Anke Brüning-Richardson

• BSc, PhD
• Group Leader at University of Huddersfield

Background Glioblastoma multiforme (GBM) is the most prevalent primary brain tumour, with an incidence of 2 per 100,000. The standard clinical treatments do not sufficiently target cell migration and invasion, leading to recurrence after surgical resection and resistance after chemotherapy and radiotherapy. Pre-clinical studies are being conducted...

Cancer has accompanied humankind for 1000s of years. Earliest evidence for cancer related deaths can be found in Egyptian mummies and references to cancer are recorded in the scriptures of Roman and Greek scholars. Cancer derives its name from its crab like appearance as described by Hippocrates leading to the term ‘carcinos’—cancer. With increasin...

This textbook gives an insight into the importance of cell migration in health during development, wound healing and immune responses as well as in disease with particular focus on cancer. The reader will learn about the different ways cells migrate to allow cellular changes during development to occur, as well as responses to injury and threat by...

BACKGROUND The Rho GTPase activating proteins (ARHGAPs) perform vital roles in the regulation of the Rho GTPases with direct effect on cellular plasticity and cell migration/invasion. We recently reported on the role of five ARHGAPs, identified by a microarray screen, in morphological plasticity in established and patient-derived Glioblastoma (GBM)...

A schematic diagram of a proposed neural circuit for high temperature‐induced feeding inhibition. Acute high temperature exposure activates excitatory neurons in the parabrachial nucleus brain area, promotes the release of vascular endothelial growth factor A from tanycytes, and acts on agouti‐related protein neurons in the ARC brain area to inhibi...

Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumour recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumour dissemination and regrowth. One current aim of GBM research focuses o...

Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumor recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumor dissemination and regrowth. One current aim of GBM research focusses on...

Background Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur. Results Using RNA sequencing data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumors, we identify two re...

Viruses have always accompanied human life and impacted our health. Recent developments in the medical field have highlighted that it is possible to exploit the requirement of a virus to replicate within a host cell. For example, viruses can be genetically engineered to specifically target, enter and finally destroy tumour cells. These viruses are...

The migration and invasion of cancer cells are central to metastatic disease, the main cause of death in cancer patients. One of the hallmarks of cancer is that tumour cells can leave the original tumour, migrate and invade distant tissues. Tumour cells can migrate via several different mechanisms. Solid epithelial-derived tumours initially dissemi...

Cell migration is of great relevance to researchers studying development, wound healing, the immune system and its responses and diseases associated with deregulated cell migration. The study of cell migration has been made possible by the development of a huge variety of experimental set-ups in 2D and 3D focussing on specific aspects of cell migra...

Cell migration is a fundamental biological process that supports and drives vital developments in humans. It drives embryonic growth and plays an important role in our ability to respond to damages as observed in wound healing or to external threats by foreign invaders as part of our immune responses. It follows that defective cell migration associ...

AIMS The kynurenine (Kyn) pathway plays an important role in the pathogenesis of many cancers including glioblastomas (GBMs). The enzymes, indoleamine-2,3-dioxygenase (IDO1) and tryptophan-2,3-dioxygenase (TDO2), regulate the first and rate-limiting step resulting in the formation of N-formyl-kynurenine, which is then readily converted into Kyn by...

AIMS One of the hallmarks of cancer is cell migration and invasion, a striking feature of glioblastoma (GBM). The highly migratory potential of tumour cells enables recurrence of GBM tumours leading to poor survival and patient death. We recently characterised a panel of migrastatic inhibitors and reported on the ability of glioma cells to overcome...

We asked young scientists to “name a discovery that inspired you and then describe it in exactly six words.” Read a selection of their responses here. Follow NextGen Voices on Twitter with hashtag #NextGenSci.

Glioblastoma (GBM) brain tumours lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumours almost always fatally recur. Using RNAseq data from 107 pairs of pre- and post-standard treatment locally recurrent IDHwt GBM tumours, we identified two responder subtypes based...

Spheroids and organoids are increasingly popular three-dimensional (3D) cell culture models. Spheroid models are more physiologically relevant to a tumor compared to two-dimensional (2D) cultures and organoids are a simplified version of an organ with similar composition. Spheroids are often only formed from a single cell type which does not repres...

Glioblastomas (GBM) account for poor prognosis and dismal survival rates in patients due to their highly aggressive infiltrative nature to rapidly migrate within the brain. Experimental treatments for GBMs using animal models often elicit severe side effects and there are major doubts regarding the usefulness of such in vivo models when undergoing...

AIMS Glioblastomas (GBMs) are characterised by highly hypoxic regions and the ability to invade into healthy brain tissue promoting tumour dissemination and recurrence; the development of novel anti-migratory inhibitors to target cell invasion and recurrence must consider varying treatment responses in this tumour background. As proof of principle...

AIMS Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite aggressive treatment, a resistant tumour recurs in practically all patients. We therefore aimed to better understand the mechanisms driving this treatment resistance through investigating changes in gene expression across pairs of primary and recurrent GBM...

AIMS A faithful representation of real tumour conditions in vivo such as a 3D glioma spheroid in a 3D experimental setting has become highly desirable for brain tumour research as it aids the study of tumour behaviour such as cell invasion and initiation of metastasis. However, data resulting from such studies need to be accurately analysed to corr...

Three-dimensional (3D) spheroid cultures are generating increasing interest in cancer research, e.g. for the evaluation of pharmacological effects of novel small molecule inhibitors. This is mainly due to the fact that such 3D structures reflect physiological characteristics of tumours and the cellular microenvironments they reside in more faithful...

The authors wish to make the following corrections to this paper [1] [...]

Spheroids and organoids are increasingly popular three-dimensional (3D) cell culture models. Spheroid models are more physiologically relevant to a tumour compared to two-dimensional (2D) cultures and organoids are a simplified version of an organ with similar composition. Both can be used in cell migration studies, disease modelling and drug disco...

Cancer cell invasion is a precondition for tumour metastasis and represents one of the most devastating characteristics of cancer. The development of drugs targeting cell migration, known as migrastatics, may improve the treatment of highly invasive tumours such as glioblastoma (GBM). In this study, investigations into the role of the cell adhesion...

Glioblastoma (GBM) is the most common and aggressive primary brain tumour, yet little progress has been made towards providing better treatment options for patients diagnosed with this devastating condition over the last few decades. The complex nature of the disease, heterogeneity, highly invasive potential of GBM tumours and until recently, reduc...

Background: Previous data on glycogen synthase kinase 3 (GSK-3) inhibition in cancer models support a cytotoxic effect with selectivity for tumor cells compared to normal tissue but the effect of these inhibitors in glioma has not been widely studied. Here, we investigate their potential as cytotoxics in glioma. Methods: We assessed the effect o...

The limitations of two-dimensional analysis in three-dimensional (3D) cellular imaging impair the accuracy of research findings in biological studies. Here, we report a novel 3D approach to acquisition, analysis and interpretation of tumour spheroid images. Our research interest in mesenchymal–amoeboid transition led to the development of a workflo...

Introduction Targeting the infiltrative nature of GBMs with anti-migratory drugs as combination treatment for prevention of tumour recurrence is an attractive disease management option. One such class of drugs are the GSK-3 inhibitors 6-bromoindirubin-3′-oximes (BIO). BIO has been proposed for use in combination therapy, however, the administration...

Drug discovery and development in cancer research is increasingly being based on drug screens in a 3D format. Novel inhibitors targeting the migratory and invasive potential of cancer cells, and consequently the metastatic spread of disease, are being discovered and considered as complementary treatments in highly invasive cancers such as gliomas....

BACKGROUND Targeting kinases as regulators of cellular processes that drive cancer progression is a promising approach to improve patient outcome in GBM management. The glycogen synthase kinase 3 (GSK-3) plays a role in cancer progression and is known for its pro-proliferative activity in gliomas. The anti-proliferative and cytotoxic effects of the...

The characterisation of a new anti-migratory drug for combination treatment of glioma.

The user has requested enhancement of the downloaded file. JARID2 facilitates transcriptional reprogramming in glioblastoma in response to standard 1 treatment 2 ABSTRACT 21 Background: Glioblastoma (GBM) is a fatal and incurable brain cancer with a dismal prognosis. In

The heterogeneous and invasive nature of pediatric gliomas poses significant treatment challenges, highlighting the importance of identifying novel chemotherapeutic targets. Recently, recurrent Fibroblast growth factor receptor 1 (FGFR1) mutations in pediatric gliomas have been reported. Here, we explored the clinical relevance of FGFR1 expression,...

Immunofluorescence images for SF188 and IN2688 labeled for FGFR1 (green), pFGFR1 (green), actin (phalloidin, red), and DNA (DAPI, blue) and merged images of the three channels. The panels are presented in the same order as shown for the images in Figure 4. Scale bar = 50 microns.

Graphic representation of morphological features observed in 2D cultures in response to stimulation with FGF2 ligand and treatment with inhibitor. Morphological changes in cell size were observed after stimulation with FGF2 and treatment with inhibitor as indicated.

Graphic representation of morphological features observed in migratory cells of 3D spheroid cultures in response to stimulation with FGF2 ligand and treatment with inhibitor. Morphological changes in migrating cells away from original spheroid cores were observed after stimulation with FGF2 and treatment with inhibitor.

BACKGROUND Three-dimensional tumour spheroid models are increasingly used in cancer research. However, imaging for quantification analysis of spheroids in drug testing has remained primarily based on 2D methodologies. Imaging 3D structures in 2D can cause discrepancies and introduce interpretive bias. We previously described a novel method to creat...

INTRODUCTION Gliomas are intrinsic brain tumours characterised by their highly invasive, malignant and aggressive nature. Persistently poor prognoses highlight the urgent clinical need to identify novel approaches and therapeutic targets to improve glioma management. Recently we reported a correlation of fibroblast growth factor receptor 1 (FGFR1)...

Aims: The aim of this study was to explore the correlation of hTERT splice variant expression with MCPH1/BRIT1 and BRCA1 expression in epithelial ovarian cancer (EOC) samples. Background: Telomerase activation can contribute to the progression of tumors and the development of cancer. However, the regulation of telomerase activity remains unclear...

Cell migration is one of the hallmarks of cancer. Cancer cells can adopt two main migratory strategies displaying either a mesenchymal or amoeboid phenotype. Targeting cell migration presents an opportunity in improving treatment of invasive and migratory tumours, however the cellular mechanisms that control the cell migration phenotypes in high-gr...

INTRODUCTION Targeting the migratory behaviour of invading cells in high grade paediatric gliomas represents an attractive combination therapy with current treatment options. Migration involves highly regulated microtubule dynamics that have been linked to the acetylation status of tubulin. MI192 is a selective histone deacetylase inhibitor that ha...

INTRODUCTION Paediatric high-grade gliomas (pHGGs) are highly invasive tumours associated with extremely poor prognosis. There is urgent clinical need to develop novel therapeutic strategies that can target the process of tumour migration and invasion. Fibroblast growth factor receptors (FGFRs) are transmembrane receptor tyrosine kinases associated...

INTRODUCTION Glioblastoma multiforme remains one of the most difficult to treat cancers due to the highly infiltrative nature of cancer cells. Targeting the invasive properties of glioblastoma presents a novel treatment avenue. Recently, specific GSK-3 beta (GSK3b) inhibitors such as Bio-Indirubin (BIO), have been described that inhibit the migrato...

One of the most devastating hallmarks of cancer is cell migration/invasion, a prerequisite for tumour metastasis. Targeting this cellular phenomenon offers an opportunity to improve the treatment of invasive and highly migratory tumours such as Glioblastoma multiforme, and to better understand the cellular mechanisms controlling cell migration. Pre...

INTRODUCTION Glycogen synthase kinase-3 (GSK-3) has been implicated as a potential target in glioblastoma migration and invasion. Here we investigated the effects of GSK-3 inhibition on downstream effector genes and discovered a novel GSK-3 /b-catenin/ARHGAP migration axis that drives glioblastoma invasion. METHODS Expression arrays of glioblastom...

INTRODUCTION Our previous research in anti-migratory intervention in paediatric gliomas has highlighted the need for novel treatments to target tumour invasion based on individual tumour biology. Recurrent fibroblast growth factor receptor 1 (FGFR1) mutations in paediatric gliomas have been recently reported. Here we characterised cell migration in...

BACKGROUND Histone deacetylase inhibitors (HDACi) are increasingly investigated as potential therapeutics in various cancers, including the most common brain malignancy, glioblastoma multiforme (GBM). The compound MI-192 has demonstrated selective inhibition of subtypes HDAC2 and 3, reportedly involved in tubulin acetylation and mitosis which drive...

Background: CNS tumors, including medulloblastoma and pediatric glioblastoma (pGBM) account for the majority of solid pediatric malignancies. There remains an unmet need to identify novel treatment approaches in poor prognosis and relapsed pediatric brain tumors, where therapeutic options are limited. Small-molecule B-cell lymphoma 2 (BCL-2) famil...

Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are invasive tumours with poor survival. Oncolytic virotherapy, initially devised as a direct cytotoxic treatment, is now also known to act via immune-mediated mechanisms. Here we investigate a previously unreported mechanism of action – the inhibition of migration and...

BACKGROUND: Small molecule inhibitors of the mitotic kinases, including the Aurora kinase inhibitor MLN8237, are being investigated as novel therapeutic agents for the treatment of solid cancers including malignant brain tumours. However, resistance has been observed and anti-apoptotic proteins of the BCL-2 family have been shown to promote cell su...

INTRODUCTION: High-grade gliomas feature prominently among the most devastating cancers due to their prevalence in the younger population, highly invasive nature and low 5-year survival. Despite a combined treatment regime of surgical resection, radiation therapy and chemotherapy most patients die within 1 year of initial diagnosis. Alternative, no...

INTRODUCTION: A highly invasive phenotype is a hallmark of the malignant process in Glioblastoma multiforme, which remains a poorly understood field. The diffuse and infiltrative nature of these cancers presents a need for novel, anti-migratory treatment to prevent tumour cells migrating to healthy parts of the brain and to improve the success of t...

Abstract INTRODUCTION: High-grade gliomas feature prominently among the most devastating cancers due to their prevalence in the younger population, highly invasive nature and low 5-year survival. Despite a combined treatment regime of surgical resection, radiation therapy and chemotherapy most patients die within 1 year of initial diagnosis. Altern...

This book "Mononegaviruses of Veterinary Importance", Volume 2 complements the first volume "Mononegaviruses of Veterinary Importance: Pathobiology and Molecular Diagnosis". This book discusses the epidemiology and control of Mononegaviruses that pose a significant threat to animals in terms of severity and epidemiological risk. It also addresses v...

Targeting infiltrating tumour cells is an attractive way of combating cancer invasion and metastasis. Here we describe a novel and reproducible method for high content analysis of invading cells using multicellular tumour spheroid assays in a high grade glioma model. Live cell imaging of spheroids generated from glioma cell lines, U87 and U251, gav...

Background: Paediatric high grade glioma (pHGG) and diffuse intrinsic pontine glioma (DIPG) are highly aggressive brain tumours. Their invasive phenotype contributes to their limited therapeutic response, and novel treatments that block brain tumour invasion are needed. Methods: Here, we examine the migratory characteristics and treatment effect...

BACKGROUND: Glioblastomas are highly malignant tumours characterized by an invasive phenotype, which limits response to standard treatment including surgery, radiation and chemotherapy. Targeting the migratory properties of glioma cells may offer an alternative means to improve disease management. We recently developed a 96 well-based in vitro coll...

INTRODUCTION: Glioblastoma multiforme (GBM) is a fast growing, highly invasive malignant brain tumour. Inhibition of tumour cell migration into normal brain tissue represents a major target for treatment. Glycogen synthase kinase (GSK-3) inhibition has been associated with reduced GBM invasion in in vitro and in vivo models. Targeting this pathway...

Mutations in the MCPH1 (Microcephalin) and ASPM (abnormal spindle-like microcephaly associated) genes cause primary microcephaly. Both are centrosomal associated proteins involved in mitosis. Microcephalin plays an important role in DNA damage response and ASPM is required for correct division of proliferative neuro-epithelial cells of the developi...

The purpose of this book is to provide a timely and comprehensive review on all the mononegaviruses of veterinary importance. The book is divided into two sections. Section I deals with 13 mononegaviruses (Bornaviruses, Avian Paramyxoviruses serotypes 1 to 10, Hendra and Nipah viruses, Canine distemper virus, Peste des petits ruminants virus, Rinde...

Bluetongue virus (BTV) is an arbovirus that is responsible for 'bluetongue', an economically important disease of livestock. Although BTV is well characterised at the protein level, less is known regarding its interaction with host cells. During studies of virus inclusion body formation we observed what appeared to be a large proportion of cells in...

Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon. NuMA protein levels in normal and tumour tissues, ovarian cell lines and primary cultures of malignant cells derived from ovarian ascitic fluids were analysed by Affymetrix microarray analysis, immuno...

Mitotic activity in cell cultures of malignant cells derived from ascitic fluids is mirrored in associated tumour tissue samples. A) Tumour tissue sample 1101 with low mitotic activity (mitotic index in culture = 0%). B) Tissue sample 1124 with high mitotic activity (mitotic index in culture = 1.9%). Arrows indicate mitotic cells. (PDF)