Adult Stromal Cells Derived from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death both In Vitro and In Vivo

1932-6203 (Electronic) Journal Article Research Support, Non-U.S. Gov'tBACKGROUND: Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC) spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC) on pancreatic tumor cell proliferation. PRINCIPAL FINDINGS: Co-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate). ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth. CONCLUSION: These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Hepatitis E, what’s the real issue?

International audienceHepatitis E Virus (HEV) infection is a worldwide disease and the primary cause of acute viral hepatitis in the world with an estimated 20 million cases every year and 70 000 deaths. Hepatitis E is a waterborne infection in the developing countries. In these countries, HEV genotypes 1 and 2 cause large outbreaks and affect young subjects, resulting in significant mortality in pregnant women and patients with cirrhosis. In the developed countries, HEV genotypes 3 and 4 are responsible for autochthonous, sporadic hepatitis and transmission is zoonotic. Parenteral transmission by the transfusion of blood products has been identified as a potential new mode of transmission. The prevalence of positive HEV viraemia in blood donors in Europe ranges from 1/600 to 1/2500 in highly endemic European countries. HEV can cause neurological disorders and chronic infections in immunocompromised patients. The progression of acute hepatitis E is usually asymptomatic and resolves spontaneously. Diagnostic tools include anti-HEV IgM antibodies in serum and/or viral RNA detection in the blood or the stools by PCR. Ribavirin is used to treat chronic infection. A vaccine has been developed in China

Feeding ecology of two deep-sea skates bycaught on demersal longlines off Kerguelen Islands, Southern Indian Ocean

International audienceElasmobranchs, and particularly skates (Rajiforms), are commonly caught in fisheries worldwide as targeted catch or bycatch. Their life history traits make them particularly sensitive to elevated fishing mortality, especially in slow-growing deep-sea species. Knowledge of their ecology is key to ensure effective conservation and mitigation measures, especially dietary references to understand trophic relationships within the ecosystem. This study presents the first comprehensive description of diet composition and trophic position of two skate species (Bathyraja eatonii and B. irrasa) caught as bycatch in the French Patagonian toothfish (Dissostichus eleginoides) fishery in the Indian sector of the Southern Ocean (Kerguelen waters). Stomach content and stable isotopic analyses were performed on both species according to sex and maturity stage. DNA barcoding analysis was performed on prey tissue samples to identify or confirm identification of prey items found in stomachs. Overall, both skate species were generalist feeders with high δ15N values. The higher δ15N values of B. irrasa result in a higher estimated trophic position than B. eatonii. The diet of B. eatonii mainly consisted of fish, pelagic crustaceans and squids, while B. irrasa preyed more on benthic crustaceans, fish and annelids. While sex had no effect on diet and trophic position for both species, maturity stage influenced the prey composition of B. irrasa. Annelids and isopods were prevalent in the stomachs of immature individuals of B. irrasa, while mature individuals fed more on decapods and fish. Our results revealed a wide range of prey items for these two generalist predators (>57 species). Understanding the diet, trophic position and trophic relationships of B. eatonii and B. irrasa is critical to a better comprehension of the impact of the exploitation of top predators on the subantarctic demersal ecosystem

Does HEV‐3 subtype play a role in the severity of acute hepatitis E?

International audienceHepatitis E virus genotype 3 (HEV-3) is a major aetiologic agent of acute hepatitis in industrialized countries. Two main HEV-3 subtypes are found in Europe: subtypes 3c and 3f. We have analysed the clinical and biological parameters from 100 French immunocompetent patients with an HEV subtype 3f or subtype 3c infection, included in a prospective multicentre study. Stepwise regression analysis found that infections with HEV subtype 3f were associated with fever (OR: 6.1 95%CI: 1.4-26.1), have a greater virus load (OR: 7.4; 95%CI: 1.3-42.2) and require more frequent hospitalization (OR: 7.6; 95%CI: 1.1-51.4) than those infected with subtype 3c. The directed acyclic graph strengthens the multivariate analyses indicating a direct link between the HEV subtype, HEV RNA concentration, fever and hospitalization. Further studies on patients in other European countries are needed to confirm this relationship and determine the underlying mechanis

Expression of the transcription factor Klf6 in cirrhosis, macronodules, and hepatocellular carcinoma.

International audienceBACKGROUND AND AIMS: Macronodules (MN) occurring in cirrhosis are considered to be precursor lesions for hepatocellular carcinoma (HCC). However, early molecular events in hepatocellular carcinogenesis are poorly understood. The aim of this study was to compare gene expression profiling between cirrhotic tissues, MN, and HCC, to identify genes early involved in liver carcinogenesis. METHODS: Tissues were obtained from explanted livers: nine cirrhosis, 10 MN, and seven HCC. Total RNAs were extracted by RNeasy and reverse transcribed with labelled [(33)P]-alpha ATP. Hybridations were performed on Atlas Human Cancer 1.2 membranes (1176 genes). RESULTS: A two-way hierarchical clustering algorithm successfully isolated specific gene expression profiles when comparing MN, cirrhosis, and HCC. A total of 16 and 14 genes were up- and down-expressed, respectively, in HCC as compared to cirrhotic tissues. The molecular signature of MN was characterized by the down-expression of 23 and 42 genes as compared to cirrhosis and HCC, respectively. Among them, Klf6 was down-expressed in all MN samples whereas it was over-expressed in cirrhosis and HCC. This result was confirmed at RNA level by quantitative real time-polymerase chain reaction and at protein level by Western blotting. However, no mutation in the exon 2 of Klf6 was detected. CONCLUSION: We identified a molecular signature of MN characterized by a down-expression of several genes. One of them, Klf6 was found to be down-expressed in all MN without evidence of somatic mutations in the exon 2. This gene could be involved at an early stage of hepatocarcinogenesis

Versatile Synthetic Approach for Selective Diversification of Bicyclic Aza-Diketopiperazines

International audienc

The Prevalence of Hepatitis E in a Patient Cohort Presenting With Addictive Injection Behavior

International audienceIntroduction: Hepatitis E is the most common cause of acute viral hepatitis worldwide. Seroprevalence is approximately 15% in developed countries, and 22% in France. hepatitis E virus (HEV) can be transmitted via transfusions and therefore possibly intravenous (IV) drug use. Hepatitis E serology is routinely tested in patients who seek medical advice for addictive injection behavior at the addiction treatment, support and prevention unit of Toulouse University Hospital. We assume that hepatitis E is more prevalent in patients presenting with addictive injection behavior than in the general French population.Methods: Hepatitis E serological assays [immunoglobulin M (IgM) and IgG] were carried out for all patients presenting with addictive injection behavior during an initial evaluation. The controls were taken from a cohort of 3,353 blood donors living in southern France and who donated blood during the first 2 weeks of October 2011.Results: We included 52 patients presenting with addictive injection behavior and 103 healthy controls matched for age, sex, and area of residence. We found no difference between patients and controls for the prevalence of hepatitis E: patients vs. healthy controls: positive IgGs: 42.31%, 95% confidence interval (CI) (28.73–56.80%) vs. 43.43%, 95% CI (33.50–53.77%) (p = 0.89) and positive IgMs: 3.85%, 95% CI (0.47–13.22%) vs. 4.85%, 95% CI (0.16–10.97%) (p = 0.57).Conclusion: There was no difference in HEV seroprevalence between IV drug users and the general population, suggesting that the IV route of HEV infection is not significant in this population