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Neuropathological and genomic characterization of glioblastoma-induced rat model: How similar is it to humans for targeted therapy?
Authors:Farzaneh Sharifzad  Hamed Yasavoli-Sharahi  Saeid Mardpour  Esmaeil Fakharian  Hassan Nikuinejad  Yasaman Heydari  Soura Mardpour  Adeleh Taghikhani  Reza khellat  Somayeh Vafaei  Sahar Kiani  Saeid Ghavami  Marek Łos  Mehdi Noureddini  Marzieh Ebrahimi  Javad Verdi  Amir Ali Hamidieh
Institution:1. Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, Iran;2. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Department of Developmental Biology, University of Science and Culture, Tehran, Iran;3. Department of Radiology Medical Imaging Center, Imam Khomeini Hospital, Tehran, Iran

Department of Radiology, Iran University of Medical Sciences, Tehran, Iran;4. Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, Iran

Department of Neurosurgery, Kashan University of Medical Sciences, Kashan, Iran;5. Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, Iran

Nephrology and Urology Research Center, Baqiyataallah University of Medical Sciences, Tehran, Iran;6. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Department of Medical Physics, Tarbiat Modares University, Tehran, Iran;7. Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran;8. Department of Immunology, Medical School, Tarbiat Modares University, Tehran, Iran;9. Shafa Hospital Pathobiology Laboratory, Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran;10. Department of Molecular Medicine, Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran;11. Department of Human Anatomy & Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada

Children's Hospital Research Institute of Manitoba, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada

Research Institute of Oncology and Hematology, Department of Human Anatomy and Cell Science, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada;12. Biotechnology Centre, Silesian Technical University of Technology, Gliwice, Poland;13. Pediatric Stem Cell Transplant Department, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran

Abstract:Glioblastoma multiforme (GBM) is a unique aggressive tumor and mostly develops in the brain, while rarely spreading out of the central nervous system. It is associated with a high mortality rate; despite tremendous efforts having been made for effective therapy, tumor recurrence occurs with high prevalence. To elucidate the mechanisms that lead to new drug discovery, animal models of tumor progression is one of the oldest and most beneficial approaches to not only investigating the aggressive nature of the tumor, but also improving preclinical research. It is also a useful tool for predicting novel therapies' effectiveness as well as side effects. However, there are concerns that must be considered, such as the heterogeneity of tumor, biological properties, pharma dynamic, and anatomic shapes of the models, which have to be similar to humans as much as possible. Although several methods and various species have been used for this approach, the real recapitulation of the human tumor has been left under discussion. The GBM model, which has been verified in this study, has been established by using the Rat C6 cell line. By exploiting bioinformatic tools, the similarities between aberrant gene expression and pathways have been predicted. In this regard, 610 common genes and a number of pathways have been detected. Moreover, while magnetic resonance imaging analysis enables us to compare tumor features between these two specious, pathological findings provides most of the human GBM characteristics. Therefore, the present study provides genomics, pathologic, and imaging evidence for showing the similarities between human and rat GBM models.
Keywords:drug target therapy  gene expression  glioblastoma multiforme  protein−protein interaction  rat model
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