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Therapeutic Hypothesis Testing With Rodent Brain Tumor Models.

ABSTRACT: The development and application of rodent models for preclinical testing of novel therapeutics and approaches for treating brain tumors has been a mainstay of neuro-oncology preclinical research for decades, and is likely to remain so into the foreseeable future. These models serve as an important point of entry for analyzing the potential efficacy of experimental therapies that are being considered for clinical trial evaluation. Although rodent brain tumor models have seen substantial change, particularly since the introduction of genetically engineered mouse models, certain principles associated with the use of these models for therapeutic testing are enduring, and form the basis for this review. Here we discuss the most common rodent brain tumor models while directing specific attention to their usefulness in preclinical evaluation of experimental therapies. These models include genetically engineered mice that spontaneously or inducibly develop brain tumors; syngeneic rodent models in which cultured tumor cells are engrafted into the same strain of rodent from which they were derived; and patient-derived xenograft models in which human tumor cells are engrafted in immunocompromised rodents. The emphasis of this review is directed to the latter.

SUBMITTER: Wainwright DA

PROVIDER: S-EPMC5398994 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Therapeutic Hypothesis Testing With Rodent Brain Tumor Models.

Wainwright Derek A DA Horbinski Craig M CM Hashizume Rintaro R James C David CD

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20170401 2

The development and application of rodent models for preclinical testing of novel therapeutics and approaches for treating brain tumors has been a mainstay of neuro-oncology preclinical research for decades, and is likely to remain so into the foreseeable future. These models serve as an important point of entry for analyzing the potential efficacy of experimental therapies that are being considered for clinical trial evaluation. Although rodent brain tumor models have seen substantial change, p ...[more]

PMID: 28321824

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Project description:Different literature reviews of gambling disorder (GD) neurobiology have been focused on human studies, others have focused on rodents, and others combined human and rodent studies. The main question of this review was: which are the main neurotransmitters systems and brain structures relevant for GD based on recent rodent studies? This work aims to review the experimental findings regarding the rodent´s neurobiology of GD. A search in the Pub Med database was set (October 2012-October 2017) and 162 references were obtained. After screening, 121 references were excluded, and only 41 references remained from the initial output. More, other 25 references were added to complement (introduction section, neuroanatomical descriptions) the principal part of the work. At the end, a total of 66 references remained for the review. The main conclusions are: 1) according to studies that used noninvasive methods for drug administration, some of the neurotransmitters and receptors involved in behaviors related to GD are: muscarinic, N-methyl-D-aspartate (NMDA), cannabinoid receptor 1 (CB1), cannabinoid receptor 2 (CB2), dopamine 2 receptor (D2), dopamine 3 receptor (D3), and dopamine 4 receptor (D4); 2) moreover, there are other neurotransmitters and receptors involved in GD based on studies that use invasive methods of drug administration (eg, brain microinjection); example of these are: serotonin 1A receptor (5-HT1A), noradrenaline receptors, gamma-aminobutyric acid receptor A (GABAA), and gamma-aminobutyric acid receptor B (GABAB); 3) different brain structures are relevant to behaviors linked to GD, like: amygdala (including basolateral amygdala (BLA)), anterior cingulate cortex (ACC), hippocampus, infralimbic area, insular cortex (anterior and rostral agranular), nucleus accumbens (NAc), olfactory tubercle (island of Calleja), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), prefrontal cortex (PFC) - subcortical network, striatum (ventral) and the subthalamic nucleus (STN); and 4) the search for GD treatments should consider this diversity of receptor/neurotransmitter systems and brain areas.

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Therapeutic Hypothesis Testing With Rodent Brain Tumor Models.

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Therapeutic Hypothesis Testing With Rodent Brain Tumor Models.

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