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1. Epitranscriptomic mechanisms of androgen signalling and prostate cancer

Author

Patke, Rodhan, Harris, Anna E., Woodcock, Corinne L., Thompson, Rachel, Santos, Rute, Kumari, Amber, Allegrucci, Cinzia, Archer, Nathan, Gudas, Lorraine J., Robinson, Brian D., Persson, Jenny L., Fray, Rupert, Jeyapalan, Jennie, Rutland, Catrin S., Rakha, Emad, Madhusudan, Srinivasan, Emes, Richard D., Muyangwa-Semenova, Musalwa, Alsaleem, Mansour, de Brot, Simone, Green, William, Ratan, Hari, Mongan, Nigel P., and Lothion-Roy, Jennifer

Published
2024
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5. Ureteroscopic treatment of urolithiasis: How do we measure and optimise outcomes?

Author

Smith, Daron, Rossi, Sabrina Helena, Smith, Yuko, Pietropaolo, Amelia, Joshi, Hrishi, and Ratan, Hari

Abstract

Background: Patients with urolithiasis have access to a wide range of efficacious therapeutic surgical options, including shockwave lithotripsy (SWL), retrograde ureteric or intrarenal surgery with semi-rigid and flexible ureteroscopes (URS or fURS) and percutaneous nephrolithotomy (PCNL). In recent years, there have been many peer-reviewed publications evaluating new techniques and new equipment, such as pulse-modulated Holmium:YAG and thulium fibre lasers. However, when reviewing this extensive literature, it becomes apparent that there is no consensus on what constitutes a 'successful' stone treatment outcome. Objectives: The purpose of this article is to review the existing measures of 'success' after the ureteroscopic treatment of urolithiasis and to promote a standardised and holistic approach to reporting outcomes in clinical trials. Methods: Our narrative review focussed on studies examining measures of success in urolithiasis treatment published within the last 10 years. Conclusions: Due to markedly different reported outcome measures of treatments for urolithiasis, comparing results between studies can be difficult. In addition to measuring clinical outcomes, there is an increasing acknowledgement of the importance of patient-reported outcome measures (PROMs) in determining treatment success, and the need to consider the cost-effectiveness and environmental sustainability of various treatments. We suggest that all future studies on this common urological condition should incorporate holistic and tranpsarent outcome measures. Level of evidence: Not applicable [ABSTRACT FROM AUTHOR]

Published
2024
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6. Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles

Author

Brown, Thomas J., primary, Rutland, Catrin S., additional, Choi, Katie K., additional, Tse, Feng, additional, Peffers, Mandy J., additional, Mongan, Nigel P., additional, Arkill, Kenton P., additional, Ritchie, Alison, additional, Clarke, Philip A., additional, Ratan, Hari, additional, Allegrucci, Cinzia, additional, Grabowska, Anna M., additional, and James, Victoria, additional

Published
2024
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7. Combinatorial chemoprevention of prostate cancer

Author

Ratan, Hari Lakshmi

Subjects
616.99463061
Abstract

Improved understanding of the molecular biology of prostate cancer has lead to the identification and development of a number of agents which may be well suited to the task of chemoprevention. In the work described here, two novel agents, resveratrol and gefitinib, have been evaluated for their anticancer effects using in vitro and in vivo models of prostate cancer. Specifically, the hypothesis that these two agents can act synergistically to achieve a greater antineoplastic effect has been tested. Resveratrol is a diet-derived naturally-occurring polyphenol which displays anti-oxidant and anti-inflammatory properties. Gefitinib (ZD1839. "Iressa", AstraZeneca Pharmaceuticals) is a small molecule inhibitor of the epidermal growth factor (EGFR) tyrosine kinase. EGFR is increasingly implicated in prostatic carcinogenesis. The results presented here demonstrate that both resveratrol and gefitinib inhibit the proliferation of hormone-sensitive and hormone-resistant cells in vitro, although there was no synergy between these two compounds. Both compounds modulate cell cycle kinetics causing arrest in various phases of the cycle. Gefitinib was shown to effectively abrogate EGFR phosphorylation in prostate cancer cell lines. No effect of resveratrol on oxidative DNA damage in prostate cancer cells was observed and its effects on COX-2 expression could not be evaluated. Gefitinib potently inhibited the development of DU145 xenografts in a nude mouse model of prostate cancer. No significant effect of resveratrol could be seen in the same mouse model. These results suggest that gefitinib may well have a role to play in the chemotherapy and chemoprevention of prostate cancer. Despite its potent in vitro antiproliferative effects, further in vivo evaluation of resveratrol is required prior to its use alone or in combination with other agents can be recommended in prostate cancer.

Published
2004

8. Supplementary Figure 7 from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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9. Data from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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10. Supplementary Figure 4 from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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11. Supplementary Methods from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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12. Supplementary Figure 5 from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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13. Supplementary Table 1 from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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14. Supplementary Figure 6 from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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15. Supplementary Figure 3 from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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16. Supplementary Figure 1 from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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17. Supplementary Figure 2 from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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18. Supplementary Figure Legends from 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors

Author

Onion, David, primary, Argent, Richard H., primary, Reece-Smith, Alexander M., primary, Craze, Madeleine L., primary, Pineda, Robert G., primary, Clarke, Philip A., primary, Ratan, Hari L., primary, Parsons, Simon L., primary, Lobo, Dileep N., primary, Duffy, John P., primary, Atherton, John C., primary, McKenzie, Andrew J., primary, Kumari, Rajendra, primary, King, Peter, primary, Hall, Brett M., primary, and Grabowska, Anna M., primary

Published
2023
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26. Communication tools in the COVID-19 era and beyond which can optimise professional practice and patient care

Author

Clement, Keiran David, primary, Zimmermann, Eleanor F, additional, Bhatt, Nikita R, additional, Light, Alexander, additional, Gao, Chuanyu, additional, Kulkarni, Meghana, additional, Norris, Joseph M, additional, Gallagher, Kevin M J, additional, Cambridge, William A, additional, Shah, Taimur T, additional, Ratan, Hari L, additional, Smith, Daron, additional, and Kasivisvanathan, Veeru, additional

Published
2020
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30. 3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors

Author

Onion, David, Argent, Richard H., Reece-Smith, Alex M., Craze, Madeleine L., Pineda, Robert G., Clarke, Philip A., Ratan, Hari L., Parsons, Simon L., Lobo, Dileep N., Duffy, John P., Atherton, John C., McKenzie, Andrew J., Kumari, Rajendra, King, Peter, Hall, Brett M., and Grabowska, Anna M.

Abstract

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR.

Published
2016

31. Early multicentre experience of ultra-mini percutaneous nephrolithotomy in the UK

Author

Pullar, Ben, primary, Havranek, Eric, additional, Blacker, Tony J R, additional, Datta, Sam N, additional, Somani, Bhaskar, additional, Sriprasad, Seshadri, additional, Ratan, Hari, additional, Scriven, Sharon, additional, Choong, Simon, additional, Smith, R Daron, additional, Mackie, Simon, additional, Watson, Graham, additional, and Wiseman, Oliver J, additional

Published
2016
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32. KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer–a targeted molecular approach

Author

Green, William JF, primary, Ball, Graham, additional, Hulman, Geoffrey, additional, Johnson, Catherine, additional, Van Schalwyk, Gerry, additional, Ratan, Hari L, additional, Soria, Daniel, additional, Garibaldi, Jonathan M, additional, Parkinson, Richard, additional, Hulman, Joshua, additional, Rees, Robert, additional, and Powe, Desmond G, additional

Published
2016
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33. Early multicentre experience of ultra-mini percutaneous nephrolithotomy in the UK.

Author

Pullar, Ben, Havranek, Eric, Blacker, Tony J. R., Datta, Sam N., Somani, Bhaskar, Sriprasad, Seshadri, Ratan, Hari, Scriven, Sharon, Choong, Simon, Smith, R. Daron, Mackie, Simon, Watson, Graham, and Wiseman, Oliver J.

Abstract

Objectives: Ultra-mini percutaneous nephrolithotomy (UMP) is a novel technique recently introduced allowing percutaneous renal access to stones using a specially modified 11 or 13 Fr sheath, a 6 Fr nephroscope, and permits laser fragmentation and stone evacuation. This study aimed to review the early practice of UMP in the UK. Methods: All centres in the UK which had performed UMP were contacted to submit data. Data were submitted to a central database from nine centres around the UK who performed UMP between July 2013 and December 2014. Data were collected on patient, stone, operative factors and outcomes. Results: A total of 32 UMP cases were performed in the contributing centres. Stone size ranged from 7 mm×5 mm to 24 mm×24 mm across the 32 cases, with a mean of 13 mm×10 mm. Stone-free rates were excellent with 31/32 cases stone-free post procedure; 26/32 patients were left without a nephrostomy tube. Complications were uncommon; there were two Clavien 1 complications in this series (6%). Conclusion: This study has shown the efficacy of UMP during its introduction into UK practice. It is likely that UMP will become a useful addition to the armamentarium to treat renal stones, especially smaller stones in the lower pole calyx, and in specialised cases such as paediatric stone disease and in patients with stones in calyceal diverticulae. [ABSTRACT FROM AUTHOR]

Published
2017
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37. 3-dimensional patient-derived lung cancer assays reveal resistance to standards-of-care promoted by stromal cells but sensitivity to histone deacetylase inhibitors

Author

Onion, David, Argent, Richard H., Reece-Smith, Alex M., Craze, Madeleine L., Pineda, Robert G., Clarke, Philip A., Ratan, Hari L., Parsons, Simon L., Lobo, Dileep N., Duffy, John P., Atherton, John C., McKenzie, Andrew J., Kumari, Rajendra, King, Peter, Hall, Brett M., Grabowska, Anna M., Onion, David, Argent, Richard H., Reece-Smith, Alex M., Craze, Madeleine L., Pineda, Robert G., Clarke, Philip A., Ratan, Hari L., Parsons, Simon L., Lobo, Dileep N., Duffy, John P., Atherton, John C., McKenzie, Andrew J., Kumari, Rajendra, King, Peter, Hall, Brett M., and Grabowska, Anna M.

Abstract

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor–derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non–small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753–63. ©2016 AACR.

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38. KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach

Author

Green, William J.F., Ball, Graham, Hulman, Geoffrey, Johnson, Catherine, Van Schalwyk, Gerry, Ratan, Hari L., Soria, Daniel, Garibaldi, Jonathan M., Parkinson, Richard, Hulman, Joshua, Rees, Robert, Powe, Desmond G., Green, William J.F., Ball, Graham, Hulman, Geoffrey, Johnson, Catherine, Van Schalwyk, Gerry, Ratan, Hari L., Soria, Daniel, Garibaldi, Jonathan M., Parkinson, Richard, Hulman, Joshua, Rees, Robert, and Powe, Desmond G.

Abstract

Background:There remains a need to identify and validate biomarkers for predicting prostate cancer (CaP) outcomes using robust and routinely available pathology techniques to identify men at most risk of premature death due to prostate cancer. Previous immunohistochemical studies suggest the proliferation marker Ki67 might be a predictor of survival, independently of PSA and Gleason score. We performed a validation study of Ki67 as a marker of survival and disease progression and compared its performance against another candidate biomarker, DLX2, selected using artificial neural network analysis. Methods: A tissue microarray (TMA) was constructed from transurethral resected prostatectomy histology samples (n=192). Artificial neural network analysis was used to identify candidate markers conferring increased risk of death and metastasis in a public cDNA array. Immunohistochemical analysis of the TMA was carried out and univariate and multivariate tests performed to explore the association of tumour protein levels of Ki67 and DLX2 with time to death and metastasis. Results: Univariate analysis demonstrated Ki67 as predictive of CaP-specific survival (DSS; P=0.022), and both Ki67 (P=0.025) and DLX2 (P=0.001) as predictive of future metastases. Multivariate analysis demonstrated Ki67 as independent of PSA, Gleason score and D’Amico risk category for DSS (HR=2.436,P=0.029) and both Ki67 (HR=3.296,P=0.023) and DLX2 (HR=3.051,P=0.003) as independent for future metastases. Conclusions: High Ki67 expression is only present in 6.8% of CaP patients and is predictive of reduced survival and increased risk of metastasis, independent of PSA, Gleason score and D’Amico risk category. DLX2 is a novel marker of increased metastasis risk found in 73% patients and 8.2% showed co-expression with a high Ki67 score. Two cancer cell proliferation markers, Ki67 and DLX2, may be able to inform clinical decision-making when identifying patients for active surveillance.

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39. 3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal Cells but Sensitivity to Histone Deacetylase Inhibitors.

Author

Onion D, Argent RH, Reece-Smith AM, Craze ML, Pineda RG, Clarke PA, Ratan HL, Parsons SL, Lobo DN, Duffy JP, Atherton JC, McKenzie AJ, Kumari R, King P, Hall BM, and Grabowska AM

Subjects
Animals, Antineoplastic Agents pharmacology, Biomarkers, Epithelial-Mesenchymal Transition drug effects, Histone Deacetylase Inhibitors pharmacology, Humans, In Vitro Techniques, Lung Neoplasms surgery, Neoplasm Staging, Phenotype, Stromal Cells metabolism, Tissue Culture Techniques, Tumor Microenvironment drug effects, Xenograft Model Antitumor Assays, Antineoplastic Agents therapeutic use, Drug Resistance, Neoplasm, Histone Deacetylase Inhibitors therapeutic use, Lung Neoplasms diagnosis, Lung Neoplasms drug therapy, Standard of Care, Stromal Cells drug effects
Abstract

There is a growing recognition that current preclinical models do not reflect the tumor microenvironment in cellular, biological, and biophysical content and this may have a profound effect on drug efficacy testing, especially in the era of molecular-targeted agents. Here, we describe a method to directly embed low-passage patient tumor-derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by coculture with patient-derived cancer-associated fibroblasts (CAF). A range of solid tumors proved amenable to growth and pharmacologic testing in this 3D assay. A study of 30 early-stage non-small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standard-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers. Mol Cancer Ther; 15(4); 753-63. ©2016 AACR., (©2016 American Association for Cancer Research.)

Published
2016
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