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Radiogenomics as an Integrated Approach to Glioblastoma Precision Medicine (2024)
Journal Article
Sanchez, I., & Rahman, R. (2024). Radiogenomics as an Integrated Approach to Glioblastoma Precision Medicine. Current Oncology Reports, https://doi.org/10.1007/s11912-024-01580-z

Purpose of Review Isocitrate dehydrogenase wild-type glioblastoma is the most aggressive primary brain tumour in adults. Its infiltrative nature and heterogeneity confer a dismal prognosis, despite multimodal treatment. Precision medicine is increa... Read More about Radiogenomics as an Integrated Approach to Glioblastoma Precision Medicine.

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.-H. (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.

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.-H. (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.

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.

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.-H. (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.-H. (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), Article 208. 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.

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.