A novel 3-dimensional (3D) microfluidics device to model the tumor microenvironment (TME).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 704-704
Author(s):  
Bradley A. Krasnick ◽  
Ye Bi ◽  
Maddy Goedegebuure ◽  
Peter S. Goedegebuure ◽  
Venktesh S. Shirure ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Cell Line ◽  
Colorectal Tumor ◽  
Lung Fibroblasts ◽  
Air Plasma ◽  
Fibrin Gel ◽  
Central Chamber ◽  
Colorectal Tumor Cell

704 Background: In vitro models of cancer have led to significant therapeutic advances. Despite the widespread use of in vitro tissue culture, the ability to directly evaluate human biology is limited by the inability to model the complex, 3D nature of the TME. We introduce a novel, microfluidic-based system of 3D human micro-tumors perfused with a network of human micro-vessels which could overcome the shortcomings of current in vitro systems. Methods: The micro-device was created by casting polydimethylsiloxane (PDMS) onto master molds, which are then bonded to a flat PDMS sheet using air plasma. Normal human lung fibroblasts (NHLF) and GFP labelled endothelial colony forming cell derived endothelial cells (EC-FCECs) were loaded in a fibrin gel at a 1:2 ratio into the central tissue chamber. Media was introduced through the microfluidic lines. The vascular network was developed with complete EGM2 media under nominal interstitial flow. Colorectal tumor cell lines labelled with mCherry were loaded to the side chambers on the seventh day after NHLF and EC loading. Bevacizumab or TGF- β were added on the second day after tumor cell loading. Results: Micro-vessels formed in the central chamber in 5-7 days after loading. The vessels were perfused with 70KDa fluorescent (red) dextran, and displayed intact vessel wall barrier. A suspension of a colorectal tumor cell line was loaded into the device side chambers, next to a fully developed vasculature. The tumor cells drove angiogenesis into the side chambers, and at the same time tumor began to migrate into the central chamber and within the vessel lumen. The angiogenesis induced by tumor cells can be pharmacologically inhibited, and the migration/ intravasation of tumor cells can be stimulated by TGF-β. Conclusions: Our novel micro-device system can be used as a functional in vitro system that can model the tumor micro-environment. This system has the advantage over current in vitro and in vivo systems in that it is high-throughput, rapid, cost-effective, and recreates many features of the 3D TME. We are currently expanding the platform to incorporate immune cells and designing a completely autologous system to test cancer immunotherapeutics.

dSLIM Immunomodulators Induce Anti-Tumor Responses Both In Vitro and In Vivo.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1727-1727
Author(s):  
Manuel Schmidt ◽  
Javier de Cristobal ◽  
Astrid Sander ◽  
Bernadette Brzezicha ◽  
Sven A. König Merediz ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Neutralizing Antibodies ◽  
De Novo ◽  
Tumor Cell Line ◽  
Control Group ◽  
Γδt Cells ◽  
Ifn Γ

Abstract Cytosine-guanine (CpG) motifs containing oligonucleotides (ODN) are commonly used for immunomodulatory purpose in cancer therapy and for the treatment of allergic diseases since they resemble bacterial DNA and serve as “danger signals”. These CpG-ODNs promote predominately a TH1-response with secretion of IL-12 and IFN-γ, In addition their broad potential includes activation of B-cell proliferation, monocyte stimulation and secretion of IgM and IL-6, and stimulation of plasmacytoid DC to produce IFN-α/-β and thus γδT-cells and NK-cells to express CD69 and secrete IFN-γ. Usually phosphorothioate (PS) modifications are to enhance the stability, but these are leading to several side-effects, like severe organ enlargements, morphological changes and immunosuppression in mice. We designed immunomodulatory molecules based on short covalently-closed dumbbell-like structures (dSLIM) to stabilize the DNA without the otherwise necessary PS-modification. To evaluate the anti-tumor effect of the dSLIM molecules we developed an in vitro anti-tumor assay. This assay uses supernatant from dSLIM-activated human PBMCs for incubation with tumor cells in vitro. We observed increased apoptosis and necrosis of the HT-29 tumor cell line after incubation with supernatant from dSLIM-treated PBMC which was significantly higher than the effect of supernatant from non-treated PBMC. In addition, supernatant from dSLIM-treated PBMC increased the expression of HLA-ABC on the tumor cells, a pre-requisite for tumor cell recognition by the immune system. These effects were confirmed with human HEK293 and murine Renca cell lines. Analyzing the effect with neutralizing antibodies to various apoptosis-related cytokines, we observed a crucial role of IFN-γ but not IFN-α or TNFα. To investigate the anti-tumor effects of dSLIM in vivo, we employed a SKH1 murine model which is prone to spontaneous development of papillomas. Using chemicals for initiation and weekly promotion of de novo papilloma development we compared groups of weekly s.c. or i.p. dSLIM injections, respectively, with the PBS control group. The number of papilloma developing mice was significantly lower in the dSLIM groups and the total number of papillomas on all mice was reduced by approximately 50%. In conclusion, we showed that dSLIM immunomodulators exhibit potent anti-tumor effects in vitro and in vivo.

Comparison of the X-Radiation, Drug and Ultraviolet-Radiation Responses of Clones Isolated from a Human Colorectal Tumor Cell Line

2004 ◽  
Vol 161 (3) ◽  
pp. 326-334 ◽  
Author(s):  
Sami S. Qutob ◽  
Asha S. Multani ◽  
S. Pathak ◽  
Y. Feng ◽  
Wayne S. Kendal ◽  
...  
Keyword(s):  
Ultraviolet Radiation ◽  
Tumor Cell ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Colorectal Tumor ◽  
Colorectal Tumor Cell

scholarly journals Aberrant methylation of the ATM promoter correlates with increased radiosensitivity in a human colorectal tumor cell line

Oncogene ◽  
2002 ◽  
Vol 21 (24) ◽  
pp. 3864-3871 ◽  
Author(s):  
Wan-ju Kim ◽  
Quynh N Vo ◽  
Meena Shrivastav ◽  
Tamara A Lataxes ◽  
Kevin D Brown
Keyword(s):  
Tumor Cell ◽  
Cell Line ◽  
Tumor Cell Line ◽  
Colorectal Tumor ◽  
Aberrant Methylation ◽  
Colorectal Tumor Cell

In vivo and in vitro antitumor activity of oxaliplatin in combination with cetuximab in human colorectal tumor cell lines expressing different level of EGFR

2005 ◽  
Vol 57 (6) ◽  
pp. 709-718 ◽  
Author(s):  
Diane Balin-Gauthier ◽  
Jean-Pierre Delord ◽  
Philippe Rochaix ◽  
Valérie Mallard ◽  
Fabienne Thomas ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Cell ◽  
Cell Lines ◽  
Colorectal Tumor ◽  
Tumor Cell Lines ◽  
Colorectal Tumor Cell

scholarly journals Studies of cloned Friend erythroleukemia tumor cells. Modulation of the tumor-specific cytologic T lymphocyte response by infectious Friend virus production in vitro.

1980 ◽  
Vol 151 (3) ◽  
pp. 726-742 ◽  
Author(s):  
F Plata ◽  
M M Goodenow ◽  
F Lilly
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Tumor Cell Line ◽  
Virus Production ◽  
Target Cells ◽  
Cytolytic T Lymphocytes ◽  
Friend Virus ◽  
High Degree ◽  
Complex Manner

The HFL/b tumor cell line, induced by Friend erythroleukemia virus in BALB.B mice, was used to study the relation between virus production or nonproduction and the antigens recognized by Friend virus-specific cytolytic T lymphocytes (CTL). Analysis of clones and subclones of these tumor cells revealed a high degree of heterogeneity with respect to the production and release into culture fluids of infectious Friend virus in vitro, ranging from high levels to low or undetectable levels of virus production. Although no major differences could be detected among the antibody-defined serotypes of the various clones, the susceptibility of cells of individual HFL/b clones to attack by Friend virus-specific CTL varied widely, and those clones which produced large amounts of infectious virus provided the most sensitive target cells. It was also apparent that production of infectious Friend virus was inhibitory to CTL generation in syngeneic mixed leukocyte-tumor cell cultures. Friend erythroleukemia virus-producing cells thus appeared to interact in a complex manner with the host CTL response by modulating their production of infectious Friend virus.

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