A reliable model system that is relevant to the disease in question is a critical asset to achieve development of safe and effective therapeutics. It is in particular relevant for glioblastoma, since this tumor is composed of heterogeneous multiple types of tumor cells in patients. Recent studies identified that application of the spheroid cultures enables us to maintain the original phenotypic and genetic characteristics of the parental tumors. Core C will utilize its current services to collect additional glioblastoma spheroids (GSs) from affected patients and uncover the phenotypic and genotypic characteristics of these GSs are particularly relevant to each project as detailed in aim 2. Specifically, we will establish spheroid cultures from surgical specimens and perform in vivo tumorigenicity assay to determine if our samples are able to recapitulate patients' tumors histopathologically. We also would plan to provide these services on an ongoing basis for all five years of the grant since characterized GSs transferred to each project may require re-characterization. As such, this Core will provide services essential to all 4 projects. Significance of this Core as a central biorepository will eliminate variability amongst the projects, ensuring that all projects utilize the same GSs for the proposed experiments.

Public Health Relevance

Increasing bodies of evidence suggest that long-term cultures of tumor cells in serum-containing medium, including conventional cell lines, result in undesired phenotypic and genetic transformation of the original tumors. Our spheroid cultures from surgical specimens will create concrete path for the proposed projects to target the right kinds of tumor cells to evaluate therapeutics. Characterization of the samples with the proposed spheroid cultures will also deepen our understanding of the diseases in question.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA163205-05
Application #
9229535
Study Section
Special Emphasis Panel (ZCA1-RPRB-J)
Project Start
Project End
2018-09-17
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
5
Fiscal Year
2017
Total Cost
$128,081
Indirect Cost
$2,397
Name
Ohio State University
Department
Type
Domestic Higher Education
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Dai, Hong-Sheng; Caligiuri, Michael A (2018) Molecular Basis for the Recognition of Herpes Simplex Virus Type 1 Infection by Human Natural Killer Cells. Front Immunol 9:183
Chen, Luxi; Youssef, Youssef; Robinson, Cameron et al. (2018) CD56 Expression Marks Human Group 2 Innate Lymphoid Cell Divergence from a Shared NK Cell and Group 3 Innate Lymphoid Cell Developmental Pathway. Immunity 49:464-476.e4
Victor, Aaron R; Weigel, Christoph; Scoville, Steven D et al. (2018) Epigenetic and Posttranscriptional Regulation of CD16 Expression during Human NK Cell Development. J Immunol 200:565-572
Kim, Yangjin; Yoo, Ji Young; Lee, Tae Jin et al. (2018) Complex role of NK cells in regulation of oncolytic virus-bortezomib therapy. Proc Natl Acad Sci U S A 115:4927-4932
Sadahiro, Hirokazu; Kang, Kyung-Don; Gibson, Justin T et al. (2018) Activation of the Receptor Tyrosine Kinase AXL Regulates the Immune Microenvironment in Glioblastoma. Cancer Res 78:3002-3013
Scoville, Steven D; Nalin, Ansel P; Chen, Luxi et al. (2018) Human AML activates the aryl hydrocarbon receptor pathway to impair NK cell development and function. Blood 132:1792-1804
Chan, Wing Keung; Kang, Siwen; Youssef, Youssef et al. (2018) A CS1-NKG2D Bispecific Antibody Collectively Activates Cytolytic Immune Cells against Multiple Myeloma. Cancer Immunol Res 6:776-787
Nakashima, Hiroshi; Alayo, Quazim A; Penaloza-MacMaster, Pablo et al. (2018) Modeling tumor immunity of mouse glioblastoma by exhausted CD8+ T cells. Sci Rep 8:208
Marzulli, M; Mazzacurati, L; Zhang, M et al. (2018) A Novel Oncolytic Herpes Simplex Virus Design based on the Common Overexpression of microRNA-21 in Tumors. J Gene Ther 3:
Russell, Luke; Swanner, Jessica; Jaime-Ramirez, Alena Cristina et al. (2018) PTEN expression by an oncolytic herpesvirus directs T-cell mediated tumor clearance. Nat Commun 9:5006

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