1,721,221 research outputs found
Observações sobre o uso clínico de interferon alfa como modulador da expressão de antígenos de superfície em melanoma maligno metastático
Get PDFo autor avaliou a capacidade de retenção do anticorpo monoclonal22528S, o qual reconhece antígenos de alto peso molecular na. superficie de células de melanoma maligno humano, em 49 pacientes com confirmação histopatológica da neoplasia, após a administração endovenosa do anticorpo marcado com tecnécio, e posterior quantificação da captação tumor/tecido normal, através de imunocintilografia. Uma vez confirmada a segurança do método e a localização preferencial do imunoconjugado no tecido tumoral, o autor estudou o efeito do interferon alfa como modulador da expressão de antígenos de superficie e, por conseguinte, o seu potencial impacto na retenção do imunoconjugado no tecido tumoral. Utilizando o paciente como seu próprio controle, foi possível observar um incremento na retenção do imunoconjugado em sítios metastáticos pré-definidos em 8/10 pacientes. Dada a complexidade do fenômeno e o limitado número de casos estudados, optou-se pelo não tratamento estatístico dos dados e sim por sua discussão sob a forma preliminar. Pôde-se caracterizar uma tendência à maior concentração do imunoconjugado no tumor após o uso do interferon alfa. Cabe ressaltar que, em um caso, foi documentada conversão de uma metástase não-captante em uma lesão altamente captante após a administração do imunomodulador. Esta estratégia não havia sido estudada previamente em pacientes portadores desta neoplasia. Considerando a potencial aplicação diagnóstica e \ terapêutica do uso de anticorpos monoclonais em neoplasias malignas, esta observação de um efeito modulador da expressão de antígenos tumorais específicos, através da administração concomitante de interferon alfa, aumentando a retenção do anticorpo no tecido tumoral, poderá vir a representar um valioso recurso no futuro.The author evaluated the ability of the monoclonal antibody 22825S, which recognizes high-molecular weight cell surfàce antigens in human malignant melanoma, of being retained preferentially in 49 patients with histopathologically-proven malignant melanoma, following the intravenous administration of the thecnecium-labelled monoclonal ,antibody. The retention of the immunoconjugate in the tumor versus normal tissues was measured using irrilllunocintilographic tools. Following the documentation of the safety, feasibility and preferential antibody retention in the tumor tissue of melanoma patients, the author studied the effect of alpha-interferon as a modulator of cell surface antigen expression and thus, its impact on the retention of the immunoconjugate in the tumor. Using each patient as his own control, an enhancement of antibody localization in the tumor was demonstrated in 8 out of 10 cases. Due to the complexity of this phenomenon and the limited number of patients, the author decided to describe the results as preliminary observations without application of statistical tools. Notably, the administration of alpha interferon was able to convert a "cold" but histopathologically-confirmed metastatic lesion in one patient in a highly positive site, as quantified by immunocintilography. To the knowledge of the author, the above strategy was never applied to malignant melanoma patients before. Considering the potential application of monoclonal antibodies in cancer \ diagnostic and therapy, the above mentioned provocative observation of a modulatory effect of tumor antigens expression by interferons in men, leading to an increased retention of the antibody at the tumor site, may have important applications in the future
Ensaios clínicos com derivados das podofilotoxinas em pacientes portadores de sarcoma de Kaposi associado à síndrome de imunodeficiência adquirida (SK-SIDA)
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
International scientific collaboration in HIV and HPV: a network analysis
Get PDFResearch endeavours require the collaborative effort of an increasing number of individuals. International scientific collaborations are particularly important for HIV and HPV co-infection studies, since the burden of disease is rising in developing countries, but most experts and research funds are found in developed countries, where the prevalence of HIV is low. The objective of our study was to investigate patterns of international scientific collaboration in HIV and HPV research using social network analysis. Through a systematic review of the literature, we obtained epidemiological data, as well as data on countries and authors involved in co-infection studies. The collaboration network was analysed in respect to the following: centrality, density, modularity, connected components, distance, clustering and spectral clustering. We observed that for many low- and middle-income countries there were no epidemiological estimates of HPV infection of the cervix among HIV-infected individuals. Most studies found only involved researchers from the same country (64%). Studies derived from international collaborations including high-income countries and either low- or middle-income countries had on average three times larger sample sizes than those including only high-income countries or low-income countries. The high global clustering coefficient (0.9) coupled with a short average distance between researchers (4.34) suggests a “small-world phenomenon.” Researchers from high-income countries seem to have higher degree centrality and tend to cluster together in densely connected communities. We found a large well-connected community, which encompasses 70% of researchers, and 49 other small isolated communities. Our findings suggest that in the field of HIV and HPV, there seems to be both room and incentives for researchers to engage in collaborations between countries of different income-level. Through international collaboration resources available to researchers in high-income countries can be efficiently used to enroll more participants in low- and middle-income countries.<br/
Observações preliminares sobre a segurança e a atividade anti-tumoral da combinação do agente hipometilador do DNA decitabina com daunorubicina como tratamento de primeira linha em pacientes com leucemia mielóide aguda
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Avaliação genotípica e fenotípica da farmacocinética do irinotecano e sua relação com a ocorrência de toxicidade no tratamento do câncer
Get PDFIntrodução: Irinotecano (IRI) é um pró-fármaco convertido em seu metabólito ativo SN-38 pela ação das carboxilesterases hepáticas. O SN-38 é o principal responsável pela resposta antitumoral do IRI e também pelas toxicidades limitantes da dose, neutropenia e diarreia. O polimorfismo UGT1A1 * 28 está associado a neutropenia grave e / ou diarreia. CYP3A também desempenha um papel na inativação de IRI. Nosso objetivo é caracterizar a biotransformação do IRI e SN-38 no grupo estudado, estabelecendo sua relação com as variáveis genéticas, bioquímicas e demográficas avaliadas, bem como com a ocorrência de efeitos tóxicos associados à quimioterapia. Métodos: Foram incluídos pacientes com indicação oncológica para tratamento com protocolos com IRI. Uma amostra de sangue foi coletada 15 minutos após a infusão para determinar as concentrações de IRI, SN-38 e SN-38G. Os dados de eventos adversos foram analisados e classificados a partir de consultas clínicas. As concentrações de IRI, SN-38 e SN-38G no plasma foram medidas por cromatografia líquida de alta eficiência. Os polimorfismos de UGT1A1, CYP3A e DYPD foram avaliados. As razões farmacocinéticas foram comparadas entre grupos de toxicidade e genótipos pelo teste de Mann-Whitney. Variáveis quantitativas foram associadas à análise de correlação de Spearman. As associações entre grupos de toxicidade e genótipos e fenótipos UGT1A1, CYP3A e DPYD foram examinadas por meio de testes de qui-quadrado ou exato de Fisher. A avaliação dos pontos de corte da razão de dose [SN38] / IRI para identificar qualquer evento adverso grave e diarreia foi definida usando a área sob a análise da curva característica operada pelo receptor (ROC). Um valor de P ≤ 0,05 foi considerado estatisticamente significativo. Resultados Quarenta e três pacientes foram incluídos neste estudo de janeiro de 2019 a janeiro de 2020. A frequência de eventos adversos de grau 3 ou 4 (G3 / 4) foi de 39,5%. Os principais eventos adversos G3 / 4 foram: diarreia (30,2%) e neutropenia (27,9%). . Detectou-se que 9,3% dos pacientes apresentavam o genótipo UGT1A1 * 28 / * 28. Considerando a graduação da atividade do UGT1A1 prevista a partir do genótipo, 34,9% apresentaram atividade metabólica extensa, 51,2% intermediária e 9,3% reduzida. A pontuação da atividade do CYP3A foi: 4,7% eram metabolizadores lentos, 58,1% eram metabolizadores intermediários e 34,9% eram metabolizadores extensos. A relação de dose SN 38 / IRI foi maior em pacientes com eventos adversos graves, com uma mediana de 0,1 (0,075-0,12) versus 0,049 (0,038-0,076) no grupo sem toxicidade grave, p <0,00001. A relação de dose [SN38] / IRI teve uma área sob a curva ROC de 0,823 (IC 95% 0,69-0,956) para detectar qualquer evento adverso grave e 0,833 (IC 95% 0,694 - 0,973) para detectar diarreia grave. os pacientes com atividade UGT1A1 reduzida, encontramos que 75% tinham diarreia grave, comparando com 5% e 13,3% nos grupos de atividade intermediária e extensa, respectivamente. Conclusão Uma população brasileira com dados farmacogenéticos e farmacocinéticos foi caracterizada. A medida da dose SN38 / IRI apresentou correlação significativa com eventos adversos graves e apresentou bons resultados como ferramenta diagnóstica, com alta sensibilidade e especificidade. A atividade reduzida de UGT1A1 foi relacionada a diarreia grave.Introduction: IRI is a prodrug converted to its active metabolite SN-38 through the action of liver carboxylesterases. SN-38 is the main responsible for the antitumor response of IRI, and also for the dose-limiting toxicities, neutropenia and diarrhea. UGT1A1*28 polymorphism is associated with severe neutropenia and/or diarrhea. CYP3A also plays a role in the inactivation of IRI. We aim to characterize the biotransformation of IRI and SN-38 in the studied group, establishing its relationship with the genetic, biochemical and demographic variables evaluated, as well as with the occurrence of toxic effects associated with chemotherapy. Methods: Patients with oncologic indication to treatment with protocols with IRI were included . A blood sample was collected 15 min after the infusion to determine concentrations of IRI, SN- 38, and SN-38G. Adverse event data were analyzed and graded from clinical consultations. IRI, SN-38 and SN-38G concentrations in plasma were measured by high-performance liquid chromatography. The polymorphisms of UGT1A1, CYP3A and DYPD were assessed. Pharmacokinetics ratios were compared between toxicity groups and genotypes by Mann- Whitney test. Quantitative variables were associated with Spearman correlation analysis. Associations among groups of toxicity and UGT1A1, CYP3A, and DPYD genotypes and phenotypes were examined through Chi-square or Fisher exact tests. The evaluation of [SN38]/IRI dose ratio cut-offs for identifying any severe adverse event and diarrhea was set using area under the receiver operated characteristic (ROC) curve analysis. A P-value of ≤ 0.05 was considered statistically significant. Forty-three patients were included in this study from January of 2019 to January of 2020. The frequency of grade 3 or 4 (G3/4) adverse events was 39.5%. The main adverse events G3/4 were: diarrhea (30.2%) and neutropenia (27.9%). . It was detected that 9.3% of patients showed the UGT1A1*28/*28 genotype. Considering the graduation of UGT1A1 activity predicted from genotype, 34.9% had extensive, 51.2% intermediate and 9.3% reduced metabolic activity. CYP3A activity score was: 4,7% were slow metabolizers, 58,1% were intermediante metabolizers and 34,9% were extensive metabolizers. The SN 38/IRI dose ratio was higher in patients with serious adverse events, with a median of 0.1 (0.075-0.12) versus 0.049 (0.038-0.076) in the group without severe toxicity, p <0.00001. [SN38]/IRI dose ratio had an area under the ROC curve of 0.823 (95% CI 0.69-0.956) to detect any severe adverse event and 0.833 (95%CI 0.694 – 0.973) to detect severe diarrhea. the patients with reduced UGT1A1 activity, we found that 75% had severe diarrhea, comparing to 5% and 13.3% in the groups of intermediate and extensive activity, respectively. Conclusion A brazilian population with pharmacogenetic, and pharmacokinetic data was characterized. The measuremet of the SN38/IRI dose showed a significant correlation with serious adverse events and showed good results as a diagnostic tool, with high sensitivity and specificity. Reduced UGT1A1 activity was related to severe diarrhea
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Expressão do receptor de tropomiosina quinase B em melanoma : associação com fatores prognósticos
Get PDFBase teórica: Normalmente, a ativação dos receptores de tropomiosina relacionados à quinase (TRKs) pelas neurotrofinas (NTs) estimulam as vias intracelulares envolvidas na sobrevida e na proliferação celular. A desregulação da sinalização NT/TRK pode afetar o prognóstico de várias neoplasias. Os dados sobre a expressão de NTs e TRKs no melanoma cutâneo são limitados e não está claro se as vias de sinalização NT/TRK estão envolvidas na origem e progressão dessa neoplasia. Objetivo: Nós examinamos se a expressão de NT/TRK difere em relação aos estágios e subtipos de melanoma cutâneo, e se está associada com o prognóstico e a sobrevida dos pacientes com essa neoplasia. Métodos: Foi realizado um estudo transversal, no qual foi analisado através de imunohistoquímica, as expressões de TrkB e BDNF, além da expressão de outro TRK, o TrkA, e de seu coefetor, o NGF, em 154 amostras de melanoma. Nós investigamos as associações da expressão de NT/TRK com diferentes fatores prognósticos para melanoma, sobrevida livre de recidiva (SLR) e sobrevida global (SG). Também foram avaliadas 48 amostras de pele normal e lesões cutâneas pigmentares benignas. Resultados: Das 154 amostras de melanoma, 81 (58,3%) foram imunopositivas para TrkB, 113 (81,3%) foram imunopositivas para BDNF, 77 (55,4%) foram imunopositivas para TrkA, e 104 (75,4%) foram imunopositivas para NGF. Encontramos forte associação entre a expressão de NT/TRK e vários fatores prognósticos, incluindo estágio TNM (p<0,001), subtipo histológico (p<0,001) e nível de Clark (p<0,05). Também foi encontrada associação entre a imunopositividade das NTs e TRKs, e piores resultados de SG (p<0,05, exceto TrkB) e SLR (p<0,05 em todos). Conclusão: Nossos resultados mostram uma forte associação entre a expressão de NT/TRK, a progressão do melanoma cutâneo e um pior prognóstico.Background: Normally, activation of tropomyosin-related kinase (TRK) receptors by neurotrophins (NTs) stimulates intracellular pathways involved in cell survival and proliferation. Dysregulation of NT/TRK signaling may affect neoplasm prognosis. Data on NT and TRK expression in melanomas are limited and it is unclear whether NT-TRK signaling pathways are involved in the origin and progression of this neoplasm. Objective: We examined whether NT/TRK expression differs across different cutaneous melanoma grades and subtypes and whether it is associated with melanoma prognosis and survival.!! Methods: A cross-sectional study was performed in which the expression of TrkA, TrkB, nerve growth factor (NGF), and brain-derived neurotrophoic factor (BDNF) were analyzed by immunohistochemistry (IHC) of 154 melanoma samples. We investigated NT/TRK expression associations with prognostic factors for melanoma, relapse-free survival (RFS), and overall survival (OS).!We also evaluated 48 samples of normal skin or benign pigment cell lesions. Results: Of the 154 melanoma samples, 81 (58.3%) were TrkB immunopositive, 113 (81.3%) were BDNF immunopositive, 77 (55.4%) were TrkA immunopositive, and 104 (75.4%) were NGF immunopositive. We found NT/TRK expression associated strongly with several clinical prognostic factors, including tumor-node-metastasis (TNM) stage (p < 0.001), histological subtype (p < 0.001), and Clark level (p < 0.05), as well as with a worse OS (p < 0.05 for all, except TrkB) and RFS (p < 0.05 for all). Conclusion: Our results show strong associations of NT/TRK expression with melanoma stage progression and a poor prognosis
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