Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinib

Expression of tyrosine kinase receptor AXL is associated with worse outcome of metastatic renal cell carcinomas treated with sunitinibBackground: Renal cell carcinoma (RCC) represents 2%-3% of all cancers of the Western countries. Currently, sunitinib, a receptor tyrosine kinase inhibitor, particularly of PDGF and VEGF receptors, is the first-line therapy for metastatic RCC (mRCC), with significant improvement in clinical outcome. However, there is a lack of predictive biomarkers of sunitinib response. Recently, others and our group suggested that the receptor tyrosine kinase AXL may modify the response to sunitinib. Objective: To study the expression of AXL in a series patients with of mRCC treated with sunitinib and to correlate it with patient's clinic-pathological features and therapeutic response. Material and methods: Sixty-four patients with mRCC (51 clear cell carcinomas (CCCs) and 13 non-CCCs) were evaluated for AXL expression by immunohistochemistry in the primary tumor. Results: AXL positivity was observed in 47% (30/64) of cases, namely in 43% (22/51) of CCCs and 61% (8/13) of non-CCC. Considering only the clear cell subtype, the univariate analysis showed that AXL expression was statistically associated with a poor prognosis, with a median overall survival of 13 months vs. 43 months in patients with negative AXL. In this subtype, along with the AXL positivity, other prognostic factors were absence of nephrectomy, Karnofsky performance status, more than 1 site of metastasis and liver metastasis. Moreover, AXL expression was associated with shorter progression to sunitinib. Overall, the multivariate survival analysis showed that absence of nephrectomy (HR = 4.85, P = 0.001), more than 1 site of metastasis (HR = 2.99, P = 0.002), bone metastasis (HR = 2.95, P = 0.001), together with AXL expression (HR = 2.01, P = 0.048) were independent poor prognostic factor in patients with mRCC. Conclusion: AXL expression was associated with worse clinical outcome and may be an important prognostic biomarker in sunitinibtreated patients with metastatic renal cell carcinoma.this study was supported by Barretos Cancer Hospital Internal Research Funds (PAIP) of participant authors. Rui Manuel Reis is recipient of a National Council of Technological and Scientific Development (CNPq) scholarship.info:eu-repo/semantics/publishedVersio

The metabolic microenvironment of melanomas: prognostic value of MCT1 and MCT4

BRAF mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. BRAF mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. NRAS mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.This work was supported by FAPESP grant to VLV (2012/04194-1) and CP (2015/25351-6). VMG received a doctoral fellowship (SFRH/BD/51997/2012) from Fundacao para a Ciencia e a Tecnologia (FCT) and ON. 2 SR&TD Integrated Program (NORTE-07-0124-FEDER-000017) co-funded by Programa Operacional Regional do Norte (ON.2- O Novo Norte), Quadro de Referencia Estrategico Nacional (QREN), through Fundo Europeu de Desenvolvimento Regional (FEDER).info:eu-repo/semantics/publishedVersio

Immunological profiles of patients from endemic areas infected with Schistosoma mansoni

Crude extracts of eggs (SEA) adult worms (SWAP) or cercariae (Cerc) have been used to stimulate Peripheral Blood Mononuclear cells (PBMC) and have provided rather distinct profiles of responses in different types of patients. In genenral it is clear that patients with early infections respond strongly to SEA while response to SWAP are developed more slowly. As infection progresses into the more chronic phases, a general pattern is seen whic leads to lower anti-SEA proliferative responses in the face of higher responses to SWAP and variable anti-cerc responsiveness. Cured not re-exposed patients express very high levels of anti-SEA proliferation. It has recently been seen that those individuals who live in endemic areas and have continued water contact, but are reapeatedly stool-negative (who are presumed to have self-cured or be putatively resistant; endemic normals) are strongly responsive to antigenic extracts, particularly to SEA. Furthermore, our results show that endemic normal individuals have significantly higher IFN gamma production upon PBMC stimulation with schistosome antigens than infected individuals. With the emergence of more studies it is becoming apparent that both the intensity and the prevalence of a given area may influence or shape the general responsiveness of the population under study

Open innovation in public management: analysis of the Brazilian action plan for Open Government Partnership

Este estudo objetivou analisar o Plano de Ação brasileiro para o Governo Aberto, baseado na teoria da inovação aberta na gestão pública. Utilizou-se de uma pesquisa documental, com vistas a aprofundar o conhecimento do fenômeno em questão. O documento foi escolhido intencionalmente, por ser exemplo basilar das políticas públicas relacionadas à inovação aberta brasileira. Os resultados mostram que os compromissos firmados pelo governo brasileiro estão consoantes com o processo de inovação aberta pública. As ações previstas no Plano estão especificamente relacionadas a transparência, abertura de dados e preparação do corpo estatal para o processo aberto de inovação. _________________________________________________________________________________________ RESUMEN: Este estudio tuvo como objetivo analizar el Plan de Acción de Brasil para el Gobierno Abierto con base en la teoría de la innovación abierta en la gestión pública. Se utilizó una investigación documental, con el fin de profundizar el conocimiento en el fenómeno en cuestión. El documento fue elegido intencionadamente porque es fundamental para las políticas públicas relacionadas con la innovación abierta brasileña. Los resultados muestran que los compromisos asumidos por el gobierno brasileño son compatibles con el proceso de innovación abierta pública. En concreto, las acciones contenidas en el plan están relacionados con la transparencia, los datos abiertos y preparación de la estructura de gobierno para el proceso abierto de innovación. _________________________________________________________________________________________ ABSTRACT: This study aims to analyze the Brazilian action plan for Open Government, based on the theory of open innovation in public management. Documentary research was used, in order to deepen of the knowledge the phenomenon being discussed . The document was intentionally chosen because it is essential for public policies related to Brazilian open innovation The results show that the commitments made by the Brazilian government are compatible with the public open innovation process. The actions in the Plan are related specifically to transparency, open data and preparation of the governance body for the open innovation process

Is the gastrointestinal stromal tumor arising in the rectovaginal septum an extragastrointestinal entity? A time for reflection

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Deregulated microRNAs Are Associated with Patient Survival and Predicted to Target Genes That Modulate Lung Cancer Signaling Pathways

(1) Background: Although the advances in diagnostic and treatment strategies, lung cancer remains the leading cause of cancer-related deaths, worldwide, with survival rates as low as 16% in developed countries. Low survival rates are mainly due to late diagnosis and the lack of effective treatment. Therefore, the identification of novel, clinically useful biomarkers is still needed for patients with advanced disease stage and poor survival. Micro(mi)RNAs are non-coding RNAs and potent regulators of gene expression with a possible role as diagnostic, prognostic and predictive biomarkers in cancer. (2) Methods: We applied global miRNA expression profiling analysis using TaqMan® arrays in paired tumor and normal lung tissues (n = 38) from treatment-naïve patients with lung adenocarcinoma (AD; n = 23) and lung squamous cell carcinoma (SCC; n = 15). miRNA target genes were validated using The Cancer Genome Atlas (TCGA) lung AD (n = 561) and lung SCC (n = 523) RNA-Seq datasets. (3) Results: We identified 33 significantly deregulated miRNAs (fold change, FC ≥ 2.0 and p < 0.05) in tumors relative to normal lung tissues, regardless of tumor histology. Enrichment analysis confirmed that genes targeted by the 33 miRNAs are aberrantly expressed in lung AD and SCC, and modulate known pathways in lung cancer. Additionally, high expression of miR-25-3p was significantly associated (p < 0.05) with poor patient survival, when considering both tumor histologies. (4) Conclusions: miR-25-3p may be a potential prognostic biomarker in non-small cell lung cancer. Genes targeted by miRNAs regulate EGFR and TGFβ signaling, among other known pathways relevant to lung tumorigenesis

The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4

<p><i>BRAF</i> mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. <i>BRAF</i> mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. <i>NRAS</i> mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.</p

WUE and CO₂ Estimations by Eddy Covariance and Remote Sensing in Different Tropical Biomes

The analysis of gross primary production (GPP) is crucial to better understand CO2 exchanges between terrestrial ecosystems and the atmosphere, while the quantification of water-use efficiency (WUE) allows for the estimation of the compensation between carbon gained and water lost by the ecosystem. Understanding these dynamics is essential to better comprehend the responses of environments to ongoing climatic changes. The objective of the present study was to analyze, through AMERIFLUX and LBA network measurements, the variability of GPP and WUE in four distinct tropical biomes in Brazil: Pantanal, Amazonia, Caatinga and Cerrado (savanna). Furthermore, data measured by eddy covariance systems were used to assess remotely sensed GPP products (MOD17). We found a distinct seasonality of meteorological variables and energy fluxes with different latent heat controls regarding available energy in each site. Remotely sensed GPP was satisfactorily related with observed data, despite weak correlations in interannual estimates and consistent overestimations and underestimations during certain months. WUE was strongly dependent on water availability, with values of 0.95 gC kg−1 H2O (5.79 gC kg−1 H2O) in the wetter (drier) sites. These values reveal new thresholds that had not been previously reported in the literature. Our findings have crucial implications for ecosystem management and the design of climate policies regarding the conservation of tropical biomes, since WUE is expected to change in the ongoing climate change scenario that indicates an increase in frequency and severity of dry periods

Sólidos de revolução

Esta coleção reúne objetos interativos para o ensino da Geometria Espacial, especificamente os sólidos de revolução, tais como esfera, cilindro e con