A systematic review and meta‐analysis of gene therapy in animal models of cerebral glioma: why did promise not translate to human therapy?

Hirst, Theodore C.; Vesterinen, Hanna M.; Conlin, S.; Egan, Kieren; Antonić, Ana; McLean, Aaron Lawson; Macleod, Malcolm; Grant, Robin; Brennan, Paul M.; Sena, Emily; Whittle, Ian R.

doi:10.1002/ebm2.6

Cited by 16 publications

(26 citation statements)

References 59 publications

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“…However, findings from different laboratories, often from small studies, are inconsistent. Systematic reviews and meta-analysis are techniques to provide an unbiased and transparent summary of existing research [ 13 , 14 ]. They can be helpful in the design of clinical trials [ 15 , 16 ] and in understanding discrepancies between the results of preclinical and clinical trials [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

D-galactose-induced brain ageing model: A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices

et al. 2017

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Animal models are commonly used in brain ageing research. Amongst these, models where rodents are exposed to d-galactose are held to recapitulate a number of features of ageing including neurobehavioral and neurochemical changes. However, results from animal studies are often inconsistent. To better understand the characteristics of the model and effects of d-galactose on neurobehavioral and neurochemical outcomes in rodents we performed a systematic review and meta-analysis. We applied random-effects meta-analysis to evaluate the effect of study features. Our results give an overview of the characteristics of the dgalactose rodent ageing model, including neurobehavioral and neurochemical outcomes. We found that few studies took measures to reduce risks of bias, and substantial heterogeneity in the reported effects of d-galactose in included studies. This highlights the need for improvements in the use of the d-galactose rodent ageing model if it is to provide useful in the development of drugs to treat human ageing.

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Section: Introductionmentioning

confidence: 99%

D-galactose-induced brain ageing model: A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices

et al. 2017

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“…Human glioma is derived from the neural ectoderm and is the most common type of primary malignant tumor in human brains (1). Also in China, human gliomas are the most common type of intracranial tumor, accounting for 40-50% (2).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑370 suppresses the progression and proliferation of human astrocytoma and glioblastoma by negatively regulating β‑catenin and causing activation of FOXO3a

et al. 2017

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Abstract. Certain microRNAs (miRs) regulate the progression and metastasis of various cancer types. In the present study, the role of miR-370 in the progression and proliferation of human astrocytoma and glioblastoma cells was assessed and the underlying molecular mechanism was investigated. miR-370 levels in clinical specimens of human glioma and peritumoral tissues were determined by reverse-transcription quantitative PCR. Oligonucleotide mimics and inhibitors were transfected into the U-251MG human astrocytoma cell line and the and U-87MG glioblastoma cell line and the cell viability of was determined by an MTT assay. The expression of β-catenin and forkhead box protein (FOX)O3a was determined by western blot analysis. The results revealed that the expression of miR-370 in human glioma tissues was significantly decreased compared with that in peritumoral tissues. The miR-370 levels in patients with grade III/IV gliomas were significantly decreased compared with those in grade I/II. Transfection with miR-370 mimics inhibited the proliferation of U-251MG and U-87MG cells. Furthermore, the miR-370 levels were negatively correlated with β-catenin and positively correlated with nuclear FOXO3a. In conclusion, miR-370 inhibited the proliferation of human glioma cells by regulating the levels of β-catenin and the activation of FOXO3a, suggesting that miR-370 was a tumor suppressor in the progression of human astrocytoma and glioblastoma cells. IntroductionHuman glioma is derived from the neural ectoderm and is the most common type of primary malignant tumor in human brains (1). Also in China, human gliomas are the most common type of intracranial tumor, accounting for 40-50% (2). In recent years, the risk for gliomas has been gradually increasing in young adults (3). On the World Health Organization tumor grading scale, primary gliomas are normally divided into low-grade glioma, such as fibrillary astrocytomas and pilocytic astrocytomas, and high-grade glioma, including glioblastoma and anaplastic astrocytoma (4,5).Clinical therapy of glioma depends on the size, type, grade and location of the tumor, as well as the age and overall health of the patient, and mainly consists of surgical resection followed by radiotherapy, chemotherapy, Chinese medicine treatment, gene therapy, immunotherapy and psychotherapy (6,7). However, the overall mortality rate remains high in glioma patients (8,9). It is therefore important and urgent to clarify the mechanisms of the genesis of human gliomas, which may be helpful for providing approaches for the therapy of human gliomas.MicroRNAs (miRNAs/miRs) are a class of small non-coding RNA molecules of approximately 21-25 nucleotides in length, which are conserved in plants, animals and certain types of virus (10). miRNAs are involved in the regulation of gene expression through RNA silencing and post-transcriptional gene silencing via binding to the 3'-untranslated region (3'-UTR) of specific mRNAs (11,12). miRNAs regulate diverse aspects of development and physiology, such as metabolic d...

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“…The Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES) group have shown—for a range of experimental neurological diseases including glioma, stroke and multiple sclerosis—that reporting of measures to reduce risk of bias (such as randomisation and blinding) is poor and that publication bias is frequently present. These factors lead to a significant overstatement of perceived treatment efficacy [ 21 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Trastuzumab in Animal Models of Breast Cancer: A Systematic Review and Meta-Analysis

et al. 2016

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BackgroundBreast cancer is the most frequent cancers and is the second leading cause of cancer death among women. Trastuzumab is an effective treatment, the first monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). To inform the development of other effective treatments we report summary estimates of efficacy of trastuzumab on survival and tumour volume in animal models of breast cancer.MethodsWe searched PubMed and EMBASE systematically to identify publications testing trastuzumab in animal models of breast cancer. Data describing tumour volume, median survival and animal features were extracted and we assessed quality using a 12-item checklist. We analysed the impact of study design and quality and evidence for publication bias.ResultsWe included data from 83 studies reporting 169 experiments using 2076 mice. Trastuzumab treatment caused a substantial reduction in tumour growth, with tumours in treated animals growing to 32.6% of the volume of tumours in control animals (95%CI 27.8%-38.2%). Median survival was prolonged by a factor of 1.45 (1.30–1.62). Many study design and quality features accounted for between-study heterogeneity and we found evidence suggesting publication bias.ConclusionWe have found trastuzumab to be effective in animal breast cancer models across a range of experimental circumstances. However the presence of publication bias and a low prevalence of measures to reduce bias provide a focus for future improvements in preclinical breast cancer research.

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A systematic review and meta‐analysis of gene therapy in animal models of cerebral glioma: why did promise not translate to human therapy?

Cited by 16 publications

References 59 publications

D-galactose-induced brain ageing model: A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices

D-galactose-induced brain ageing model: A systematic review and meta-analysis on cognitive outcomes and oxidative stress indices

MicroRNA‑370 suppresses the progression and proliferation of human astrocytoma and glioblastoma by negatively regulating β‑catenin and causing activation of FOXO3a

The Efficacy of Trastuzumab in Animal Models of Breast Cancer: A Systematic Review and Meta-Analysis

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