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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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7. 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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9. 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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11. List of Contributors

Author

Adya, Ashok K., primary, Agarwal, Neelesh, additional, Agrawal, Udita, additional, Azevedo, Vasco, additional, Bahadur, Shiv, additional, Banerjee, Subhadip, additional, Barh, Debmalya, additional, Bharadwaj, Mausumi, additional, Bhatt, Anant Narayan, additional, Bhattacharjee, Atanu, additional, Biswas, Sayan, additional, Biyani, Madhu, additional, Biyani, Manish, additional, Canetta, Elisabetta, additional, Chakrabarti, Manoj K., additional, Chanda, Joydeb, additional, Chandra, Partha K., additional, Chaturvedi, Rakhi, additional, Chauhan, Ankit, additional, Chowbina, Sudhir, additional, Chowdhuri, D. Kar, additional, Chowdhury, Madhumita Roy, additional, Das, Mukul, additional, Datta, Amrita, additional, Dube, Devyani, additional, Dubey, Sudhisha, additional, Dutta, Shanta, additional, Dwarakanath, Bilikere Srinivasa Rao, additional, Dwivedi, Premendra D., additional, Gaur, Rajarshi Kumar, additional, Ghosh, Preetam, additional, Gimpel, Jessica L., additional, Gupta, Abhik, additional, Gupta, Anuj Kumar, additional, Gupta, Madhu, additional, Gupta, UD, additional, Harwansh, Ranjit K., additional, Hazra, Rajat, additional, Hoque, Kazi Mirajul, additional, Hussain, Showket, additional, Jain, Pooja, additional, Jyoti, Anurag, additional, Kamal, Shivali, additional, Kanjilal, Satyajyoti, additional, Kashyap, Sudhir Kumar, additional, Katiyar, Chandra Kant, additional, Khan, Fahim Halim, additional, Khan, Zafar K., additional, Khanna, Suchit, additional, Khurana, Satyendra Mohan Paul, additional, Kumar, Aruna, additional, Kumar, Naveen, additional, Kumar, Sandeep, additional, Kumar, Vineet, additional, Kumar, Vipin, additional, Lokman, Noor A, additional, Maherchandani, Sunil, additional, Marwal, Avinash, additional, Masih, Shet, additional, Maurya, Pawan Kumar, additional, Mehrotra, Ravi, additional, Mishra, Ayushi, additional, Mody, Nishi, additional, Mondal, Debasis, additional, Mukherjee, Pulok K., additional, Mukherjee, Soumen, additional, Nalluri, Joseph J., additional, Nishigaki, Koichi, additional, Nishu, Nishu, additional, Oehler, Martin K, additional, Patel, Bhakti, additional, Pore, Debasis, additional, Purushothaman, Pravinkumar, additional, Ram, K. Ravi, additional, Reza Khorramizadeh, M., additional, Ricciardelli, Carmela, additional, Saadat, Farshid, additional, Saha, Malay Kumar, additional, Salawu, Emmanuel O., additional, Shanker, Rishi, additional, Sharma, Rajeev, additional, Singh, Anchal, additional, Singh, Gulshan, additional, Singh, Mithilesh, additional, Singh, Neha, additional, Singh, Surinder Pal, additional, Srivastava, Priyanka, additional, Suckow, Mark A., additional, Das, Surajit, additional, Tripathi, Richa, additional, Upadhyaya, Kailash C., additional, Uppal, Timsy, additional, Verma, Alok Kumar, additional, Verma, Anju, additional, Verma, Ashish Swarup, additional, Verma, Megha, additional, Verma, Mudit, additional, Verma, Mukesh, additional, Verma, Poonam, additional, Verma, Subhash Chandra, additional, Verma, Vipin, additional, Vyas, Suresh P., additional, Yadav, Dinesh K., additional, Yadav, Neelam, additional, Yamanaka, Koji, additional, and Yiannakopoulou, Eugenia Ch., additional

Published
2020
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14. 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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17. 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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18. 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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19. 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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20. 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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21. 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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22. 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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23. 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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24. 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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25. 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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26. 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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27. 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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28. 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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29. 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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30. 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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31. 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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32. 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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33. 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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34. 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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35. 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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36. 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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41. 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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47. 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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50. 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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