The two faces of tumor-associated macrophages and their clinical significance in colorectal cancer

© 2019 Pinto, Rios, Durães, Ribeiro, Machado, Mantovani, Barbosa, Carneiro and Oliveira. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Macrophages are one of the immune populations frequently found in colorectal tumors and high macrophage infiltration has been associated with both better and worst prognosis. Importantly, according to microenvironment stimuli, macrophages may adopt different polarization profiles, specifically the pro-inflammatory or M1 and the anti-inflammatory or M2, which display distinct functions. Therefore, concomitantly with the number of tumor-associated macrophages (TAMs), their characterization is fundamental to unravel their relevance in cancer. Here, we profiled macrophages in a series of 150 colorectal cancer (CRC) cases by immunohistochemistry, using CD68 as a macrophage lineage marker, CD80 as a marker of pro-inflammatory macrophages, and CD163 as a marker of anti-inflammatory macrophages. Quantifications were performed by computer-assisted analysis in the intratumoral region, tumor invasive front, and matched tumor adjacent normal mucosa (ANM). Macrophages, specifically the CD163+ ones, were predominantly found at the tumor invasive front, whereas CD80+ macrophages were almost exclusively located in the ANM, which suggests a predominant anti-inflammatory polarization of TAMs. Stratification according to tumor stage revealed that macrophages, specifically the CD163+ ones, are more prevalent in stage II tumors, whereas CD80+ macrophages are predominant in less invasive T1 tumors. Specifically in stage III tumors, higher CD68, and lower CD80/CD163 ratio associated with decreased overall survival. Importantly, despite the low infiltration of CD80+ cells in colorectal tumors, multivariate logistic regression revealed a protective role of these cells regarding the risk for relapse. Overall, this work supports the involvement of distinct microenvironments, present at the intra-tumor, invasive front and ANM regions, on macrophage modulation, and uncovers their prognostic value, further supporting the relevance of including macrophage profiling in clinical settings.This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework of the project MAGICIAM: a MAcrophaGe Immunomodulatory-delivery system to prevent Cancer Invasion and Metastasis (POCI-01-0145-FEDER-031859). FCT further supported this work under MP PhD grant (PD/BD/81103/2011), CD post-doctoral grant (SFRH/BPD/99442/2014), and MO FCT Investigator grant (IF/01066/2012).info:eu-repo/semantics/publishedVersio

Association between Polymorphisms in Antioxidant Genes and Inflammatory Bowel Disease

Inflammation is the driving force in inflammatory bowel disease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn's disease (CD) and ulcerative colitis (UC). Single nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn's disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). Moreover, we found nominal significant associations between SOD2 and Crohn's disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies.info:eu-repo/semantics/publishedVersio

Consequences Of On-Track Competition In Railways By Use Of Simulations

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Correlations between agronomic traits and path analysis for silage production in maize hybrids

<div><p>ABSTRACT The aim of the current study is to estimate the correlation coefficients and the consequence of genotypic correlations on direct and indirect effects through path analysis between agronomic traits of maize hybrids used for silage production. Eight (8) topcross hybrids and seven (7) checks were analyzed in completely randomized blocks, with six replications, in two environments: Campos do Goytacazes and Itaocara counties – Rio de Janeiro State, in the crop year 2015/2016. The following agronomic traits were assessed: plant height, first ear height, culm diameter, number of ears, ear yield with straw at silage maturity, ear yield without straw at silage maturity, grain yield at silage maturity, grains ratio in the fresh matter and fresh matter yield. The highest correlation estimates were found between the variables ear yield without straw and grain yield, and between ear yield with straw and ear yield without straw, with magnitudes 0.95 and 0.92, respectively. The coefficient of determination was high, which indicates that the assessed components explain most of the existing variation in fresh matter yield. According to the path analysis, the trait showing the strongest direct effect on fresh matter yield was the ear yield with straw at silage maturity, in association with the high correlation (r = 0.91), which showed the possibility of achieving significant gains through indirect selection.</p></div

Association between Polymorphisms in Antioxidant Genes and Inflammatory Bowel Disease.

Inflammation is the driving force in inflammatory bowel disease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn's disease (CD) and ulcerative colitis (UC). Single nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn's disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). Moreover, we found nominal significant associations between SOD2 and Crohn's disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies

Correlations between agronomic traits and path analysis for silage production in maize hybrids

<div><p>ABSTRACT The aim of the current study is to estimate the correlation coefficients and the consequence of genotypic correlations on direct and indirect effects through path analysis between agronomic traits of maize hybrids used for silage production. Eight (8) topcross hybrids and seven (7) checks were analyzed in completely randomized blocks, with six replications, in two environments: Campos do Goytacazes and Itaocara counties – Rio de Janeiro State, in the crop year 2015/2016. The following agronomic traits were assessed: plant height, first ear height, culm diameter, number of ears, ear yield with straw at silage maturity, ear yield without straw at silage maturity, grain yield at silage maturity, grains ratio in the fresh matter and fresh matter yield. The highest correlation estimates were found between the variables ear yield without straw and grain yield, and between ear yield with straw and ear yield without straw, with magnitudes 0.95 and 0.92, respectively. The coefficient of determination was high, which indicates that the assessed components explain most of the existing variation in fresh matter yield. According to the path analysis, the trait showing the strongest direct effect on fresh matter yield was the ear yield with straw at silage maturity, in association with the high correlation (r = 0.91), which showed the possibility of achieving significant gains through indirect selection.</p></div