De Novo Aml Exhibits Greater Microenvironment Dysregulation Compared To Aml With Myelodysplasia-related Changes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T-lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRC-derived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1 beta, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu.7Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Focus-and-Context Skeleton-Based Image Simplification Using Saliency Maps

Medial descriptors offer a promising way for representing, simplifying, manipulating, and compressing images. However, to date, these have been applied in a global manner that is oblivious to salient features. In this paper, we adapt medial descriptors to use the information provided by saliency maps to selectively simplify and encode an image while preserving its salient regions. This allows us to improve the trade-off between compression ratio and image quality as compared to the standard dense-skeleton method while keeping perceptually salient features, in a focus-and-context manner. We show how our method can be combined with JPEG to increase overall compression rates at the cost of a slightly lower image quality. We demonstrate our method on a benchmark composed of a broad set of images

De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes

The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T-lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRC-derived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1 beta, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Univ Estadual Campinas, Hematol & Transfus Med Ctr, Hemoctr Unicamp, Inst Nacl Ciencia & Tecnol Sangue, Sao Paulo, BrazilUniv Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biol Sci, Sao Paulo, BrazilFed Univ Vale do Sao Francisco, Paulo Afonso, BA, BrazilUniv Fed Sao Paulo, Dept Biol Sci, Sao Paulo, BrazilWeb of Scienc

IRS2 (insulin receptor substrate 2)

Insulin receptor substrate 2 (IRS2) belongs to the insulin receptor substrate protein family and was initially discovered as an alternative route for signaling mediated by the insulin receptor. Currently, IRS2 has been well-established to mediate mitogenic and antiapoptotic signaling from several important cellular receptors. In the last years, many studies have indicated that IRS2 participates in the regulation of important biological processes involved in cancer phenotype, including cell proliferation, clonogenicity, metabolism and survival. The present review contains data on IRS2 DNA/RNA, protein encoded and function

Stathmin 1 Inhibition Amplifies Ruxolitinib-induced Apoptosis In Jak2(v617f) Cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)The JAK/STAT pathway is constitutively activated in myeloproliferative neoplasms and can be inhibited by ruxolitinib, a selective JAK1/2 inhibitor. The JAK2(V617F) mutation leads to constitutive STAT3 phosphorylation and potentially leads to inhibition of Stathmin 1 activity via STAT3. In support of this hypothesis, we found that, in HEL JAK2(V617F) cells, ruxolitinib treatment decreased STAT3 and Stathmin 1 association, induced Stathmin 1 activation and microtubule instability. Silencing of Stathmin 1 significantly reduced cell proliferation and clonal growth, and increased apoptosis induced by ruxolitinib. Stathmin 1 silencing also prevented ruxolitinib-induced microtubule instability. To phenocopy the effect of Stathmin 1 inhibition, cells were treated with paclitaxel, a microtubule-stabilizing drug, in association or not with ruxolitinib; combined treatment significantly increased apoptosis, when compared to monotherapy. Notably, Stathmin 1 mRNA levels were highly expressed in CD34(+) cells from primary myelofibrosis patients. We then proposed that an undesired effect of ruxolitinib treatment may constitute Stathmin 1 activation and microtubule instability in JAK2(V617F) cells. Induction of microtubule stability, through Stathmin 1 silencing or paclitaxel treatment, combined with ruxolitinib could be an effective strategy for promoting apoptosis in JAK2(V617F) cells.6302957329584Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [610021/2009-5, 2011/06840-5, 2011/51959-0, 2012/09982-8, 2014/23092-0

Estudo comparativo de duas diferentes modalidades de analgesia controlada pelo paciente após cirurgia cardíaca

INTRODUCTION: Acute and severe pain is frequent in patients who undergo cardiothoracic surgery. Patient controlled analgesia (PCA) can be used to manage postoperative pain. OBJECTIVE: To compare analgesia of morphine PCA alone (without continous infusion) with morphine PCA plus a continuous infusion on postoperative period after cardiac surgery and to evaluate pain scores, morphine consumption, number of demand, patient satisfaction and side effects. METHODS: Randomized trial was conducted to assess patients who underwent cardiac surgery receiving either morphine PCA alone or morphine PCA plus continous infusion. In the post operative period, PCA was started at extubation in both regiments according to randomization. Pain intensity, morphine consumption, number of demand, satisfaction and side effects were assessed at zero, six, twelve, eighteen, twenty four and thirty hours after patients' extubation. RESULTS: The study enrolled 100 patients. 50 patients received morphine PCA alone, (Group A) and 50 patients received morphine PCA plus a background infusion, (Group B). Group B patients had less demand, consumed more morphine and were more satisfied regarding analgesia. No statistical differences were shown between groups related to pain intensity, and side effects. CONCLUSIONS: Pain control was effective and similar in both groups. Morphine PCA alone seems to be better for postoperative pain manage in cardiac surgery, due to its less morphine expense with the same effectiveness.INTRODUÇÃO: A dor aguda e intensa faz parte do cotidiano dos pacientes que realizam cirurgia cardíaca, e para o controle da dor, pode-se dispor da analgesia controlada pelo paciente (PCA -Patient controlled analgesia). OBJETIVO: Comparar a analgesia utilizando PCA sem infusão contínua com PCA mais infusão contínua de morfina no pós-operatório de cirurgia cardíaca e avaliar a intensidade dolorosa, consumo analgésico, número de solicitações analgésicas, satisfação e efeitos colaterais. MÉTODOS: Ensaio clínico randomizado em que foram estudados pacientes submetidos a cirurgias cardíacas, que utilizaram PCA com e sem infusão intravenosa de morfina. No pós-operatório, ao se extubar os pacientes, foi instalada PCA nas duas modalidades, conforme o sorteio. Intensidade dolorosa, consumo analgésico, número de solicitações analgésicas, satisfação e efeitos colaterais foram avaliados no momento da extubação e nas 6, 12, 18, 24 e 30 horas seguintes. RESULTADOS: Foram avaliados 100 pacientes, sendo 50 no grupo (A) que recebeu PCA sem infusão contínua de morfina, e 50 no grupo (B) que utilizou PCA com infusão contínua de morfina. Pacientes do grupo (B) consumiram mais morfina, solicitaram menos vezes, e ficaram mais satisfeitos com a analgesia. Não se observaram diferenças significantes entre os grupos quanto à intensidade da dor e aos efeitos colaterais. CONCLUSÕES: O controle da dor foi eficiente e similar em ambos os grupos estudados. A mesma eficácia de analgesia e o menor consumo de morfina sugerem que PCA sem infusão contínua de morfina seja a melhor opção no controle da dor no pós-operatório de cirurgia cardíaca.Clinics HospitalFederal University of São PauloHeart InstituteHeart Institute Heart Surgical Diseases GroupUNIFESPSciEL

“Building a global community:” a critical analysis on Facebook’s discourse technologization estrategies

Este trabalho tem como objetivo identificar como se dão os processos de tecnologização do discurso na sociedade contemporânea a partir da utilização das redes sociais digitais. Para isso, analisou-se o texto “Construindo uma Comunidade Global”, do cocriador do Facebook, Mark Zuckerberg. Por meio da análise crítica do discurso, observou-se como se manifestam discursivamente as ideologias neoliberalistas cuja finalidade é manipular e controlar os indivíduos para que estes permaneçam conectados nas comunidades digitais.Este trabajo tiene como objetivo observar cómo se desarrollan los procesos de tecnologización del discurso en la sociedad contemporánea, a partir del uso de las redes sociales digitales. En este contexto, se analizó el texto “Construyendo una comunidad global”, del cocreador de Facebook, Mark Zuckerberg. A partir del análisis crítico del discurso, se observó cómo se manifiestan discursivamente las ideologías neoliberalistas cuyo propósito es manipular y controlar a los individuos para que permanezcan conectados en comunidades digitales.This study aims to observe how the processes of technologization of discourse occurs in contemporary society based on the use of online social networks. To this end, the letter “Building a Global Community,” written by Mark Zuckerberg, Facebook’s co-founder, was analyzed in the light of critical discourse analysis (CDA). The results evince the discursive manifestations of neoliberal ideologies, which seek to manipulate and control individuals as to keep them connected to digital communities