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Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models (2024)
Journal Article
Cavanagh, R. J., Monteiro, P. F., Moloney, C., Travanut, A., Mehradnia, F., Taresco, V., …Alexander, C. (2024). Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models. Biomaterials Science, 12(7), 1822-1840. https://doi.org/10.1039/d3bm01931d

Combinations of the topoisomerase II inhibitor doxorubicin and the poly (ADP-ribose) polymerase inhibitor olaparib offer potential drug-drug synergy for the treatment of triple negative breast cancers (TNBC). In this study we performed in vitro scree... Read More about Free drug and ROS-responsive nanoparticle delivery of synergistic doxorubicin and olaparib combinations to triple negative breast cancer models.

Wireless electrical–molecular quantum signalling for cancer cell apoptosis (2023)
Journal Article
Jain, A., Gosling, J., Liu, S., Wang, H., Stone, E. M., Chakraborty, S., …Rawson, F. J. (2024). Wireless electrical–molecular quantum signalling for cancer cell apoptosis. Nature Nanotechnology, 19, 106-114. https://doi.org/10.1038/s41565-023-01496-y

Quantum biological tunnelling for electron transfer is involved in controlling essential functions for life such as cellular respiration and homoeostasis. Understanding and controlling the quantum effects in biology has the potential to modulate biol... Read More about Wireless electrical–molecular quantum signalling for cancer cell apoptosis.

Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers (2023)
Journal Article
Moloney, C., Mehradnia, F., Cavanagh, R. J., Ibrahim, A., Pearce, A. K., Ritchie, A. A., …Alexander, C. (2023). Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers. Biomaterials Science, 11, 6545-6560. https://doi.org/10.1039/d3bm00609c

The therapeutic efficacy of nanomedicines is highly dependent on their access to target sites in the body, and this in turn is markedly affected by their size, shape and transport properties in tissue. Although there have been many studies in this ar... Read More about Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers.

Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence (2023)
Journal Article
Andrieux, G., Das, T., Griffin, M., Straehle, J., Paine, S. M., Beck, J., …Chakraborty, S. (2023). Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence. Genome Medicine, 15, Article 48. https://doi.org/10.1186/s13073-023-01207-1

Background Spatiotemporal heterogeneity originating from genomic and transcriptional variation was found to contribute to subtype switching in isocitrate dehydrogenase-1 wild-type glioblastoma (GBM) prior to and upon recurrence. Fluorescence-guide... Read More about Spatially resolved transcriptomic profiles reveal unique defining molecular features of infiltrative 5ALA-metabolizing cells associated with glioblastoma recurrence.

Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS (2023)
Journal Article
He, W., Edney, M. K., Paine, S. M. L., Griffiths, R. L., Scurr, D. J., Rahman, R., & Kim, D. (2023). Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS. Analytical Chemistry, 95(14), 5994-6001. https://doi.org/10.1021/acs.analchem.2c05807

Glioblastoma (GBM) is an incurable brain cancer with a median survival of less than two years from diagnosis. The standard treatment of GBM is multimodality therapy comprising surgical resection, radiation, and chemotherapy. However, prognosis remain... Read More about Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS.

Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain (2023)
Journal Article
Muresan, P., Woodhams, S., Smith, F., Taresco, V., Shah, J., Wong, M., …Marlow, M. (2023). Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain. Nanomedicine: Nanotechnology, Biology and Medicine, 49, Article 102664. https://doi.org/10.1016/j.nano.2023.102664

We investigated how the biodistribution of cannabidiol (CBD) within the central nervous system (CNS) is influenced by two different formulations, an oil-in-water (O/W) nanoemulsion and polymer-coated nanoparticles (PCNPs). We observed that both CBD f... Read More about Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain.

Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting (2023)
Journal Article
Martins, C., Araújo, M., Malfanti, A., Pacheco, C., Smith, S. J., Ucakar, B., …Sarmento, B. (in press). Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting. Small, Article 2300029. https://doi.org/10.1002/smll.202300029

Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, w... Read More about Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting.

Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery (2023)
Journal Article
Adekeye, A. O., Needham, D., & Rahman, R. (2023). Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery. Pharmaceutics, 15(2), Article 599. https://doi.org/10.3390/pharmaceutics15020599

Metabolic reprogramming, through increased uptake of cholesterol in the form of low-density lipoproteins (LDL), is one way by which cancer cells, including high grade gliomas (HGG), maintain their rapid growth. In this study, we determined LDL recept... Read More about Low-Density Lipoprotein Pathway Is a Ubiquitous Metabolic Vulnerability in High Grade Glioma Amenable for Nanotherapeutic Delivery.

Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials (2023)
Journal Article
Rahman, R., Janowski, M., Killick-Cole, C. L., Singleton, W. G. B., Campbell, E., Walczak, P., …Walker, D. A. (2023). Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials. Cancers, 15(3), Article 857. https://doi.org/10.3390/cancers15030857

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30–40% means the majority are cured, although two-thirds have life-long disabi... Read More about Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials.

Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site (2022)
Journal Article
Muresan, P., McCrorie, P., Smith, F., Vasey, C., Taresco, V., Scurr, D. J., …Marlow, M. (2023). Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site. European Journal of Pharmaceutics and Biopharmaceutics, 182, 53-61. https://doi.org/10.1016/j.ejpb.2022.11.016

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 s... Read More about Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site.

Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers (2022)
Journal Article
Mehradnia, F., Moloney, C., Cavanagh, R., Pearce, A. K., Ritchie, A., Clarke, P., …Alexander, C. (2022). Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers. British Journal of Pharmacy, 7(2), https://doi.org/10.5920/bjpharm.1173

The therapeutic efficacy of anticancer nanocarriers ishighly dependent on their size, shape, targeting ability, and stimuli-responsiveness. Herein, we studied the in vivo therapeutic efficacy ofDoxorubicin (Dox) loaded redox responsive micellar-like... Read More about Histopathological impact of Redox-responsive methacrylamide based micellar nanoparticles on Orthotopic Models of Triple Negative Breast Cancers.

Electric field responsive nanotransducers for glioblastoma (2022)
Journal Article
Jain, A., Jobson, I., Griffin, M., Rahman, R., Smith, S., & Rawson, F. J. (2022). Electric field responsive nanotransducers for glioblastoma. Bioelectronic Medicine, 8, Article 17. https://doi.org/10.1186/s42234-022-00099-7

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 curre... Read More about Electric field responsive nanotransducers for glioblastoma.

Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism (2022)
Journal Article
Wood, J., Abdelrazig, S., Evseev, S., Ortori, C., Castellanos-Uribe, M., May, S. T., …Rahman, R. (2022). Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism. Cancers, 14(16), Article 3873. https://doi.org/10.3390/cancers14163873

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 alterna... Read More about Lipoprotein Deprivation Reveals a Cholesterol-Dependent Therapeutic Vulnerability in Diffuse Glioma Metabolism.

Metabolic modeling-based drug repurposing in Glioblastoma (2022)
Journal Article
Tomi-Andrino, C., Pandele, A., Winzer, K., King, J., Rahman, R., & Kim, D. (2022). Metabolic modeling-based drug repurposing in Glioblastoma. Scientific Reports, 12, Article 11189. https://doi.org/10.1038/s41598-022-14721-w

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... Read More about Metabolic modeling-based drug repurposing in Glioblastoma.

EPCT-03. Working together to accelerate the preclinical to clinical translation of drug delivery systems for children’s brain tumours (2022)
Journal Article
Campbell, E., Aquilina, K., Dandapani, M., Walker, D., & Rahman, R. (2022). EPCT-03. Working together to accelerate the preclinical to clinical translation of drug delivery systems for children’s brain tumours. Neuro-Oncology, 24(Supplement 1), i36-i36. https://doi.org/10.1093/neuonc/noac079.131

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 deliver... Read More about EPCT-03. Working together to accelerate the preclinical to clinical translation of drug delivery systems for children’s brain tumours.

Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery (2022)
Journal Article
McCrorie, P., Rowlinson, J., Scurr, D. J., Marlow, M., & Rahman, R. (2022). Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery. Pharmaceutics, 14(3), Article 571. https://doi.org/10.3390/pharmaceutics14030571

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 penetrati... Read More about Detection of Label-Free Drugs within Brain Tissue Using Orbitrap Secondary Ion Mass Spectrometry as a Complement to Neuro-Oncological Drug Delivery.

Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors (2022)
Journal Article
Branter, J., Estevez-Cebrero, M., Diksin, M., Griffin, M., Castellanos-Uribe, M., May, S., …Smith, S. (2022). Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors. International Journal of Molecular Sciences, 23(4), Article 1982. https://doi.org/10.3390/ijms23041982

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 e... Read More about Genome-Wide Expression and Anti-Proliferative Effects of Electric Field Therapy on Pediatric and Adult Brain Tumors.

Investigating histidinylated highly branched poly(lysine) for siRNA delivery (2021)
Journal Article
Alazzo, A., Gumus, N., Gurnani, P., Stolnik, S., Rahman, R., Spriggs, K., & Alexander, C. (2022). Investigating histidinylated highly branched poly(lysine) for siRNA delivery. Journal of Materials Chemistry B, 10(2), 236-246. https://doi.org/10.1039/d1tb01793d

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 bas... Read More about Investigating histidinylated highly branched poly(lysine) for siRNA delivery.

Impedimetric Characterization of Bipolar Nanoelectrodes with Cancer Cells (2021)
Journal Article
Robinson, A. J., Jain, A., Rahman, R., Abayzeed, S., Hague, R. J., & Rawson, F. J. (2021). Impedimetric Characterization of Bipolar Nanoelectrodes with Cancer Cells. ACS Omega, 6(44), 29495-29505. https://doi.org/10.1021/acsomega.1c03547

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 applica... Read More about Impedimetric Characterization of Bipolar Nanoelectrodes with Cancer Cells.

Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM) (2021)
Journal Article
Vasilev, A., Sofi, R., Smith, S. J., Rahman, R., Teschemacher, A. G., & Kasparov, S. (2021). Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM). Biomedicines, 9(10), Article 1453. https://doi.org/10.3390/biomedicines9101453

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 rec... Read More about Feasibility of Photodynamic Therapy for Glioblastoma with the Mitochondria-Targeted Photosensitizer Tetramethylrhodamine Methyl Ester (TMRM).

CG7379 and ING1 suppress cancer cell invasion by maintaining cell–cell junction integrity (2021)
Journal Article
Rusu, A. D., Cornhill, Z. E., Coutiño, B. C., Uribe, M. C., Lourdusamy, A., Markus, Z., …Georgiou, M. (2021). CG7379 and ING1 suppress cancer cell invasion by maintaining cell–cell junction integrity. Open Biology, 11(9), Article 210077. https://doi.org/10.1098/rsob.210077

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 role... Read More about CG7379 and ING1 suppress cancer cell invasion by maintaining cell–cell junction integrity.

Rationally designed drug delivery systems for the local treatment of resected glioblastoma (2021)
Journal Article
Bastiancich, C., Malfanti, A., Préat, V., & Rahman, R. (2021). Rationally designed drug delivery systems for the local treatment of resected glioblastoma. Advanced Drug Delivery Reviews, 177, Article 113951. https://doi.org/10.1016/j.addr.2021.113951

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... Read More about Rationally designed drug delivery systems for the local treatment of resected glioblastoma.

Sequential Orbitrap Secondary Ion Mass Spectrometry and Liquid Extraction Surface Analysis-Tandem Mass Spectrometry-Based Metabolomics for Prediction of Brain Tumor Relapse from Sample-Limited Primary Tissue Archives (2021)
Journal Article
Meurs, J., Scurr, D. J., Lourdusamy, A., Storer, L. C., Grundy, R. G., Alexander, M. R., …Kim, D. (2021). Sequential Orbitrap Secondary Ion Mass Spectrometry and Liquid Extraction Surface Analysis-Tandem Mass Spectrometry-Based Metabolomics for Prediction of Brain Tumor Relapse from Sample-Limited Primary Tissue Archives. Analytical Chemistry, 93(18), 6947-6954. https://doi.org/10.1021/acs.analchem.0c05087

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 extr... Read More about Sequential Orbitrap Secondary Ion Mass Spectrometry and Liquid Extraction Surface Analysis-Tandem Mass Spectrometry-Based Metabolomics for Prediction of Brain Tumor Relapse from Sample-Limited Primary Tissue Archives.

Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues (2021)
Journal Article
Rahman, R., Woodward, A., Pandele, A., Abdelrazig, S., Ortori, C., Khan, I., …Kim, D. (2021). Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues. Metabolites, 11(4), Article 240. https://doi.org/10.3390/metabo11040240

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 simu... Read More about Integrated Metabolomics and Transcriptomics Using an Optimised Dual Extraction Process to Study Human Brain Cancer Cells and Tissues.

Polymer pro-drug nanoparticles for sustained release of cytotoxic drugs evaluated in patient-derived glioblastoma cell lines and in situ gelling formulations (2021)
Journal Article
Vasey, C. E., Cavanagh, R. J., Taresco, V., Moloney, C., Smith, S., Rahman, R., & Alexander, C. (2021). Polymer pro-drug nanoparticles for sustained release of cytotoxic drugs evaluated in patient-derived glioblastoma cell lines and in situ gelling formulations. Pharmaceutics, 13(2), https://doi.org/10.3390/pharmaceutics13020208

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... Read More about Polymer pro-drug nanoparticles for sustained release of cytotoxic drugs evaluated in patient-derived glioblastoma cell lines and in situ gelling formulations.

Modulating the biological function of protein by tailoring the adsorption orientation on nanoparticles (2020)
Journal Article
Jain, A., Trindade, G. F., Hicks, J. M., Potts, J. C., Rahman, R., J. M. Hague, R., …Rawson, F. J. (2021). Modulating the biological function of protein by tailoring the adsorption orientation on nanoparticles. Journal of Colloid and Interface Science, 587, 150-161. https://doi.org/10.1016/j.jcis.2020.12.025

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 adsorpti... Read More about Modulating the biological function of protein by tailoring the adsorption orientation on nanoparticles.

Biomedical engineering approaches to enhance therapeutic delivery for malignant glioma (2020)
Journal Article
McCrorie, P., Vasey, C. E., Smith, S. J., Marlow, M., Alexander, C., & Rahman, R. (2020). Biomedical engineering approaches to enhance therapeutic delivery for malignant glioma. Journal of Controlled Release, 328, 917-931. https://doi.org/10.1016/j.jconrel.2020.11.022

© 2020 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 c... Read More about Biomedical engineering approaches to enhance therapeutic delivery for malignant glioma.

Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours (2020)
Journal Article
McCrorie, P., Mistry, J., Taresco, V., Lovato, T., Fay, M., Ward, I., …Rahman, R. (2020). Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours. European Journal of Pharmaceutics and Biopharmaceutics, 157, 108-120. https://doi.org/10.1016/j.ejpb.2020.10.005

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 tu... Read More about Etoposide and olaparib polymer-coated nanoparticles within a bioadhesive sprayable hydrogel for post-surgical localised delivery to brain tumours.

Functionalized block co-polymer pro-drug nanoparticles with anti-cancer efficacy in 3D spheroids and in an orthotopic triple negative breast cancer model (2020)
Journal Article
Taresco, V., Abelha, T. F., Cavanagh, R. J., Vasey, C. E., Anane-Adjei, A. B., Pearce, A. K., …Alexander, C. (2021). Functionalized block co-polymer pro-drug nanoparticles with anti-cancer efficacy in 3D spheroids and in an orthotopic triple negative breast cancer model. Advanced Therapeutics, 4(1), Article 2000103. https://doi.org/10.1002/adtp.202000103

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... Read More about Functionalized block co-polymer pro-drug nanoparticles with anti-cancer efficacy in 3D spheroids and in an orthotopic triple negative breast cancer model.

Modulating the Biological Function of Protein by Tailoring the Adsorption Orientation on Nanoparticles (2020)
Other
Jain, A., Trindade, G., Hicks, J. M., Potts, J. C., Rahman, R., Hague, R., …Rawson, F. Modulating the Biological Function of Protein by Tailoring the Adsorption Orientation on Nanoparticles

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 adsorpti... Read More about Modulating the Biological Function of Protein by Tailoring the Adsorption Orientation on Nanoparticles.

Identifying the spatial and temporal dynamics of molecularly-distinct glioblastoma sub-populations (2020)
Journal Article
Morris, B., Curtin, L., Hawkins-Daarud, A., Hubbard, M. E., Rahman, R., Smith, S. J., …Owen, M. R. (2020). Identifying the spatial and temporal dynamics of molecularly-distinct glioblastoma sub-populations. Mathematical Biosciences and Engineering, 17(5), 4905-4941. https://doi.org/10.3934/mbe.2020267

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 t... Read More about Identifying the spatial and temporal dynamics of molecularly-distinct glioblastoma sub-populations.

Metabolism based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential (2020)
Journal Article
Smith, S. J., Rowlinson, J., Estevez-Cebrero, M., Onion, D., Ritchie, A., Clarke, P., …Rahman, R. (2020). Metabolism based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential. Neuro-Oncology Advances, 2(1), Article vdaa087. https://doi.org/10.1093/noajnl/vdaa087

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 ut... Read More about Metabolism based isolation of invasive glioblastoma cells with specific gene signatures and tumorigenic potential.

A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion (2020)
Journal Article
Canales Coutino, B., Cornhill, Z. E., Couto, A., Mack, N. A., Rusu, A. D., Nagarajan, U., …Georgiou, M. (2020). A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion. iScience, 23(6), Article 101237. https://doi.org/10.1016/j.isci.2020.101237

© 2020 The Authors Metastasis is the leading cause of death for patients with cancer. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumor growth toward malignancy. Advances in... Read More about A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion.

Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas (2020)
Journal Article
Martin, S., Yao, A., Storr, S. J., Al-Hadyan, K., Rahman, R., Smith, S., …Paine, S. (2020). Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas. Molecular Neurobiology, 57(7), 2889–2901. https://doi.org/10.1007/s12035-020-01928-z

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 pr... Read More about Thioredoxin system protein expression is associated with poor clinical outcome in adult and paediatric gliomas and medulloblastomas.

Development of Pyrazolo[3,4- d]pyrimidine Kinase Inhibitors as Potential Clinical Candidates for Glioblastoma Multiforme (2020)
Journal Article
Greco, C., Taresco, V., Pearce, A. K., Vasey, C. E., Smith, S., Rahman, R., …Schenone, S. (2020). Development of Pyrazolo[3,4- d]pyrimidine Kinase Inhibitors as Potential Clinical Candidates for Glioblastoma Multiforme. ACS Medicinal Chemistry Letters, 11(5), 657-663. https://doi.org/10.1021/acsmedchemlett.9b00530

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 t... Read More about Development of Pyrazolo[3,4- d]pyrimidine Kinase Inhibitors as Potential Clinical Candidates for Glioblastoma Multiforme.

Using Light for Therapy of Glioblastoma Multiforme (GBM) (2020)
Journal Article
Kasparov, Vasilev, Teschemacher, Sofi, Smith, & Rahman, R. (2020). Using Light for Therapy of Glioblastoma Multiforme (GBM). Brain Sciences, 10(2), Article 75. https://doi.org/10.3390/brainsci10020075

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 chemotherap... Read More about Using Light for Therapy of Glioblastoma Multiforme (GBM).

Role of Self‐Assembly Conditions and Amphiphilic Balance on Nanoparticle Formation of PEG‐PDLLA Copolymers in Aqueous Environments (2019)
Journal Article
Phan, H., Minut, R. I., McCrorie, P., Vasey, C., Larder, R. R., Krumins, E., …Pearce, A. K. (2019). Role of Self‐Assembly Conditions and Amphiphilic Balance on Nanoparticle Formation of PEG‐PDLLA Copolymers in Aqueous Environments. Journal of Polymer Science Part A: Polymer Chemistry, 57(17), 1801-1810. https://doi.org/10.1002/pola.29451

The production of well-defined and reproducible poly-meric nanoparticles (NPs), in terms of size and stability in biological environments, is undoubtedly a fundamental challenge in the formulation of novel and more effective nanomedicines. The adopti... Read More about Role of Self‐Assembly Conditions and Amphiphilic Balance on Nanoparticle Formation of PEG‐PDLLA Copolymers in Aqueous Environments.

Overall survival in malignant glioma is significantly prolonged by neurosurgical delivery of etoposide and temozolomide from a thermo-responsive biodegradable paste (2019)
Journal Article
Smith, S. J., Tyler, B., Gould, T. W., Veal, G. J., Gorelick, N. L., Rowlinson, J., …Rahman, R. (2019). Overall survival in malignant glioma is significantly prolonged by neurosurgical delivery of etoposide and temozolomide from a thermo-responsive biodegradable paste. Clinical Cancer Research, 25(16), 5094-5106. https://doi.org/10.1158/1078-0432.ccr-18-3850

Purpose: High-grade glioma (HGG) treatment is limited by the inability of otherwise potentially efficacious drugs to penetrate the blood brain barrier. We evaluate the unique intra-cavity delivery mode and translational potential of a blend of poly(D... Read More about Overall survival in malignant glioma is significantly prolonged by neurosurgical delivery of etoposide and temozolomide from a thermo-responsive biodegradable paste.

Amplification-free and direct fluorometric determination of telomerase activity in cell lysates using chimeric DNA-templated silver nanoclusters (2019)
Journal Article
Lee, S. T., Rahman, R., Muthoosamy, K., Mohamed, N. A. H., Mohamed, H., Su, X. D., …New, S. Y. (2019). Amplification-free and direct fluorometric determination of telomerase activity in cell lysates using chimeric DNA-templated silver nanoclusters. Microchimica Acta, 186(2), Article 81. https://doi.org/10.1007/s00604-018-3194-7

A fluorogenic probe has been developed for determination of telomerase activity using chimeric DNA-templated silver nanoclusters (AgNCs). The formation of AgNCs was investigated before (route A) and after (route B) telomerase elongation reaction. Bot... Read More about Amplification-free and direct fluorometric determination of telomerase activity in cell lysates using chimeric DNA-templated silver nanoclusters.

Structure-optimized interpolymer polyphosphazene complexes for effective gene delivery against glioblastoma (2018)
Journal Article
Hsu, W., Sánchez-Gómez, P., Gomez-Ibarlucea, E., Ivanov, D. P., Rahman, R., Grabowska, A. M., …Garcia-Fuentes, M. (2019). Structure-optimized interpolymer polyphosphazene complexes for effective gene delivery against glioblastoma. Advanced Therapeutics, 2(3), Article 1800126. https://doi.org/10.1002/adtp.201800126

Safe and efficient gene delivery vectors will enhance the prospects for polynucleotide-based therapies. Herein a new approach toward structurally optimized gene vector design based on the preparation of clickable poly(allylamino-phosphazene)s that ca... Read More about Structure-optimized interpolymer polyphosphazene complexes for effective gene delivery against glioblastoma.

The invasive region of glioblastoma defined by 5ALA guided surgery has an altered cancer stem cell marker profile compared to central tumour (2017)
Journal Article
Smith, S. J., Diksin, M., Chhaya, S., Sairam, S., Estevez-Cebrero, M. A., & Rahman, R. (2017). The invasive region of glioblastoma defined by 5ALA guided surgery has an altered cancer stem cell marker profile compared to central tumour. International Journal of Molecular Sciences, 18(11), https://doi.org/10.3390/ijms18112452

Glioblastoma, a WHO grade IV astrocytoma, is a highly aggressive and heterogeneous tumour that infiltrates deeply into surrounding brain parenchyma, making complete surgical resection impossible. Despite chemo-radiotherapy, the residual cell populati... Read More about The invasive region of glioblastoma defined by 5ALA guided surgery has an altered cancer stem cell marker profile compared to central tumour.

The molecular and phenotypic basis of the glioma invasive perivascular niche (2017)
Journal Article
Diksin, M., Smith, S. J., & Rahman, R. (2017). The molecular and phenotypic basis of the glioma invasive perivascular niche. International Journal of Molecular Sciences, 18(11), Article 2342. https://doi.org/10.3390/ijms18112342

Gliomas are devastating brain cancers that have poor prognostic outcomes for their patients. Short overall patient survival is due to a lack of durable, efficacious treatment options. Such therapeutic difficulties exist, in part, due to several gliom... Read More about The molecular and phenotypic basis of the glioma invasive perivascular niche.

Evaluation of a novel antibody to define histone 3.3 G34R mutant brain tumours (2017)
Journal Article
Haque, F., Varlet, P., Puntonet, J., Storer, L., Bountali, A., Rahman, R., …Grundy, R. G. (2017). Evaluation of a novel antibody to define histone 3.3 G34R mutant brain tumours. Acta Neuropathologica Communications, 5, 1-9. https://doi.org/10.1186/s40478-017-0449-1

Missense somatic mutations affecting histone H3.1 and H3.3 proteins are now accepted as the hallmark of paediatric diffuse intrinsic pontine gliomas (DIPG), non-brain stem paediatric high grade gliomas (pHGG) as well as a subset of adult glioblastoma... Read More about Evaluation of a novel antibody to define histone 3.3 G34R mutant brain tumours.

Highlights of children with Cancer UK’s workshop on drug delivery in paediatric brain tumours (2016)
Journal Article
Nailor, A., Walker, D. A., Jacques, T. S., Warren, K. E., Brem, H., Kearns, P. R., …Kilday, J. (2016). Highlights of children with Cancer UK’s workshop on drug delivery in paediatric brain tumours. ecancermedicalscience, 10(630), https://doi.org/10.3332/ecancer.2016.630

The first Workshop on Drug Delivery in Paediatric Brain Tumours was hosted in London by the charity Children with Cancer UK. The goals of the workshop were to break down the barriers to treating central nervous system (CNS) tumours in children, leadi... Read More about Highlights of children with Cancer UK’s workshop on drug delivery in paediatric brain tumours.

Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response (2015)
Journal Article
Smith, S. J., Ward, J. H., Tan, C., Grundy, R. G., & Rahman, R. (2015). Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response. Oncotarget, 6(26), 22191-22205. https://doi.org/10.18632/oncotarget.4339

Aims: Recent studies have observed that cells from high-grade glial tumors are capable of assuming an endothelial phenotype and genotype, a process termed ‘vasculogenic mimicry’ (VM). Here we model and manipulate VM in dynamic 3-dimensional (3D) glio... Read More about Endothelial-like malignant glioma cells in dynamic three dimensional culture identifies a role for VEGF and FGFR in a tumor-derived angiogenic response.

Expression alterations define unique molecular characteristics of spinal ependymomas (2015)
Journal Article
Lourdusamy, A., Rahman, R., & Grundy, R. G. (2015). Expression alterations define unique molecular characteristics of spinal ependymomas. Oncotarget, 6(23), https://doi.org/10.18632/oncotarget.3715

Ependymomas are glial tumors that originate in either intracranial or spinal regions. Although tumors from different regions are histologically similar, they are biologically distinct. We therefore sought to identify molecular characteristics of spin... Read More about Expression alterations define unique molecular characteristics of spinal ependymomas.

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma (2014)
Journal Article
Smith, S. J., Rahman, C. V., Ritchie, A. A., Gould, T. W., Ward, J. H., Shakesheff, K. M., …Clarke, P. A. (2014). Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma. Annals of The Royal College of Surgeons of England, 96(7), 495-501. https://doi.org/10.1308/003588414X13946184903568

Introduction: The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into th... Read More about Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma.

EM-010, Gene expression profiling of pediatric ependymomas from the posterior fossa reveals key differences with adult ependymomas (2014)
Journal Article
Lourdusamy, A., Rogers, H., Rahman, R., Ward, J., & Grundy, R. (2014). EM-010, Gene expression profiling of pediatric ependymomas from the posterior fossa reveals key differences with adult ependymomas. Neuro-Oncology, 16(Suppl_1), i19

BACKGROUND: Ependymoma in children and adults show distinct pathogenesis, biology, and clinical features, it is important to elucidate the transcriptional features that distinguish pediatric ependymomas from adults arising in same anatomical region.... Read More about EM-010, Gene expression profiling of pediatric ependymomas from the posterior fossa reveals key differences with adult ependymomas.

RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells (2014)
Journal Article
Lagah, S., Tan, I., Radhakrishnan, P., Hirst, R. A., Ward, J. H., O'Callaghan, C., …Rahman, R. (2014). RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells. PLoS ONE, 9(1), Article e86187. https://doi.org/10.1371/journal.pone.0086187

Background Telomeric 3’ overhangs can fold into a four-stranded DNA structure termed G-quadruplex (G4), a formation which inhibits telomerase. As telomerase activation is crucial for telomere maintenance in most cancer cells, several classes of G4... Read More about RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells.

Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix (2013)
Journal Article
Rahman, C. V., Smith, S. J., Morgan, P. S., Langmack, K. A., Clarke, P. A., Ritchie, A. A., …Rahman, R. (2013). Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix. PLoS ONE, 8(10), Article e77435. https://doi.org/10.1371/journal.pone.0077435

INTRODUCTION Polymer-based delivery systems offer innovative intra-cavity administration of drugs, with the potential to better target micro-deposits of cancer cells in brain parenchyma beyond the resected cavity. Here we evaluate clinical utility... Read More about Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix.

Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition (2012)
Journal Article
Smith, S. J., Wilson, M., Ward, J. H., Rahman, C. V., Peet, A. C., Macarthur, D. C., …Rahman, R. (2012). Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition. PLoS ONE, 7(12), Article e52335. https://doi.org/10.1371/journal.pone.0052335

INTRODUCTION Physiologically relevant pre-clinical ex vivo models recapitulating CNS tumor micro-environmental complexity will aid development of biologically-targeted agents. We present comprehensive characterization of tumor aggregates generated... Read More about Recapitulation of tumor heterogeneity and molecular signatures in a 3D brain cancer model with decreased sensitivity to histone deacetylase inhibition.

Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms (2012)
Journal Article
Tan, T. C., Rahman, R., Jaber-Hijazi, F., Felix, D. A., Chen, C., Louis, E. J., & Aboobaker, A. (2012). Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms. Proceedings of the National Academy of Sciences, 109(11), https://doi.org/10.1073/pnas.1118885109

In most sexually reproducing animals, replication and maintenance of telomeres occurs in the germ line and during early development in embryogenesis through the use of telomerase. Somatic cells generally do not maintain telomere sequences, and these... Read More about Telomere maintenance and telomerase activity are differentially regulated in asexual and sexual worms.

Histone deacetylase inhibition as an anticancer telomerase-targeting strategy (2011)
Journal Article
Rahman, R., & Grundy, R. (2011). Histone deacetylase inhibition as an anticancer telomerase-targeting strategy. International Journal of Cancer, 129(12), 2765-2774. doi:10.1002/ijc.26241

Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. The mech... Read More about Histone deacetylase inhibition as an anticancer telomerase-targeting strategy.

Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma (2010)
Journal Article
Rahman, R., Smith, S., Rahman, C., & Grundy, R. (2010). Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma. Journal of Oncology, 2010, 1-16. https://doi.org/10.1155/2010/251231

Despite advances in surgery, radiation therapy, and chemotherapeutics, patients with malignant glioma have a dismal prognosis. The formations of aberrant tumour vasculature and glioma cell invasion are major obstacles for effective treatment. Angioge... Read More about Antiangiogenic therapy and mechanisms of tumor resistance in malignant glioma.

Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion (2010)
Journal Article
Hussein, D., Punjaruk, W., Storer, L. C. D., Shaw, L., Othman, R. T., Peet, A., …Coyle, B. (2011). Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion. Neuro-Oncology, 13(1), 70-83. https://doi.org/10.1093/neuonc/noq144

Reliable model systems are needed to elucidate the role cancer stem cells (CSCs) play in pediatric brain tumor drug resistance. The majority of studies to date have focused on clinically distinct adult tumors and restricted tumor types. Here, the CSC... Read More about Pediatric brain tumor cancer stem cells: cell cycle dynamics, DNA repair, and etoposide extrusion.

Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells (2010)
Journal Article
Rahman, R., Osteso-Ibanez, T., Hirst, R. A., Levesley, J., Kilday, J., Quinn, S., …Grundy, R. G. (2010). Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells. Molecular Cancer Therapeutics, 9(9), 2568-2581. https://doi.org/10.1158/1535-7163.mct-10-0272

Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. However,... Read More about Histone Deacetylase Inhibition Attenuates Cell Growth with Associated Telomerase Inhibition in High-Grade Childhood Brain Tumor Cells.

Pediatric Ependymoma: Biological Perspectives (2009)
Journal Article
Kilday, J., Rahman, R., Dyer, S., Ridley, L., Lowe, J., Coyle, B., & Grundy, R. (2009). Pediatric Ependymoma: Biological Perspectives. Molecular Cancer Research, 7(6), 765-786. https://doi.org/10.1158/1541-7786.mcr-08-0584

Pediatric ependymomas are enigmatic tumors that continue to present a clinical management challenge despite advances in neurosurgery, neuroimaging techniques, and radiation therapy. Difficulty in predicting tumor behavior from clinical and histologic... Read More about Pediatric Ependymoma: Biological Perspectives.

Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm (2009)
Journal Article
Rahman, R., Heath, R., & Grundy, R. (2009). Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm. BBA - Molecular Basis of Disease, 1792(4), 280-288. doi:10.1016/j.bbadis.2009.01.011

Brain tumours are a diverse group of neoplasms that continue to present a formidable challenge in our attempt to achieve curable intervention. Our conceptual framework of human brain cancer has been redrawn in the current decade. There is a gathering... Read More about Cellular immortality in brain tumours: an integration of the cancer stem cell paradigm.

Telomeric 3?-overhang length is associated with the size of telomeres (2008)
Journal Article
Rahman, R., Forsyth, N. R., & Cui, W. (2008). Telomeric 3?-overhang length is associated with the size of telomeres. Experimental Gerontology, 43(4), 258-265. doi:10.1016/j.exger.2008.01.005

Telomeres are specialized DNA/protein complexes that cap eukaryotic chromosome ends as T-loop structures and maintain genomic integrity. Vertebrate telomeric DNA consists of tandem double-strand repeats which terminate in a 3 0 single-strand G-rich o... Read More about Telomeric 3?-overhang length is associated with the size of telomeres.

Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth (2006)
Journal Article
Rahman, R., Mo, L., & Cui, W. (2006). Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth. Biochemical and Biophysical Research Communications, 350(3), 796-802. doi:10.1016/j.bbrc.2006.09.125

Telomerase catalytic subunit (TERT) seems a key factor controlling telomerase activity, telomere length, and cell growth. To further address this issue, we forced expression of a catalytically inactive mutant human TERT (hTERT) in hTERT-immortalised... Read More about Telomerase with mutated catalytic motifs has dominant negative effects on telomerase activity and inhibits cell growth.