Canine visceral hemangiosarcoma treated with surgery alone or surgery and doxorubicin: 37 cases (2005-2014).

The purpose of this retrospective study was to determine survival times and prognostic factors of dogs with visceral hemangiosarcoma (HSA) treated with surgery alone or surgery and doxorubicin. Medical records from 2 hospitals from 2005 to 2014 were searched for dogs with histopathologically confirmed visceral HSA. Data relevant to patient demographics, tumor characteristics, and outcomes were abstracted. The most common primary organ affected was the spleen; however, primary tumor location had no influence on prognosis. Twenty-three dogs were treated with surgery alone, while 14 dogs were treated with surgery and doxorubicin. There was a significant difference in survival times between dogs treated with surgery alone and with surgery followed by doxorubicin (66 days versus 274 days). Dogs with stage I tumors (196 days) had a longer median survival time (MST) than dogs with stage II (117 days) and stage III (23 days) disease. The overall MST was 179 days with a 1-year survival rate of 29.2%.

Hémangiosarcome viscéral canin traité par la chirurgie seule et la doxorubicine : 37 cas (2005­2014). Le but de cette étude rétrospective consistait à déterminer les temps de survie et les facteurs de pronostic des chiens atteints d'un hémangiosarcome (HSE) viscéral traités à l'aide de la chirurgie seule ou de la chirurgie et de la doxorubicine. Les dossiers médicaux de deux cliniques de 2005 à 2014 ont été fouillés pour trouver des chiens avec un HSE viscéral confirmé par histopathologie. Les données pertinentes pour les données démographiques du patient, les caractéristiques de la tumeur et les résultats ont été extraits des dossiers. L'organe primaire le plus couramment affecté était la rate. Cependant, l'emplacement primaire de la tumeur n'avait aucune influence sur le pronostic. Vingt-trois chiens ont été traités par la chirurgie seule, tandis que 14 chiens ont été traités par la chirurgie et la doxorubicine. Il y avait une différence importante dans les temps de survie entre les chiens traités par la chirurgie seule et la chirurgie suivie de la doxorubicine (66 jours contre 274 jours). Les chiens ayant des tumeurs de stade I (196 jours) avaient un temps de survie médian (TSM) plus long que les chiens atteints d'une maladie de stade II (117 jours) et de stade III (23 jours). Le TSM général était de 179 jours avec un taux de survie après 1 an de 29,2 %.(Traduit par Isabelle Vallières).

ß-ionone modulates the expression of miRNAs and genes involved in the metastatic phenotype of microdissected persistent preneoplastic lesions in rats submitted to hepatocarcinogenesis.

MicroRNAs (miRNAs) are post-transcriptional gene expression regulators which expression is frequently altered in hepatocellular carcinoma (HCC). ß-ionone (ßI) is noted for its ability to inhibit persistent preneoplastic lesions (pPNLs) in liver rats. We evaluated the expression of miRNAs involved in carcinogenesis and possible targets modulated by ßI, in pPNLs and surrounding of microdissected tissues. Rats subjected to resistant hepatocyte model were treated during promotion stage with ßI (16 mg/100 g body weight) or corn oil (CO; 0.25 mL/100 g body weight; controls). Five animals receive no treatment (NT). In CO group, 38 and 29 miRNAs showed reduced expression relative to NT (P < 0.05) in pPNLs and surrounding, respectively. No miRNAs showed increased expression in surrounding of the CO compared to NT group; however, 30 miRNAs showed increased expression (P ≤ 0.05) in pPNLs of the CO group. There was no difference between ßI and CO groups (P > 0.05) in the expression of miRNAs in surrounding. In pPNLs ßI increased expression of miR-122 and miR-34a (P ≤ 0.05) and reduced of Igf2 (P ≤ 0.05), target of the latter, compared to CO. Additionally, ßI decreased the expression of miR-181c and its target Gdf2 (P ≤ 0.05). ßI reduced the expression of miR-181b and miR-708 (P ≤ 0.05) and increased the expression of their respective target mRNAs Timp3 and Mtss1 (P ≤ 0.05), relative to CO group. Modulation of miRNAs target genes by ßI was confirmed in vitro. ßI is a promising chemopreventive agent in the initial stages of hepatocarcinogenesis, as it modulates the expression of the miRNAs and target genes that can alter the metastatic phenotype of HCC. © 2016 Wiley Periodicals, Inc.

Consumption of Brazil nuts with high selenium levels increased inflammation biomarkers in obese women: A randomized controlled trial.

OBJECTIVE: Increased inflammatory response is an important factor in the pathophysiology of obesity. The mineral selenium (Se), of which one of the main food sources is the Brazil nut, has important antioxidant and anti-inflammatory functions through the action of selenoproteins. Thus, the evaluation of the influence of this micronutrient in this context is of great relevance. The aim of this study was to evaluate the effects of Brazil nut intake with high Se concentrations on inflammatory biomarkers and its relation to Se status in obese women. METHODS: A randomized controlled clinical trial was carried out with 55 women recruited at Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to either the Brazil nut group (BN) or the control group (CO) and followed up for 2 mo. The BN group consumed 1 unit/d of Brazil nuts (∼ 1261 µg/Se); the CO group did not receive any intervention. At baseline and after 2 mo, analysis of biochemical parameters related to Se status, oxidative stress, and inflammatory biomarkers were performed. RESULTS: At baseline, both groups did not present Se deficiency. In the BN group, a significant increase (P < 0.05) in all Se biomarkers and in gene expression of several proinflammatory parameters (interleukin-6, tumor necrosis factor-α, and Toll-like receptors 2 and 4) were observed after the intervention period. No changes were observed for the CO group. CONCLUSION: Although there were no changes in plasma inflammatory biomarkers levels, a significant increase in gene expression may be an indication of a proinflammatory stimulus in obesity, induced by the consumption of Brazil nuts with high Se levels.

Brazil nut intake increases circulating miR-454-3p and miR-584-5p in obese women.

The Brazil nut is an excellent source of selenium (Se), an essential micronutrient for human health. In this study, we hypothesized that Brazil nut intake modulates circulating microRNAs (miRNAs) in obese women and aimed to evaluate the effects of this nut intake on circulating miRNAs in women with obesity or metabolic syndrome (MetS). A randomized controlled clinical trial was conducted on 54 subjects recruited from the Clinical Hospital in São Paulo, Brazil. Patients were randomly assigned to 2 groups: a Brazil nut group (BN group, n = 29) and a control group (CO group, n = 25); both were monitored for 2 months. BN group members were instructed to consume 1 Brazil nut (approximately 1261 µg/Se) per day; CO group members were instructed not to consume any. Biochemical parameters related to Se status and 25 circulating miRNAs in plasma were evaluated in all patients both at baseline and after 2 months. Expression levels of 2 miRNAs (miR-454-3p and miR-584-5p) were significantly increased after Brazil nut intake. To investigate the effect of MetS on circulating miRNAs at baseline, we performed comparisons between women with MetS (n = 23) and women without MetS (others, n = 31). Circulating miR-375 levels were significantly lower (P = .012) in women with MetS. In conclusion, our findings suggested that a daily intake of 1 Brazil nut increased circulating miR-454-3p and miR-584-5p expression levels in obese women, and our network analysis indicated a link between Se intake, vitamin D metabolism, and calcium homeostasis.

Tumor-infiltrating plasmacytoid dendritic cells promote immunosuppression by Tr1 cells in human liver tumors.

CD4+ type 1 T regulatory (Tr1) cells have a crucial role in inducing tolerance. Immune regulation by these cells is mainly mediated through the secretion of high amounts of IL-10. Several studies have suggested that this regulatory population may be involved in tumor-mediated immune-suppression. However, direct evidence of a role for Tr1 cells in human solid tumors is lacking. Using ex vivo isolated cells from individuals with hepatocellular carcinoma (HCC; n = 39) or liver metastases from colorectal cancer (LM-CRC; n = 60) we identify a CD4+FoxP3-IL-13-IL-10+ T cell population in tumors of individuals with primary or secondary liver cancer that is characterized as Tr1 cells by the expression of CD49b and the lymphocyte activation gene 3 (LAG-3) and strong suppression activity of T cell responses in an IL-10 dependent manner. Importantly, the presence of tumor-infiltrating Tr1 cells is correlated with tumor infiltration of plasmacytoid dendritic cells (pDCs). pDCs exposed to tumor-derived factors enhance IL-10 production by Tr1 cells through up-regulation of the inducible co-stimulatory ligand (ICOS-L). These findings suggest a role for pDCs and ICOS-L in promoting intra-tumoral immunosuppression by Tr1 cells in human liver cancer, which may foster tumor progression and which might interfere with attempts of immunotherapeutic intervention.