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3. Single-cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype

Author

Valdés-Mora, Fátima, Salomon, Robert, Gloss, Brian Stewart, Law, Andrew Man Kit, Venhuizen, Jeron, Castillo, Lesley, Murphy, Kendelle Joan, Magenau, Astrid, Papanicolaou, Michael, Rodriguez de la Fuente, Laura, Roden, Daniel Lee, Colino-Sanguino, Yolanda, Kikhtyak, Zoya, Farbehi, Nona, Conway, James Ronald William, Sikta, Neblina, Oakes, Samantha Richelle, Cox, Thomas Robert, O’Donoghue, Seán Ignatius, Timpson, Paul, Ormandy, Christopher John, and Gallego-Ortega, David

Published
2021
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5. Supplementary Fig. S5 from Emergence of Enzalutamide Resistance in Prostate Cancer is Associated with BCL-2 and IKKB Dependencies

Author

Liang, Yi, primary, Jeganathan, Sujeeve, primary, Marastoni, Stefano, primary, Sharp, Adam, primary, Figueiredo, Ines, primary, Marcellus, Richard, primary, Mawson, Amanda, primary, Shalev, Zvi, primary, Pesic, Aleksandra, primary, Sweet, Joan, primary, Guo, Haiyang, primary, Uehling, David, primary, Gurel, Bora, primary, Neeb, Antje, primary, He, Housheng Hansen, primary, Montgomery, Bruce, primary, Koritzinsky, Marianne, primary, Oakes, Samantha, primary, de Bono, Johann S., primary, Gleave, Martin, primary, Zoubeidi, Amina, primary, Wouters, Bradly G., primary, and Joshua, Anthony M., primary

Published
2023
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6. Supplementary Table 4 from Emergence of Enzalutamide Resistance in Prostate Cancer is Associated with BCL-2 and IKKB Dependencies

Author

Liang, Yi, primary, Jeganathan, Sujeeve, primary, Marastoni, Stefano, primary, Sharp, Adam, primary, Figueiredo, Ines, primary, Marcellus, Richard, primary, Mawson, Amanda, primary, Shalev, Zvi, primary, Pesic, Aleksandra, primary, Sweet, Joan, primary, Guo, Haiyang, primary, Uehling, David, primary, Gurel, Bora, primary, Neeb, Antje, primary, He, Housheng Hansen, primary, Montgomery, Bruce, primary, Koritzinsky, Marianne, primary, Oakes, Samantha, primary, de Bono, Johann S., primary, Gleave, Martin, primary, Zoubeidi, Amina, primary, Wouters, Bradly G., primary, and Joshua, Anthony M., primary

Published
2023
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7. Supplementary Table 1 from Emergence of Enzalutamide Resistance in Prostate Cancer is Associated with BCL-2 and IKKB Dependencies

Author

Liang, Yi, primary, Jeganathan, Sujeeve, primary, Marastoni, Stefano, primary, Sharp, Adam, primary, Figueiredo, Ines, primary, Marcellus, Richard, primary, Mawson, Amanda, primary, Shalev, Zvi, primary, Pesic, Aleksandra, primary, Sweet, Joan, primary, Guo, Haiyang, primary, Uehling, David, primary, Gurel, Bora, primary, Neeb, Antje, primary, He, Housheng Hansen, primary, Montgomery, Bruce, primary, Koritzinsky, Marianne, primary, Oakes, Samantha, primary, de Bono, Johann S., primary, Gleave, Martin, primary, Zoubeidi, Amina, primary, Wouters, Bradly G., primary, and Joshua, Anthony M., primary

Published
2023
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8. Supplementary Table 2 from Emergence of Enzalutamide Resistance in Prostate Cancer is Associated with BCL-2 and IKKB Dependencies

Author

Liang, Yi, primary, Jeganathan, Sujeeve, primary, Marastoni, Stefano, primary, Sharp, Adam, primary, Figueiredo, Ines, primary, Marcellus, Richard, primary, Mawson, Amanda, primary, Shalev, Zvi, primary, Pesic, Aleksandra, primary, Sweet, Joan, primary, Guo, Haiyang, primary, Uehling, David, primary, Gurel, Bora, primary, Neeb, Antje, primary, He, Housheng Hansen, primary, Montgomery, Bruce, primary, Koritzinsky, Marianne, primary, Oakes, Samantha, primary, de Bono, Johann S., primary, Gleave, Martin, primary, Zoubeidi, Amina, primary, Wouters, Bradly G., primary, and Joshua, Anthony M., primary

Published
2023
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9. Supplementary Table 3 from Emergence of Enzalutamide Resistance in Prostate Cancer is Associated with BCL-2 and IKKB Dependencies

Author

Liang, Yi, primary, Jeganathan, Sujeeve, primary, Marastoni, Stefano, primary, Sharp, Adam, primary, Figueiredo, Ines, primary, Marcellus, Richard, primary, Mawson, Amanda, primary, Shalev, Zvi, primary, Pesic, Aleksandra, primary, Sweet, Joan, primary, Guo, Haiyang, primary, Uehling, David, primary, Gurel, Bora, primary, Neeb, Antje, primary, He, Housheng Hansen, primary, Montgomery, Bruce, primary, Koritzinsky, Marianne, primary, Oakes, Samantha, primary, de Bono, Johann S., primary, Gleave, Martin, primary, Zoubeidi, Amina, primary, Wouters, Bradly G., primary, and Joshua, Anthony M., primary

Published
2023
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11. Molecular therapy selection in treatment-refractory advanced cancers: A retrospective cohort study determining the utility of TOPOGRAPH knowledge base.

Author

Lin, Frank Po-Yen, primary, Thavaneswaran, Subotheni, additional, Grady, John P., additional, Napier, Christine E, additional, Kansara, Maya, additional, Sebastian, Lucille, additional, Kee, Damien, additional, Oakes, Samantha R., additional, Blackburn, James, additional, Scott, Hamish S., additional, Glover, Anthony, additional, Fox, Stephen B., additional, Goldstein, David, additional, Leo, Paul, additional, Amanuel, Benhur, additional, Desai, Jayesh, additional, Lee, Chee Khoon, additional, Ballinger, Mandy L., additional, Simes, John, additional, and Thomas, David Morgan, additional

Published
2022
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12. TNFAIP3 Reduction-of-Function Drives Female Infertility and CNS Inflammation

Author

Zammit, Nathan W., primary, McDowell, Joseph, additional, Warren, Joanna, additional, Muskovic, Walter, additional, Gamble, Joanne, additional, Shi, Yan-Chuan, additional, Kaczorowski, Dominik, additional, Chan, Chia-Ling, additional, Powell, Joseph, additional, Ormandy, Chris, additional, Brown, David, additional, Oakes, Samantha R., additional, and Grey, Shane T., additional

Published
2022
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13. Additional file 7 of Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O’Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., and Ormandy, Christopher J.

Abstract

Additional file 7: Fig. S5. Effect of PD-L1 and MT Oas2 on primary tumor initiation and expansion in parous mice. Examples of tumor growth curves of individual mice. The 2nd/3rd and 4th mammary glands were palpated twice weekly and tumor growth was estimated by measurement of the major and minor axis of individual tumors using calipers. Y axis is placed at the day of tumor detection on the x axis as day 0. Black diamonds show a treatment with IP IgG or PD-L1 antibodies and red diamonds indicate parity. WT = wild type, MT = MT Oas2 MT/MT = homozygous MT Oas2.

Published
2022
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14. Additional file 8 of Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O’Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., and Ormandy, Christopher J.

Abstract

Additional file 8: Fig. S6. Effect of PD-L1 and MT Oas2 on primary tumor initiation and expansion in parous mice. Two-way Kaplan–Meier survival analysis for the indicated periods and endpoints, and for the indicated genotypes and treatments (PD-L1 or IgG IP), of mouse cohorts. P values and hazard ratios (HR) calculated by the log-rank test using GraphPad Prism. n = 8 WT PD-L1, 8 WT IgG, 14 MT PD-L1, 15 MT IgG.

Published
2022
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15. Additional file 6 of Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O’Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., and Ormandy, Christopher J.

Abstract

Additional file 6: Fig. S4. Flow cytometry gating strategy for monocytes and neutrophils known as myeloid-derived suppressor cells. Series of gates used to quantify monocytes and neutrophils using flow cytometry.

Published
2022
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16. Additional file 5 of Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O’Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., and Ormandy, Christopher J.

Abstract

Additional file 5: Fig. S3. Effects of MT Oas2 on T cells in parous mice. A screening of various T-cell parameters was undertaken in mammary tumors, lymph nodes, spleen and thymus. Error bars are standard error of the mean and p values calculated by Student’s t test (all non-significant). Axes represent % of total cells passing the previous gate. Genotypes, WT/WT homozygous wildtype Oas2, MT/MT homozygous mutant Oas2.

Published
2022
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17. Additional file 1 of Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O’Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., and Ormandy, Christopher J.

Abstract

Additional file 1: Table S1. Antibodies, concentration and antigen retrieval conditions for immunohistochemistry. All reagents were from Leica BOND or DAKO for automated or manual IHC (as specified). Visualization of antigen–antibody complexes was performed using the DAB + liquid substrate chromogen system (K3467).

Published
2022
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18. Additional file 3 of Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O’Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., and Ormandy, Christopher J.

Abstract

Additional file 3: Fig. S1. Effect of MT Oas2 on primary tumor expansion in parous mice. Examples of tumor growth curves of individual mice. The left- and right-hand side 2nd/3rd and 4th mammary glands were palpated twice weekly and tumor growth was estimated by measurement of the major and minor axis of each gland using calipers. Y axis is placed at parity indicated on the x axis as day 0. Numbers show the total number of glands with tumors detected, the number that showed a period of no growth, and the number that showed regression at or following parity. W, wild type; M, MT; W/W, homozygous wild type; M/M, homozygous MT.

Published
2022
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19. Additional file 4 of Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O’Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., and Ormandy, Christopher J.

Subjects
reproductive and urinary physiology
Abstract

Additional file 4: Fig. S2. Effect of MT Oas2 on primary tumor initiation and expansion in nulliparous and parous mice. Two-way Kaplan–Meier survival analysis for the indicated periods and endpoints, and for the indicated genotypes, WT wildtype Oas2, MT mutant Oas2, and parity status of mouse cohorts (20 per group). P values and hazard ratios (HR) calculated by the log-rank test using GraphPad Prism. n = 19 MT parous, 21 WT parous, 20 MT nulliparous and 19 WT nulliparous.)

Published
2022
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20. Additional file 2 of Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O’Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., and Ormandy, Christopher J.

Abstract

Additional file 2: Table S2. Antibodies used for flow cytometry. Panel name, antibody name by antigen recognized and conjugated fluorochrome, the antibody supplier and catalogue number and final diluted concentration for each is shown.

Published
2022
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22. Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases

Author

Ho, Wing-Hong Jonathan, primary, Law, Andrew M. K., additional, Masle-Farquhar, Etienne, additional, Castillo, Lesley E., additional, Mawson, Amanda, additional, O’Bryan, Moira K., additional, Goodnow, Christopher C., additional, Ortega, David Gallego, additional, Oakes, Samantha R., additional, and Ormandy, Christopher, additional

Published
2021
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23. Strategies for targeting the tumour microenvironment using high fidelity 3D culture systems

Author

Gallego-Ortega, David, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Valdes-Mora, Fatima, Children's Cancer Institute Australia for Medical Research, Faculty of Medicine, UNSW, Oakes, Samantha, National Breast Cancer Foundation, Ormandy, Chris, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Law, Andrew, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW, Gallego-Ortega, David, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Valdes-Mora, Fatima, Children's Cancer Institute Australia for Medical Research, Faculty of Medicine, UNSW, Oakes, Samantha, National Breast Cancer Foundation, Ormandy, Chris, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, and Law, Andrew, Clinical School - St Vincent's Hospital, Faculty of Medicine, UNSW

Abstract

The heterogenous tumour microenvironment (TME) has been well established in the progression of cancer and patient outcome. In particular, the success of anticancer therapy is influenced by various constituents and intercommunicating networks within the TME. Drug development research often focuses on targeting cancer cells alone without considering all the cellular and non-cellular components of the TME, which plays a crucial role in chemoresistance and disease relapse. Thus, there is a necessity to understand the individual features of the TME in order to deliver a more personalised therapy that improves the rate of successful outcomes while reducing the recurrence of the disease. However, the mechanisms of acquired drug resistance and pharmacokinetics within the tumour still remains elusive. Currently, there is a lack of high-throughput methods suitable to study the functional effects of anticancer drugs on tumour samples where the interplay between cancer cells and the TME remains intact.This thesis embodies the work in the development of the ALTEN (Alginate-based Tissue Engineering) platform, a biomimetic hydrogel system for rapid functional testing of anticancer drugs in explanted tumours. The alginate hydrogels provides a 3D scaffold that resembles the native extracellular matrix (ECM) that preserve the original characteristics of the tumour to permit detailed assessment of the TME and the complex molecular interactions between cell species. Here, we use high-resolution single-cell RNA-seq technologies to analyse the molecular effects of anticancer treatments within the tumour to study the mechanisms of acquired drug resistance.The combination of ALTEN and scRNA-seq technology enable high-throughput and high-resolution screening of tumour explants exposed to cytotoxic agents and immunomodulators. The impact of drug therapies within an intact TME could be evaluated to 1) determine treatment efficacy and 2) characterise drug resistant cancer populations.In summar

Published
2021

27. A Signal-seeking Phase Iia Trial of Palbociclib in Advanced Cancers With Cell Cycle Pathway Alterations – A Substudy of the Molecular Screening and Therapeutics (Most) Program

Author

Thavaneswaran, Subotheni, primary, Sebastian, Lucille, additional, Kansara, Maya, additional, Ballinger, Mandy, additional, Espinoza, David, additional, Lin, Frank, additional, Lee, Chee, additional, Sjoquist, Katrin, additional, Grady, John, additional, Cowley, Mark, additional, Joshua, Anthony, additional, Qiu, Min, additional, Oakes, Samantha, additional, Simes, John, additional, and Thomas, David, additional

Published
2021
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28. Emergence of Enzalutamide Resistance in Prostate Cancer is Associated with BCL-2 and IKKB Dependencies

Author

Liang, Yi, primary, Jeganathan, Sujeeve, additional, Marastoni, Stefano, additional, Sharp, Adam, additional, Figueiredo, Ines, additional, Marcellus, Richard, additional, Mawson, Amanda, additional, Shalev, Zvi, additional, Pesic, Aleksandra, additional, Sweet, Joan, additional, Guo, Haiyang, additional, Uehling, David, additional, Gurel, Bora, additional, Neeb, Antje, additional, He, Housheng Hansen, additional, Montgomery, Bruce, additional, Koritzinsky, Marianne, additional, Oakes, Samantha, additional, de Bono, Johann S., additional, Gleave, Martin, additional, Zoubeidi, Amina, additional, Wouters, Bradly G., additional, and Joshua, Anthony M., additional

Published
2021
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31. Y4 receptor knockout rescues fertility in ob/ob mice

Author

Sainsbury, Amanda, Schwarzer, Christoph, Couzens, Michelle, Jenkins, Arthur, Oakes, Samantha R., Ormandy, Christopher J., and Herzog, Herbert

Subjects
Genetic research -- Analysis, Fertility -- Genetic aspects, Neuropeptides -- Genetic aspects, Gonadotropin -- Physiological aspects, Hormones -- Genetic aspects, Proteins -- Receptors, Reproduction -- Genetic aspects, Hypothalamus -- Physiological aspects, Biological sciences
Abstract

Research has been conducted on the hypothalamic neuropeptide Y, responsible for the energy balance regulation and reproduction. The hypothesis that under the high hypothalamic neuropeptide Y level conditions this neuropeptide could modulate reproductive functions via Y4 receptor activation has been tested and the results are discussed.

Published
2002

33. ELF5 modulates the estrogen receptor cistrome in breast cancer

Author

Piggin, Catherine L., primary, Roden, Daniel L., additional, Law, Andrew M. K., additional, Molloy, Mark P., additional, Krisp, Christoph, additional, Swarbrick, Alexander, additional, Naylor, Matthew J., additional, Kalyuga, Maria, additional, Kaplan, Warren, additional, Oakes, Samantha R., additional, Gallego-Ortega, David, additional, Clark, Susan J., additional, Carroll, Jason S., additional, Bartonicek, Nenad, additional, and Ormandy, Christopher J., additional

Published
2020
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34. Single Cell Transcriptomics Reveals Involution Mimicry During the Specification of the Basal Breast Cancer Subtype

Author

Valdes-Mora, Fatima, primary, Salomon, Robert, additional, Gloss, Brian, additional, Law, Andrew MK, additional, Castillo, Lesley, additional, Murphy, Kendelle, additional, Venhuizen, Jeron, additional, Magenau, Astrid, additional, Papanicolau, Michael, additional, Rodriguez de la Fuente, Laura, additional, Roden, Daniel L., additional, Colino-Sanguino, Yolanda, additional, Kikhtyak, Zoya, additional, Farbehi, Nona, additional, Conway, James RW, additional, Oakes, Samantha R., additional, Sikta, Neblina, additional, O'Donoghue, Seán I., additional, Cox, Thomas R., additional, Timpson, Paul, additional, Ormandy, Christopher J., additional, and Gallego Ortega, David, additional

Published
2020
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35. High Notch1 protein expression is an early event in breast cancer development and is associated with the HER-2 molecular subtype

Author

Zardawi, Sarah J, Zardawi, Ibrahim, McNeil, Catriona M, Millar, Ewan K A, McLeod, Duncan, Morey, Adrienne L, Crea, Paul, Murphy, Niamh C, Pinese, Mark, Lopez-Knowles, Elena, Oakes, Samantha R, Ormandy, Christopher J, Qiu, Min Ru, Hamilton, Anne, Spillane, Andrew, Lee, Cheok Soon, Sutherland, Robert L, Musgrove, Elizabeth A, and OʼToole, Sandra A

Published
2010
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36. Socs2 and Elf5 Mediate Prolactin-Induced Mammary Gland Development

Author

Harris, Jessica, Stanford, Prudence M., Sutherland, Kate, Oakes, Samantha R., Naylor, Matthew J., Robertson, Fiona G., Blazek, Katrina D., Kazlauskas, Michael, Hilton, Heidi N., Wittlin, Sergio, Alexander, Warren S., Lindeman, Geoffrey J., Visvader, Jane E., and Ormandy, Christopher J.

Published
2006

41. Single cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype

Author

Valdes-Mora, Fatima, primary, Salomon, Robert, additional, Gloss, Brian, additional, Law, Andrew MK., additional, Castillo, Lesley, additional, Murphy, Kendelle J., additional, Venhuizen, Jeron, additional, Magenau, Astrid, additional, Papanicolau, Michael, additional, de la Fuente, Laura Rodriguez, additional, Roden, Daniel L., additional, Colino-Sanguino, Yolanda, additional, Kikhtyak, Zoya, additional, Farbehi, Nona, additional, Conway, James RW., additional, Oakes, Samantha R., additional, Sikta, Neblina, additional, O’Donoghue, Seán I., additional, Cox, Thomas R, additional, Timpson, Paul, additional, Ormandy, Christopher J., additional, and Gallego-Ortega, David, additional

Published
2019
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44. Inhibition of activin signaling in lung adenocarcinoma increases the therapeutic index of platinum chemotherapy

Author

Marini, Kieren D., primary, Croucher, David R., additional, McCloy, Rachael A., additional, Vaghjiani, Vijesh, additional, Gonzalez-Rajal, Alvaro, additional, Hastings, Jordan F., additional, Chin, Venessa, additional, Szczepny, Anette, additional, Kostyrko, Kaja, additional, Marquez, Cesar, additional, Jayasekara, W. Samantha N., additional, Alamgeer, Muhammad, additional, Boolell, Vishal, additional, Han, Jeremy Z. R., additional, Waugh, Todd, additional, Lee, Hong Ching, additional, Oakes, Samantha R., additional, Kumar, Beena, additional, Harrison, Craig A., additional, Hedger, Mark P., additional, Lorensuhewa, Nirmal, additional, Kita, Badia, additional, Barrow, Ross, additional, Robinson, Bruce W., additional, de Kretser, David M., additional, Wu, Jianmin, additional, Ganju, Vinod, additional, Sweet-Cordero, E. Alejandro, additional, Burgess, Andrew, additional, Martelotto, Luciano G., additional, Rossello, Fernando J., additional, Cain, Jason E., additional, and Watkins, D. Neil, additional

Published
2018
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45. The role of MCL-1 in triple negative breast cancer

Author

Ormandy, Christopher, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Oakes, Samantha, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Gallego-Ortega, David, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Young, Adelaide, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Ormandy, Christopher, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Oakes, Samantha, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, Gallego-Ortega, David, Garvan Institute of Medical Research, Faculty of Medicine, UNSW, and Young, Adelaide, Garvan Institute of Medical Research, Faculty of Medicine, UNSW

Abstract

Triple negative breast cancer (TNBC) has a relatively poor prognosis and has a higher chance of relapse in comparison with the other subtypes of breast cancer. Thus the need for novel targeted treatment strategies. Myeloid cell leukaemia-1 (MCL-1) is an essential mediator of cell survival and contributes to chemo-resistance in a range of malignancies, indicating that inhibition of MCL-1 may be beneficial, a topic explored in this thesis. A genetic antagonist approach was utilised, with the generation of stable inducible models of BIMs2A (a MCL-1 specific inhibitor) in MDA-MB-231 and MDA-MB-468 cell lines. MCL-1 acted as a survival factor in vitro in MDA-MB-468 cells and in vivo in both TNBC cell lines in a refined mammary intraductal xenograft model. MCL-1 antagonism in MDA-MB-468 cells resulted in sensitisation to a range of chemotherapeutic agents in vitro. MCL-1 inhibition of TNBC xenografts in vivo revealed a significant reduction of metastasis to the lung and loss of MDA-MB-231 invasion was also observed in elegant 3D organotypic assays, suggesting a novel role of MCL-1 in TNBC cell line migration. Mechanistic insight behind the suppression of metastasis was provided through proteomic approaches. Kinomic profiling revealed multiple pathways were perturbed as a result of MCL-1 inhibition, including SRC family kinase (SFK) mediated pathways involved in cell motility. Loss of activity of the cytoskeletal modulating protein Cofilin-1 was validated using biochemical approaches. Tandem mass spectrometry of immune-precipitates of endogenous MCL-1 complexes from MDA-MB-468 cells indicated a direct association with Cofilin-1, validated through proximity ligation assays in MDA-MB-231 cells. A combinatorial approach of MCL-1 antagonism with SFK inhibitor dasatinib resulted in an enhanced suppression of MDA-MB-231 invasion in 3D organotypic assays in vitro, while the combination significantly inhibited MDA-MB-231 tumour progression in vivo. This thesis provides evidence th

Published
2017

47. The Ets transcription factor E1f5 specifies mammary alveolar cell fate

Author

Oakes, Samantha R., Naylor, Matthew J., Asselin-Labat, Marie-Liesse, Blazek, Katrina D., Gardiner-Garden, Margaret, Hilton, Heidi N., Kazlauskas, Michael, Pritchard, Melanie A., Chodosh, Lewis A., Pfeffer, Peter L., Lindeman, Geoffrey J., Visvader, Jane E., and Ormandy, Christopher J.

Subjects
Cell differentiation -- Research, Epithelium -- Research, Genetic transcription -- Research, Biological sciences
Abstract

A study about knockout of the prolactin-regulated Ets transcription factor E1F5 that prevents formation of the secretary epithelium during pregnancy in mice is reported. Result shows that E1f5 is essential for normal alveolar development and lactation due to regulation of the CD61* progenitor cell population and also provides link between prolactin, transcriptional events, and alveolar development.

Published
2008

49. Andy’s Algorithms: new automated digital image analysis pipelines for FIJI

Author

Law, Andrew M. K., primary, Yin, Julia X. M., additional, Castillo, Lesley, additional, Young, Adelaide I. J., additional, Piggin, Catherine, additional, Rogers, Samuel, additional, Caldon, Catherine Elizabeth, additional, Burgess, Andrew, additional, Millar, Ewan K. A., additional, O’Toole, Sandra A., additional, Gallego-Ortega, David, additional, Ormandy, Christopher J., additional, and Oakes, Samantha R., additional

Published
2017
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50. A mutation in the viral sensor 2’-5’-oligoadenylate synthetase 2 causes failure of lactation

Author

Oakes, Samantha R., primary, Gallego-Ortega, David, additional, Stanford, Prudence M., additional, Junankar, Simon, additional, Au, Wendy Wing Yee, additional, Kikhtyak, Zoya, additional, von Korff, Anita, additional, Sergio, Claudio M., additional, Law, Andrew M. K., additional, Castillo, Lesley E., additional, Allerdice, Stephanie L., additional, Young, Adelaide I. J., additional, Piggin, Catherine, additional, Whittle, Belinda, additional, Bertram, Edward, additional, Naylor, Matthew J., additional, Roden, Daniel L., additional, Donovan, Jesse, additional, Korennykh, Alexei, additional, Goodnow, Christopher C., additional, O’Bryan, Moira K., additional, and Ormandy, Christopher J., additional

Published
2017
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