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43 results on '"Ricciardelli, Carmela"'

3. Pre-clinical validation of a pan-cancer CAR-T cell immunotherapy targeting nfP2X7

Author

Bandara, Veronika, Foeng, Jade, Gundsambuu, Batjargal, Norton, Todd S., Napoli, Silvana, McPeake, Dylan J., Tyllis, Timona S., Rohani-Rad, Elaheh, Abbott, Caitlin, Mills, Stuart J., Tan, Lih Y., Thompson, Emma J., Willet, Vasiliki M., Nikitaras, Victoria J., Zheng, Jieren, Comerford, Iain, Johnson, Adam, Coombs, Justin, Oehler, Martin K., Ricciardelli, Carmela, Cowin, Allison J., Bonder, Claudine S., Jensen, Michael, Sadlon, Timothy J., McColl, Shaun R., and Barry, Simon C.

Published
2023
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6. Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation.

Author

Khetan, Riya, Eldi, Preethi, Lokman, Noor A., Ricciardelli, Carmela, Oehler, Martin K., Blencowe, Anton, Garg, Sanjay, Pillman, Katherine, and Albrecht, Hugo

Subjects
RNA sequencing, OVARIAN cancer, G protein coupled receptors, NANOMEDICINE, GENE expression
Abstract

Genetic heterogeneity in ovarian cancer indicates the need for personalised treatment approaches. Currently, very few G-protein coupled receptors (GPCRs) have been investigated for active targeting with nanomedicines such as antibody-conjugated drugs and drug-loaded nanoparticles, highlighting a neglected potential to develop personalised treatment. To address the genetic heterogeneity of ovarian cancer, a future personalised approach could include the identification of unique GPCRs expressed in cancer biopsies, matched with personalised GPCR-targeted nanomedicines, for the delivery of lethal drugs to tumour tissue before, during and after surgery. Here we report on the systematic analysis of public ribonucleic acid-sequencing (RNA-seq) gene expression data, which led to prioritisation of 13 GPCRs as candidates with frequent overexpression in ovarian cancer tissues. Subsequently, primary ovarian cancer cells derived from ascites and ovarian cancer cell lines were used to confirm frequent gene expression for the selected GPCRs. However, the expression levels showed high variability within our selection of samples, therefore, supporting and emphasising the need for the future development of case-to-case personalised targeting approaches. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Engineered CAR‐T cells targeting the non‐functional P2X purinoceptor 7 (P2X7) receptor as a novel treatment for ovarian cancer

Author

Bandara, Veronika, primary, Niktaras, Victoria M, additional, Willett, Vasiliki J, additional, Chapman, Hayley, additional, Lokman, Noor A, additional, Macpherson, Anne M, additional, Napoli, Silvana, additional, Gundsambuu, Batjargal, additional, Foeng, Jade, additional, Sadlon, Timothy J, additional, Coombs, Justin, additional, McColl, Shaun R, additional, Barry, Simon C, additional, Oehler, Martin K, additional, and Ricciardelli, Carmela, additional

Published
2024
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9. Abstract 5545: Assessing LGR5 expression levels on colorectal cancer tissue samples for use in LGR5-targeting CAR-T cell therapy clinical trial

Author

Thompson, Emma J., primary, Bandara, Veronika, additional, Gundsambuu, Batjargal, additional, Napoli, Silvana, additional, Mills, Stuart, additional, Foeng, Jade, additional, McPeake, Dylan, additional, Tyllis, Timona, additional, Abbott, Caitlin, additional, Cowin, Allison, additional, Sadlon, Timothy, additional, McColl, Shaun, additional, Ricciardelli, Carmela, additional, Barry, Simon C., additional, and Bonder, Claudine S., additional

Published
2023
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10. Data from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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11. Data from The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome

Author

Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Jindal, Shalini, primary, Butler, Lisa M., primary, Leung, Samuel, primary, McNeil, Catriona M., primary, O'Toole, Sandra A., primary, Ebrahimie, Esmaeil, primary, Millar, Ewan K.A., primary, Sakko, Andrew J., primary, Ruiz, Alexandra I., primary, Vowler, Sarah L., primary, Huntsman, David G., primary, Birrell, Stephen N., primary, Sutherland, Robert L., primary, Palmieri, Carlo, primary, Hickey, Theresa E., primary, and Tilley, Wayne D., primary

Published
2023
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12. Supplementary Figure 1 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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13. Supplementary Figure 3 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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14. Supplementary Figure 2 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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15. Supplementary Figure 5 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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16. Supplementary Table 2 from Comparative Biomarker Expression and RNA Integrity in Biospecimens Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies

Author

Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Jindal, Shalini, primary, Dodd, Thomas J., primary, Cohen, Penelope A., primary, Marshall, Villis R., primary, Sutherland, Peter D., primary, Samaratunga, Hemamali, primary, Kench, James G., primary, Dong, Ying, primary, Wang, Hong, primary, Clements, Judith A., primary, Risbridger, Gail P., primary, Sutherland, Robert L., primary, Tilley, Wayne D., primary, and Horsfall, David J., primary

Published
2023
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17. Supplementary Table 2 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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18. Supplementary Figures from The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome

Author

Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Jindal, Shalini, primary, Butler, Lisa M., primary, Leung, Samuel, primary, McNeil, Catriona M., primary, O'Toole, Sandra A., primary, Ebrahimie, Esmaeil, primary, Millar, Ewan K.A., primary, Sakko, Andrew J., primary, Ruiz, Alexandra I., primary, Vowler, Sarah L., primary, Huntsman, David G., primary, Birrell, Stephen N., primary, Sutherland, Robert L., primary, Palmieri, Carlo, primary, Hickey, Theresa E., primary, and Tilley, Wayne D., primary

Published
2023
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19. Supplementary Figure 4 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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20. Supplementary Figure Legends from The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome

Author

Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Jindal, Shalini, primary, Butler, Lisa M., primary, Leung, Samuel, primary, McNeil, Catriona M., primary, O'Toole, Sandra A., primary, Ebrahimie, Esmaeil, primary, Millar, Ewan K.A., primary, Sakko, Andrew J., primary, Ruiz, Alexandra I., primary, Vowler, Sarah L., primary, Huntsman, David G., primary, Birrell, Stephen N., primary, Sutherland, Robert L., primary, Palmieri, Carlo, primary, Hickey, Theresa E., primary, and Tilley, Wayne D., primary

Published
2023
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21. Supplementary Figure Legend from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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22. Supplementary methods from The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome

Author

Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Jindal, Shalini, primary, Butler, Lisa M., primary, Leung, Samuel, primary, McNeil, Catriona M., primary, O'Toole, Sandra A., primary, Ebrahimie, Esmaeil, primary, Millar, Ewan K.A., primary, Sakko, Andrew J., primary, Ruiz, Alexandra I., primary, Vowler, Sarah L., primary, Huntsman, David G., primary, Birrell, Stephen N., primary, Sutherland, Robert L., primary, Palmieri, Carlo, primary, Hickey, Theresa E., primary, and Tilley, Wayne D., primary

Published
2023
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23. Supplementary Tables from The Magnitude of Androgen Receptor Positivity in Breast Cancer Is Critical for Reliable Prediction of Disease Outcome

Author

Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Jindal, Shalini, primary, Butler, Lisa M., primary, Leung, Samuel, primary, McNeil, Catriona M., primary, O'Toole, Sandra A., primary, Ebrahimie, Esmaeil, primary, Millar, Ewan K.A., primary, Sakko, Andrew J., primary, Ruiz, Alexandra I., primary, Vowler, Sarah L., primary, Huntsman, David G., primary, Birrell, Stephen N., primary, Sutherland, Robert L., primary, Palmieri, Carlo, primary, Hickey, Theresa E., primary, and Tilley, Wayne D., primary

Published
2023
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24. Supplementary Table 1 from Comparative Biomarker Expression and RNA Integrity in Biospecimens Derived from Radical Retropubic and Robot-Assisted Laparoscopic Prostatectomies

Author

Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Jindal, Shalini, primary, Dodd, Thomas J., primary, Cohen, Penelope A., primary, Marshall, Villis R., primary, Sutherland, Peter D., primary, Samaratunga, Hemamali, primary, Kench, James G., primary, Dong, Ying, primary, Wang, Hong, primary, Clements, Judith A., primary, Risbridger, Gail P., primary, Sutherland, Robert L., primary, Tilley, Wayne D., primary, and Horsfall, David J., primary

Published
2023
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25. Supplementary Table 1 from Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development

Author

Bianco-Miotto, Tina, primary, Chiam, Karen, primary, Buchanan, Grant, primary, Jindal, Shalini, primary, Day, Tanya K., primary, Thomas, Mervyn, primary, Pickering, Marie A., primary, O'Loughlin, Melissa A., primary, Ryan, Natalie K., primary, Raymond, Wendy A., primary, Horvath, Lisa G., primary, Kench, James G., primary, Stricker, Phillip D., primary, Marshall, Villis R., primary, Sutherland, Robert L., primary, Henshall, Susan M., primary, Gerald, William L., primary, Scher, Howard I., primary, Risbridger, Gail P., primary, Clements, Judith A., primary, Butler, Lisa M., primary, Tilley, Wayne D., primary, Horsfall, David J., primary, and Ricciardelli, Carmela, primary

Published
2023
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26. Data from Androgen Receptor Inhibits Estrogen Receptor-α Activity and Is Prognostic in Breast Cancer

Author

Peters, Amelia A., primary, Buchanan, Grant, primary, Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Centenera, Margaret M., primary, Harris, Jonathan M., primary, Jindal, Shalini, primary, Segara, Davendra, primary, Jia, Li, primary, Moore, Nicole L., primary, Henshall, Susan M., primary, Birrell, Stephen N., primary, Coetzee, Gerhard A., primary, Sutherland, Robert L., primary, Butler, Lisa M., primary, and Tilley, Wayne D., primary

Published
2023
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27. Data from Control of Androgen Receptor Signaling in Prostate Cancer by the Cochaperone Small Glutamine–Rich Tetratricopeptide Repeat Containing Protein α

Author

Buchanan, Grant, primary, Ricciardelli, Carmela, primary, Harris, Jonathan M., primary, Prescott, Jennifer, primary, Yu, Zoe Chiao-Li, primary, Jia, Li, primary, Butler, Lisa M., primary, Marshall, Villis R., primary, Scher, Howard I., primary, Gerald, William L., primary, Coetzee, Gerhard A., primary, and Tilley, Wayne D., primary

Published
2023
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28. Supplementary Tables 1-3 from Androgen Receptor Inhibits Estrogen Receptor-α Activity and Is Prognostic in Breast Cancer

Author

Peters, Amelia A., primary, Buchanan, Grant, primary, Ricciardelli, Carmela, primary, Bianco-Miotto, Tina, primary, Centenera, Margaret M., primary, Harris, Jonathan M., primary, Jindal, Shalini, primary, Segara, Davendra, primary, Jia, Li, primary, Moore, Nicole L., primary, Henshall, Susan M., primary, Birrell, Stephen N., primary, Coetzee, Gerhard A., primary, Sutherland, Robert L., primary, Butler, Lisa M., primary, and Tilley, Wayne D., primary

Published
2023
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29. Supplementary Data 1-4 from Control of Androgen Receptor Signaling in Prostate Cancer by the Cochaperone Small Glutamine–Rich Tetratricopeptide Repeat Containing Protein α

Author

Buchanan, Grant, primary, Ricciardelli, Carmela, primary, Harris, Jonathan M., primary, Prescott, Jennifer, primary, Yu, Zoe Chiao-Li, primary, Jia, Li, primary, Butler, Lisa M., primary, Marshall, Villis R., primary, Scher, Howard I., primary, Gerald, William L., primary, Coetzee, Gerhard A., primary, and Tilley, Wayne D., primary

Published
2023
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32. Reducing the Invasiveness of Low- and High-Grade Endometrial Cancers in Both Primary Human Cancer Biopsies and Cell Lines by the Inhibition of Aquaporin-1 Channels.

Author

Khan, Sidra, Lokman, Noor A., Oehler, Martin K., Ricciardelli, Carmela, and Yool, Andrea J.

Subjects
IN vitro studies, DISEASE progression, BIOPSY, CANCER invasiveness, ION channels, IMMUNOHISTOCHEMISTRY, TREATMENT effectiveness, COMPARATIVE studies, GENE expression, ENDOMETRIAL tumors, DESCRIPTIVE statistics, RESEARCH funding, CELL lines, MEMBRANE proteins, POLYMERASE chain reaction, MOLECULAR structure, TUMOR grading
Abstract

Simple Summary: A major clinical concern for patients with endometrial cancer is the aggressive spread of cancer cells into other tissue regions, worsening symptoms, eluding medical therapy, disrupting organ functions, and increasing risk of relapse. As reported here, drug-like agents that we have found block the ion channel function of a specific membrane protein known as Aquaporin-1 (AQP1) can be used to inhibit invasiveness of endometrial cancer cells. In vitro invasion assays were done with cell lines originally established from endometrial cancers, in parallel with assays on primary endometrial cancer cells isolated from endometrial cancer tissue at the time of surgery. The exciting discovery was that the AQP1 ion channel blockers inhibited invasiveness of both low- and high-grade endometrial cancer types in established cell lines and primary cancer cells at doses that did not cause toxic side effects. Low toxicity is encouraging for potential co-administration with other first-line treatments. Pharmacological agents optimized from lead compounds could be invaluable for slowing the progression of both low- and high grade cancers, including a challenging subset which are unresponsive to current hormone-based therapies. Further work on refining structures of the drugs, their distribution and clearance will be needed for progress towards bench-to-bedside clinical translation. Aquaporin (AQP) channels in endometrial cancer (EC) cells are of interest as pharmacological targets to reduce tumor progression. A panel of compounds, including AQP1 ion channel inhibitors (AqB011 and 5-(phenoxymethyl) furan-2-carbaldehyde, PMFC), were used to test the hypothesis that inhibition of key AQPs can limit the invasiveness of low- and high-grade EC cells. We evaluated the effects on transwell migration in EC cell lines (Ishikawa, MFE-280) and primary EC cells established from surgical tissues (n = 8). Quantitative PCR uncovered classes of AQPs not previously reported in EC that are differentially regulated by hormonal signaling. With estradiol, Ishikawa showed increased AQPs 5, 11, 12, and decreased AQPs 0 and 4; MFE-280 showed increased AQPs 0, 1, 3, 4, 8, and decreased AQP11. Protein expression was confirmed by Western blot and immunocytochemistry. AQPs 1, 4, and 11 were colocalized with plasma membrane marker; AQP8 was intracellular in Ishikawa and not detectable in MFE-280. AQP1 ion channel inhibitors (AqB011; PMFC) reduced invasiveness of EC cell lines in transwell chamber and spheroid dispersal assays. In Ishikawa cells, transwell invasiveness was reduced ~41% by 80 µM AqB011 and ~55% by 0.5 mM 5-PMFC. In MFE-280, 5-PMFC inhibited invasion by ~77%. In contrast, proposed inhibitors of AQP water pores (acetazolamide, ginsenoside, KeenMind, TGN-020, IMD-0354) were not effective. Treatments of cultured primary EC cells with AqB011 or PMFC significantly reduced the invasiveness of both low- and high-grade primary EC cells in transwell chambers. We confirmed the tumors expressed moderate to high levels of AQP1 detected by immunohistochemistry, whereas expression levels of AQP4, AQP8, and AQP11 were substantially lower. The anti-invasive potency of AqB011 treatment for EC tumor tissues showed a positive linear correlation with AQP1 expression levels. In summary, AQP1 ion channels are important for motility in both low- and high-grade EC subtypes. Inhibition of AQP1 is a promising strategy to inhibit EC invasiveness and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Chemoresistant Cancer Cell Lines Are Characterized by Migratory, Amino Acid Metabolism, Protein Catabolism and IFN1 Signalling Perturbations

Author

Acland, Mitchell, primary, Lokman, Noor A., additional, Young, Clifford, additional, Anderson, Dovile, additional, Condina, Mark, additional, Desire, Chris, additional, Noye, Tannith M., additional, Wang, Wanqi, additional, Ricciardelli, Carmela, additional, Creek, Darren J., additional, Oehler, Martin K., additional, Hoffmann, Peter, additional, and Klingler-Hoffmann, Manuela, additional

Published
2022
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37. Invasiveness of endometrial cancer cell lines is potentiated by estradiol and blocked by a traditional medicine Guizhi Fuling at clinically relevant doses.

Author

Sidra Khan, Varricchio, Alanah, Ricciardelli, Carmela, and Yool, Andrea J.

Subjects
ENDOMETRIAL cancer, CELL lines, CANCER invasiveness, TRADITIONAL medicine, CANCER cells, ESTROGEN
Abstract

The Traditional Chinese medicine, Guizhi Fuling (here called Fuling), has been confirmed in meta-analysis studies to reduce recurrence of endometriosis and improve pregnancy outcomes; however, the possible use of Fuling as a fertility-preserving treatment in endometrial cancer has not previously been tested. Results here are the first to demonstrate dose-dependent inhibition of cell motility by Fuling in two endometrial cancer cell lines, classified as Grade I which is responsive to progesterone treatment, and Grade III (MFE-280) which is resistant. The major outcome of this study was the novel demonstration that Fuling (30-80 pg/ml) significantly inhibits invasiveness in both high and low grades of EC cells, achieving 70-80% block of trans-barrier migration without cytotoxicity. This effective dose range is estimated to be comparable to that used in human clinical trials and traditional practice. Results here further show that clinically relevant doses of Fuling override the motility-promoting effects of estradiol in endometrial cancer cell lines. Medroxyprogesterone acetate has to date been the standard therapy to treat metastatic or inoperable endometrial cancers; however, success rates are low with high rates of recurrence, due in part to acquired resistance to medroxyprogesterone acetate therapy. The discovery here that Fuling appears to control the spread of treatment-resistant advanced cancers is an exciting prospect. [ABSTRACT FROM AUTHOR]

Published
2023
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38. Disabled-2 (DAB2): A Key Regulator of Anti- and Pro-Tumorigenic Pathways.

Author

Price, Zoe K., Lokman, Noor A., Yoshihara, Masato, Kajiyama, Hiroaki, Oehler, Martin K., and Ricciardelli, Carmela

Subjects
TRANSFORMING growth factors-beta, ENDOCYTOSIS, EPITHELIAL-mesenchymal transition, COATED vesicles, ADAPTOR proteins, PROTEIN kinases, CELLULAR signal transduction
Abstract

Disabled-2 (DAB2), a key adaptor protein in clathrin mediated endocytosis, is implicated in the regulation of key signalling pathways involved in homeostasis, cell positioning and epithelial to mesenchymal transition (EMT). It was initially identified as a tumour suppressor implicated in the initiation of ovarian cancer, but was subsequently linked to many other cancer types. DAB2 contains key functional domains which allow it to negatively regulate key signalling pathways including the mitogen activated protein kinase (MAPK), wingless/integrated (Wnt) and transforming growth factor beta (TGFβ) pathways. Loss of DAB2 is primarily associated with activation of these pathways and tumour progression, however this review also explores studies which demonstrate the complex nature of DAB2 function with pro-tumorigenic effects. A recent strong interest in microRNAs (miRNA) in cancer has identified DAB2 as a common target. This has reignited an interest in DAB2 research in cancer. Transcriptomics of tumour associated macrophages (TAMs) has also identified a pro-metastatic role of DAB2 in the tumour microenvironment. This review will cover the broad depth literature on the tumour suppressor role of DAB2, highlighting its complex relationships with different pathways. Furthermore, it will explore recent findings which suggest DAB2 has a more complex role in cancer than initially thought. [ABSTRACT FROM AUTHOR]

Published
2023
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39. Pre-clinical validation of a novel pan-cancer CAR-T cell immunotherapy against nfP2X7

Author

Bandara, Veronika, primary, Foeng, Jade, additional, Gundsambuu, Batjargal, additional, Norton, Todd, additional, Napoli, Silvana, additional, McPeake, Dylan, additional, Tyllis, Timona, additional, Rad, Elaheh Rohani, additional, Abbott, Caitlin, additional, Mills, Stuart, additional, Tan, Lih, additional, Willet, Vasiliki, additional, Nikitaras, Victoria, additional, Johnson, Adam, additional, Coombs, Justin, additional, Oehler, Martin, additional, Ricciardelli, Carmela, additional, Cowin, Allison, additional, Bonder, Claudine, additional, Jensen, Michael, additional, Sadlon, Timothy, additional, McColl, Shaun, additional, and barry, simon, additional

Published
2021
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40. Plasma‐activated media selectively induces apoptotic death via an orchestrated oxidative stress pathway in high‐grade serous ovarian cancer cells.

Author

Davies, Lorena T., Ganesen, Raja, Toubia, John, Hong, Sung‐Ha, Kumar KC, Sushil, Oehler, Martin K., Ricciardelli, Carmela, Szili, Endre J., Robinson, Nirmal, and Pitman, Melissa R.

Subjects
*CANCER patients, *GLOW discharges, *ELECTRIC discharges, *OVARIAN cancer, *ATMOSPHERIC pressure
Abstract

High‐grade serous ovarian cancer (HGSOC) is the most common and aggressive type of ovarian cancer. Due to a lack of an early detection test and overt symptoms, many patients are diagnosed at a late stage where metastasis makes treatment very challenging. Furthermore, the current standard treatment for HGSOC patients, consisting of debulking surgery and platinum‐taxane chemotherapy, reduces quality of life due to debilitating side‐effects. Sadly, 80–90% of patients diagnosed with advanced stage ovarian cancer will die due to treatment resistance. As such, novel therapeutic strategies for HGSOC that are both more effective and less toxic are urgently required. Here we describe the assessment of cold atmospheric pressure (CAP) gas discharge technology as a novel treatment strategy in pre‐clinical models of HGSOC. Plasma‐activated media (PAM) was generated using cell growth media. HGSOC cell lines, patient ascites cells and primary tissue explants were tested for their response to PAM via analysis of cell viability, cell death and oxidative stress assays. Our data show that PAM treatment can be more effective than standard carboplatin chemotherapy at selectively targeting ovarian cancer cells in primary patient samples. Further, we also observed PAM to induce apoptosis in HGSOC cancer cell lines via induction of oxidative stress and mitochondrial‐mediated apoptosis. These findings suggest that PAM is a viable therapeutic strategy to test in in vivo models of ovarian cancer, with a view to develop an intraperitoneal PAM‐based therapy for HGSOC patients. Our studies validate the ability of PAM to selectively target tumour tissue and ascites cells. This work supports the development of PAM towards in vivo validation and translation into clinical practice. [ABSTRACT FROM AUTHOR]

Published
2024
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41. Label-Free Quantification Mass Spectrometry Identifies Protein Markers of Chemotherapy Response in High-Grade Serous Ovarian Cancer

Author

Georgia Arentz, Parul Mittal, Manuela Klingler-Hoffmann, Mark R. Condina, Carmela Ricciardelli, Noor A. Lokman, Gurjeet Kaur, Martin K. Oehler, Peter Hoffmann, Arentz, Georgia, Mittal, Parul, Klingler-Hoffmann, Manuela, Condina, Mark R, Ricciardelli, Carmela, Lokman, Noor A, Kaur, Gurjeet, Oehler, Martin K, and Hoffmann, Peter

Subjects
Cancer Research, chemotherapy resistance, ovarian cancer, Oncology, mass spectrometry
Abstract

Refereed/Peer-reviewed Eighty percent of ovarian cancer patients initially respond to chemotherapy, but the majority eventually experience a relapse and die from the disease with acquired chemoresistance. In addition, 20% of patients do not respond to treatment at all, as their disease is intrinsically chemotherapy resistant. Data-independent acquisition nano-flow liquid chromatography–mass spectrometry (DIA LC-MS) identified the three protein markers: gelsolin (GSN), calmodulin (CALM1), and thioredoxin (TXN), to be elevated in high-grade serous ovarian cancer (HGSOC) tissues from patients that responded to chemotherapy compared to those who did not; the differential expression of the three protein markers was confirmed by immunohistochemistry. Analysis of the online GENT2 database showed that mRNA levels of GSN, CALM1, and TXN were decreased in HGSOC compared to fallopian tube epithelium. Elevated levels of GSN and TXN mRNA expression correlated with increased overall and progression-free survival, respectively, in a Kaplan–Meier analysis of a large online repository of HGSOC patient data. Importantly, differential expression of the three protein markers was further confirmed when comparing parental OVCAR-5 cells to carboplatin-resistant OVCAR-5 cells using DIA LC-MS analysis. Our findings suggest that GSN, CALM1, and TXN may be useful biomarkers for predicting chemotherapy response and understanding the mechanisms of chemotherapy resistance. Proteomic data are available via ProteomeXchange with identifier PXD033785.

Published
2023
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42. Real-time cytotoxicity assays as a pre-clinical screening tool for LGR5-targeting CAR-T cells for treatment of solid tumors

Author

Thompson, Emma J, Bandara, Veronika, Sadlon, Timothy, Gundsambuu, Batjargal, Tan, Lih Yin, Ricciardelli, Carmela, Barry, Simon C, Bonder, Claudine S, and Annual Meeting of the American-Association-for-Cancer-Research (AACR) New Orleans, LA 8-13 April 2022

Subjects
CAR-T cells, cancer cells, solid tumors
Abstract

Current challenges for CAR-T therapies in solid tumors relate to target specificity and T cell penetration of the tumor. A key determinant in CAR-T selection for clinical trials is the potency and persistence of the selected CAR-T to kill cancerous cells. This is often difficult to determine across different donors and batches. Additionally, these characteristics can be difficult to determine in vitro in a rapid, high-throughput manner. In this study we have utilized real-time impedance cytotoxicity assays to screen LGR5-targeting CAR-T cells. LGR5 is a well described cancer stem cell antigen implicated in tumor initiation and metastasis, and prognosis of colon, ovarian and neuroblastoma cancers. Impedance measurements are taken continuously, providing comprehensive real-time information about CAR-T cell efficiency over time, which is not achievable with single timepoint cytotoxicity assays. Through this validation process we have been able to concurrently test different Effector to Target (E:T) ratios and different CAR constructs to accurately and directly compare CAR-T killing efficiency. This readout is a key indicator of CAR-T potency. Similar to inhibitory concentration 50 (IC50) or lethal dose 50 (LD50) data, CAR-T potency can be expressed in a measure as kill time 50 (KT50), and represents the time required for the CAR-T to stimulate cytolysis in 50% of the target cancer cells. KT50 data was key to the selection of our lead clinical candidate; CNA3103. In addition to selection of our lead candidate, real-time impedance technology has allowed us to screen a broad range of LGR5-expressing cancer types. Our data indicates that CNA3103 can effectively target colon, neuroblastoma, and ovarian cancer cells in vitro. Real-time impedance assay has allowed us to analyze cancer cells with different levels of LGR5 expression to confirm the specificity of our CAR-T cells and to develop an understanding of how LGR5 expression levels might impact cancer cell killing. The data also indicates that our LGR5 targeting CAR-T cells have the potential to repeatedly kill, i.e. the same CAR-T cell is able to move on from one cancer cell to another and remain cytotoxic. Taken together, real-time cytotoxicity assays provide valuable pre-clinical data, enabling the selection of CNA3103 as our LRG5-CAR-T clinical candidate. This technology may also assist in patient and dose selection within a clinical trial.

Published
2022

43. Using GPCRs as molecular beacons to target ovarian cancer with nanomedicines

Author

Riya Khetan, Cintya Dharmayanti, Todd A. Gillam, Eric Kübler, Manuela Klingler-Hoffmann, Carmela Ricciardelli, Martin K. Oehler, Anton Blencowe, Sanjay Garg, Hugo Albrecht, Khetan, Riya, Dharmayanti, Cintya, Gillam, Todd A, Kübler, Eric, Klingler-Hoffmann, Manuela, Ricciardelli, Carmela, Oehler, Martin K, Blencowe, Anton, Garg, Sanjay, and Albrecht, Hugo

Subjects
active targeting, internalization, Cancer Research, GPCR, ovarian cancer, Oncology, nanoparticle, receptor, drug delivery, G protein-coupled receptor, ligand
Abstract

Refereed/Peer-reviewed The five-year survival rate for women with ovarian cancer is very poor despite radical cytoreductive surgery and chemotherapy. Although most patients initially respond to platinum-based chemotherapy, the majority experience recurrence and ultimately develop chemoresistance, resulting in fatal outcomes. The current administration of cytotoxic compounds is hampered by dose-limiting severe adverse effects. There is an unmet clinical need for targeted drug delivery systems that transport chemotherapeutics selectively to tumor cells while minimizing off-target toxicity. G protein-coupled receptors (GPCRs) are the largest family of membrane receptors, and many are overexpressed in solid tumors, including ovarian cancer. This review summarizes the progress in engineered nanoparticle research for drug delivery for ovarian cancer and discusses the potential use of GPCRs as molecular entry points to deliver anti-cancer compounds into ovarian cancer cells. A newly emerging treatment paradigm could be the personalized design of nanomedicines on a case-by-case basis.

Published
2022

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