P38 MAPK expression and activation predicts failure of response to CHOP in patients with Diffuse Large B-Cell Lymphoma

The p38 MAPK is constitutively activated in B-NHL cell lines and regulates chemoresistance. Accordingly, we hypothesized that activated p38 MAPK may be associated with the in vivo unresponsiveness to chemotherapy in B-NHL patients.Tissue microarrays generated from eighty untreated patients with Diffused Large B Cell Lymphoma (DLBCL) were examined by immunohistochemistry for the expression of p38 and phospho p38 (p-p38) MAPK. In addition, both Bcl-2 and NF-κB expressions were determined. Kaplan Meier analysis was assessed.Tumor tissues expressed p38 MAPK (82 %) and p-p38 MAPK (30 %). Both p38 and p-p38 MAPK expressions correlated with the high score performance status. A significant correlation was found between the expression p-p38 and poor response to CHOP. The five year median follow-up FFS was 81 % for p38(-) and 34 % for p38(+) and for OS was 83 % for p38(-) and 47 % for p38(+). The p-p38(+) tissues expressed Bcl-2 and 90 % of p-p38(-) where Bcl-2(-). The coexpression of p-p38 and Bcl-2 correlated with pool EFS and OS. There was no correlation between the expression of p-p38 and the expression of NF-κB.The findings revealed, for the first time, that a subset of patients with DLBCL and whose tumors expressed high p-p38 MAPK responded poorly to CHOP therapy and had poor EFS and OS. The expression of p38, p-p38, Bcl2 and the ABC subtype are significant risk factors both p38 and p-p38 expressions remain independent prognostic factors

Transcriptional and Microenvironmental Landscape of Macrophage Transition in Cancer: A Boolean Analysis

The balance between pro- and anti-inflammatory immune system responses is crucial to face and counteract complex diseases such as cancer. Macrophages are an essential population that contributes to this balance in collusion with the local tumor microenvironment. Cancer cells evade the attack of macrophages by liberating cytokines and enhancing the transition to the M2 phenotype with pro-tumoral functions. Despite this pernicious effect on immune systems, the M1 phenotype still exists in the environment and can eliminate tumor cells by liberating cytokines that recruit and activate the cytotoxic actions of TH1 effector cells. Here, we used a Boolean modeling approach to understand how the tumor microenvironment shapes macrophage behavior to enhance pro-tumoral functions. Our network reconstruction integrates experimental data and public information that let us study the polarization from monocytes to M1, M2a, M2b, M2c, and M2d subphenotypes. To analyze the dynamics of our model, we modeled macrophage polarization in different conditions and perturbations. Notably, our study identified new hybrid cell populations, undescribed before. Based on the in vivo macrophage behavior, we explained the hybrid macrophages’ role in the tumor microenvironment. The in silico model allowed us to postulate transcriptional factors that maintain the balance between macrophages with anti- and pro-tumoral functions. In our pursuit to maintain the balance of macrophage phenotypes to eliminate malignant tumor cells, we emulated a theoretical genetically modified macrophage by modifying the activation of NFκB and a loss of function in HIF1-α and discussed their phenotype implications. Overall, our theoretical approach is as a guide to design new experiments for unraveling the principles of the dual host-protective or -harmful antagonistic roles of transitional macrophages in tumor immunoediting and cancer cell fate decisions

Acute myelogenous leukemia switch lineage upon relapse to acute lymphoblastic leukemia: a case report

Acute leukemia, the most common form of cancer in children, accounts for approximately 30% of all childhood malignancies, with acute lymphoblastic leukemia being five times more frequent than acute myeloid leukemia. Lineage switch is the term that has been used to describe the phenomenon of acute leukemias that meet the standard French-American-British system criteria for a particular lineage (either lymphoid or myeloid) upon initial diagnosis, but meet the criteria for the opposite lineage at relapse. Many reports have documented conversions of acute lymphoblastic leukemia to acute myeloid leukemia

estudos artísticos

A revista Gama prossegue o aprofundamento da sua linha editorial específica e dentro do projeto mais alargado de desafiar criadores a debaterem e apresentar a obra de outros criadores, dentro do espaço descentrado que é o universo dos idiomas ibéricos. Trata-se de, dentro deste tema mais abrangente, revisitar arquivos, autores de épocas um pouco recuadas, de resgatar do esquecimento o património que existe e urge apresentar, discutir, colocar em ação, fazer funcionar, pela voz dos artistas. A arte necessita de ser ativada por intermédio do pensamento, e com ele, do discurso. Há vozes silenciosas que aguardam olhos, ouvidos, inquietações, deslumbramentos. Quando uma peça é descoberta é como se voltasse a ser feita: esse é o paradoxo do documento. A arte é vestígio e ao mesmo tempo universalidade, eternidade. É local e total. É sempre, em simultâneo, sem contradição, facto e possibilidade, presença e ausência. Os vinte e quatro artigos apresentados neste número cinco da Revista Gama oferecem outros tantos pontos de vista sobre os discursos artísticos. Recupera-se obra desconhecida, mostram-se obras, descobrem-se autores desaparecidos. Aqui a arte depositou-se, precipitou-se, tornou-se visível ao resgate. O resgate, operação de amor, é feito por artistas. Os públicos estão no futuro, à nossa espera.info:eu-repo/semantics/publishedVersio

Implementation of a roadmap for the comprehensive diagnosis, follow-up, and research of childhood leukemias in vulnerable regions of Mexico: results from the PRONAII Strategy

The main objective of the National Project for Research and Incidence of Childhood Leukemias is to reduce early mortality rates for these neoplasms in the vulnerable regions of Mexico. This project was conducted in the states of Oaxaca, Puebla, and Tlaxcala. A key strategy of the project is the implementation of an effective roadmap to ensure that leukemia patients are the target of maximum benefit of interdisciplinary collaboration between researchers, clinicians, surveyors, and laboratories. This strategy guarantees the comprehensive management of diagnosis and follow-up samples of pediatric patients with leukemia, centralizing, managing, and analyzing the information collected. Additionally, it allows for a precise diagnosis and monitoring of the disease through immunophenotype and measurable residual disease (MRD) studies, enhancing research and supporting informed clinical decisions for the first time in these regions through a population-based study. This initiative has significantly improved the diagnostic capacity of leukemia in girls, boys, and adolescents in the regions of Oaxaca, Puebla, and Tlaxcala, providing comprehensive, high-quality care with full coverage in the region. Likewise, it has strengthened collaboration between health institutions, researchers, and professionals in the sector, which contributes to reducing the impact of the disease on the community

Advances in Hematopoietic Stem Cell Research

This book provides a comprehensive overview in our understanding of the biology and therapeutic potential of hematopoietic stem cells, and is aimed at those engaged in stem cell research: undergraduate and postgraduate science students, investigators and clinicians. Starting from fundamental principles in hematopoiesis, Advances in Hematopoietic Stem Cell Research assemble a wealth of information relevant to central mechanisms that may regulate differentiation, and expansion of hematopoietic stem cells in normal conditions and during disease