and prolonged duration of response. The DC, thanks to its particular ability of antigen presentation and lymphocyte stimulation, are able to reverse the poor antitumor immune response experienced by patients with cancer. The DC can be obtained from various sources, using different protocols to generate differentiation and maturation, and are administered by various routes such as subcutaneous, intravenous or intranodal. The wide variety of protocols resulted in heterogeneous clinical responses.


Assuntos
Humanos , Células Dendríticas/imunologia , Vacinação/métodos , Vacinas Anticâncer/imunologia , Neoplasias/terapia , Linfócitos T/imunologia , Apresentação de Antígeno/imunologia , Antígenos de Neoplasias/imunologia , Neoplasias/imunologia
13.
Int. braz. j. urol ; 42(3): 449-455, tab, graf
Artigo em Inglês | LILACS | ID: lil-785729

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.


Assuntos
Humanos , Masculino , 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
14.
São Paulo; s.n; 2016. [92] p. ilus, tab, graf.
Tese em Português | LILACS | ID: biblio-870868

RESUMO

O câncer é a doença que mais mata pessoas com idade abaixo de 85 anos e é um problema de saúde pública. Os tumores podem expressar em determinada fase de seu desenvolvimento proteínas anômalas que podem ser alvo de métodos diagnósticos e de intervenções terapêuticas. A expressão de NY-ESO-1 é detectada em 20 a 40% dos melanomas. Há evidências que esta expressão é mais freqüente em tumores de estágios mais avançados e está associada a um pior prognóstico. OBJETIVOS: determinar a frequência de expressão da proteína NY-ESO-1 no melanoma cutâneo e tentar correlacioná-la com o índice de Breslow, aspectos histopatológicos do melanoma, incluindo o infiltrado linfocítico tumoral, e a morbi-mortalidade dos pacientes. MÉTODOS: o presente estudo é longitudinal de coorte retrospectiva e foi realizado de agosto de 2009 a outubro de 2015. Foram selecionados 89 melanomas de 87 pacientes do Ambulatório de Tumores do Departamento de Dermatologia da FMUSP, divididos em 3 grupos, sendo: grupo 1: 34 melanomas com índice de Breslow <= 1,0 mm; grupo 2: 29 melanomas com índice de Breslow entre 1,1 - 4,0 mm e grupo 3: 26 melanomas com índice de Breslow >= 4,0 mm. As lâminas dos exames anátomo-patológicos destes pacientes foram revisadas quanto ao diagnóstico de melanoma, seu índice de Breslow e a presença de infiltrado linfocítico tumoral. A seguir, realizou-se exame de imunohistoquímica para a determinação da presença do antígeno NY-ESO-1 em todos os 89 tumores coletados e em mais 20 nevos (11 displásicos e 9 intradérmicos) escolhidos ao acaso. Através da revisão dos dados do prontuário, foram obtidos os dados clínicos de: idade, sexo, raça, fototipo da pele, local de aparecimento do melanoma, status do linfonodo sentinela quando realizado, desenvolvimento de metástases e sobrevida dos pacientes. Os dados anátomo-patológicos do tumor analisados foram: tipo histológico, presença de ulceração, e tipo de infiltrado linfocítico tumoral. Nos melanomas que apresentavam...


Cancer is the disease that leads to the greatest number of deaths in people over 85 years old and it has become a major public health problem. Tumors may express aberrantly proteins during certain phases of their development, which can be target for diagnostic or treatment purposes. NY-ESO-1 is detected in 20 to 40% of melanomas. There is evidence that it is more frequent in advanced stages and that is associated with a worse prognosis. OBJECTIVES: to determine the frequency of NY-ESO-1 protein expression in cutaneous melanoma and to try to correlate it to Breslow index, melanoma histopathological aspects, including the tumor infiltrating lymphocytes, and patients morbi-mortality. METHODS: the present study is longitudinal of retrospective cohort. The research was carried on from August 2009 to October 2015. Eighty nine melanomas were selected from 87 patients in Oncology Outpatient Clinic, Dermatology Division, University of São Paulo and divided in 3 groups, such as: group 1: 34 melanomas with Breslow index <= 1,0 mm; group 2: 29 melanomas with Breslow index between 1,1 - 4,0 mm e group 3: 26 melanomas with Breslow index >= 4,0 mm. All specimens were reviewed for diagnostic, Breslow index and tumor infiltrating lymphocytes. After that, immunohistoquimical test for the presence of NY-ESO-1 antigen was performed in all 89 melanomas collected and in 20 nevi (11 dysplastic nevi and 9 dermal nevi) that were randomly chosen. By reviewing clinical charts, the following data was obtained: age, sex, skin phototype, site of the tumor, lymph node sentinel status, development of metastases and survival of the patients. The histological data analyzed was: histological melanoma type, presence of ulceration, grade of tumor infiltrating lymphocytes. In those melanomas that had tumor infiltrating lymphocytes, we performed immunohistoquimical tests for the presence of CD3+, CD8+, FoxP3+ and CD8+FoxP3+ (double positive) cells. RESULTS: antigen NY-ESO-1 was...


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias , Imuno-Histoquímica , Imunoterapia , Melanoma , Neoplasias , Sobrevida
15.
Braz. j. med. biol. res ; 49(11): e5620, 2016. graf
Artigo em Inglês | LILACS | ID: lil-797890

RESUMO

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model. Consequently, we constructed a DNA vaccine containing the PSCA and the CTLA-4 gene. Vaccination with the CTLA4-fused DNA not only induced a much higher level of anti-PSCA antibody, but also increased PSCA-specific T cell response in mice. To evaluate the anti-tumor efficacy of the plasmids, murine models with PSCA-expressing tumors were generated. After injection of the tumor-bearing mouse model, the plasmid carrying the CTLA4 and PSCA fusion gene showed stronger inhibition of tumor growth than the plasmid expressing PSCA alone. These observations emphasize the potential of the CTLA4-fused DNA vaccine, which could represent a promising approach for tumor immunotherapy.


Assuntos
Animais , Masculino , Camundongos , Antígenos de Neoplasias/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Antígeno CTLA-4/uso terapêutico , Proteínas de Neoplasias/uso terapêutico , Plasmídeos/uso terapêutico , Neoplasias da Próstata/terapia , Vacinas de DNA/uso terapêutico , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Vacinas Anticâncer/imunologia , Antígeno CTLA-4/genética , Antígeno CTLA-4/imunologia , Modelos Animais de Doenças , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/uso terapêutico , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/metabolismo , Plasmídeos/genética , Neoplasias da Próstata/imunologia , Proteínas Recombinantes de Fusão/uso terapêutico , Vacinas de DNA/genética
16.
Pesqui. vet. bras ; 35(11): 906-912, nov. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-767760

RESUMO

Dendritic cells have attracted great interest from researchers as they may be used as targets of tumor immune evasion mechanisms. The main objective of this study was to evaluate the relationship between the dendritic cells (DCs) subpopulation in simple type mammary carcinomas in female dogs. Two groups of samples were used: the control group consisted of 18 samples of mammary tissue without changes and the tumor group with 26 simple type mammary carcinomas. In these groups, we evaluated the immunodetection of immature and mature myeloid DCs, plasmacytoid DCs and MHC-II. In mammary tumor, mature myeloid DCs predominated in the peritumoral region, while immature myeloid DCs and plasmacytoid DCs were evident in the intratumoral region. Immunostaining of MHC-II was visualized in mammary acini (control group), in tumor cells and inflammatory infiltration associated with tumors. The comparison between the control and tumor groups showed a statistically significant difference between immature myeloid DCs, mature myeloid DCs and plasmacytoid DCs. The immunodetection of MHC-II was not significant when comparing the groups. The predominance of immature DCs in the tumor group is possibly related to an inefficient immune response, promoting the development and survival of tumor cells. The presence of plasmacytoid DCs in the same group suggests a worse prognosis for female dogs with mammary tumors. Therefore, the ability of differentiation of canine dendritic cells could be influenced by neoplastic cells and by the tumor microenvironment...


As células dendríticas têm despertado grande interesse dos pesquisadores, pois podem ser alvo dos mecanismos de evasão imune do tumor. O objetivo principal deste estudo foi avaliar a relação entre as subpopulações de células dendríticas (DCs) nos carcinomas mamários do tipo simples em cadelas. Dois grupos de amostras foram utilizados, o grupo controle composto por 18 amostras de tecido mamário sem alterações e o grupo tumor com 26 carcinomas mamários do tipo simples. Nestes grupos foram avaliadas a imunodetecção de DCs mieloides imaturas e maduras, DCs plasmocitoides e de MHC-II. Nas mamas com tumor, as DCs mieloides maduras predominaram na região peritumoral, enquanto que as DCs mieloides imaturas e as DCs plasmocitoides foram evidentes na região intratumoral. A imunomarcação do MHC-II foi visualizada nos ácinos mamários (grupo controle), nas células tumorais e no infiltrado inflamatório associado aos tumores. Na comparação entre os grupos controle e tumor houve diferença estatística significativa entre as DCs mieloides imaturas, DCs mieloides maduras e DCs plasmocitoides. A imunodetecção de MHC-II não foi significativa na comparação entre os grupos. A predominância de DCs imaturas no grupo tumor, possivelmente, está relacionada com uma resposta imune ineficiente, favorecendo o desenvolvimento e a sobrevivência das células tumorais. A presença das DCs plasmocitoides no mesmo grupo sugere um prognóstico pior para cadelas com tumores de mama. Portanto, a capacidade de diferenciação das células dendríticas caninas poderia ser influenciada pelas células neoplásicas e pelo microambiente tumoral...


Assuntos
Animais , Feminino , Cães , Antígenos de Neoplasias/imunologia , Células Dendríticas/fisiologia , Células Mieloides/fisiologia , Neoplasias Mamárias Animais/ultraestrutura , Imuno-Histoquímica/veterinária , Técnicas Histológicas/veterinária
17.
Int. braz. j. urol ; 41(5): 849-858, Sept.-Oct. 2015. tab, graf
Artigo em Inglês | LILACS | ID: lil-767051

RESUMO

ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/patologia , Células Epiteliais/patologia , Células-Tronco Neoplásicas/patologia , Neoplasias da Próstata/patologia , Células Estromais/patologia , Actinas/análise , Adenocarcinoma/química , Antígenos de Neoplasias/análise , Biomarcadores Tumorais/análise , Progressão da Doença , Proteínas de Ligação a DNA/análise , Células Epiteliais/química , Receptor alfa de Estrogênio/análise , /análise , Proteínas Ligadas por GPI/análise , Imuno-Histoquímica , Fator de Crescimento Insulin-Like I/análise , /análise , Gradação de Tumores , Proteínas de Neoplasias/análise , Células-Tronco Neoplásicas/química , Neoplasias da Próstata/química , Células Estromais/química , Microambiente Tumoral , Fatores de Transcrição/análise , Vimentina/análise
18.
Rev. Inst. Med. Trop. Säo Paulo ; 57(supl.19): 21-24, Sept. 2015.
Artigo em Inglês | LILACS | ID: lil-762057

RESUMO

SUMMARYParacoccidioidomycosis (PCM), caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2%) of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.


RESUMOA paracoccidioidomicose (PCM), causada por Paracoccidioides spp, é importante micose endêmica na América Latina. Com base em diferenças filogenéticas, existem duas espécies reconhecidas de Paracoccidioides, P. brasiliensis e P. lutzii, no entanto, a patogênese e as manifestações clínicas de ambas são indistinguíveis atualmente. Aproximadamente 1853 (~51,2%) de 3583 mortes confirmadas, atribuídas a micoses sistêmicas de 1996-2006, no Brasil foram causadas por PCM. Tratamento antifúngico é necessário para pacientes com PCM. O tratamento inicial dura de dois a seis meses e derivados de sulfa, anfotericina B, azóis e terbinafina são utilizados na prática clínica; no entanto, apesar da terapêutica prolongada, as recaídas ainda são um problema. Uma resposta imune celular eficaz, tendendo a Th1, é essencial para controlar a doença que pode ser induzida por antígenos exógenos, ou moduladas por vacinas profiláticas ou terapêuticas. A estimulação de células B ou a transferência passiva de anticorpos monoclonais também são meios importantes que podem ser utilizados para melhorar a eficácia do tratamento da paracoccidioidomicose no futuro. Esta revisão detalha criticamente os principais desafios que o desenvolvimento de uma vacina para combater a PCM enfrenta.


Assuntos
Animais , Humanos , Camundongos , Antígenos de Fungos/imunologia , Vacinas Fúngicas/imunologia , Paracoccidioides/imunologia , Paracoccidioidomicose/terapia , Vacinas de DNA/imunologia , Antígenos de Neoplasias/imunologia , Glicoproteínas/imunologia , Paracoccidioidomicose/imunologia , Fragmentos de Peptídeos/imunologia
19.
Hist. ciênc. saúde-Manguinhos ; 22(1): 115-141, Jan-Mar/2015.
Artigo em Inglês | LILACS, BDS | ID: lil-741517

RESUMO

This study centers on relationships among national and international actors in preparation of the first health policy document for East Timor, under the United Nations transitional administration, between 1999 and 2002. International cooperation support for the health system rehabilitation process during the post-conflict period is analyzed as part of reconstruction of the State in parallel with construction of the country's political and institutional framework. Knowledge, ideas, "ways of doing," and induced and accepted practices permeate an interplay of power relationships that condition both national political alliance-building and the architecture of international aid, pointing to input to a discussion of how these mechanisms interact at different conjunctures and times in different negotiating frameworks. .


Dedica-se, aqui, às relações entre diferentes atores na elaboração do primeiro documento de política de saúde para o Timor-Leste, sob a administração transitória das Nações Unidas, de 1999 a 2002. O apoio da cooperação internacional no processo de reabilitação do sistema de saúde no período pós-conflito é analisado como parte da reconstrução do Estado e concomitante à construção do arcabouço político e institucional no país. Conhecimentos, ideias, "modos de fazer" e práticas induzidas e aceitas entremeiam um jogo de relações de poder que condiciona tanto a articulação política nacional quanto a arquitetura da ajuda externa, apontando elementos para a discussão de como esses mecanismos se organizam em conjunturas diferentes de negociação.


Assuntos
Humanos , Antígenos de Neoplasias/análise , Carcinoma de Células Escamosas/química , DNA Topoisomerases Tipo II/análise , Proteínas de Ligação a DNA/análise , Neoplasias de Cabeça e Pescoço/química , Imuno-Histoquímica , /análise , Mucosa/química , Lesões Pré-Cancerosas/química , Biomarcadores Tumorais/análise , Biópsia , Estudos de Casos e Controles , Carcinoma de Células Escamosas/patologia , Diagnóstico Diferencial , Progressão da Doença , Neoplasias de Cabeça e Pescoço/patologia , Mucosa/patologia , Valor Preditivo dos Testes , Lesões Pré-Cancerosas/patologia , Fatores de Tempo
20.
Clinics ; 70(3): 169-172, 03/2015. tab
Artigo em Inglês | LILACS | ID: lil-747107

RESUMO

BACKGROUND: To evaluate the macrophage migration inhibitory factor and E-selectin levels in patients with acute coronary syndrome. MATERIALS/METHODS: We examined the plasma migration inhibitory factor and E-selectin levels in 87 patients who presented with chest pain at our hospital. The patients were classified into two groups according to their cardiac status. Sixty-five patients had acute myocardial infarction, and 22 patients had non-cardiac chest pain (non-coronary disease). We designated the latter group of patients as the control group. The patients who presented with acute myocardial infarction were further divided into two subgroups: ST-elevated myocardial infarction (n = 30) and non-ST elevated myocardial infarction (n = 35). RESULTS: We found higher plasma migration inhibitory factor levels in both acute myocardial infarction subgroups than in the control group. However, the E-selectin levels were similar between the acute myocardial infarction and control patients. In addition, we did not find a significant difference in the plasma migration inhibitory factor levels between the ST elevated myocardial infarction and NST-elevated myocardial infarction subgroups. DISCUSSION: The circulating concentrations of migration inhibitory factor were significantly increased in acute myocardial infarction patients, whereas the soluble E-selectin levels were similar between acute myocardial infarction patients and control subjects. Our results suggest that migration inhibitory factor may play a role in the atherosclerotic process. .


Assuntos
Animais , Feminino , Camundongos , /metabolismo , Interferon gama/metabolismo , Neoplasias Mamárias Animais/imunologia , Esferoides Celulares/imunologia , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Auxiliares-Indutores/metabolismo , Alginatos , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Quitosana , /genética , /imunologia , Ácido Glucurônico , Granzimas/metabolismo , Ácidos Hexurônicos , Imunidade Celular , Interferon gama/genética , Interferon gama/imunologia , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/patologia , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Microambiente Tumoral
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