Ruman Rahman

Ruman Rahman
University of Nottingham | Notts · School of Medicine

BSc PhD

About

176
Publications
11,566
Reads
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1,102
Citations
Citations since 2016
111 Research Items
751 Citations
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2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
Introduction
Brain cancer genetics, cancer metabolism, biomaterial-based drug delivery
Skills and Expertise
Additional affiliations
August 2020 - present
University of Nottingham
Position
  • Professor (Associate)

Publications

Publications (176)
Article
INTRODUCTION Childhood medulloblastoma (MB) and atypical teratoid/rhabdoid tumours (AT/RT) are malignant brain tumours occurring in the posterior fossa, for which prognoses remains particularly poor for the MB Group 3 subtype characterised by amplification of the Myc oncogene and for AT/RT in general. Current in vitro models for these neoplasms rel...
Article
Local intracranial drug delivery for high-grade glioma has been developed over the last two decades with chemotherapeutic agents administered immediately adjuvant to neurosurgery to overcome poor blood brain barrier permeability. In addition to this, the incorporation of nanoparticles (NPs) into local drug delivery systems (DDS) can result in incre...
Article
Systemic drug delivery to the central nervous system (CNS) has been historically impeded by the presence of the blood brain barrier rendering many therapies inefficacious to any cancer cells residing within the brain. Therefore, local drug delivery systems are being developed to overcome this shortfall. Here we have manufactured polymeric microneed...
Article
Full-text available
Background Electric field therapies such as Tumor Treating Fields (TTFields) have emerged as a bioelectronic treatment for isocitrate dehydrogenase wild-type and IDH mutant grade 4 astrocytoma Glioblastoma (GBM). TTFields rely on alternating current (AC) electric fields (EF) leading to the disruption of dipole alignment and induced dielectrophoresi...
Poster
Full-text available
The therapeutic efficacy of anticancer nanocarriers is highly dependent on their size, shape, targeting ability, and stimuli-responsiveness. Herein, we studied the in vivo therapeutic efficacy of Doxorubicin (Dox) loaded redox responsive micellar-like nanoparticles (MNPs) based on Hyperbranched 2-hydroxypropyl methacrylamide (HPMA) via histopatholo...
Article
Full-text available
Poor outcomes associated with diffuse high-grade gliomas occur in both adults and children, despite substantial progress made in the molecular characterisation of the disease. Targeting the metabolic requirements of cancer cells represents an alternative therapeutic strategy to overcome the redundancy associated with cell signalling. Cholesterol is...
Article
Full-text available
The therapeutic efficacy of anticancer nanocarriers ishighly dependent on their size, shape, targeting ability, andstimuli-responsiveness. Herein, we studied the in vivo therapeutic efficacy ofDoxorubicin (Dox) loaded redox responsive micellar-like nanoparticles (MNPs)based on linear 2-hydroxypropyl methacrylamide (HPMA) via histopathologicalevalua...
Preprint
Electric field therapies such as Tumor Treating Fields (TTFields) have emerged as a bioelectronic treatment for isocitrate dehydrogenase wild-type and IDH mutant grade 4 astrocytoma Glioblastoma (GBM). TTFields rely on alternating current (AC) electric fields (EF) leading to the disruption of dipole alignment and induced dielectrophoresis during cy...
Article
Full-text available
The manifestation of intra- and inter-tumor heterogeneity hinders the development of ubiquitous cancer treatments, thus requiring a tailored therapy for each cancer type. Specifically, the reprogramming of cellular metabolism has been identified as a source of potential drug targets. Drug discovery is a long and resource-demanding process aiming at...
Article
Full-text available
There have been no significant improvements in the treatments for childhood and adolescent High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), which have a very poor prognosis. These cancers harbour mutations affecting histone 3 (H3) proteins, 80% of DIPGs harbour histone H3.1 and H3.3 K27M somatic mutations whilst 30% of pH...
Article
Full-text available
Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3...
Article
Full-text available
Paediatric high grade gliomas (pHGG) are the leading cause of cancer-related death in children. Histone H3.3 mutations are an important hallmark of pHGG, but their underlying oncogenic mechanisms are incompletely understood. Towards identifying molecular effectors that may be therapeutically effective, we employed proteomic profiling and determined...
Article
Full-text available
Children's brain tumours are the biggest cancer killer in children and young adults. Several techniques, such as intra-cerebrospinal fluid chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems, electric field therapy, and intra-arterial and intra-nasal chemotherapy, have the potenti...
Article
Full-text available
Background: We have previously reported that the endocannabinoid receptor inverse agonist AM630 is a potent inhibitor of isocitrade dehydrogenase-1 wild-type glioblastoma (GBM) core tumour cell proliferation. To uncover the mechanism behind the anti-tumour effects we have performed a transcriptional analysis of AM630 activity both in the tumour co...
Article
Full-text available
Historically, pre-clinical neuro-oncological drug delivery studies have exhaustively relied upon overall animal survival as an exclusive measure of efficacy. However, with no adopted methodology to both image and quantitate brain parenchyma penetration of label-free drugs, an absence of efficacy typically hampers clinical translational potential, r...
Article
Full-text available
The lack of treatment options for high-grade brain tumors has led to searches for alternative therapeutic modalities. Electrical field therapy is one such area. The Optune™ system is an FDA-approved novel device that delivers continuous alternating electric fields (tumor treating fields—TTFields) to the patient for the treatment of primary and recu...
Article
Full-text available
The temporary silencing of disease-associated genes utilising short interfering RNA (siRNA) is a potent and selective route for addressing a wide range of life limiting disorders. However, the few clinically approved siRNA therapies rely on lipid based formulations, which although potent, provide limited chemical space to tune the stability, effica...
Article
Spatiotemporal heterogeneity of glioblastoma (GBM) originating from genomic and transcriptional variation in spatially distinct sites, may contribute to subtype switching in GBM prior to and upon recurrence. Fluorescence-guided neurosurgical resection utilizing 5-aminolevulinic acid (5ALA) has enabled the isolation of infiltrative margin tumor cell...
Article
INTRODUCTION Children's brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children, including intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electr...
Article
Ependymoma (EPN) is the second most common malignant paediatric brain tumour with a five-year survival rate of only 25% following relapse. While molecular heterogeneity between EPN tumours is well understood, little is known concerning spatially-distinct intratumour heterogeneity within patients. In this context, we present a multi-omics integratio...
Article
Full-text available
Merging of electronics with biology, defined as bioelectronics, at the nanoscale holds considerable promise for sensing and modulating cellular behavior. Advancing our understanding of nanobioelectronics will facilitate development and enable applications in biosensing, tissue engineering, and bioelectronic medicine. However, studies investigating...
Article
Aims Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 a...
Article
Aims Children's brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric f...
Article
Full-text available
One of the most challenging problems in the treatment of glioblastoma (GBM) is the highly infiltrative nature of the disease. Infiltrating cells that are non-resectable are left behind after debulking surgeries and become a source of regrowth and recurrence. To prevent tumor recurrence and increase patient survival, it is necessary to cleanse the a...
Article
Full-text available
INTRODUCTION Brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the outlook for these children, including intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems, electric field therapy, and intr...
Article
Full-text available
Approximately 90% of cancer-related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage...
Preprint
Full-text available
Spatiotemporal-heterogeneity originating from genomic and transcriptional variation contributes to subtype switching in GBM prior to and upon recurrence. Fluorescence-guided neurosurgical resection utilizing 5-aminolevulinic acid (5ALA) enables the isolation of infiltrative margin tumor cells (5ALA+) from a non-neoplastic background within neighbor...
Article
Glioblastoma (GBM) is a particularly aggressive brain cancer associated with high recurrence and poor prognosis. The standard of care, surgical resection followed by concomitant radio- and chemotherapy, leads to low survival rates. The local delivery of active agents within the tumor resection cavity has emerged as an attractive means to initiate o...
Article
Full-text available
Introduction Brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric field therapy, as well as in...
Preprint
Full-text available
Spatiotemporal-heterogeneity of glioblastoma (GBM) originating from the genomic and transcriptional variation in spatially distinct intra-tumor sites, may contribute to subtype switching in GBM prior to and upon recurrence. Fluorescence-guided neurosurgical resection utilizing 5-aminolevulinic acid (5ALA) has enabled the isolation of infiltrative m...
Article
Full-text available
We present here a novel surface mass spectrometry strategy to perform untargeted metabolite profiling of formalin-fixed paraffin-embedded pediatric ependymoma archives. Sequential Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) and liquid extraction surface analysis-tandem mass spectrometry (LESA-MS/MS) permitted the detection of 887 metabol...
Article
Full-text available
The integration of untargeted metabolomics and transcriptomics from the same population of cells or tissue enhances the confidence in the identified metabolic pathways and understanding of the enzyme-metabolite relationship. Here, we optimised a simultaneous extraction method of metabolites/lipids and RNA from ependymoma cells (BXD-1425). Relative...
Article
Full-text available
Glioblastoma (GBM) is the most common, malignant and aggressive brain tumour in adults. Despite the use of multimodal treatments, involving surgery, followed by concomitant radiotherapy and chemotherapy, the median survival for patients remains less than 15 months from diagnosis. Low penetration of drugs across the blood-brain barrier (BBB) is a do...
Article
Full-text available
Bioelectronic medicine is a treatment modality that uses electricity to treat disease by altering the body's electrical communication systems. All cells are electrically active, in that they possess bioelectric circuitry generating a resting membrane potential and endogenous electric fields that influence cell functions and communication. There is...
Article
Protein orientation in nanoparticle-protein conjugates plays a crucial role in binding to cell receptors and ultimately, defines their targeting efficiency. Therefore, understanding fundamental aspects of the role of protein orientation upon adsorption on the surface of nanoparticles (NPs) is vital for the development of clinically important protei...
Article
Full-text available
There have been no significant improvements in the treatments for childhood High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), which continue to have a very poor prognosis. These cancers harbor mutations affecting histone 3 (H3) proteins; 80% of DIPGs with histone H3 K27M somatic mutations whilst 30% of pHGGs exhibit H3.3 G...
Article
Full-text available
Improvements in the treatments for childhood and adolescent brain tumours, High-Grade Glioma (pHGG) and Diffuse Intrinsic Pontine Glioblastoma (DIPG), have not advanced much and they continue to carry a very poor prognosis. These brain tumours are now defined by mutations affecting histone 3 proteins, indeed 80% of DIPGs harbour histone H3.1 and H3...
Article
Full-text available
Ependymoma (EPN) is the second most common malignant paediatric brain tumour, which despite extensive genomic sequencing, no novel therapeutic options have been discovered. Multi-omics are anticipated to reveal dysregulated pathways that may be predictive of patient-specific biomarkers. Given the close association between gene expression, active bi...
Article
Full-text available
We review the challenges of next-generation therapeutics for both systemic and localised delivery to brain tumours and discuss how recent engineering advances may be used to enhance brain penetration of systemic delivery therapies. The unmet clinical need which drug delivery seeks to address is discussed with reference to the therapy obstacles that...
Article
Full-text available
Glioblastoma is a malignant brain tumour with a median survival of 14.6 months from diagnosis. Despite maximal surgical resection and concurrent chemoradiotherapy, reoccurrence is inevitable. To try combating the disease at a stage of low residual tumour burden immediately post-surgery, we propose a localised drug delivery system comprising of a sp...
Preprint
Full-text available
Approximately 90% of cancer related deaths can be attributed to a tumour's ability to spread. We have identified CG7379, the fly orthologue of human ING1, as a potent invasion suppressor. ING1 is a type II tumour suppressor with well-established roles in the transcriptional regulation of genes that control cell proliferation, response to DNA damage...
Article
Full-text available
Amphiphilic block co‐polymers composed of poly(ethylene glycol)‐co‐poly(lactide)‐co‐poly(2‐((tert‐butoxycarbonyl)amino)‐3‐propyl carbonate) (PEG‐pLA‐pTBPC) are synthesized in monomer ratios and arrangements to enable assembly into nanoparticles with different sizes and architectures. These materials are based on components in clinical use, or known...
Preprint
div> Protein orientation in nanoparticle-protein conjugates plays a crucial role in binding to cell receptors and ultimately, defines their targeting efficiency. Therefore, understanding fundamental aspects of the role of protein orientation upon adsorption on the surface of nanoparticles (NPs) is vital for the development of clinically important...
Preprint
Full-text available
We present here a novel surface mass spectrometry strategy to perform untargeted metabolite profiling of formalin-fixed paraffin-embedded (FFPE) pediatric ependymoma archives. Sequential Orbitrap secondary ion mass spectrometry (3D OrbiSIMS) and liquid extraction surface analysis-tandem MS (LESA-MS/MS) permitted the detection of 887 metabolites (16...
Article
Full-text available
Glioblastomas (GBMs) are the most aggressive primary brain tumours and have no known cure. Each individual tumour comprises multiple sub-populations of genetically-distinct cells that may respond differently to targeted therapies and may contribute to disappointing clinical trial results. Image-localized biopsy techniques allow multiple biopsies to...
Preprint
Full-text available
Surgically-resected biopsies from childhood brain tumors are archived in a formalin-fixed paraffin-embedded (FFPE) state. Identified key tumor regions are conserved through the fabrication of tissue microarrays (TMA). The vast amount of TMA libraries available have the potential to be used for metabolite profiling; however, due to incompatibility o...
Article
Full-text available
Background Glioblastoma (GBM) is a highly aggressive brain tumor with rapid subclonal diversification, harboring molecular abnormalities that vary temporo-spatially, a contributor to therapy resistance. Fluorescence guided neurosurgical resection utilizes administration of 5-aminolevulinic acid (5ALA) generating individually fluorescent tumor cells...
Preprint
p>The merging of electronics with biology at the nanoscale holds considerable promise for sensing and modulating cellular behavior. Advancing our understanding of nano-bioelectronics will facilitate development and enable applications in biosensing, tissue engineering and bioelectronic medicine. However, studies investigating the electrical effects...
Article
Full-text available
The thioredoxin (Trx) system is an important enzyme family that regulates cellular redox homeostasis. Protein expression of Trx system family members has been assessed in various cancers and linked to various clinicopathological variables, disease progression, treatment response and survival outcomes but information is lacking in brain tumours. Exp...
Article
Full-text available
Metastasis is the leading cause of death for cancer patients. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumour growth towards malignancy. Advances in genome characterisation technologies have been very successful in identifying commonly mutated or misregulated genes in a...
Preprint
Full-text available
Glioblastomas (GBMs) are the most aggressive primary brain tumours and have no known cure. Each individual tumour comprises multiple sub-populations of genetically-distinct cells that may respond differently to targeted therapies and may contribute to disappointing clinical trial results. Image-localized biopsy techniques allow multiple biopsies to...
Article
Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor. Residual cells at the tumor margin are responsible for up to 85% of GBM recurrences after standard treatment. Despite this evidence, the identification of compounds active on this cell population is still an underexplored field. Herein, starting from the knowledge that kinase...
Article
Full-text available
: Glioblastoma multiforme (GBM) is the most malignant form of primary brain tumour with extremely poor prognosis. The current standard of care for newly diagnosed GBM includes maximal surgical resection followed by radiotherapy and adjuvant chemotherapy. The introduction of this protocol has improved overall survival, however recurrence is essentia...
Article
Despite multimodal treatment, the median survival of Glioblastoma multiforme (GBM) patients remains less than 15 months, in considerable part due to diffusely infiltrative disease. Better treatment methods are necessary to eradicate residual tumour burden remaining beyond the resection cavity boundary. It is hypothesised that incorporating drug-loa...
Article
Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery. Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to...
Article
Glioblastomas (GBMs) are known to be complex tumors comprising multiple subpopulations of genetically-distinct cancer cells; it is thought that this genetic variation is a major factor in the lack of observed survival benefit of treatment regimes that target one of these subpopulations. The field of radiogenomics seeks to study correlations between...
Article
Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery. Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to...
Article
Glioblastoma therapeutic challenges are in considerable part due to myriad survival mechanisms which allow malignant cells to repurpose signalling pathways within discreet microenvironments. These Darwinian adaptations facilitate invasion into brain parenchyma and perivascular space. We hypothesised that pre-clinical modelling of glioma invasion by...
Article
There has been considerable interest in repurposing the poly ADP ribose polymerase inhibitor and purported radiosensitiser olaparib (Lynparza), with a recent dose escalation study of olaparib plus temozolomide in recurrent GBM showing good tolerance (Fulton et al 2018). Due to systemic therapy-associated caveats such as dose-limiting toxicities and...