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1. Pseudomonas aeruginosa exotoxin T induces potent cytotoxicity against a variety of murine and human cancer cell lines.

Author

Goldufsky, Joe, Wood, Stephen, Hajihossainlou, Behnam, Rehman, Tooba, Majdobeh, Omar, Kaufman, Howard, Ruby, Carl, and Shafikhani, Sasha

Subjects
ADP Ribose Transferases, Animals, Antineoplastic Agents, Cell Line, Tumor, Cell Survival, Female, GTPase-Activating Proteins, Humans, Mice
Abstract

In patients with malignancy, the major barrier to achieving complete response is emergence of resistance to current chemotherapeutic agents. One of the major mechanisms by which tumour cells become resistant to therapies is by altering cellular drug targets through mutations and/or deletions. Resistance by this mechanism is achieved more easily if the drug has limited cellular targets and/or processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) targets six proteins that are required for cancer cell survival and proliferation, it is highly unlikely for cancer cells to develop resistance to this toxin. We assessed ExoTs cytotoxicity against multiple invasive and highly resistant tumour cell lines in order to evaluate its potential as a chemotherapeutic agent. Our data demonstrated that ExoT induced potent cytotoxicity in all tumour cell lines that we examined. Collectively, our data highlighted the potential of ExoT as a possible chemotherapeutic candidate for the treatment of cancer.

Published
2015

2. List of Contributors

Author

Adair, Jennifer E., primary, Ahmed, Jahangir, additional, Alusi, Ghassan, additional, Amit, Doron, additional, Antonia, Scott J., additional, Auci, Dominick L., additional, August, David A., additional, Balvers, Rutger K., additional, Baranyi, Lajos, additional, Beard, Brian C., additional, Brennig, Sebastian, additional, Broussard, Elizabeth K., additional, Bryson, Paul D., additional, Byrnes, Andrew P., additional, Cecil, Denise L., additional, Chan, Tim, additional, Comins, Charlie, additional, de Vries, Christiaan R., additional, DiPaola, Robert S., additional, Dirven, Clemens M.F., additional, Disis, Mary L., additional, Dropulic, Boro, additional, Embree, Heather, additional, Epperly, Michael W., additional, Fueyo, Juan, additional, Fujiwara, Toshiyoshi, additional, Fung, Hua, additional, Gabriel, Emmanuel, additional, Ganapath, Vidya, additional, Gerson, Stanton L., additional, Gill, Steven, additional, Gilon, Michal, additional, Goldufsky, Joe, additional, Gomez-Manzano, Candelaria, additional, Grandis, Jennifer Rubin, additional, Greenberger, Joel S., additional, Greiner, John W., additional, Gujrati, Maneesh, additional, Gulley, James L., additional, Hajitou, Amin, additional, Harrington, Kevin J., additional, Hatefi, Arash, additional, Heller, Loree C., additional, Heller, Richard, additional, Hemminki, Akseli, additional, Hemminki, Otto, additional, Herberman, Ronald B., additional, Herendeen, Daniel, additional, Hochberg, Abraham, additional, Hodge, James W., additional, Holt, Gregory E., additional, Huang, Ying, additional, Hyun, Insoo, additional, Jiang, Hong, additional, Kagawa, Shunsuke, additional, Karjoo, Zahra, additional, Kaufman, Howard, additional, Ke, Chien-Chih, additional, Kiem, Hans-Peter, additional, Kimmelman, Jonathan, additional, Klein, Sarah R., additional, Kuroda, Shinji, additional, Kwon, Seong Young, additional, Lachmann, Nico, additional, Lage, Hermann, additional, Lamfers, Martine L.M., additional, Lattime, Edmund C., additional, Lemoine, Nicholas R., additional, Lewis, Jonathan, additional, Liao, John B., additional, Libutti, Steven K., additional, Lin, Yuan, additional, Liu, Ren-Shyan, additional, Lu, Zheng-Rong, additional, Madan, Ravi A., additional, Matouk, Imad, additional, Melcher, Alan, additional, Miller, Andrew D., additional, Min, Jung-Joon, additional, Moritz, Thomas, additional, Mulé, James J., additional, Natsume, Atsushi, additional, Nianiaris, Nastasia, additional, Nishimura, Michael I., additional, Palena, Claudia, additional, Pandha, Hardev, additional, Pastoriza, Jessica, additional, Pinder-Schenck, Mary C., additional, Piya, Sujan, additional, Poplin, Elizabeth, additional, Puskas, John A., additional, Quinn, Thomas, additional, Rao, Ankit, additional, Reese, Jane S., additional, Relph, Kate, additional, Rojas, Juan J., additional, Saenger, Yvonne, additional, Schlom, Jeffrey, additional, Shannon, Kevin, additional, Shirley, Shawna A., additional, Simpson, Guy R., additional, Sivendran, Shanthi, additional, Slepushkin, Vladimir, additional, Songsivilai, Sirirurg, additional, Steven, Neil, additional, Thomas, Sufi Mary, additional, Thorne, Steve H., additional, Tsang, Kwong-Yok, additional, Tsujiuchi, Takashi, additional, Wakabayashi, Toshihiko, additional, Wang, Pin, additional, Wang, Xinxin, additional, Wang, Yaohe, additional, Weiss, Robert E., additional, White, Edward, additional, Yagawa, Yohsuke, additional, Yata, Teerapong, additional, Yuan, Ming, additional, and Yuan, Ziqiang, additional

Published
2014
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5. Oncolytic virus therapy for cancer

Author

Kaufman, Howard, Goldufsky,Joe, Sivendran, Harcharik,Sara, Pan,Michael, Bernardo,Sebastian, Stern,Richard H, Friedlander,Philip, Ruby,Carl, and Saenger,Yvonne

Subjects
Oncolytic Virotherapy, viruses
Abstract

Joe Goldufsky,1 Shanthi Sivendran,3 Sara Harcharik,4 Michael Pan,4 Sebastian Bernardo,4 Richard H Stern,5 Philip Friedlander,4 Carl E Ruby,1,2 Yvonne Saenger,4 Howard L Kaufman1,2 Departments of 1Immunology & Microbiology and 2Surgery, Rush University Medical Center, Chicago IL, USA 3Hematology/Oncology Medical Specialists, Lancaster General Health, Lancaster, PA, USA, and Departments of 4Medical Oncology and 5Radiology, Tisch Cancer Institute, The Mount Sinai School of Medicine, New York, NY, USA Abstract: The use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. In addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and reovirus. The clinical development of oncolytic viral therapy has accelerated in the last few years, with several vectors entering clinical trials for a variety of cancers. In this review, current strategies to optimize the therapeutic effectiveness and safety of the major oncolytic viruses are discussed, and a summary of current clinical trials is provided. Further investigation is needed to characterize better the clinical impact of oncolytic viruses, but there are increasing data demonstrating the potential promise of this approach for the treatment of human and animal cancers. Keywords: cancer, gene therapy, oncolytic therapy, virus, treatment

Published
2013

7. List of Contributors

Author

Adair, Jennifer E., Ahmed, Jahangir, Alusi, Ghassan, Amit, Doron, Antonia, Scott J., Auci, Dominick L., August, David A., Balvers, Rutger K., Baranyi, Lajos, Beard, Brian C., Brennig, Sebastian, Broussard, Elizabeth K., Bryson, Paul D., Byrnes, Andrew P., Cecil, Denise L., Chan, Tim, Comins, Charlie, de Vries, Christiaan R., DiPaola, Robert S., Dirven, Clemens M.F., Disis, Mary L., Dropulic, Boro, Embree, Heather, Epperly, Michael W., Fueyo, Juan, Fujiwara, Toshiyoshi, Fung, Hua, Gabriel, Emmanuel, Ganapath, Vidya, Gerson, Stanton L., Gill, Steven, Gilon, Michal, Goldufsky, Joe, Gomez-Manzano, Candelaria, Grandis, Jennifer Rubin, Greenberger, Joel S., Greiner, John W., Gujrati, Maneesh, Gulley, James L., Hajitou, Amin, Harrington, Kevin J., Hatefi, Arash, Heller, Loree C., Heller, Richard, Hemminki, Akseli, Hemminki, Otto, Herberman, Ronald B., Herendeen, Daniel, Hochberg, Abraham, Hodge, James W., Holt, Gregory E., Huang, Ying, Hyun, Insoo, Jiang, Hong, Kagawa, Shunsuke, Karjoo, Zahra, Kaufman, Howard, Ke, Chien-Chih, Kiem, Hans-Peter, Kimmelman, Jonathan, Klein, Sarah R., Kuroda, Shinji, Kwon, Seong Young, Lachmann, Nico, Lage, Hermann, Lamfers, Martine L.M., Lattime, Edmund C., Lemoine, Nicholas R., Lewis, Jonathan, Liao, John B., Libutti, Steven K., Lin, Yuan, Liu, Ren-Shyan, Lu, Zheng-Rong, Madan, Ravi A., Matouk, Imad, Melcher, Alan, Miller, Andrew D., Min, Jung-Joon, Moritz, Thomas, Mulé, James J., Natsume, Atsushi, Nianiaris, Nastasia, Nishimura, Michael I., Palena, Claudia, Pandha, Hardev, Pastoriza, Jessica, Pinder-Schenck, Mary C., Piya, Sujan, Poplin, Elizabeth, Puskas, John A., Quinn, Thomas, Rao, Ankit, Reese, Jane S., Relph, Kate, Rojas, Juan J., Saenger, Yvonne, Schlom, Jeffrey, Shannon, Kevin, Shirley, Shawna A., Simpson, Guy R., Sivendran, Shanthi, Slepushkin, Vladimir, Songsivilai, Sirirurg, Steven, Neil, Thomas, Sufi Mary, Thorne, Steve H., Tsang, Kwong-Yok, Tsujiuchi, Takashi, Wakabayashi, Toshihiko, Wang, Pin, Wang, Xinxin, Wang, Yaohe, Weiss, Robert E., White, Edward, Yagawa, Yohsuke, Yata, Teerapong, Yuan, Ming, and Yuan, Ziqiang

Published
2013
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8. Oncolytic virus therapy for cancer.

Author

Goldufsky, Joe, Sivendran, Shanthi, Harcharik, Sara, Pan, Michael, Bernardo, Sebastian, Stern, Richard H., Friedlander, Philip, Ruby, Carl E., Saenger, Yvonne, and Kaufman, Howard L.

Published
2013
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