development of new and better animal models of glioma would be needed for in vivo evaluation of potential chemotherapeutic and adjunctive therapies for brain tumors. The extensive contributions involving animal models by investigators such as Bigner and Wilson have directed the biological study and adjunctive therapy of brain tumors over the past 25 years. This review is meant to supplement and update information in this already well-documented field. The justification and need for accurate, representative animal models of glioma remain today just as great as in 1970
Daniel L. Peterson, Peter J. Sheridan and Willis E. Brown Jr.
Xin Hong, Kevin K. Nelson, Ana C. deCarvalho and Steven N. Kalkanis
astrocytomas. 28 In contrast to its widely reported overexpression in a variety of tumors, heparanase was found to be decreased in gliomas in 1 published study. 44 As this finding stems from a single study, however, further evidence is needed to verify the true level of heparanase expression—and the potential role of heparanase in encouraging tumor growth—in gliomas. The present study was undertaken to examine heparanase expression in human glioma tissues. Heparanase expression in 2 brain tumor orthotopic animal models was also determined with IHC staining. Our results
Wesley Hsu, I-Mei Siu, Gustavo Pradilla, Ziya L. Gokaslan, George I. Jallo and Gary L. Gallia
contrast, the majority of institutional series report that no patient with a high-grade spinal cord astrocytoma survives after 2 years. 6 , 7 , 12 , 14 , 15 At present, there is no clearly defined chemotherapeutic regimen for spinal cord gliomas beyond the context of clinical trials. Advances in the diagnosis and management of patients with spinal cord tumors have been limited due to the rarity of the disease and the limitations of current animal models of spinal cord glioma. The ideal spinal cord tumor model would possess a number of characteristics, including the
Saleh R. Kashba, Nirav J. Patel, Michael Grace, Vivienne S. Lee, Newsha Raoufi-Rad, Jude V. Amal Raj, Thi Thuy Hong Duong and Marcus Stoodley
cannot be treated using current methods. 9 An improved method of treating AVMs is required for these patients. One potential new treatment is to induce thrombosis in the AVM vessels using molecular techniques that target endothelial changes induced by radiosurgery. Development of such a treatment requires an animal model that mimics the characteristics of human AVMs. We have developed an animal model that shares hemodynamic, structural, and molecular characteristics with human AVMs. 6 , 20 These characteristics make this model suitable for studying the early
Leandro R. Piedimonte, Ian K. Wailes and Howard L. Weiner
Mutations in one of two genes, TSC1 and TSC2, result in a similar disease phenotype by disrupting the normal interaction of their protein products, hamartin and tuberin, which form a functional signaling complex. Disruption of these genes in the brain results in abnormal cellular differentiation, migration, and proliferation, giving rise to the characteristic brain lesions of tuberous sclerosis complex (TSC) called cortical tubers. The most devastating complications of TSC affect the central nervous system and include epilepsy, mental retardation, autism, and glial tumors. Relevant animal models, including conventional and conditional knockout mice, are valuable tools for studying the normal functions of tuberin and hamartin and the way in which disruption of their expression gives rise to the variety of clinical features that characterize TSC. In the future, these animals will be invaluable preclinical models for the development of highly specific and efficacious treatments for children affected with TSC.
Ren Lin, Lili Luo, Yiran Gong, Jingsheng Zheng, Shuiyue Wang, Junjie Du and Daoshu Luo
epigenetic regulation in the TREZ, especially under conditions of TN. Therefore, we designed the present study to examine the acetylation of histone H3K9, H3K18, and H3K27 in the TREZ in an animal model of TN that was induced by chronic compression of the trigeminal nerve root. Methods Antibodies Acetyl histone H3K9 (C5B11) rabbit monoclonal antibody (mAb; 1:50 dilution), acetyl histone H3K18 (D8Z5H) rabbit mAb (1:50 dilution), and acetyl histone H3K27 (D5E4) rabbit mAb (1:50 dilution) primary antibodies were purchased from Cell Signaling Technology. Rabbit anti
David R. Blatt, William A. Friedman, Frank J. Bova, Daniel P. Theele and J. Parker Mickle
few experimental studies of radiosurgery in the literature, the development of a reproducible animal model is crucial. Recently, we reported on the development of a device for animal radiosurgery and on the characterization of a dose-response curve for linear accelerator (LINAC) radiosurgery in a cat model. 3, 17 In that study, the radiobiological effects of a range of doses were studied at one time point (6 months postirradiation) and histological and magnetic resonance (MR) imaging correlation were obtained. In the current experiment, one biologically effective
Zita A. Sibenaller, Arnold B. Etame, Mushtaq M. Ali, Manali Barua, Terry A. Braun, Thomas L. Casavant and Timothy C. Ryken
Animal models have been used extensively to discern the molecular biology of diseases and to gain insight into treatments. Nevertheless, discrepancies in the effects of treatments and procedures have been encountered during the transition from these animal models to application of the information to clinical trials in humans. To assess the genetic similarities between human gliomas and four cell lines used routinely in animal models, the authors used microarray technology to characterize the similarities and differences in gene expression.
To define the changes in gene expression, normal rat astrocytes were compared with four rat glioma cell lines (C6, 9L, F98, and RG2). The data were analyzed using two different methods: fold-change analysis and statistical analysis with t statistics. The gene products that were highlighted after intersecting the lists generated by the two methods of analysis were scrutinized against changes in gene expression reported in the literature. Tumorigenesis involves three major steps: the accumulation of genetic alterations, uncontrolled growth, and selected survival of transformed cells. The discussion of the results focuses attention on genes whose primary function is in pathways involved in glioma proliferation, infiltration, and neovascularization. A comparative microarray analysis of differentially expressed genes for four of the commonly used rat tumor cell lines is presented here.
Due to the variances between the cell lines and results from analyses in humans, caution must be observed in interpreting as well as in the translation of information learned from animal models to its application in human trials.
Roberto Spiegelmann, William A. Friedman, Frank J. Bova, Daniel P. Theele and J. Parker Mickle
is poorly understood. The large number of uncontrollable variables in clinical radiosurgical series diminishes the value of these studies as a source of accurate data relating to these issues. Experimental studies on single-fraction radiation are scarce. Information based on the application of conventional irradiation techniques cannot easily be extrapolated to this clinical setting. The development of a reproducible animal model of radiosurgery is therefore crucial, and more so as the number of patients subjected to this treatment modality increases swiftly. The
Bryan W. Cunningham, Nadim J. Hallab, Nianbin Hu and Paul C. McAfee
procedures commenced following protocol approval by the University of Maryland Biotechnology Institute's Institutional Animal Care and Use Committee. Animal Model and Treatment Groups A total of 120 skeletally mature Harlan Sprague-Dawley New Zealand White rabbits (weight range 3.8–4.2 kg) were included in this study and randomized into 12 groups based on treatment procedure (n = 10 per group). Five animals from each group were sacrificed at postoperative time intervals of 3 months (n = 60) and 6 months (n = 60). The treatment groups were as follows: 1) sham (control