77 research outputs found
Arsenic trioxide as a possible radiosensitizer in pediatric medulloblastoma cell lines
No full textO meduloblastoma (MB) é o tumor maligno cerebral mais frequente em crianças e adolescentes. Trata-se de uma doença heterogênea sob o aspecto genético, sendo reconhecido ao menos 12 subgrupos genético-moleculares, com impacto na apresentação clínicopatológica. Pacientes do subgrupo SHH apresentam mutação somática em genes da via Hedgehog, incluindo PTCH1, SUFU, SMO e ativação dos genes GLI1 e GLI2. Mutações no gene TP53 também podem estar presentes, particularmente em crianças acima de 3 anos, e conferem um pior prognóstico. O trióxido de arsênio (ATO) possui ação inibitória sobre os genes da via SHH, mas pouco se sabe sobre sua ação no MB. O presente estudo objetivou avaliar os potenciais efeitos citotóxicos e radiossensibilizantes do ATO sobre as linhagens de MB pediátrico grupo SHH (ONS-76: TP53-selvagem; DAOY: TP53-mutado c.725G>T e UW402, TP53-mutado c.464C>A). Foram comparadas as taxas de proliferação celular, clonogenicidade e apoptose nas linhagem de MB antes e após o tratamento com ATO. Também foi avaliada a clonogenicidade da associação droga e irradiação. Foram investigadas proteínas responsáveis pelo reparo dos danos causados ao DNA (Rad51 e Ku86) através de Western Blot. Foi realizada análise da expressão gênica relativa por QPCR e estudados genes que integram a via SHH, assim como efetores finais desta via de sinalização. A viabilidade celular foi monitorada nos tempos de 24 à 120 horas pelo ensaio de resazurina. A taxa de apoptose foi mensurada por meio de marcação com anexina e iodeto de propídio e avaliada por citometria de fluxo. Os ensaios foram realizados em triplicata e analisados por One Way e Two Way ANOVA, utilizando o pós-teste Bonferroni, e sendo considerados resultados significativos valores de pA). Cell proliferation, clonogenicity and apoptosis were compared in the MB strains following ATO treatment. The clonogenicity assay of ATO combined with irradiation was also evaluated. We investigated proteins responsible for repairing DNA damage and performed Western blotting of the Rad51 and Ku86 proteins. Gene expression analysis was performed using the real-time PCR. Selected genes integrating the SHH pathway as well as final effectors of signaling were also assesed. Cell viability was monitored at endpoints from 24 to 120h by the resazurin assay. The rate of apoptosis was measured by labeling with annexin and propidium iodide, as assessed by flow cytometry. The assays were performed in triplicate and analyzed by One Way and Two Way ANOVA, using the Bonferroni post-test, and being considered significant results a p value less than 0.05. It was possible to observe a decrease in cell viability in the three studied strains. In addition, there was a significant decrease in clonogenic capacity. There was also an increase in the apoptosis rates in the lineages, being above 70% of cell death for the DAOY lineage. It was found that the ATO treatment radiosensitized the UW402 strain - TP53-mutated. No association with time and dose of ATO and irradiation on the repair proteins was found. The study of the relative expressions of the studied genes demonstrated inhibition, mainly in the mutant line of interest DAOY and UW-402, a SHHTP53 mutated cell-line. These in vitro findings point to a cytotoxic effect of ATO on pediatric medulloblastoma lines, with a potential radiosensitizing effect. This study offers rationale for further assesment of ATO on SHH-MB, either alone or along with radiotherapy as a preclinical drug
Data for: Spatial genetic structure of a keystone long‑lived semiarid shrub: historical efects prevail but do not cancel the impact of recent severe habitat loss on genetic diversity
No full textThis is the data corresponding to the paper: González-Robles, A., Manzaneda, A. J., Salido, T., Valera, F., García, C., Fernández-Ocaña, A. M., & Rey, P. J. (2020). Spatial genetic structure of a keystone long-lived semiarid shrub: historical effects prevail but do not cancel the impact of recent severe habitat loss on genetic diversity. Conservation Genetics, 21(5), 853-867. (doi: https://doi.org/10.1007/s10592-020-01291-5) . For study design and sampling methods, please see the paper or contact with the corresponding author
Uso de OK-432 em crianças com linfangioma OK-432 therapy for lymphangioma in children
No full textOBJETIVO: Relatar a experiência no uso do OK-432 para tratamento de linfangiomas em crianças. MÉTODOS: Estudo retrospectivo de 19 crianças com linfangioma tratadas com OK-432 no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP, durante o período de 1999 a 2003. RESULTADOS: Todos os pacientes apresentaram alguma resposta ao OK-432, 12 pacientes apresentaram regressão total, sete apresentaram regressão parcial variando de 50% a 80%. Os pacientes apresentaram febre após a aplicação da droga com duração de 2 a 10 dias. Não se observaram cicatrizes após a aplicação do OK-432. CONCLUSÕES: A droga OK-432 é segura, eficaz e pode ser utilizada como primeira escolha no tratamento de pacientes com linfangiomas devido à excelente resposta, podendo tornar desnecessária a realização de cirurgia. Em pacientes com resposta parcial, podem ser realizadas novas aplicações de OK-432 ou cirurgia menos mutilante, devido à redução das dimensões da lesão.OBJECTIVE: To report the experience with OK-432 therapy for lymphangioma in children. METHODS: Retrospective study of 19 children with lymphangioma treated with OK-432 in Ribeirão Preto, state of São Paulo, Brazil, between 1999 and 2003. RESULTS: All patients presented response to OK-432, 12 had total shrinkage and seven had partial shrinkage varying from 50% to 80%. Patients had fever after injections of OK-432 for 2 to 10 days, no damage to the overlying skin was observed. CONCLUSION: OK-432 is safe, effective and can be used as primary choice of treatment of patients with lymphangiomas because of the excellent response. In these cases surgery should not be necessary. In patients with partial regression new injections of OK-432 must be used to shrink the lesion. Thereby safely surgery could be made
3q27 Aberrations in a Childhood Ovary Teratoma With Associated Malignant Germ Cell Component
No full textCytogenetic Studies of childhood ovary tumors have been poorly described. in the present article, the cytogenetic findings of an ovarian teratoma with malignant germ cell (yolk-sac) component occurring in an 8-year-old female are detailed. GTG-banding showed a karyotype of 46,XX, t(3;20)(q27;q13.3) [4]/46,XX, del3q27 [3]/46,XX [30]. Previous Studies have demonstrated common sites of loss of heterozygosity at 3q27-q28 region in different types of cancer, suggesting the presence of tumor Suppressor genes within this region. Pediatr Blood Cancer 2009;52:398-401. (C) 2008 Wiley-Liss, Inc.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP[07/54236-4]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP[06/04827-3
Rheological Behaviour of WMA-Modified Asphalt Binders with Crumb Rubber
No full textCrumb rubber (CR) is one of the materials most widely used in the road infrastructure industry due to its mechanical and environmental benefits as an asphalt binder modifier. Nonetheless, CR decreases the workability of mixes by increasing the viscosity of the binder, leading to an increase in the production temperatures of asphalt mixes. However, warm mix technologies can reduce the temperature demand associated with these processes. The preceding explains the growing interest in producing rubberised asphalt binders incorporating warm mix asphalt (WMA) additives. In this research, the mechanical and rheological properties of a 60/70 penetration grade asphalt binder modified with CR (at a dosage of 15, 18 and 21% by the wet process) and WMA chemical additives (Evotherm M1 and Iterlow T) were investigated. Laboratory tests included penetration, softening point, rotational viscosity, frequency sweep through dynamic shear rheometer (DSR), and multiple stress creep recovery (MSCR) tests. The results indicate that CR increases the stiffness of the asphalt binder, which is reflected in a lower penetration grade and improved softening point. It also improves its rutting resistance but decreases fatigue performance. Furthermore, it has been shown that under the conditions studied, the higher the CR content, the more elevated the degree of stiffness and performance of the asphalt binder. On the other hand, WMA technology decreases asphalt stiffness and performance at high temperatures
Anti-CD20 monoclonal antibody therapy and minimal residual disease status of T-cell/histiocyte-rich large B cell non-Hodgkin lymphoma
No full textCryptic SYT/SXX1 fusion gene in high-grade biphasic synovial sarcoma with unique complex rearrangement and extensive BCL2 overexpression
No full textSynovial sarcomas are high-grade malignant mesenchymal tumors that account for 10% of all soft-tissue sarcomas. Almost 95% of these tumors are characterized by a nonrandom chromosomal abnormality, t(X;18)(p11.2;q11.2), that is observed in both biphasic and monophasic variants. In this article, we present the case of a 57-year-old woman diagnosed with high-grade biphasic synovial sarcoma in which conventional cytogenetic analysis revealed the constant presence of a unique t(18;22)(q12;q13), in addition to trisomy 8. The rearrangement was confirmed by fluorescence in situ hybridization. The use of the whole chromosome painting probes WCPX did not detect any rearrangements involving chromosome X, although reverse-transcriptase polymerase chain reaction (PCR) analysis demonstrated the conspicuous presence of a SYT/SXX1 fusion gene. Spectral karyotyping (SKY) was also performed and revealed an insertion of material from chromosome 18 into one of the X chromosomes at position Xp11.2. Thus, the karyotype was subsequently interpreted as 47,X,der(X)ins(X;18) (p11.2;q11.2q11.2),der(18)del(18)(q11.2q11.2)t(18;22)(q12;q13),der(22)t(18;22). Real-time PCR analysis of BCL2 expression in the tumor sample showed a 433-fold increase. This rare finding exemplifies that thorough molecular-cytogenetic analyses are required to elucidate complex and/or cryptic tumor-specific translocations. (C) 2010 Elsevier Inc. All rights reserved.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[06/04827-3]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[07/54236-4
Ethical analysis of the golden rule in light of John Stuart Mill utilitarianism.
No full textA partir de la lectura de El utilitarismo de John Stuart Mill, este trabajo busca realizar, por un lado, una caracterización de la propuesta ética milleana; y, por otro, caracterizar la regla de oro desde dos perspectivas: una religiosa y otra secular. Esto se realiza con el propósito de responder a las siguientes preguntas: ¿es compatible la regla de oro, desde una perspectiva religiosa, con el utilitarismo de Mill? Y ¿es compatible la regla de oro, desde una perspectiva secular, con el utilitarismo de Mill?Licenciado en FilosofíaPregradoFrom the reading of The Utilitarianism by John Stuart Mill, this work wants to propose, on the one hand, a characterization of the Mill’s ethical proposal. On the other hand, it is intended to characterize its guiding principle from two perspectives: religious and secular one. This is done with the purpose of answering the following questions: Is the guiding principle compatible, from a religious perspective, with Mill's utilitarianism? And is the guiding principle, from a secular perspective, compatible with Mill's utilitarianism
Economic evaluation of housing subsidy systems: a methodology with application to Morocco
No full textMost countries do not use one single type of housing subsidy but combine many of them. The author provides operational criteria that allow evaluation of systems of housing subsidies, both at the individual program level and at the aggregate (country) level. The author examines the public finance assessment criteria used by different authors to analyze subsidy programs and confront them systematically. The author ends up with a map of criteria, which covers the range of topics interesting to policymakers. For each criterion, the author tries to provide empirical measures that can be retrieved from existing programs. The author then provides an aggregation method allowing a synthesis of diagnoses about the quality of the housing subsidies system at the country level. The aggregation technique offers a simple way to visualize the main features of a subsidy system, as well as the effects on the system of reforms or improvements of particular programs. The author applies the methodology to the system prevailing in Morocco in 1995 and 2004. The analysis shows that the most visible subsidies might not have been the most inefficient, nor the most resource consuming for the state. Examination of policy changes since 1995 shows that while the most visible subsidies received nearly all the government's attention, large invisible subsidies remain at the heart of Morocco's housing policy. The framework used here is very general and can be used to compare the Moroccan system with those of similar countries.Environmental Economics&Policies,Public Sector Economics&Finance,Housing Finance,Banks&Banking Reform,Non Bank Financial Institutions,Public Sector Economics&Finance,Banks&Banking Reform,Housing Finance,Non Bank Financial Institutions,Municipal Financial Management
Cytogenetic findings in pediatric radiation-induced atypical meningioma after treatment of medulloblastoma: case report and review of the literature
No full textIonizing radiation is the most recognized risk factor for meningioma in pediatric long-term cancer survivors. Information in this rare setting is exceptional. We report the clinical and cytogenetic findings in a radiation-induced atypical meningioma following treatment for desmoplastic medulloblastoma in a child. This is the second study to describe the cytogenetic aspects on radiation-induced meningiomas in children. Chromosome banding analysis revealed a 46, XX, t(1;3)(p22;q12), del(1)(p?)[8]/46, XX[12]. Loss of chromosome 1p as a consequence of irradiation has been proposed to be more important in the development of secondary meningiomas in adults. Deletions in the short arm of chromosome 1 also appear to be a shared feature in both pediatric cases so far analyzed.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2010/15,717-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP
- …
