{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/78446"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/78446","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Targeting Mitochondria for Rhabdomyosarcoma Therapy","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Gokhale, Abhiram"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Chandra, Dhyan","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-10-25T14:35:49Z","date_published":"2018-10-25T14:35:49Z","updated_at":"2026-07-27T19:05:09Z","subjects":["oncology","pharmaceutical sciences","molecular biology","cancer sciences"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/78446","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Chandra, Dhyan","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Gokhale, Abhiram"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-10-25T14:35:49Z","2018","2018-08-05 18:39:08"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["oncology","pharmaceutical sciences","molecular biology","cancer sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/78446"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","Rhabdomyosarcoma (RMS) is a malignant soft-tissue sarcoma in children, accounting for about 40% of pediatric soft-tissue tumors. The two main subtypes of RMS widely studied are embryonal RMS (eRMS) and alveolar RMS (aRMS). Current therapies include chemotherapy and radiation, which are very limited, highly cytotoxic, and have higher chances of recurrence. Although, survival rates have not significantly improved for past three decades, there have been no substantial changes in the treatment strategies, which points out to the need of the hour to develop new approaches to combat rhabdomyosarcoma. The previous study in our lab suggested that the rhabdomyosarcoma cells produce high levels of mitochondrial reactive oxygen species (mito ROS), and because of defective oxidative phosphorylation complexes, along with high levels of mitochondrial unfolded protein response (mtUPR) components. This study hypothesizes a therapeutic intervention targeting the mtUPR machinery, which would increase the load of unfolded proteins in the cells that would further elevate the oxidative stress, skewing the cells towards apoptosis. For this, we screened a library of small molecules against mitochondrial protease that is a component of mtUPR machinery. The screening results showed one promising small molecule DCEM 2, which we studied further. Our results show that DCEM 2 treatment at micro molar levels increased the oxidative stress, ubiquitinated proteins, and caspase- 3 activation whereas it reduced cell viability in both aRMS and eRMS cells with minimal effect on normal myoblast cells. Moreover, the DCEM 2 treatment drastically reduced the oxygen consumption rate and reduces the aRMS signature fusion protein PAX3- FOXO1 levels. Overall, our data suggest that targeting the mtUPR components would be a promising therapeutic strategy for ROS driven cancers like rhabdomyosarcoma.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Targeting Mitochondria for Rhabdomyosarcoma Therapy"]}]}],"canonical_facts":{"dc:contributor":["Chandra, Dhyan","Roswell Park"],"dc:creator":["Gokhale, Abhiram"],"dc:date":["2018-10-25T14:35:49Z","2018","2018-08-05 18:39:08"],"dc:description":["M.S.","Rhabdomyosarcoma (RMS) is a malignant soft-tissue sarcoma in children, accounting for about 40% of pediatric soft-tissue tumors. The two main subtypes of RMS widely studied are embryonal RMS (eRMS) and alveolar RMS (aRMS). Current therapies include chemotherapy and radiation, which are very limited, highly cytotoxic, and have higher chances of recurrence. Although, survival rates have not significantly improved for past three decades, there have been no substantial changes in the treatment strategies, which points out to the need of the hour to develop new approaches to combat rhabdomyosarcoma. The previous study in our lab suggested that the rhabdomyosarcoma cells produce high levels of mitochondrial reactive oxygen species (mito ROS), and because of defective oxidative phosphorylation complexes, along with high levels of mitochondrial unfolded protein response (mtUPR) components. This study hypothesizes a therapeutic intervention targeting the mtUPR machinery, which would increase the load of unfolded proteins in the cells that would further elevate the oxidative stress, skewing the cells towards apoptosis. For this, we screened a library of small molecules against mitochondrial protease that is a component of mtUPR machinery. The screening results showed one promising small molecule DCEM 2, which we studied further. Our results show that DCEM 2 treatment at micro molar levels increased the oxidative stress, ubiquitinated proteins, and caspase- 3 activation whereas it reduced cell viability in both aRMS and eRMS cells with minimal effect on normal myoblast cells. Moreover, the DCEM 2 treatment drastically reduced the oxygen consumption rate and reduces the aRMS signature fusion protein PAX3- FOXO1 levels. Overall, our data suggest that targeting the mtUPR components would be a promising therapeutic strategy for ROS driven cancers like rhabdomyosarcoma.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/78446"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["oncology","pharmaceutical sciences","molecular biology","cancer sciences"],"dc:title":["Targeting Mitochondria for Rhabdomyosarcoma Therapy"],"dc:type":["Thesis","Text"]},"updated_at":"2026-07-27T19:05:09Z"}