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Hypoxia and macrophages act in concert towards a beneficial outcome in colon ca...

Martins, F; Oliveira, R; Cavadas, B; Pinto, F; Cardoso, AP; Castro, F; Sousa, B; Pinto, ML; Silva, AJ; Adão, D; Loureiro, JP; Pedro, N; Reis, RM

In colon cancer, the prognostic value of macrophages is controversial, and it is still unknown how hypoxia modulates macrophage–cancer cell crosstalk. To unravel this, co-cultures of human primary macrophages and colon cancer cells were performed at 20% and 1% O2, followed by characterization of both cellular components. Different colon cancer patient cohorts were analyzed for hypoxia and immune markers, and th...


Role of Genetic Ancestry in 1,002 Brazilian Colorectal Cancer Patients From Bar...

Durães, RO; Berardinelli, GN; Costa, AM; Scapulatempo-Neto, C; Pereira, R; Oliveira, MA; Guimarães, DP; Reis, RM

Background: Colorectal cancer (CRC) is the third most frequent and the second deadliest cancer worldwide. The ethnic structure of the population has been gaining prominence as a cancer player. The purpose of this study was to determine the genetic ancestry of Brazilian CRC patients. Moreover, we intended to interrogate its impact on patients' clinicopathological features. Methods: Retrospective observational co...


WNT6 is a novel oncogenic prognostic biomarker in human glioblastoma

Gonçalves, CS; Vieira de Castro, J; Pojo, M; Martins, EP; Queirós, S; Chautard, E; Taipa, R; Pires, MM; Pinto, AA; Pardal, F; Custódia, C; Faria, CC

Glioblastoma (GBM) is a universally fatal brain cancer, for which novel therapies targeting specific underlying oncogenic events are urgently needed. While the WNT pathway has been shown to be frequently activated in GBM, constituting a potential therapeutic target, the relevance of WNT6, an activator of this pathway, remains unknown. Methods: WNT6 protein and mRNA levels were evaluated in GBM. WNT6 levels were...


Effects of the functional HOTAIR rs920778 and rs12826786 genetic variants in gl...

Xavier-Magalhães, A; Oliveira, AI; Vieira de Castro, J; Pojo, M; Gonçalves, CS; Lourenço, T; Viana-Pereira, M; Costa, S; Linhares, P; Vaz, R; Nabiço, R

Abnormal expression of the long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is oncogenic in several human cancers, including gliomas. The HOTAIR single nucleotide polymorphisms (SNPs) rs920778 (C > T) and rs12826786 (C > T) present in the intronic enhancer and promoter regions of HOTAIR, respectively, are associated with expression, cancer susceptibility, and patient prognosis in some tumor ...


Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilc...

Gama, JB; Pereira, C; Simões, PA; Celestino, R; Reis, RM; Barbosa, DJ; Pires, HR; Carvalho, C; Amorim, J; Carvalho, AX; Cheerambathur, DK; Gassmann, R

The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal b...


Significance of glycolytic metabolism-related protein expression in colorectal ...

Martins, SF; Amorim, R; Viana-Pereira, M; Pinheiro, C; Costa, RA; Silva, P; Couto, C; Alves, S; Fernandes, S; Vilaça, S; Falcão, J; Marques, H

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cas...


Hotspot TERT promoter mutations are rare events in testicular germ cell tumors

Cárcano, FM; Vidal, DO; van Helvoort Lengert, A; Neto, CS; Queiroz, L; Marques, H; Baltazar, F; da Silva Martinelli, CM; Soares, P; da Silva, EC

The abnormal activation of telomerase, codified by the telomerase reverse transcriptase (TERT) gene, is related to one of cancer hallmarks. Hotspot somatic mutations in the promoter region of TERT, specifically the c.-124:C>T and c.-146:C>T, were recently identified in a range of human cancers and have been associated with a more aggressive behavior. Testicular germ cell tumors frequently exhibit a good prognos...


A transcriptomic signature mediated by HOXA9 promotes human glioblastoma initia...

Pojo, M; Gonçalves, CS; Xavier-Magalhães, A; Oliveira, AI; Gonçalves, T; Correia, S; Rodrigues, AJ; Costa, S; Pinto, L; Pinto, AA; Lopes, JM; Reis, RM

Glioblastoma is the most malignant brain tumor, exhibiting remarkable resistance to treatment. Here we investigated the oncogenic potential of HOXA9 in gliomagenesis, the molecular and cellular mechanisms by which HOXA9 renders glioblastoma more aggressive, and how HOXA9 affects response to chemotherapy and survival. The prognostic value of HOXA9 in glioblastoma patients was validated in two large datasets from...


Immunoglobulin genes implicated in glioma risk

Pandey, JP; Kaur, N; Costa, N; Amorim, J; Nabico, R; Linhares, P; Vaz, R; Viana-Pereira, M; Reis, RM

Both genetic and environmental factors are thought to be causal in gliomagenesis. Several genes have been implicated in glioma development, but the putative role of a major immunity-related gene complex member, immunoglobulin heavy chain γ (IGHG) has not been evaluated. Prior observations that IGHG-encoded γ marker (GM) allotypes exhibit differential sensitivity to an immunoevasion strategy of cytomegalovirus, ...


The Impact of Polymorphic Variations in the 5p15, 6p12, 6p21 and 15q25 Loci on ...

de Mello, RA; Ferreira, M; Soares-Pires, F; Costa, S; Cunha, J; Oliveira, P; Hespanhol, V; Reis, RM

INTRODUCTION: Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore, this study was performed to assess the role of those variants in non-small cell lung cancer (NSCLC) risk and prognosis in a Portuguese population. MATERIALS AND METHODS: Blood from patients with NSCLC was prospectively collected. To perform an associati...


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