Human tumor-associated macrophage and monocyte transcriptional landscapes reveal cancer-specific reprogramming, biomarkers and therapeutic targets

The roles of tumor-associated macrophages (TAMs) and circulating monocytes in human cancer are poorly understood. Here, we show that monocyte subpopulation distribution and transcriptomes are significantly altered by the presence of endometrial and breast cancer. Furthermore, TAMs from endometrial and breast cancers are transcriptionally distinct from monocytes and their respective tissue-resident macrophages. We identified a breast TAM signature that is highly enriched in aggressive breast cancer subtypes and associated with shorter disease-specific survival. We also identified an auto-regulatory loop between TAMs and cancer cells driven by tumor necrosis factor alpha involving SIGLEC1 and CCL8, which is self-reinforcing through the production of CSF1. Together these data provide direct evidence that monocyte and macrophage transcriptional landscapes are perturbed by cancer, reflecting patient outcomes

Moderate Exercise Attenuates Lipopolysaccharide-induced Inflammation And Associated Maternal And Fetal Morbidities In Pregnant Rats

45102102Meeting of the International-Federation-of-Placenta-Associations (IFPA) - Placenta-Back to the BasicsSEP 13-16, 2016Portland, O

Postpartum alterations following inflammation in rat pregnancy: a discovery proteomic analysis

Women with a history of preeclampsia have an increased risk of subsequent cardiovascular and metabolic disease. While aberrant inflammation during pregnancy is associated with the development of preeclampsia, whether maternal inflammation increases the risk of disease later in life is unclear. Using a rat model we determined whether aberrant inflammation in pregnancy alters the levels of plasma proteins associated with cardiovascular and metabolic disease risk in the postpartum period. Pregnant rats were administered lipopolysaccharide (LPS) or saline on gestational days 13.5–16.5 to induce inflammation. Non-pregnant controls consisted of age-matched female rats subjected to similar administration of LPS or saline. Examination of the proteomic profile of plasma collected 16 weeks after delivery or from non-pregnant controls using liquid chromatography-tandem mass spectrometry revealed 100 differentially expressed proteins. Moreover, we identified 188 proteins in pregnant rats, of which 49 were differentially expressed in saline- vs LPS-treated dams. Of the 49 proteins regulated by LPS, 28 were pregnancy specific. PANTHER classification software, DAVID database and Ingenuity Pathways analysis revealed that the differentially expressed proteins in pregnant saline vs LPS-treated rats are associated with alterations in lipid and glucose metabolism and atherosclerosis, all of which may contribute to cardiovascular and metabolic disease risk. Results from proteomic and pathway analyses were validated by immunoassay of three serum proteins selected a priori and by assessment of serum metabolites. This discovery study demonstrates that aberrant inflammation during pregnancy results in long-lasting postpartum physiological alterations known to be associated with metabolic and cardiovascular disease.</jats:p

Moderate exercise attenuates lipopolysaccharide-induced inflammation and associated maternal and fetal morbidities in pregnant rats

sem informação45102102Meeting of the International-Federation-of-Placenta-Associations (IFPA) - Placenta-Back to the Basicssem informaçã

Moderate Exercise Attenuates Lipopolysaccharide-Induced Inflammation and Associated Maternal and Fetal Morbidities in Pregnant Rats.

Fetal growth restriction (FGR) and coagulopathies are often associated with aberrant maternal inflammation. Moderate-intensity exercise during pregnancy has been shown to increase utero-placental blood flow and to enhance fetal nutrition as well as fetal and placental growth. Furthermore, exercise is known to reduce inflammation. To evaluate the effect of moderate-intensity exercise on inflammation associated with the development of maternal coagulopathies and FGR, Wistar rats were subjected to an exercise regime before and during pregnancy. To model inflammation-induced FGR, pregnant rats were administered daily intraperitoneal injections of E. coli lipopolysaccharide (LPS) on gestational days (GD) 13.5-16.5 and sacrificed at GD 17.5. Control rats were injected with saline. Maternal hemostasis was assessed by thromboelastography. Moderate-intensity exercise prevented LPS-mediated increases in white blood cell counts measured on GD 17.5 and improved maternal hemostasis profiles. Importantly, our data reveal that exercise prevented LPS-induced FGR. Moderate-intensity exercise initiated before and maintained during pregnancy may decrease the severity of maternal and perinatal complications associated with abnormal maternal inflammation

Exercise prevented LPS-induced fetal growth restriction.

LPS significantly reduced fetal weights/litter size in sedentary rats (Se+LPS), whereas fetal weights in exercised rats treated with LPS (Ex+LPS) trended (p = 0.07) towards being significantly higher than in the Se+LPS cohort (A). Although the proportion of growth restricted fetuses trended towards being increased in Se+LPS rats than in Se+Saline rats [7], exercise did not significantly alter this proportion in the present study (B). FGR, fetal growth restriction. Ex+LPS (number of pups = 41, litter size varied 5 to 11), Ex+Saline (number of pups = 63; range in litter size = 4–19), Se+LPS (number of pups = 258), Se+Saline (number of pups = 305) (A); Ex+LPS (n = 5), Ex+Saline (n = 5), Se+LPS (n = 28), Se+Saline (n = 22) (B).</p

IFPA Meeting 2011 workshop report I: Placenta: Predicting future health; roles of lipids in the growth and development of feto-placental unit; placental nutrient sensing; placental research to solve clinical problems – A translational approach

Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2011 there were twelve themed workshops, four of which are summarized in this report. These workshops related to both basic science and clinical research into placental growth and nutrient sensing and were divided into 1) placenta: predicting future health; 2) roles of lipids in the growth and development of feto-placental unit; 3) placental nutrient sensing; 4) placental research to solve clinical problems: a translational approach