42 research outputs found
Telomerase and pluripotency factors jointly regulate stemness in pancreatic cancer stem cells
© 2021 by the authors.To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the “stemness” maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patients.This research was funded by a Max Eder Fellowship of the German Cancer Aid (111746), a German Cancer Aid Priority Program ‘Translational Oncology’ 70112505, by a Collaborative Research Centre grant (316249678—SFB 1279) of the German Research Foundation, and by a Hector Foundation Cancer Research grant (M65.1) to P.C.H., B.S.J. is supported by a Rámon y Cajal Merit Award (RYC2012-12104) from the Ministerio de Economía y Competitividad, Spain and a Coordinated grant (GC16173694BARB) from the Fundación Asociación Española Contra el Cáncer (AECC). K.W. is supported by a Baustein 3.2 by Ulm University
Telomerase and pluripotency factors jointly regulate stemness in pancreatic cancer stem cells
To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) in primary patient-derived pancreatic cancer cells. We show that CSCs have higher telomerase activity and longer telomeres than bulk tumor cells. Inhibition of telomerase activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted in CSC marker depletion, abrogation of sphere formation in vitro and reduced tumorigenicity in vivo. Furthermore, we identify a positive feedback loop between stemness factors (NANOG, OCT3/4, SOX2, KLF4) and telomerase, which is essential for the self-renewal of CSCs. Disruption of the balance between telomerase activity and stemness factors eliminates CSCs via induction of DNA damage and apoptosis in primary patient-derived pancreatic cancer samples, opening future perspectives to avoid CSC-driven tumor relapse. In the present study, we demonstrate that telomerase regulation is critical for the “stemness” maintenance in pancreatic CSCs and examine the effects of telomerase inhibition as a potential treatment option of pancreatic cancer. This may significantly promote our understanding of PDAC tumor biology and may result in improved treatment for pancreatic cancer patientsThis research was funded by a Max Eder Fellowship of the German Cancer Aid (111746), a
German Cancer Aid Priority Program ‘Translational Oncology’ 70112505, by a Collaborative Research
Centre grant (316249678—SFB 1279) of the German Research Foundation, and by a Hector Foundation
Cancer Research grant (M65.1) to P.C.H., B.S.J. is supported by a Rámon y Cajal Merit Award (RYC-
2012-12104) from the Ministerio de Economía y Competitividad, Spain and a Coordinated grant
(GC16173694BARB) from the Fundación Asociación Española Contra el Cáncer (AECC). K.W. is
supported by a Baustein 3.2 by Ulm University
Cost effectiveness of ulcerative colitis treatment in Germany: a comparison of two oral formulations of mesalazine
<p>Abstract</p> <p>Background</p> <p>The treatment of ulcerative colitis (UC) can place a substantial financial burden on healthcare systems. The anti-inflammatory compound 5-aminosalicylic acid (5-ASA; mesalazine) is the recommended first-line treatment for patients with UC. In this analysis, the incremental cost effectiveness ratio (ICER) of two oral formulations of 5-ASA (Mezavant<sup>® </sup>and Asacol<sup>®</sup>) is examined in the treatment of patients with mild-to-moderate, active UC in Germany.</p> <p>Methods</p> <p>A Markov cohort model was developed to assess the cost effectiveness of Mezavant compared with Asacol over a 5-year period in the German Statutory Health Insurance (SHI). Drug pricing details for 2009 were applied throughout the model, and overall resource use was determined and also fitted to 2009 from published results of a large cross sectional study of German SHI patients. Cost per quality adjusted life year (QALY) was the primary endpoint for this study. Remission rates were obtained using data from a randomised, phase III trial of Mezavant with an active Asacol reference arm and a long-term, open label, safety and tolerability trial of Mezavant. Uncertainty in the study model was assessed using one-way and probabilistic sensitivity analyses applying a Monte Carlo simulation.</p> <p>Results</p> <p>Over a 5-year period, healthcare costs for patients receiving Mezavant were 624 Euro lower than for patients receiving Asacol. Additionally, patients receiving Mezavant gained 0.011 QALYs or 18 more days in remission compared with Asacol. One-way sensitivity analyses suggest that these results are driven by both differences in the acquisition cost between mesalazine formulations and differences in treatment efficacy. Furthermore, sensitivity analyses suggest a probability of 76% for cost savings and higher QALYs with Mezavant compared with Asacol. If adherence and its influence on the remission rates and the risk of developing colorectal cancer were included in the model, the results might have even been more favorable to Mezavant due to its once daily dosing regimen.</p> <p>Conclusions</p> <p>This model suggests that patients treated with Mezavant may achieve increased time in remission and higher QALYs, with lower direct costs to the SHI when compared with Asacol. Mezavant may therefore be a suitable first-line option for the induction and maintenance of remission in UC.</p
Single-Photon Distillation via a Photonic Parity Measurement Using Cavity QED
Single photons with tailored temporal profiles are a vital resource for
future quantum networks. Here we distill them out of custom-shaped laser pulses
that reflect from a single atom strongly coupled to an optical resonator. A
subsequent measurement on the atom is employed to herald a successful
distillation. Out of vacuum-dominated light pulses, we create single photons
with fidelity , two-and-more-photon suppression , and a
Wigner function with negative value . Our scheme applied to
state-of-the-art fiber resonators could boost the single-photon fidelity to up
to .Comment: 8 pages, 7 figures (including Supplemental Material
Bioindikation
TIB: RN 8422 (1986,18) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman
A quantum-logic gate between distant quantum-network modules
The big challenge in quantum computing is to realize scalable multi-qubit
systems with cross-talk free addressability and efficient coupling of
arbitrarily selected qubits. Quantum networks promise a solution by integrating
smaller qubit modules to a larger computing cluster. Such a distributed
architecture, however, requires the capability to execute quantum-logic gates
between distant qubits. Here we experimentally realize such a gate over a
distance of 60m. We employ an ancillary photon that we successively reflect
from two remote qubit modules, followed by a heralding photon detection which
triggers a final qubit rotation. We use the gate for remote entanglement
creation of all four Bell states. Our non-local quantum-logic gate could be
extended both to multiple qubits and many modules for a tailor-made multi-qubit
computing register.Comment: 9 pages, 4 figures, 3 tables (including Supplemental Material
Signatures of spatial inversion asymmetry of an optical lattice observed in matter-wave diffraction
A compendium of RNA-binding proteins that regulate microRNA biogenesis.
During microRNA (miRNA) biogenesis, two endonucleolytic reactions convert stem-loop-structured precursors into mature miRNAs. These processing steps can be posttranscriptionally regulated by RNA-binding proteins (RBPs). Here, we have used a proteomics-based pull-down approach to map and characterize the interactome of a multitude of pre-miRNAs. We identify similar to 180 RBPs that interact specifically with distinct pre-miRNAs. For functional validation, we combined RNAi and CRISPR/Cas-mediated knockout experiments to analyze RBP-dependent changes in miRNA levels. Indeed, a large number of the investigated candidates, including splicing factors and other mRNA processing proteins, have effects on miRNA processing. As an example, we show that TRIM71/LIN41 is a potent regulator of miR-29a processing and its inactivation directly affects miR-29a targets. We provide an extended database of RBPs that interact with pre-miRNAs in extracts of different cell types, highlighting a widespread layer of co- and posttranscriptional regulation of miRNA biogenesis