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2. Moving towards a personalised understanding of the nutritional impact of self-expanding metallic stents (SEMS) in gastro-oesophageal cancer: A retrospective case note review of a tertiary referral oncology centre.

Author

Cunningham, Aimee, primary, Alattal, Taibah, additional, Foulkes, Lindsey, additional, Lewis, Alexandra R, additional, Backen, Alison Catherine, additional, Williamson, Fiona, additional, McQueenie, Esther, additional, Owen-Holt, Vikki, additional, Williams, Kate, additional, Hubner, Richard, additional, Waddell, Tom, additional, Valpione, Sara, additional, Laasch, Hans-Ulrich, additional, Mansoor, Wasat, additional, and Weaver, Jamie, additional

Published
2024
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5. Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study

Author

Mahmood, Reem D., Shaw, Danielle, Descamps, Tine, Zhou, Cong, Morgan, Robert D., Mullamitha, Saifee, Saunders, Mark, Mescallado, Nerissa, Backen, Alison, Morris, Karen, Little, Ross A., Cheung, Susan, Watson, Yvonne, O’Connor, James P. B., Jackson, Alan, Parker, Geoff J. M., Dive, Caroline, and Jayson, Gordon C.

Published
2021
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7. Prospective Observational Study of Prevalence, Assessment and Treatment of Pancreatic Exocrine Insufficiency in Patients with Inoperable Pancreatic Malignancy (PANcreatic Cancer Dietary Assessment—PanDA)

Author

Carnie, Lindsay E., primary, Shah, Dinakshi, additional, Vaughan, Kate, additional, Kapacee, Zainul Abedin, additional, McCallum, Lynne, additional, Abraham, Marc, additional, Backen, Alison, additional, McNamara, Mairéad G., additional, Hubner, Richard A., additional, Barriuso, Jorge, additional, Gillespie, Loraine, additional, Lamarca, Angela, additional, and Valle, Juan W., additional

Published
2023
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8. Circulating biomarkers during treatment in patients with advanced biliary tract cancer receiving cediranib in the UK ABC-03 trial

Author

Backen, Alison C., Lopes, Andre, Wasan, Harpreet, Palmer, Daniel H, Duggan, Marian, Cunningham, David, Anthoney, Alan, Corrie, Pippa G., Madhusudan, Srinivasan, Maraveyas, Anthony, Ross, Paul J., Waters, Justin S., Steward, William P., Rees, Charlotte, McNamara, Mairéad G., Beare, Sandy, Bridgewater, John A., Dive, Caroline, and Valle, Juan W.

Published
2018
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9. Data Supplement from The Combination of Circulating Ang1 and Tie2 Levels Predicts Progression-Free Survival Advantage in Bevacizumab-Treated Patients with Ovarian Cancer

Author

Backen, Alison, primary, Renehan, Andrew G., primary, Clamp, Andrew R., primary, Berzuini, Carlo, primary, Zhou, Cong, primary, Oza, Amit, primary, Bannoo, Selina, primary, Scherer, Stefan J., primary, Banks, Rosamonde E., primary, Dive, Caroline, primary, and Jayson, Gordon C., primary

Published
2023
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10. Plasma Tie2 is a tumor vascular response biomarker for VEGF inhibitors in metastatic colorectal cancer

Author

Jayson, Gordon C., Zhou, Cong, Backen, Alison, Horsley, Laura, Marti-Marti, Kalena, Shaw, Danielle, Mescallado, Nerissa, Clamp, Andrew, Saunders, Mark P., Valle, Juan W., Mullamitha, Saifee, Braun, Mike, Hasan, Jurjees, McEntee, Delyth, Simpson, Kathryn, Little, Ross A., Watson, Yvonne, Cheung, Susan, Roberts, Caleb, Ashcroft, Linda, Manoharan, Prakash, Scherer, Stefan J., del Puerto, Olivia, Jackson, Alan, O’Connor, James P. B., Parker, Geoff J. M., and Dive, Caroline

Published
2018
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11. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial

Author

Valle, Juan W, Wasan, Harpreet, Lopes, Andre, Backen, Alison C, Palmer, Daniel H, Morris, Karen, Duggan, Marian, Cunningham, David, Anthoney, D Alan, Corrie, Pippa, Madhusudan, Srinivasan, Maraveyas, Anthony, Ross, Paul J, Waters, Justin S, Steward, Will P, Rees, Charlotte, Beare, Sandy, Dive, Caroline, and Bridgewater, John A

Published
2015
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12. Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency (PEI) in patients with advanced pancreatic cancer (aPC): PanDA.

Author

Lamarca, Angela, primary, Carnie, Lindsay, additional, Shah, Dinakshi, additional, Vaughan, Kate, additional, Kapacee, Zainul Abedin, additional, McCallum, Lynne, additional, Abraham, Marc, additional, Backen, Alison, additional, McNamara, Mairead Geraldine, additional, Hubner, Richard A, additional, Barriuso, Jorge, additional, Gillespie, Loraine, additional, and Valle, Juan W., additional

Published
2021
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13. A phase 1 trial of intravenous 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) in patients with advanced solid tumours

Author

Horsley, Laura, Cummings, Jeff, Middleton, Mark, Ward, Tim, Backen, Alison, Clamp, Andrew, Dawson, Martin, Farmer, Hayley, Fisher, Nita, Halbert, Gavin, Halford, Sarah, Harris, Adrian, Hasan, Jurjees, Hogg, Philip, Kumaran, Gireesh, Little, Ross, Parker, Geoff J. M., Potter, Paula, Saunders, Mark, Roberts, Caleb, Shaw, Danielle, Smith, Nigel, Smythe, Jon, Taylor, Andrew, Turner, Helen, Watson, Yvonne, Dive, Caroline, Jayson, Gordon C., and A Cancer Research UK Drug Development Office Phase I clinical trial

Published
2013
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15. Additional file 1 of Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study

Author

Mahmood, Reem D., Shaw, Danielle, Descamps, Tine, Zhou, Cong, Morgan, Robert D., Saifee Mullamitha, Saunders, Mark, Nerissa Mescallado, Backen, Alison, Morris, Karen, Little, Ross A., Cheung, Susan, Watson, Yvonne, O’Connor, James P. B., Jackson, Alan, Parker, Geoff J. M., Dive, Caroline, and Jayson, Gordon C.

Subjects
Data_FILES
Abstract

Additional file 1.

Published
2021
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16. Prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with inoperable pancreatic malignancy (PANcreatic cancer Dietary Assessment (PanDA): a study protocol

Author

Carnie, Lindsay E, primary, Lamarca, Angela, additional, Vaughan, Kate, additional, Kapacee, Zainul Abedin, additional, McCallum, Lynne, additional, Backen, Alison, additional, Barriuso, Jorge, additional, McNamara, Mairéad G, additional, Hubner, Richard A, additional, Abraham, Marc, additional, and Valle, Juan W, additional

Published
2021
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18. Effect of oxaliplatin plus 5-fluorouracil or capecitabine on circulating and imaging biomarkers in patients with metastatic colorectal cancer: a prospective biomarker study

Author

Mahmood, Reem, primary, Shaw, Danielle, additional, Descamps, Tine, additional, Zhou, Cong, additional, Morgan, Robert D., additional, Mullamitha, Saifee, additional, Saunders, Mark, additional, Mescallado, Nerissa, additional, Backen, Alison, additional, Morris, Karen, additional, Little, Ross A., additional, Cheung, Susan, additional, Watson, Yvonne, additional, O’Connor, James P. B., additional, Jackson, Alan, additional, Parker, Geoff J. M., additional, Dive, Caroline, additional, and Jayson, Gordon C., additional

Published
2020
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23. Cell-death, inflammation, tumor-burden and proliferation blood biomarkers predict lung cancer radiotherapy response and correlate with tumor volume and proliferation imaging

Author

Salem, Ahmed, Mistry, Hitesh, Backen, Alison, Hodgson, Clare, Koh, Pek, Dean, Emma, Priest, Lynsey, Haslett, Kate, Trigonis, Ioannis, Jackson, Alan, Asselin, Marie-Claude, Dive, Caroline, Renehan, Andrew, Faivre-Finn, Corinne, and Blackhall, Fiona

Abstract

There is an unmet need to develop non-invasive biomarkers to stratify patients in drug-radiotherapy trials. This pilot study investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging.Patients and methodsBlood samples were collected prior and during (day-21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion and tumor-burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small-cell and non-small cell lung cancer (NSCLC) while multivariate analysis focused on NSCLC.ResultsBlood samples from 78 patients were analyzed. Sixty-one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemo-radiotherapy. Of tested baseline biomarkers, undetectable IL-1b (hazard ratio (HR) 4.02, 95% confidence interval (CI) 2.04-7.93, p

Published
2017

24. The HER3 pathway as a potential target for inhibition in patients with biliary tract cancers

Author

Lamarca, Angela, primary, Galdy, Salvatore, additional, Barriuso, Jorge, additional, Moghadam, Sharzad, additional, Beckett, Elizabeth, additional, Rogan, Jane, additional, Backen, Alison, additional, Billington, Catherine, additional, McNamara, Mairéad G., additional, Hubner, Richard A., additional, Cramer, Angela, additional, and Valle, Juan W., additional

Published
2018
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25. Capecitabine and Temozolomide in Patients with Advanced Pulmonary Carcinoid Tumours.

Author

Papaxoinis, George, Kordatou, Zoe, McCallum, Lynne, Nasralla, Magdy, Lamarca, Angela, Backen, Alison, Nonaka, Daisuke, and Mansoor, Wasat

Subjects
TEMOZOLOMIDE, CARCINOID, CANCER, INTRAMUSCULAR injections, DISEASE duration, PROGRESSION-free survival
Abstract

Background: Temozolomide and capecitabine (CAPTEM) chemotherapy is known to be active in patients with pancreatic neuroendocrine tumours. Objective: This retrospective analysis set out to describe the efficacy and toxicity of CAPTEM in patients with advanced pulmonary carcinoids (PCs). Methods: Patients were included with advanced PC who had been treated with a maximum of 6 cycles of oral temozolomide 200 mg/m2 on days 10–14 and capecitabine 750 mg/m2 b.i.d. on days 1–14, repeated every 28 days, -followed by monthly intramuscular injection of octreotide 30 mg long-acting release as maintenance treatment. Results: Of the 33 patients, all with well-differentiated PC, 61% had atypical carcinoid, 36% had Ki-67 index >10% and 42% had ≥3 organs involved by metastasis. CAPTEM was administered as first-line treatment in 42% of patients, and 17% had received prior somatostatin analogue treatment. Six patients (18%) achieved a partial response, 19 (58%) had stable disease and 8 (24%) developed progressive disease. After a median time of follow-up of 34.8 months, median progression-free survival (PFS) was 9.0 months and median overall survival 30.4 months. Median duration of disease response was 21.7 months and median duration of disease control 9.7 months. Patients with multi-organ metastasis had shorter PFS, but only when treated as second or third line with CAPTEM (p = 0.023). Conclusions: CAPTEM induced a modest response and PFS rate, comparable to other studies with temozolomide in patients with advanced PC. The efficacy of CAPTEM should be compared to that of monotherapy with temozolomide in a prospective clinical trial. [ABSTRACT FROM AUTHOR]

Published
2020
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26. Somatostatin analogue-induced pancreatic exocrine insufficiency in patients with neuroendocrine tumors: results of a prospective observational study

Author

Lamarca, Angela, primary, McCallum, Lynne, additional, Nuttall, Christina, additional, Barriuso, Jorge, additional, Backen, Alison, additional, Frizziero, Melissa, additional, Leon, Rebecca, additional, Mansoor, Was, additional, McNamara, Mairéad G, additional, Hubner, Richard A., additional, and Valle, Juan W, additional

Published
2018
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27. Inter-tumor validation, through advanced MRI and circulating biomarkers, of plasma Tie2 as the vascular response biomarker for bevacizumab.

Author

Jayson, Gordon C., primary, Zhou, Cong, additional, Horsley, Laura Hope, additional, Marti, Kalena, additional, Shaw, Danielle, additional, Mescallado, Nerissa, additional, Clamp, Andrew R., additional, Saunders, Mark P., additional, Valle, Juan W., additional, Backen, Alison Catherine, additional, Simpson, Kathryn, additional, Little, Ross, additional, Watson, Yvonne, additional, Cheung, Susan, additional, Roberts, Caleb, additional, Manoharan, Prakash, additional, Jackson, Alan, additional, O'Connor, James, additional, Parker, Geoff J M, additional, and Dive, Caroline, additional

Published
2017
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28. Targeting the Epidermal Growth Factor Receptor in Addition to Chemotherapy in Patients with Advanced Pancreatic Cancer: A Systematic Review and Meta-Analysis

Author

Chiramel, Jaseela, primary, Backen, Alison, additional, Pihlak, Rille, additional, Lamarca, Angela, additional, Frizziero, Melissa, additional, Tariq, Noor-ul-Ain, additional, Hubner, Richard, additional, Valle, Juan, additional, Amir, Eitan, additional, and McNamara, Mairéad, additional

Published
2017
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29. Molecular analysis of circulating free nucleic acids and CTC genomes in patients with pancreatic adenocarcinoma

Author

Ayub, Mahmood, primary, Gulati, Sakshi, additional, Mohan, Sumitra, additional, Rothwell, Dominic, additional, Leong, Hui Sun, additional, Chudziak, Jakub, additional, Sahoo, Sudhakar, additional, Smith, Nigel, additional, Mesquita, Barbara, additional, Antonello, Jenny, additional, Aung, Kyaw, additional, Lamarca, Angela, additional, Backen, Alison, additional, McNamara, Mairead, additional, Miller, Crispin, additional, Valle, Juan, additional, Dive, Caroline, additional, and Brady, Ged, additional

Published
2016
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30. Abstract 3960: Combined circulating tumour cell (CTC) and circulating tumor DNA (ctDNA) analysis of blood from patients with pancreatic cancer

Author

Brady, Ged, primary, Rothwell, Dominic, additional, Ayub, Mahmood, additional, Smith, Nigel, additional, Mohan, Sumitra, additional, Chudziak, Jakub, additional, Aung, Kyaw, additional, Hubner, Richard, additional, Miller, Crispin, additional, Backen, Alison, additional, Leong, Hui Sun, additional, Gulati, Sakshi, additional, Kim, Chang Sik, additional, Lamarca, Angela, additional, McNamara, Mairéad, additional, Valle, Juan, additional, and Dive, Caroline, additional

Published
2016
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31. Systematic analysis of circulating soluble angiogenesis-associated proteins in ICON7 identifies Tie2 as a biomarker of vascular progression on bevacizumab

Author

Zhou, Cong, primary, Clamp, Andrew, additional, Backen, Alison, additional, Berzuini, Carlo, additional, Renehan, Andrew, additional, Banks, Rosamonde E, additional, Kaplan, Richard, additional, Scherer, Stefan J, additional, Kristensen, Gunnar B, additional, Pujade-Lauraine, Eric, additional, Dive, Caroline, additional, and Jayson, Gordon C, additional

Published
2016
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34. Discovery and Validation of Predictive Biomarkers of Survival for Non-small Cell Lung Cancer Patients Undergoing Radical Radiotherapy: Two Proteins With Predictive Value

Author

Walker, Michael J., primary, Zhou, Cong, additional, Backen, Alison, additional, Pernemalm, Maria, additional, Williamson, Andrew J.K., additional, Priest, Lynsey J.C., additional, Koh, Pek, additional, Faivre-Finn, Corinne, additional, Blackhall, Fiona H., additional, Dive, Caroline, additional, and Whetton, Anthony D., additional

Published
2015
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35. Changes in plasma biomarkers over time in patients (pts) with advanced biliary tract cancer (ABC) treated in the UK ABC-03 randomized phase II trial.

Author

Backen, Alison Catherine, primary, McNamara, Mairead G, additional, Lopes, Andre, additional, Wasan, Harpreet, additional, Palmer, Daniel H., additional, Duggan, Marian, additional, Cunningham, David, additional, Anthoney, Alan, additional, Corrie, Philippa, additional, Madhusudan, Srinivasan, additional, Maraveyas, Anthony, additional, Ross, Paul J., additional, Waters, Justin S., additional, Steward, William P., additional, Rees, Charlotte, additional, Beare, Sandy, additional, Bridgewater, John A., additional, Dive, Caroline, additional, and Valle, Juan W., additional

Published
2015
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36. The Combination of Circulating Ang1 and Tie2 Levels Predicts Progression-Free Survival Advantage in Bevacizumab-Treated Patients with Ovarian Cancer

Author

Backen, Alison, primary, Renehan, Andrew G., additional, Clamp, Andrew R., additional, Berzuini, Carlo, additional, Zhou, Cong, additional, Oza, Amit, additional, Bannoo, Selina, additional, Scherer, Stefan J., additional, Banks, Rosamonde E., additional, Dive, Caroline, additional, and Jayson, Gordon C., additional

Published
2014
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37. An integrated characterisation of serological, pathological and functional events in doxorubicin-induced cardiotoxicity

Author

Cove-Smith, Laura, primary, Woodhouse, Neil, additional, Hargreaves, Adam, additional, Price, Sally, additional, Marsden, Melanie, additional, Betts, Catherine, additional, Brocklehurst, Simon, additional, Backen, Alison, additional, Radford, John, additional, Roberts, Ruth, additional, Schmitt, Matthias, additional, Dive, Caroline, additional, Tugwood, Jonathan, additional, Hockings, Paul, additional, and Mellor, Howard, additional

Published
2014
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38. ABC-03: A randomized phase II trial of cediranib (AZD2171) or placebo in combination with cisplatin/gemcitabine (CisGem) chemotherapy for patients (pts) with advanced biliary tract cancer (ABC).

Author

Valle, Juan W., primary, Wasan, Harpreet, additional, Jitlal, Mark, additional, Backen, Alison Catherine, additional, Palmer, Daniel H., additional, Duggan, Marian, additional, Cunningham, David, additional, Anthoney, David Alan, additional, Corrie, Philippa, additional, Madhusudan, Srinivasan, additional, Maraveyas, Anthony, additional, Ross, Paul J., additional, Waters, Justin S., additional, Steward, William P., additional, Rees, Charlotte, additional, Beare, Sandy, additional, Dive, Caroline, additional, and Bridgewater, John A., additional

Published
2014
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39. Clinical Significance and Molecular Characteristics of Circulating Tumor Cells and Circulating Tumor Microemboli in Patients With Small-Cell Lung Cancer

Author

Hou, Jian-Mei, primary, Krebs, Matthew G., additional, Lancashire, Lee, additional, Sloane, Robert, additional, Backen, Alison, additional, Swain, Rajeeb K., additional, Priest, Lynsey J.C., additional, Greystoke, Alastair, additional, Zhou, Cong, additional, Morris, Karen, additional, Ward, Tim, additional, Blackhall, Fiona H., additional, and Dive, Caroline, additional

Published
2012
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41. Regulation of Fibroblast Growth Factor-2 Activity by Human Ovarian Cancer Tumor Endothelium

Author

Whitworth, Melissa K., primary, Backen, Alison C., additional, Clamp, Andrew R., additional, Wilson, Godfrey, additional, McVey, Rhona, additional, Friedl, Andreas, additional, Rapraeger, Alan C., additional, David, Guido, additional, McGown, Alan, additional, Slade, Richard J., additional, Gallagher, John T., additional, and Jayson, Gordon C., additional

Published
2005
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44. A phase 1 trial of intravenous 4-(N-(S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) in patients with advanced solid tumours.

Author

Horsley, Laura, Cummings, Jeff, Middleton, Mark, Ward, Tim, Backen, Alison, Clamp, Andrew, Dawson, Martin, Farmer, Hayley, Fisher, Nita, Halbert, Gavin, Halford, Sarah, Harris, Adrian, Hasan, Jurjees, Hogg, Philip, Kumaran, Gireesh, Little, Ross, Parker, Geoff J. M., Potter, Paula, Saunders, Mark, and Roberts, Caleb

Subjects
CLINICAL trials, CANCER cell proliferation, GLUTATHIONE, ADENINE nucleotide translocase, MITOCHONDRIAL membranes, TARGETED drug delivery, PHARMACOKINETICS, INTRAVENOUS therapy, PHARMACODYNAMICS, THERAPEUTICS
Abstract

Background: 4-( N-( S-glutathionylacetyl)amino) phenylarsenoxide (GSAO) is a water-soluble mitochondrial toxin that binds to adenine nucleotide translocase in the inner mitochondrial membrane, thereby targeting cell proliferation. This phase 1 study investigated safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and pharmacokinetics (PK) of GSAO as a daily 1-h infusion for 5 days a week for 2 weeks in every three. Pharmacodynamics of GSAO was evaluated by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and circulating markers of angiogenesis. Methods: Patients with advanced solid tumours received GSAO in a dose-escalation trial according to a standard ‘3 + 3’ design that was guided by toxicity and, for the final dose escalation, by arsenic PK data. Results: A total of 34 patients were treated with GSAO across 9 dose levels (1.3–44.0 mg/m 2). Treatment was well tolerated with few adverse events. An additional three patients were enrolled at the 12.4 mg/m 2 dose level following a DLT of derangement of liver function tests (grade 4). At the 44.0 mg/m 2 dose level, two out of three patients had DLTs (reversible encephalopathy; paroxysmal atrial fibrillation). Conclusions: The MTD of GSAO was 22.0 mg/m 2/day. There was no biomarker evidence from DCE-MRI or circulating markers of angiogenesis of an anti-vascular effect of GSAO. [ABSTRACT FROM AUTHOR]

Published
2013
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47. Real‐world experience of immune checkpoint inhibitors in patients with solid tumours in the Top End of the Northern Territory, Australia from 2016 to 2021: a retrospective observational cohort study.

Author

Miller, Abigail R., Balino, Aries, Tun Min, Sandy, Downton, Teesha, Karanth, Narayan V., Backen, Alison, and Charakidis, Michail

Subjects
*IMMUNE checkpoint inhibitors, *DRUG side effects, *COHORT analysis, *PATIENT preferences, *OVERALL survival
Abstract

Background Aims Methods Results Conclusions Use of immune checkpoint inhibitors is growing, but clinical trial data may not apply to Indigenous patients or patients living in remote areas.To provide real‐world incidence of immune‐related adverse events (irAE) in the Top End of the Northern Territory and compare incidence between demographic subgroups.This retrospective, observational, cohort study collected data from electronic records of patients living in the Top End with solid organ cancer treated with immunotherapy between January 2016 and December 2021. The primary outcome was cumulative incidence of any‐grade and severe irAE. Secondary outcomes were overall survival, treatment duration and reason for treatment discontinuation.Two hundred and twenty‐six patients received immunotherapy. Forty‐eight (21%) lived in a remote or very remote area, and 36 (16%) were Indigenous. Cumulative incidence of any‐grade irAE was 54% (122/226 patients); incidence of severe irAE was 26% (59/226 patients). Rates were similar between Indigenous and non‐Indigenous patients of any‐grade (42% vs 56%, P = 0.11) and severe (11% vs 18%, P = 0.29) irAE. However, Indigenous patients had shorter treatment duration, more frequently discontinued treatment due to patient preference and appeared to have shorter median overall survival than non‐Indigenous patients (17.1 vs 30.4 months; hazard ratio (HR) = 1.5, 95% confidence interval (CI) = 0.92–2.66). There was no difference in mortality between remote and urban patients (median overall survival 27.5 vs 30.2 months; HR = 1.1, 95% CI = 0.7–1.7).Rates of irAE in our cohort are comparable to those in the published literature. There was no significant difference in any‐grade or severe irAE incidence observed between Indigenous and non‐Indigenous patients. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Evaluation of the CaMAL2 promoter for regulated expression of genes in <TOGGLE>Candida albicans</TOGGLE>

Author

Backen, Alison C., Broadbent, Ian D., Fetherston, Richard W., Rosamond, John D. C., Schnell, Norbert F., and Stark, Michael J. R.

Abstract

An expression vector (CIp10–MAL2p) for use in Candida albicans has been constructed in which a gene of interest can be placed under the control of the CaMAL2 maltase promoter and stably integrated at the CaRP10 locus. Using this vector to express the Candida URA3 gene from the CaMAL2 promoter, we have demonstrated tight regulation of CaURA3 expression by carbon source. Thus under conditions when the CaMAL2 promoter is not induced, expression of Candida URA3 was unable either to complement a C. albicans ura3 mutation or to confer sensitivity to 5-fluoroorotic acid, a compound which is highly toxic to URA3 strains. Since Candida albicans is an obligate diploid organism, analysis of gene function requires manipulation of both copies of any gene of interest. Our expression vector provides a strategy by which the remaining copy of a gene of interest can be placed under CaMAL2 promoter control in a strain where the first copy has been deleted, permitting analysis of gene function by manipulation of carbon source. CIp10–MAL2p should therefore provide a useful means for functional analysis of genes in C. albicans. We have used this strategy with C. albicans DPB2 to demonstrate that the gene is essential and that loss of function leads cells to adopt a hypha-like morphology as they cease proliferation. Copyright © 2000 John Wiley & Sons, Ltd.

Published
2000

49. Evaluation of the CaMAL2promoter for regulated expression of genes in Candida albicans

Author

Backen, Alison C., Broadbent, Ian D., Fetherston, Richard W., Rosamond, John D. C., Schnell, Norbert F., and Stark, Michael J. R.

Abstract

An expression vector (CIp10–MAL2p) for use in Candida albicanshas been constructed in which a gene of interest can be placed under the control of the CaMAL2maltase promoter and stably integrated at the CaRP10locus. Using this vector to express the Candida URA3gene from the CaMAL2promoter, we have demonstrated tight regulation of CaURA3expression by carbon source. Thus under conditions when the CaMAL2promoter is not induced, expression of Candida URA3was unable either to complement a C. albicans ura3mutation or to confer sensitivity to 5‐fluoroorotic acid, a compound which is highly toxic to URA3strains. Since Candida albicansis an obligate diploid organism, analysis of gene function requires manipulation of both copies of any gene of interest. Our expression vector provides a strategy by which the remaining copy of a gene of interest can be placed under CaMAL2promoter control in a strain where the first copy has been deleted, permitting analysis of gene function by manipulation of carbon source. CIp10–MAL2p should therefore provide a useful means for functional analysis of genes in C. albicans. We have used this strategy with C. albicans DPB2to demonstrate that the gene is essential and that loss of function leads cells to adopt a hypha‐like morphology as they cease proliferation. Copyright © 2000 John Wiley & Sons, Ltd.

Published
2000
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50. Cediranib or placebo in combination with cisplatin and gemcitabine chemotherapy for patients with advanced biliary tract cancer (ABC-03): a randomised phase 2 trial

Author

Valle, Juan W., Wasan, Harpreet, Lopes, Andre, Backen, Alison C., Palmer, Daniel H., Morris, Karen, Duggan, Marian, Cunningham, David, Anthoney, D. Alan, Corrie, Pippa, Srinivasan, Narayanan, Maraveyas, Anthony, Ross, Paul J., Waters, Justin S., Steward, Will P., Rees, Charlotte, Beare, Sandy, Dive, Caroline, and Bridgewater, John A.

Subjects
Oncology, Articles
Abstract

Summary Background Cisplatin and gemcitabine is the standard first-line chemotherapy regimen for patients with advanced biliary tract cancer; expression of VEGF and its receptors is associated with adverse outcomes. We aimed to assess the effect of the addition of cediranib (an oral inhibitor of VEGF receptor 1, 2, and 3) to cisplatin and gemcitabine on progression-free survival. Methods In this multicentre, placebo-controlled, randomised phase 2 study, we recruited patients aged 18 years or older with histologically confirmed or cytologically confirmed advanced biliary tract cancer from hepatobiliary oncology referral centres in the UK. Patients were eligible if they had an ECOG performance status of 0–1 and an estimated life expectancy of longer than 3 months. Patients were given first-line cisplatin and gemcitabine chemotherapy (25 mg/m2 cisplatin and 1000 mg/m2 gemcitabine [on days 1 and 8 every 21 days, for up to eight cycles]) with either 20 mg oral cediranib or placebo once a day until disease progression. We randomly assigned patients (1:1) with a minimisation algorithm, incorporating the stratification factors: extent of disease, primary disease site, previous treatment, ECOG performance status, and centre. The primary endpoint was progression-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00939848, and was closed on Sept 30, 2014; results of the final analysis for the primary endpoint are presented. Findings Between April 5, 2011, and Sept 28, 2012, we enrolled 124 patients (62 in each group). With a median follow-up of 12·2 months (IQR 7·3–18·5), median progression-free survival was 8·0 months (95% CI 6·5–9·3) in the cediranib group and 7·4 months (5·7–8·5) in the placebo group (HR 0·93, 80% CI 0·74–1·19, 95% CI 0·65–1·35; p=0·72). Patients who received cediranib had more grade 3–4 toxic effects than did patients who received placebo: hypertension (23 [37%] vs 13 [21%]; p=0·05), diarrhoea (eight [13%] vs two [3%]; p=0·05); platelet count decreased (ten [16%] vs four [6%]; p=0·09), white blood cell decreased (15 [24%] vs seven [11%]; p=0·06) and fatigue (16 [24%] vs seven [11%]; p=0·04). Interpretation Cediranib did not improve the progression-free survival of patients with advanced biliary tract cancer in combination with cisplatin and gemcitabine, which remains the standard of care. Although patients in the cediranib group had more adverse events, we recorded no unexpected toxic effects. The role of VEGF inhibition in addition to chemotherapy for patients with advanced biliary tract cancer remains investigational. Funding Cancer Research UK and AstraZeneca Pharmaceuticals.

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