Show/Hide Menu
Hide/Show Apps
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Open Science Policy
Open Science Policy
Open Access Guideline
Open Access Guideline
Postgraduate Thesis Guideline
Postgraduate Thesis Guideline
Communities & Collections
Communities & Collections
Help
Help
Frequently Asked Questions
Frequently Asked Questions
Guides
Guides
Thesis submission
Thesis submission
MS without thesis term project submission
MS without thesis term project submission
Publication submission with DOI
Publication submission with DOI
Publication submission
Publication submission
Supporting Information
Supporting Information
General Information
General Information
Copyright, Embargo and License
Copyright, Embargo and License
Contact us
Contact us
An engineered pancreatic cancer model with intra-tumoral heterogeneity of driver mutations
Date
2020-10-01
Author
Moon, Hye-ran
Ozcelikkale, Altug
Yang, Yi
Elzey, Bennett D.
Konieczny, Stephen F.
Han, Bumsoo
Metadata
Show full item record
This work is licensed under a
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
.
Item Usage Stats
216
views
0
downloads
Cite This
Pancreatic ductal adenocarcinoma (PDAC) is a complex disease with significant intra-tumoral heterogeneity (ITH). Currently, no reliable PDAC tumor model is available that can present ITH profiles in a controlled manner. We develop an in vitro microfluidic tumor model mimicking the heterogeneous accumulation of key driver mutations of human PDAC using cancer cells derived from genetically engineered mouse models. These murine pancreatic cancer cell lines have KPC (Kras and Trp53 mutations) and KIC genotypes (Kras mutation and Cdkn2a deletion). Also, the KIC genotypes have two distinct phenotypes - mesenchymal or epithelial. The tumor model mimics the ITH of human PDAC to study the effects of ITH on the gemcitabine response. The results show gemcitabine resistance induced by ITH. Remarkably, it shows that cancer cell-cell interactions induce the gemcitabine resistance potentially through epithelial-mesenchymal-transition. The tumor model can provide a useful testbed to study interaction mechanisms between heterogeneous cancer cell subpopulations.
Subject Keywords
Biochemistry
,
Bioengineering
,
General Chemistry
,
Biomedical Engineering
URI
https://hdl.handle.net/11511/68375
Journal
LAB ON A CHIP
DOI
https://doi.org/10.1039/d0lc00707b
Collections
Department of Mechanical Engineering, Article
Suggestions
OpenMETU
Core
The serum immunoglobulin G glycosylation signature of gastric cancer
Ruhaak, L. Renee; Barkauskas, Donald A.; Torres, Javier; Cooke, Cara L.; Wu, Lauren D.; Stroble, Carol; Özcan Kabasakal, Süreyya; Williams, Cynthia C.; Camorlinga, Margarita; Rocke, David M.; Lebrilla, Carlito B.; Solnick, Jay V. (Elsevier BV, 2015-03-01)
Biomarkers may facilitate detection of gastric cancer at an earlier stage and reduce mortality. Here we sought to determine if the glycosylation profile of serum immunoglobulin G (IgG) could distinguish patients with non-atrophic gastritis (NAG), duodenal ulcer (DU) and gastric cancer (GC). Serum IgG was released and analyzed using nano-LC–TOF mass spectrometry. Statistically significant false discovery rate (FDR)-adjusted p-values were observed for 18 glycans, eight that differed significantly between NAG ...
Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26
Aktas, Y; Yemisci, M; Andrieux, K; Gursoy, RN; Alonso, MJ; Fernandez-Megia, E; Novoa-Carballal, R; Quinoa, E; Riguera, R; Sargon, MF; Celik, HH; Demir, Ayhan Sıtkı; Hincal, AA; Dalkara, T; Capan, Y; Couvreur, P (American Chemical Society (ACS), 2005-11-01)
The inhibition of the caspase-3 enzyme is reported to increase neuronal cell survival following cerebral ischemia. The peptide Z-DEVD-FMK is a specific caspase inhibitor, which significantly reduces vulnerability to the neuronal cell death. However, this molecule is unable to cross the blood-brain barrier (BBB) and to diffuse into the brain tissue. Thus, the development of an effective delivery system is needed to provide sufficient drug concentration into the brain to prevent cell death. Using the avidin (...
A conjugated gold nanoparticle-azacyanine off-on-off fluorescence probe for sensitive and selective detection of G-quadruplexes
Bilgen, Ecenaz; Forough, Mehrdad; Persil Çetinkol, Özgül (Elsevier BV, 2020-09-01)
G-quadruplex secondary structures have gained significant recognition due to the discovery of their involvement in regulation of gene expression and their association with many diseases such as cancer and neurological disorders. Consequently, the need for the recognition and characterization of G-quadruplex structures has increased considerably. Here, we present a rapid, facile and sensitive off-on-off in vitro platform for G-quadruplex detection, based on the gold nanoparticle-azacyanine5 (AuNP-Aza5) conju...
Role of intracellular poroelasticity on freezing-induced deformation of cells in engineered tissues
Ghosh, Soham; Özçelikkale, Altuğ; Dutton, J. Craig; Han, Bumsoo (The Royal Society, 2016-10-01)
Freezing of biomaterials is important in a wide variety of biomedical applications, including cryopreservation and cryosurgeries. For the success of these applications to various biomaterials, biophysical mechanisms, which determine freezing-induced changes in cells and tissues, need to be well understood. Specifically, the significance of the intracellular mechanics during freezing is not well understood. Thus, we hypothesize that cells interact during freezing with the surroundings such as suspension medi...
In planta determination of GaMyb transcription factor as a target of pathogen induced microRNA, mir159
Akkaya, Mahinur; Dagdas, Gulay Gok; Dagdas, Yasin F. (2011-09-01)
One of the molecular mechanisms underlying the plant–pathogen interactions is the regulation of gene expressions in plant responses by microRNAs which are either stimulated or silenced against pathogen attacks. Among the plant miRNAs, we found that mir159 is one of which that differentially expressed upon Blumeria graminis f. sp. hordei (Bgh) infected resistant and susceptible barley lines. The study aims to confirm its role in regulating one of its putative target genes, GaMyb transcription factor, in vivo...
Citation Formats
IEEE
ACM
APA
CHICAGO
MLA
BibTeX
H.-r. Moon, A. Ozcelikkale, Y. Yang, B. D. Elzey, S. F. Konieczny, and B. Han, “An engineered pancreatic cancer model with intra-tumoral heterogeneity of driver mutations,”
LAB ON A CHIP
, pp. 3720–3732, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/68375.