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Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles (2024)
Journal Article
Brown, T. J., Rutland, C. S., Rutland, C. S., Choi, K. K., Tse, F., Pfeffers, M. J., …James, V. (2024). Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles. Frontiers in Cell and Developmental Biology, 12, Article 1354606. https://doi.org/10.3389/fcell.2024.1354606

Prostate cancer (PCa) is a leading male malignancy worldwide, often progressing to bone metastasis, with limited curative options. Extracellular vesicles (EVs) have emerged as key players in cancer communication and metastasis, promoting the formatio... Read More about Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles.

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, 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.

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.

Application of a 3D hydrogel-based model to replace use of animals for passaging patient-derived xenografts (2023)
Journal Article
Jones, S., Ashworth, J. C., Meakin, M., Collier, P., Probert, C., Ritchie, A. A., …Grabowska, A. M. (2023). Application of a 3D hydrogel-based model to replace use of animals for passaging patient-derived xenografts. In Vitro Models, 2, 99-111. https://doi.org/10.1007/s44164-023-00048-x

Purpose This 3D in vitro cancer model for propagation of patient-derived cells, using a synthetic self-assembling peptide gel, allows the formation of a fully characterised, tailorable tumour microenvironment. Unlike many existing 3D cancer models,... Read More about Application of a 3D hydrogel-based model to replace use of animals for passaging patient-derived xenografts.

Targeting FGFRs Using PD173074 as a Novel Therapeutic Strategy in Cholangiocarcinoma (2023)
Journal Article
Balasubramanian, B., Yacqub-Usman, K., Venkatraman, S., Myint, K. Z., Juengsamarn, J., Sarkhampee, P., …Tohtong, R. (2023). Targeting FGFRs Using PD173074 as a Novel Therapeutic Strategy in Cholangiocarcinoma. Cancers, 15(9), Article 2528. https://doi.org/10.3390/cancers15092528

Cholangiocarcinoma (CCA) is an architecturally complex tumour with high heterogeneity. Discovery at later stages makes treatment challenging. However, the lack of early detection methodologies and the asymptomatic nature of CCA make early diagnosis m... Read More about Targeting FGFRs Using PD173074 as a Novel Therapeutic Strategy in Cholangiocarcinoma.

Identifying new biomarkers of aggressive Group 3 and SHH medulloblastoma using 3D hydrogel models, single cell RNA sequencing and 3D OrbiSIMS imaging (2023)
Journal Article
Linke, F., Johnson, J. E. C., Kern, S., Bennett, C. D., Lourdusamy, A., Lea, D., …Coyle, B. (2023). Identifying new biomarkers of aggressive Group 3 and SHH medulloblastoma using 3D hydrogel models, single cell RNA sequencing and 3D OrbiSIMS imaging. Acta Neuropathologica Communications, 11(1), Article 6. https://doi.org/10.1186/s40478-022-01496-4

The most common malignant brain tumour in children, medulloblastoma (MB), is subdivided into four clinically relevant molecular subgroups, although targeted therapy options informed by understanding of different cellular features are lacking. Here, b... Read More about Identifying new biomarkers of aggressive Group 3 and SHH medulloblastoma using 3D hydrogel models, single cell RNA sequencing and 3D OrbiSIMS imaging.

Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects (2023)
Journal Article
Diringer, M., Coliat, P., Mathieu, C., Laurent, N., Mura, C., Banerjee, M., …Detappe, A. (2023). Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects. Small, 19(12), Article 2205961. https://doi.org/10.1002/smll.202205961

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre‐clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC... Read More about Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects.

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.

Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome (2022)
Journal Article
Sueca-Comes, M., Rusu, E. C., Grabowska, A. M., & Bates, D. O. (2022). Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome. Pharmacological Reviews, 74(4), 1136-1145. https://doi.org/10.1124/pharmrev.121.000410

The number of cancer drugs is increasing as new chemical entities are developed to target molecules, often protein kinases, driving cancer progression. In 2009, Fedorov et al. identified that of the protein kinases in the human kinome, most of the fo... Read More about Looking Under the Lamppost: The Search for New Cancer Targets in the Human Kinome.

Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers (2022)
Journal Article
Alblihy, A., Ali, R., Algethami, M., Shoqafi, A., Toss, M. S., Brownlie, J., …Madhusudan, S. (2022). Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers. npj Precision Oncology, 6(1), https://doi.org/10.1038/s41698-022-00298-0

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have... Read More about Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers.

Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts (2022)
Journal Article
Sharpe, B. P., Hayden, A., Manousopoulou, A., Cowie, A., Walker, R. C., Harrington, J., …Underwood, T. J. (2022). Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts. Cell Reports Medicine, 3(6), Article 100541. https://doi.org/10.1016/j.xcrm.2022.100541

The chemotherapy resistance of esophageal adenocarcinomas (EACs) is underpinned by cancer cell extrinsic mechanisms of the tumor microenvironment (TME). We demonstrate that, by targeting the tumor-promoting functions of the predominant TME cell type,... Read More about Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts.

Passerini chemistries for synthesis of polymer pro-drug and polymersome drug delivery nanoparticles (2022)
Journal Article
Travanut, A., Monteiro, P. F., Smith, S., Howdle, S. M., Grabowska, A. M., Kellam, B., …Alexander, C. (2022). Passerini chemistries for synthesis of polymer pro-drug and polymersome drug delivery nanoparticles. Journal of Materials Chemistry B, 10, 3895-3905. https://doi.org/10.1039/d2tb00045h

New materials chemistries are urgently needed to overcome the limitations of existing biomedical materials in terms of preparation, functionality and versatility, and also in regards to their compatibility with biological environments. Here, we show... Read More about Passerini chemistries for synthesis of polymer pro-drug and polymersome drug delivery nanoparticles.

Synthesis, characterisation and evaluation of hyperbranched N-(2-hydroxypropyl) methacrylamides for transport and delivery in pancreatic cell lines in vitro and in vivo (2022)
Journal Article
Anane-Adjei, A. B., Fletcher, N. L., Cavanagh, R. J., Houston, Z. H., Crawford, T., Pearce, A. K., …Alexander, C. (2022). Synthesis, characterisation and evaluation of hyperbranched N-(2-hydroxypropyl) methacrylamides for transport and delivery in pancreatic cell lines in vitro and in vivo. Biomaterials Science, 10(9), 2328-2344. https://doi.org/10.1039/d1bm01548f

Hyperbranched polymers have many promising features for drug delivery, owing to their ease of synthesis, multiple functional group content, and potential for high drug loading with retention of solubility. Here we prepared hyperbranched N-(2-hydroxyp... Read More about Synthesis, characterisation and evaluation of hyperbranched N-(2-hydroxypropyl) methacrylamides for transport and delivery in pancreatic cell lines in vitro and in vivo.

Targeting hypoxia regulated sodium driven bicarbonate transporters reduces triple negative breast cancer metastasis (2022)
Journal Article
Harris, A. L., Clarke, P. A., Carroll, C. P., Bolland, H., Vancauwenberghe, E., Collier, P., …McIntyre, A. (2022). Targeting hypoxia regulated sodium driven bicarbonate transporters reduces triple negative breast cancer metastasis. Neoplasia, 25, 41-52. https://doi.org/10.1016/j.neo.2022.01.003

Regions of low oxygen (hypoxia) are found in >50% of breast tumours, most frequently in the more aggressive triple negative breast cancer subtype (TNBC). Metastasis is the cause of 90% of breast cancer patient deaths. Regions of tumour hypoxia tend t... Read More about Targeting hypoxia regulated sodium driven bicarbonate transporters reduces triple negative breast cancer metastasis.

Multi-component bioresponsive nanoparticles for synchronous delivery of docetaxel and TUBB3 siRNA to lung cancer cells (2021)
Journal Article
Conte, C., Monteiro, P., Gurnani, P., Stolnik, S., Ungaro, F., Quaglia, F., …Alexander, C. (2021). Multi-component bioresponsive nanoparticles for synchronous delivery of docetaxel and TUBB3 siRNA to lung cancer cells. Nanoscale, 13(26), 11414-11426. https://doi.org/10.1039/d1nr02179f

Bioresponsive nanoparticles (NPs) are of interest for anticancer nanomedicines, owing to the possibility to ‘design in’ selective modulation of drug release at target sites. Here we describe the double emulsion formulation of redox-responsive NPs bas... Read More about Multi-component bioresponsive nanoparticles for synchronous delivery of docetaxel and TUBB3 siRNA to lung cancer cells.

ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma (2021)
Journal Article
Nasir, A., Cardall, A., Othman, R. T., Nicolaou, N., Lourdusamy, A., Linke, F., …Coyle, B. (2021). ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma. Neuro-Oncology Advances, 3(1), https://doi.org/10.1093/noajnl/vdab030

Background: Therapeutic intervention in metastatic medulloblastoma is dependent upon elucidating the underlying metastatic mechanism. We investigated whether an epithelialmesenchymal transition (EMT)-like pathway could drive medulloblastoma metastasi... Read More about ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma.

Preparation of a User-Defined Peptide Gel for Controlled 3D Culture Models of Cancer and Disease (2020)
Journal Article
Ashworth, J. C., Morgan, R. L., Lis-Slimak, K., Jones, S., Spence, K., Slater, C. E., …Merry, C. L. R. (2020). Preparation of a User-Defined Peptide Gel for Controlled 3D Culture Models of Cancer and Disease. Journal of Visualized Experiments, 166, Article e61710. https://doi.org/10.3791/61710

There is a growing awareness that cells grown in 3D better model in vivo behavior than those grown in 2D. In this protocol, we describe a simple and tunable 3D hydrogel, suitable for culturing cells and tissue in a setting that matches their native e... Read More about Preparation of a User-Defined Peptide Gel for Controlled 3D Culture Models of Cancer and Disease.

3D hydrogels reveal medulloblastoma subgroup differences and identify extracellular matrix subtypes that predict patient outcome (2020)
Journal Article
Linke, F., Aldighieri, M., Lourdusamy, A., Grabowska, A. M., Stolnik, S., Kerr, I. D., …Coyle, B. (2021). 3D hydrogels reveal medulloblastoma subgroup differences and identify extracellular matrix subtypes that predict patient outcome. Journal of Pathology, 253(3), 326-338. https://doi.org/10.1002/path.5591

© 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. Medulloblastoma (MB) is the most common malignant brain tumour in children and is subdivided into... Read More about 3D hydrogels reveal medulloblastoma subgroup differences and identify extracellular matrix subtypes that predict patient outcome.

AKT isoforms have discrete expression in Triple Negative breast cancers and roles in cisplatin sensitivity (2020)
Journal Article
Khan, S., Wadhwa, B., Paddar, M., Malik, F., Mir, S., Clarke, P. A., …Malik, F. (2020). AKT isoforms have discrete expression in Triple Negative breast cancers and roles in cisplatin sensitivity. Oncotarget, 11, 4178-4194. https://doi.org/10.18632/oncotarget.27746

AKT, a serine threonine kinase, exists in three different isoforms and is known for regulating several biological processes including tumorigenesis. In this study, we investigated the expression and net effect of the individual isoforms in triple neg... Read More about AKT isoforms have discrete expression in Triple Negative breast cancers and roles in cisplatin sensitivity.

Effects of Polymer 3D Architecture, Size, and Chemistry on Biological Transport and Drug Delivery In Vitro and in Orthotopic Triple Negative Breast Cancer Models (2020)
Journal Article
Anane‐Adjei, A. B., Pearce, A. K., Anane-Adjei, A. B., Cavanagh, R. J., Monteiro, P. F., Bennett, T. M., …Alexander, C. (2020). Effects of Polymer 3D Architecture, Size, and Chemistry on Biological Transport and Drug Delivery In Vitro and in Orthotopic Triple Negative Breast Cancer Models. Advanced Healthcare Materials, 9(22), Article 2000892. https://doi.org/10.1002/adhm.202000892

© 2020 Wiley-VCH GmbH The size, shape, and underlying chemistries of drug delivery particles are key parameters which govern their ultimate performance in vivo. Responsive particles are desirable for triggered drug delivery, achievable through archit... Read More about Effects of Polymer 3D Architecture, Size, and Chemistry on Biological Transport and Drug Delivery In Vitro and in Orthotopic Triple Negative Breast Cancer Models.