Purpose
Immunotherapies have largely failed as treatment options for pancreatic ductal adenocarcinoma (PDAC). In this field, clinical translational studies into personalized treatment are of ...fundamental importance. In our study, we model tumor-cell immune-cell interactions in a co-culture of primary human PDAC organoids and matched peripheral blood mononuclear cells (PBMCs).
Methods
Using flow cytometry, we evaluated changes in T cell subtypes upon co-culture of patient-derived PDAC organoids and matched PBMCs.
Results
After co-culturing PDAC organoids with PBMCs, we observed changes in CD4
+
, CD8
+
and Treg cell populations. We observed favorable clinical outcome in patients whose PBMCs reacted to the co-culture with organoids.
Conclusion
This experimental model allows to investigate interactions between patient derived PDAC organoids and their PBMCs. This co-culture system could serve as a preclinical platform to guide personalized therapeutic strategies in the future.
Abstract
Background
Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the overall mortality is low, around 20% of patients have a ...complicated course of disease resulting in increased morbidity and mortality. There is an emerging body of evidence that the microbiome exerts a crucial impact on the pathophysiology and course of AP. For several decades multiple clinical and laboratory parameters have been evaluated, and complex scoring systems were developed to predict the clinical course of AP upon admission. However, the majority of scoring systems are determined after several days and achieve a sensitivity around 70% for early prediction of severe AP. Thus, continued efforts are required to investigate reliable biomarkers for the early prediction of severity in order to guide early clinical management of AP patients.
Methods
We designed a multi-center, prospective clinical-translational study to test whether the orointestinal microbiome may serve as novel early predictor of the course, severity and outcome of patients with AP. We will recruit 400 AP patients and obtain buccal and rectal swabs within 72 h of admission to the hospital. Following DNA extraction, microbiome analysis will be performed using 3rd generation sequencing Oxford Nanopore Technologies (ONT) for 16S rRNA and metagenomic sequencing. Alpha- and beta-diversity will be determined and correlated to the revised Atlanta classification and additional clinical outcome parameters such as the length of hospital stay, number and type of complications, number of interventions and 30-day mortality.
Discussion
If AP patients show a distinct orointestinal microbiome dependent on the severity and course of the disease, microbiome sequencing could rapidly be implemented in the early clinical management of AP patients in the future.
Trial registration
: ClinicalTrials.gov Identifier: NCT04777812
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In Fig. 5 on p. 311 of our Phys. Lett. B 740 (2015) 303 an adjustment by 180∘ is required for the phases with respect to the L=2,M=1 wave, of the following waves: L=1,3,5 with M=1, and L=2 with M=2. ...After this correction (Fig. 5 (corrected) below), the extracted partial waves describe the angular distribution of the η(′) in the Gottfried-Jackson (GJ) frame, using Eq. (4) with implicit Condon-Shortley phase convention. The other results of our paper are not affected. The right-handed GJ coordinate system was defined by the z-axis pointing in the direction of the beam in the η(′)π− center-of-mass system and the y-axis pointing in the direction of precoilGJ×pbeamGJ.
New results for the double spin asymmetry A1p and the proton longitudinal spin structure function g1p are presented. They were obtained by the COMPASS Collaboration using polarised 200 GeV muons ...scattered off a longitudinally polarised NH3 target. The data were collected in 2011 and complement those recorded in 2007 at 160 GeV, in particular at lower values of x. They improve the statistical precision of g1p(x) by about a factor of two in the region x≲0.02. A next-to-leading order QCD fit to the g1 world data is performed. It leads to a new determination of the quark spin contribution to the nucleon spin, ΔΣ, ranging from 0.26 to 0.36, and to a re-evaluation of the first moment of g1p. The uncertainty of ΔΣ is mostly due to the large uncertainty in the present determinations of the gluon helicity distribution. A new evaluation of the Bjorken sum rule based on the COMPASS results for the non-singlet structure function g1NS(x,Q2) yields as ratio of the axial and vector coupling constants |gA/gV|=1.22±0.05 (stat.)±0.10 (syst.), which validates the sum rule to an accuracy of about 9%.
Exclusive production of ηπ− and η′π− has been studied with a 191 GeV/cπ− beam impinging on a hydrogen target at COMPASS (CERN). Partial-wave analyses reveal different odd/even angular momentum (L) ...characteristics in the inspected invariant mass range up to 3 GeV/c2. A striking similarity between the two systems is observed for the L=2,4,6 intensities (scaled by kinematical factors) and the relative phases. The known resonances a2(1320) and a4(2040) are in line with this similarity. In contrast, a strong enhancement of η′π− over ηπ− is found for the L=1,3,5 waves, which carry non-qq¯ quantum numbers. The L=1 intensity peaks at 1.7 GeV/c2 in η′π− and at 1.4 GeV/c2 in ηπ−, the corresponding phase motions with respect to L=2 are different.
Depletion of α-SMA+ myofibroblast aggravates pancreatitis in mice Allawadhi, Prince; Alnatsha, A.; Brix, N. ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
12/2023, Letnik:
23, Številka:
8
Journal Article
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