Search

Your search keyword '"Laura K, Aguilar"' showing total 3 results
Start Over Author "Laura K, Aguilar" Publisher elsevier
3 results on '"Laura K, Aguilar"'

1. Perturbing DDR signaling enhances cytotoxic effects of local oncolytic virotherapy and modulates the immune environment in glioma

Author

Marilin S. Koch, Mykola Zdioruk, Michal O. Nowicki, Alec M. Griffith, Estuardo Aguilar-Cordova, Laura K. Aguilar, Brian W. Guzik, Francesca Barone, Paul Peter Tak, Katharina Schregel, Michael S. Hoetker, James A. Lederer, E. Antonio Chiocca, Ghazaleh Tabatabai, and Sean E. Lawler

Subjects
DDR signaling, ATR, CAN-2409, glioblastoma, oncolytic therapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

CAN-2409 is a replication-deficient adenovirus encoding herpes simplex virus (HSV) thymidine kinase (tk) currently in clinical trials for treatment of glioblastoma. The expression of tk in transduced cancer cells results in conversion of the pro-drug ganciclovir into a toxic metabolite causing DNA damage, inducing immunogenic cell death and immune activation. We hypothesize that CAN-2409 combined with DNA-damage-response inhibitors could amplify tumor cell death, resulting in an improved response. We investigated the effects of ATR inhibitor AZD6738 in combination with CAN-2409 in vitro using cytotoxicity, cytokine, and fluorescence-activated cell sorting (FACS) assays in glioma cell lines and in vivo with an orthotopic syngeneic murine glioma model. Tumor immune infiltrates were analyzed by cytometry by time of flight (CyTOF). In vitro, we observed a significant increase in the DNA-damage marker γH2AX and decreased expression of PD-L1, pro-tumorigenic cytokines (interleukin-1β [IL-1β], IL-4), and ligand NKG2D after combination treatment compared with monotherapy or control. In vivo, long-term survival was increased after combination treatment (66.7%) compared with CAN-2409 (50%) and control. In a tumor re-challenge, long-term immunity after combination treatment was not improved. Our results suggest that ATR inhibition could amplify CAN-2409’s efficacy in glioblastoma through increased DNA damage while having complex immunological ramifications, warranting further studies to determine the ideal conditions for maximized therapeutic benefit.

Published
2022
Full Text
View/download PDF

2. CASE STUDY OF COMBINED GENE AND RADIATION THERAPY AS AN APPROACH IN THE TREATMENT OF CANCER

Author

BIN S. TEH, MARIA T. VLACHAKI, LAURA K. AGUILAR, BRIAN MILES, GUSTAVO AYALA, DOV KADMON, THOMAS WHEELER, TIMOTHY C. THOMPSON, E. BRIAN BUTLER, and ESTUARDO AGUILAR-CORDOVA

Subjects
Oncology, medicine.medical_specialty, Pathology, business.industry, medicine.medical_treatment, Genetic enhancement, Cancer, Tumor control, medicine.disease, Preclinical data, Combined approach, Radiation therapy, Prostate cancer, Internal medicine, medicine, business, Gene
Abstract

This chapter discusses the case study of combined gene and radiation therapy as an approach in the treatment of cancer. Combined gene therapy and radiation therapy is a novel approach in the armament against cancer. This radio/gene therapy combination may create a new spatial cooperation whereby two local treatment modalities, radiotherapy and in situ gene therapy, can lead to improved local and systemic control. Preclinical data have demonstrated the enhanced antitumor effects of this combined approach in local tumor control, prolongation of survival, and systemic control. This combined radio/gene therapy has now entered clinical phase in prostate cancer. The current approach adds a novel therapy to the standard-of-care therapy. These treatment modalities have very distinct spectra of toxicity profiles. This combined approach enhances the cancer cure without an increase in treatment-related toxicity. Early clinical results have shown the safety of this approach.

Published
2002
Full Text
View/download PDF

3. Contributors

Author

Rafat Abonour, Scott I. Abrams, Laura K. Aguilar, Estuardo Aguilar-Cordova, Steven M. Albelda, Mark R. Albertini, Gustavo Ayala, Jacques Banchereau, Christopher Baum, Christian M. Becker, Carmela Beger, Joseph R. Bertino, Patrick Blanco, Tulin Budak-Alpdogan, E. Brian Butler, Lisa H. Butterfield, Alfred E. Chang, Saswati Chatterjee, K.V. Chin, Virginia K. Clements, Mark J. Cooper, Kenneth Cornetta, James M. Croop, Samudra Dissanayake, Stephen L. Eck, James S. Economou, Laurence C. Eisenlohr, Wafik S. El-Deiry, Filip A. Farnebo, Andrew L. Feldman, Judah Folkman, Stanton L. Gerson, Mileka Gilbert, Leonard G. Gomella, David H. Gorski, William N. Hait, Mien-Chie Hung, Kevin D. Judy, Dov Kadmon, Thomas Kearney, Edsel U. Kim, David M. King, David Kirn, Omer N. Koç, Martin Krüger, Calvin J. Kuo, C. Lampert, Edmund C. Lattime, Irina V. Lebedeva, Steven K. Libutti, H. Kim Lyerly, Michael J. Mastrangelo, Helena J. Mauceri, A.M. McCall, Kevin T. McDonagh, R. Scott McIvor, Raymond D. Meng, Brian Miles, Frederick L. Moolten, Michael A. Morse, Paula J. Mroz, James J. Mulé, Smita K. Nair, Owen A. O'Connor, Wolfram Ostertag, Suzanne Ostrand-Rosenberg, A. Karolina Palucka, Beth A. Pulaski, Ling Qi, Alexander L. Rakhmilevich, Jane S. Reese, Michael Reiss, Antoni Ribas, Isabelle Rivière, Justin C. Roth, Michel Sadelain, Ruping Shao, C.A. Stein, Daniel H. Sterman, Carol Stocking, Bin S. Teh, Timothy C. Thompson, Deborah Toppmeyer, Catherine M. Verfaillie, Maria T. Vlachaki, Dorothee von Laer, Ralph R. Weichselbaum, L.M. Weiner, Thomas Wheeler, Lee G. Wilke, K.K. Wong, Flossie Wong-Staal, Duen-Hwa Yan, Steven P. Zielske, and Robert CH Zhao

Published
2002
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results