Binding of epigallocatechin gallate to the laminin–β-integrin binding site decreases neural progenitor cell adhesion and migration: Adverse outcome pathway framework supporting neurodevelopmental toxicity research and risk assessment

2015 ◽  
Vol 49 ◽  
pp. 117-118
Author(s):  
Marta Barenys ◽  
Kathrin Gassmann ◽  
Christine Baksmeier ◽  
Sabrina Heinz ◽  
Martin Schmuck ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Progenitor Cell ◽  
Adverse Outcome ◽  
Epigallocatechin Gallate ◽  
Neural Progenitor Cell ◽  
Adverse Outcome Pathway ◽  
Neurodevelopmental Toxicity ◽  
Integrin Binding Site ◽  
Cell Adhesion And Migration ◽  
And Migration

Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment

2018 ◽  
Vol 29 (1-2) ◽  
pp. 190-204 ◽  
Author(s):  
Holly M. Mortensen ◽  
John Chamberlin ◽  
Bonnie Joubert ◽  
Michelle Angrish ◽  
Nisha Sipes ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Health Risk ◽  
Human Health ◽  
Health Risk Assessment ◽  
Adverse Outcome ◽  
Human Health Risk ◽  
Human Health Risk Assessment ◽  
Adverse Outcome Pathway

scholarly journals Adverse Outcome Pathway Development for Assessment of Lung Carcinogenicity by Nanoparticles

2021 ◽  
Vol 3 ◽  
Author(s):  
Penny Nymark ◽  
Hanna L. Karlsson ◽  
Sabina Halappanavar ◽  
Ulla Vogel
Keyword(s):  
Lung Cancer ◽  
Risk Assessment ◽  
Adverse Outcome ◽  
Animal Experiments ◽  
Engineered Nanoparticles ◽  
Alternative Methods ◽  
Weight Of Evidence ◽  
Adverse Outcome Pathway ◽  
Alternative Mechanism

Lung cancer, one of the most common and deadly forms of cancer, is in some cases associated with exposure to certain types of particles. With the rise of nanotechnology, there is concern that some engineered nanoparticles may be among such particles. In the absence of epidemiological evidence, assessment of nanoparticle carcinogenicity is currently performed on a time-consuming case-by-case basis, relying mainly on animal experiments. Non-animal alternatives exist, including a few validated cell-based methods accepted for regulatory risk assessment of nanoparticles. Furthermore, new approach methodologies (NAMs), focused on carcinogenic mechanisms and capable of handling the increasing numbers of nanoparticles, have been developed. However, such alternative methods are mainly applied as weight-of-evidence linked to generally required animal data, since challenges remain regarding interpretation of the results. These challenges may be more easily overcome by the novel Adverse Outcome Pathway (AOP) framework, which provides a basis for validation and uptake of alternative mechanism-focused methods in risk assessment. Here, we propose an AOP for lung cancer induced by nanosized foreign matter, anchored to a selection of 18 standardized methods and NAMs for in silico- and in vitro-based integrated assessment of lung carcinogenicity. The potential for further refinement of the AOP and its components is discussed in relation to available nanosafety knowledge and data. Overall, this perspective provides a basis for development of AOP-aligned alternative methods-based integrated testing strategies for assessment of nanoparticle-induced lung cancer.

scholarly journals Chemical exposure and infant leukaemia: development of an adverse outcome pathway (AOP) for aetiology and risk assessment research

2017 ◽  
Vol 91 (8) ◽  
pp. 2763-2780 ◽  
Author(s):  
Olavi Pelkonen ◽  
◽  
Andrea Terron ◽  
Antonio F. Hernandez ◽  
Pablo Menendez ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Adverse Outcome ◽  
Chemical Exposure ◽  
Adverse Outcome Pathway ◽  
Assessment Research

scholarly journals Functionalized Biomimetic Hydrogels Enhance Salivary Stem/Progenitor Cell Organization

2021 ◽  
Author(s):  
Mariane Martinez ◽  
Robert L Witt ◽  
Mary C Farach-Carson ◽  
Daniel A Harrington
Keyword(s):  
Design Parameters ◽  
Internal Space ◽  
Multicellular Spheroids ◽  
Matrix Space ◽  
Hydrogel Matrix ◽  
Integrin Binding Site ◽  
Cell Adhesion And Migration ◽  
Dependent Cell ◽  
Cleavable Peptide ◽  
And Migration

Complex branched salivary structures remain challenging to replicate within implant ready hydrogels. We showed previously that hyaluronic acid (HA)-based hydrogels enable growth and organization of primary salivary-derived human stem/progenitor cells (hS/PCs) into multicellular spheroids. Here, we systematically functionalized three components of migration-permissive hydrogels to foster salivary tissue morphogenesis. We separately analyzed contributions of an enzymatically degradable crosslinker, a pendant integrin-binding site, and hydrogel porosity to best support high viability, integrin-dependent cell adhesion and migration. Structure size, frequency, and morphology were all affected by hydrogel crosslink density and integration of biofunctional peptides. Viability and proliferation data suggested that integration of integrin binding sites had the greatest effect on hS/PCs behavior. A larger internal matrix space, created by increasing both crosslinker length and PEG content, was needed to form large multicellular hS/PC structures. Peptide-modified hydrogels with more internal space shifted hS/PC organization from spheroidal, surrounded by thick basement membrane, to an asymmetric arrangement with punctate matrix proteins defining a "wrinkled" perimeter. Integrin-binding peptides activated integrin β1, with highest activation observed in hydrogels having both cleavable peptide and integrin ligand. The design parameters we prescribe allowed us to encapsulate hS/PCs in a humanized biomimetic hydrogel matrix able to support morphogenesis needed for salivary restoration.

scholarly journals Application of the Adverse Outcome Pathway Framework to Risk Assessment for Predicting Carcinogenicity of Chemicals

2018 ◽  
Vol 23 (3) ◽  
pp. 126-133 ◽  
Author(s):  
Doo Seok Kang ◽  
Jun Hyuek Yang ◽  
Hyun Soo Kim ◽  
Bon Kon Koo ◽  
Cheol Min Lee ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Adverse Outcome ◽  
Adverse Outcome Pathway
Sign in / Sign up

Export Citation Format

Share Document