scholarly journals P11.13 Radiotherapy combined with a multimodal imaging approach in a glioblastoma preclinical model

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii45-iii45
Author(s):  
D Salvatore ◽  
G Shaw ◽  
J Wright ◽  
I Teh ◽  
J Koch-Paszkowski ◽  
...  
Keyword(s):  
Treatment Response ◽  
Brain Tissue ◽  
Cell Biology ◽  
Multimodal Imaging ◽  
Fold Increase ◽  
Transport Systems ◽  
Steady Increase ◽  
Preclinical Model ◽  
Cellular Transport ◽  
Time Activity

Abstract BACKGROUND Glioblastoma multiforme (GBM) carries a poor prognosis, partly due to biological and anatomical heterogeneity. Although radiotherapy (RT) is effective, high doses damage surrounding healthy tissues. Multimodal imaging with Magnetic Resonance (MRI) and Positron Emission Tomography (PET) may represent a useful approach for identifying GBM heterogeneity and visualising metabolic tumour properties. PET radiotracer [18F]-fluciclovine is preferentially accumulated in gliomas compared to healthy brain tissue via the cellular transport systems, LAT1 and ASCT2. In this study the effect of fractionated RT using multimodal imaging including [18F]-fluciclovine uptake and immunohistochemistry (IHC) in a GBM preclinical model will be validated. MATERIAL AND METHODS Two C57BL/6J mice cohorts were injected intracranially (i.c.) with murine CT2A-luc cells and subsequently submitted to multiparametric MRI and [18F]-fluciclovine PET imaging during hemi-brain RT (3Gy on 2 days/each week) for maximum 25 days after i.c. injection. Brains were collected for IHC characterization including LAT1 and ASCT2 staining. RESULTS Preliminary data showed that both MRI and PET were effective modalities to track tumour growth in this model. PET data revealed up to greater than 3-fold increase in SUVmax from regions of interest around the tumour site compared to healthy brain tissue. Time activity curves showed a steady increase in tumour uptake over 90 minutes. MRI showed a 25% increase in T2 values in tumours relative to unaffected contralateral regions. Confirmation of treatment response through matched imaging and IHC are ongoing, from which changes in glioma cell biology as well as amino acid transporter protein levels will be analysed. CONCLUSION These preliminary results show that multimodal imaging presents novel data in the assessment of treatment response in this model and will permit parallel IHC analyses to better define GBM tumour heterogeneity aligned with imaging changes. These data will also inform an on-going clinical study using the same imaging modalities. Work at authors’ labs are supported by an Investigator initiated project from Blue Earth Diagnostics (AS, SCS) and a University of Leeds Biswas studentship (SCS, DS). Daniela Salvatore is also supported by a Scholarship provided by Molecular and Translational Medicine Doctorate School of University of Milan (Italy).

scholarly journals NeuroHeal Improves Muscle Regeneration after Injury

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 22
Author(s):  
Sara Marmolejo-Martínez-Artesero ◽  
David Romeo-Guitart ◽  
Vanesa Venegas ◽  
Mario Marotta ◽  
Caty Casas
Keyword(s):  
Satellite Cell ◽  
Muscle Regeneration ◽  
Cell Biology ◽  
Fiber Type ◽  
Traumatic Injury ◽  
Injury Rate ◽  
Scar Tissue ◽  
Medical Problem ◽  
Preclinical Model

Musculoskeletal injuries represent a challenging medical problem. Although the skeletal muscle is able to regenerate and recover after injury, the process engaged with conservative therapy can be inefficient, leading to a high re-injury rate. In addition, the formation of scar tissue implies an alteration of mechanical properties in muscle. There is still a need for new treatments of the injured muscle. NeuroHeal may be one option. Published studies demonstrated that it reduces muscle atrophy due to denervation and disuse. The main objective of the present work was to assess the potential of NeuroHeal to improve muscle regeneration after traumatic injury. Secondary objectives included characterizing the effect of NeuroHeal treatment on satellite cell biology. We used a rat model of sport-induced injury in the gastrocnemius and analyzed the effects of NeuroHeal on functional recovery by means of electrophysiology and tetanic force analysis. These studies were accompanied by immunohistochemistry of the injured muscle to analyze fibrosis, satellite cell state, and fiber type. In addition, we used an in vitro model to determine the effect of NeuroHeal on myoblast biology and partially decipher its mechanism of action. The results showed that NeuroHeal treatment advanced muscle fiber recovery after injury in a preclinical model of muscle injury, and significantly reduced the formation of scar tissue. In vitro, we observed that NeuroHeal accelerated the formation of myotubes. The results pave the way for novel therapeutic avenues for muscle/tendinous disorders.

Multimodal imaging of snap-frozen AD human brain tissue

2021 ◽  
Author(s):  
Benjamin Lochocki ◽  
Baayla D. C. Boon ◽  
Sander R. Verheul ◽  
Liron Zada ◽  
Jereon J. M. Hoozemans ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
Multimodal Imaging ◽  
Human Brain Tissue

Abstract 50: Procollagen C-endopeptidase Enhancer protein 2 (PCPE2) Deficiency Profoundly Affects Adipose Distribution in Mice and Humans and Links HDL Metabolism to Adipocyte Biology

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Sushma Kaul ◽  
Elisa Maruko ◽  
Hao Xu ◽  
Mete Civelek ◽  
Craig Glastonbury ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Visceral Fat ◽  
Cholesterol Ester ◽  
Cell Biology ◽  
Subcutaneous Fat ◽  
Inverse Correlation ◽  
Hdl Cholesterol ◽  
Fold Increase ◽  
Fat Pad ◽  
Similar Body

Procollagen C-endopeptidase enhancer protein 2 (PCPE2) modulates selective HDL cholesterol ester uptake by SR-BI. Ldlr-/-,Pcpe2-/- mice develop greater aortic atherosclerosis despite increased concentrations of enlarged plasma HDL, suggesting PCPE2 confers functionality to HDL for reverse cholesterol transport. PCPE2 is a 52 kDa glycoprotein encoded by PCOLCE2 gene most highly expressed in adipose tissue, heart and aorta. PCPE2 has 2 CUB domains separated by a short linker, with each CUB domain containing a beta-sandwich fold, mediating a variety of protein-protein interactions. PCPE2 also contains a C-terminal netrin-like domain that binds tightly to cell surface glycosaminoglycans accounting for its location in the extracellular matrix. Because of the strong inverse correlation between HDL and triglyceride levels, and the potential role of SR-BI in triglyceride-rich lipoprotein uptake we examined Ldlr-/-,Pcpe2-/-mice fed a Western diet for 25 weeks. Ldlr-/-,Pcpe2-/- mice showed 1.7 fold increase in plasma triglyceride concentrations when compared to age and gender matched Ldlr-/- mice. We also noted that despite similar body weights, Ldlr-/-,Pcpe2-/- visceral fat pad weight was reduced 60% (p<0.001, n=9 per genotype) compared to Ldlr-/- mice, while subcutaneous fat pad weight was not significantly different. This maldistribution of adipose in Ldlr-/-,Pcpe2-/- was associated with increased fasting plasma glucose levels, elevated 25% (p<0.02) over Ldlr-/- mice. In humans, analyses showed significant correlations of subcutaneous fat PCPE2 RNA expression with DEXA traits from the TwinsUK cohort; % android fat (p<0.0002), % trunk fat (p<0.0001) and % gynoid fat (p<0.04). Additional correlations between PCPE2 mRNA abundance and candidate marker expression will also be presented using 53 human visceral fat samples. Overall these data suggest that PCPE2 plays an important role in regional fat deposition linking SR-BI mediated cholesterol ester uptake to adipose cell biology.

scholarly journals Positron Emission Tomography Imaging Reveals an Importance of Saturable Liver Uptake Transport for the Pharmacokinetics of Metoclopramide

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Fabien Caillé ◽  
Sébastien Goutal ◽  
Solène Marie ◽  
Sylvain Auvity ◽  
Salvatore Cisternino ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pet Imaging ◽  
Positron Emission Tomography Imaging ◽  
Fold Increase ◽  
Transport Processes ◽  
Emission Tomography ◽  
Liver Uptake ◽  
Time Activity ◽  
Tracer Dose ◽  
Positron Emission

Positron emission tomography (PET) imaging using [11C]metoclopramide, a P-glycoprotein (P-gp) substrate, was used to investigate the contribution of transport processes to metoclopramide liver clearance. The liver kinetics obtained after injection of [11C]metoclopramide were measured using PET in rats (n=4‐5) in the absence (tracer dose) and the presence of a pharmacologic dose of metoclopramide (3 mg/kg), with or without P-gp inhibition using i.v. tariquidar (8 mg/kg). Corresponding [11C]metoclopramide kinetics and metabolism in plasma (n=3) were measured using radio-HPLC analysis. [11C]metoclopramide exposure to the liver and plasma was described by the area under the time-activity curve (AUC) of the radioactivity kinetics in the liver and parent [11C]metoclopramide kinetics in plasma, respectively. The pharmacologic dose of metoclopramide resulted in a ∼2.2-fold increase in [11C]metoclopramide AUCplasma, while P-gp inhibition did not. AUCliver was lower using the pharmacologic dose (42.9 ± 13.8 SUV·min) compared with the tracer dose (210.0 ± 32.4 SUV·min). P-gp inhibition enhanced the liver exposure in the pharmacologic condition only (81.0 ± 3.1 SUV·min). [11C]metoclopramide PET imaging suggests an unpredicted role for hepatocyte uptake transporter(s) in controlling metoclopramide pharmacokinetics in addition to the known contribution of the metabolic enzymes and the P-gp.

DCE- and DW-MRI as early imaging biomarkers of treatment response in a preclinical model of triple negative breast cancer

2017 ◽  
Vol 30 (11) ◽  
pp. e3799 ◽  
Author(s):  
Stephanie L. Barnes ◽  
Anna G. Sorace ◽  
Jennifer G. Whisenant ◽  
J. Oliver McIntyre ◽  
Hakmook Kang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Response ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Imaging Biomarkers ◽  
Preclinical Model ◽  
Early Imaging

The new target therapy to prevent weight gain associated to atypical antipsychotics: PKCβ

2017 ◽  
Vol 41 (S1) ◽  
pp. S370-S371
Author(s):  
C. Pavan ◽  
A. Rimessi ◽  
B. Zavan ◽  
V. Vindigni ◽  
P. Pinton
Keyword(s):  
Clinical Practice ◽  
Weight Gain ◽  
Side Effects ◽  
Cell Biology ◽  
Target Therapy ◽  
Premature Death ◽  
Preclinical Model ◽  
Psychomotor Tests

Antipsychotic drugs are currently used in clinical practice for a variety of mental disorders. Clozapine is the most effective medication for treatment-resistant schizophrenia, in controlling aggression and suicidal behavior in psychosis. Although clozapine is associated with a low likelihood of extrapyramidal symptoms and other neurological side effects, weight gain and metabolic side effects are well known in clinical practice exposing the patient to a greater risk of cardiovascular disorders, premature death, as well as psychosocial issues leading to non-adherence. The mechanisms underlying this pharmacologically activated disorders are still controversial. Based on our in vitro results, we have characterized in vivo the effects of the selective PKCβ inhibitor, Ruboxistaurin (LY-333531) on a preclinical model of long-term clozapine-induced weight gain. Cell biology, biochemistry and psychomotor tests have been performed on wild type and PKCβ (-/-) mutant mice to investigate the contribution of endogenous PKCβ and its pharmacological inhibitor on the neuroleptic effect of clozapine. Lastly, we also shed light on a novel aspect of the mechanism underlying of clozapine-induced weight gain, demonstrating that the clozapine-dependent PKCβ activation promote the inhibition of the lipid droplet-selective autophagy process, opening the way to new therapeutic intervention approach.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Zellulare Transportsysteme – Den Dingen Beine machen im „Internet der Dinge” (Cellular Transport Systems – Making Things Move in the “Internet of Things”)

2008 ◽  
Vol 50 (1) ◽  
Author(s):  
Michael ten Hompel ◽  
Lars Nagel
Keyword(s):  
Internet Of Things ◽  
Status Quo ◽  
Transport Systems ◽  
The Internet ◽  
Cellular Transport ◽  
Internet Der Dinge ◽  
The Internet Of Things

ZusammenfassungHochautomatisierte intralogistische Systeme sind ein in der Anwendung befindliches Domänenbeispiel intelligenter Umgebungen. Ausgehend vom Status Quo in der Kommissionierung über den Einsatz von Agenten- und RFID-Technologien, die Multiagentensimulation und die Entwicklung von intelligenten Behältern wird konsequent der Weg hin zur vollkommen autonomen Gestaltung des Materialflusses im Konzept der zellularen Transportsysteme aufgezeigt.

scholarly journals Self-recognition drives the preferential accumulation of promiscuous CD4+ T-cells in aged mice

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Neha R Deshpande ◽  
Heather L Parrish ◽  
Michael S Kuhns
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cell Biology ◽  
Fold Increase ◽  
Cell Receptor ◽  
Cd4 T Cell ◽  
Fundamental Aspect ◽  
Cell Compartment ◽  
Old Mice

T-cell recognition of self and foreign peptide antigens presented in major histocompatibility complex molecules (pMHC) is essential for life-long immunity. How the ability of the CD4+ T-cell compartment to bind self- and foreign-pMHC changes over the lifespan remains a fundamental aspect of T-cell biology that is largely unexplored. We report that, while old mice (18–22 months) contain fewer CD4+ T-cells compared with adults (8–12 weeks), those that remain have a higher intrinsic affinity for self-pMHC, as measured by CD5 expression. Old mice also have more cells that bind individual or multiple distinct foreign-pMHCs, and the fold increase in pMHC-binding populations is directly related to their CD5 levels. These data demonstrate that the CD4+ T-cell compartment preferentially accumulates promiscuous constituents with age as a consequence of higher affinity T-cell receptor interactions with self-pMHC.

Sign in / Sign up

Export Citation Format

Share Document