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/)

A new dual stainless steel cryogenic trap for efficient separation of krypton from argon and xenon

The elemental and isotopic abundances of krypton and xenon provide critical insights into processes ranging from stellar nucleosynthesis to volatile accretion and paleotemperatures on Earth. Accurate and precise determination of the krypton and xenon elemental abundance and isotopic ratios requires sample purification and noble gas separation to avoid interferences in the mass spectrometer. However, effective separation of krypton (Kr) from argon (Ar) and xenon (Xe) has remained challenging. Here, we present a new cryogenic instrument associated with a new protocol to achieve an efficient and effective separation of Kr from Ar and Xe. Using two electropolished stainless steel cryogenic traps on a single cold head, distillation of the noble gases from one trap onto the other and temperature cycling of the traps to reduce the effect of cryotrapping allows ≥ 98 % of the Kr in a sample to be recovered with &lt; 0.5 % of the Ar and &lt; 1 % of the Xe abundances of the sample. Likewise, more than 99 % of the Xe fraction can be recovered with &lt; 1 % Kr. No variations in the isotopic ratios of the separated Kr and Xe fractions are observed as a function of the signal size for air standards. Moreover, we find that krypton isotopes can be fractionated during Ar-Kr separation. We suggest that more accurate krypton isotopic compositions can be obtained by maximizing the recovered krypton fraction instead of minimizing the argon fraction within krypton

Impact of acute kidney injury on anticancer treatment dosage and long-term outcomes: a pooled analysis of European Organisation for Research and Treatment of Cancer trials.

BACKGROUND: The impact of kidney dysfunction on long-term outcomes of patients with advanced cancer remains unclear. METHODS: Patients with advanced cancer included in trials conducted by the European Organisation for Research and Treatment of Cancer were eligible for this retrospective analysis. Acute kidney injury (AKI) was identified using serum creatinine levels and using adverse events reported by investigators. The impact of baseline estimated glomerular filtration rates (eGFRs) on progression-free survival (PFS) and overall survival (OS) was investigated. Pooled estimates of the impact of AKI on dose intensity, treatment duration, PFS and OS were obtained following a meta-analytic process. RESULTS: Nine trials were included in this study, totalling 2872 metastatic patients with various tumour types and various systemic treatment types. Baseline eGFR had homogeneously no impact on PFS or OS. Most Risk, Injury, Failure, Loss of kidney function and End-stage kidney disease (RIFLE) events occurred early during the course of the treatment. AKI was not associated with an increased rate of treatment discontinuation, while it decreased the study treatment dose intensity. Occurrence of a first RIFLE event significantly and homogeneously reduced PFS (pooled hazard ratio = 1.18, 95% confidence interval 1.07-1.30; P = 0.0012), while its impact on OS was more heterogeneous across trials. CONCLUSION: AKI is associated with reduced treatment dose intensity and reduced PFS. Therefore, close monitoring of the kidney function during the first months of treatment should be included in clinical trial protocols and probably also in daily practice to enable early AKI diagnosis and management. Collaboration between oncologists and nephrologists is needed to reduce the risk of undertreatment of patients experiencing AKI.status: Published onlin

Nutritional effects of feed form, and wheat compared to maize, in the D+ and D- chicken lines selected for divergent digestion capacity

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