{"id":{"repo_id":"texas-state","oai_identifier":"oai:digital.library.txst.edu:10877/15807"},"canonical_url":"https://search.dev.ndltd.org/etd/texas-state/oai:digital.library.txst.edu:10877/15807","repository":{"repo_id":"texas-state","name":"Texas State University","base_url":"https://digital.library.txst.edu/server/oai/request"},"display":{"title":"Novel Neuroblastoma Differentiating Agents","abstract":"Neuroblastoma (NB) is the 3rd most lethal pediatric cancer. In high-risk patients, the 5-year survival rate is 40-50% after treatment. The differentiation therapy with retinoic acid (RA) is at the forefront of approaches to treat neuroblastoma; however, more than half of patients experience recurrence suggesting resistance to RA. There is currently no alternative outside of chemotherapy for patients who have developed resistance to RA; therefore, the purpose of this research is to address this insufficiency by developing novel neuroblastoma differentiating agents. A promising agent will induce differentiation while reducing the cancer cell viability. A high-content screening (HCS) was conducted to identify hit compounds. This screening measured neurite outgrowth, a phenotypic change which has been described as a marker of differentiation in neuroblastoma cell lines. From this screening, three hits that induced the desired changes in cancer cells were identified. In this work, we present analogues of a hit compound synthesized to increase potency. Currently, the mechanism of induced differentiation is unclear. However, by use of a Structure-Activity Relationship (SAR) study, the pharmacophore of the hit compound has begun to be elucidated. Understanding the chemical groups necessary for activity can give rise to more potent compounds as well as assist in future mode of action studies. Cell viability assays along with neurite outgrowth induced by the analogues of the hit compound are presented here to demonstrate the optimization of the compound potency in the BE(2)-C cell line.","abstract_html":"Neuroblastoma (NB) is the 3rd most lethal pediatric cancer. In high-risk patients, the 5-year survival rate is 40-50% after treatment. The differentiation therapy with retinoic acid (RA) is at the forefront of approaches to treat neuroblastoma; however, more than half of patients experience recurrence suggesting resistance to RA. There is currently no alternative outside of chemotherapy for patients who have developed resistance to RA; therefore, the purpose of this research is to address this insufficiency by developing novel neuroblastoma differentiating agents. A promising agent will induce differentiation while reducing the cancer cell viability. A high-content screening (HCS) was conducted to identify hit compounds. This screening measured neurite outgrowth, a phenotypic change which has been described as a marker of differentiation in neuroblastoma cell lines. From this screening, three hits that induced the desired changes in cancer cells were identified. In this work, we present analogues of a hit compound synthesized to increase potency. Currently, the mechanism of induced differentiation is unclear. However, by use of a Structure-Activity Relationship (SAR) study, the pharmacophore of the hit compound has begun to be elucidated. Understanding the chemical groups necessary for activity can give rise to more potent compounds as well as assist in future mode of action studies. Cell viability assays along with neurite outgrowth induced by the analogues of the hit compound are presented here to demonstrate the optimization of the compound potency in the BE(2)-C cell line.","abstract_has_math":false,"creators":["Laguera, Breana"],"institution":"Texas State University","degree_name":"Master of Science","degree_level":"Masters","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Kornienko, Alexander"],"committee_chairs":[],"committee_members":["Du, Liqin","Betancourt, Tania"],"year":2020,"date_issued":"2020-05","date_published":"2020-05","updated_at":"2026-07-27T21:22:34Z","subjects":["organic chemistry","medicinal chemistry","structure-activity relationship","neuroblastoma"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/10877/15807","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Kornienko, Alexander"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Du, Liqin","Betancourt, Tania"]},{"key":"dc:creator","label":"Author","values":["Laguera, Breana"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2022-05-25T16:51:30Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2022-05-25T16:51:30Z"]},{"key":"dc:date.issued","label":"Date","values":["2020-05"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Texas State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["organic chemistry","medicinal chemistry","structure-activity relationship","neuroblastoma"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10877/15807"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Neuroblastoma (NB) is the 3rd most lethal pediatric cancer. In high-risk patients, the 5-year survival rate is 40-50% after treatment. The differentiation therapy with retinoic acid (RA) is at the forefront of approaches to treat neuroblastoma; however, more than half of patients experience recurrence suggesting resistance to RA. There is currently no alternative outside of chemotherapy for patients who have developed resistance to RA; therefore, the purpose of this research is to address this insufficiency by developing novel neuroblastoma differentiating agents. A promising agent will induce differentiation while reducing the cancer cell viability. A high-content screening (HCS) was conducted to identify hit compounds. This screening measured neurite outgrowth, a phenotypic change which has been described as a marker of differentiation in neuroblastoma cell lines. From this screening, three hits that induced the desired changes in cancer cells were identified. In this work, we present analogues of a hit compound synthesized to increase potency. Currently, the mechanism of induced differentiation is unclear. However, by use of a Structure-Activity Relationship (SAR) study, the pharmacophore of the hit compound has begun to be elucidated. Understanding the chemical groups necessary for activity can give rise to more potent compounds as well as assist in future mode of action studies. Cell viability assays along with neurite outgrowth induced by the analogues of the hit compound are presented here to demonstrate the optimization of the compound potency in the BE(2)-C cell line."]},{"key":"dc:format","label":"Dc Format","values":["Text"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["1 file (.pdf)"]},{"key":"dc:title","label":"Title","values":["Novel Neuroblastoma Differentiating Agents"]}]}],"canonical_facts":{"dc:contributor.advisor":["Kornienko, Alexander"],"dc:contributor.committeemember":["Du, Liqin","Betancourt, Tania"],"dc:creator":["Laguera, Breana"],"dc:date.accessioned":["2022-05-25T16:51:30Z"],"dc:date.available":["2022-05-25T16:51:30Z"],"dc:date.issued":["2020-05"],"dc:description.abstract":["Neuroblastoma (NB) is the 3rd most lethal pediatric cancer. In high-risk patients, the 5-year survival rate is 40-50% after treatment. The differentiation therapy with retinoic acid (RA) is at the forefront of approaches to treat neuroblastoma; however, more than half of patients experience recurrence suggesting resistance to RA. There is currently no alternative outside of chemotherapy for patients who have developed resistance to RA; therefore, the purpose of this research is to address this insufficiency by developing novel neuroblastoma differentiating agents. A promising agent will induce differentiation while reducing the cancer cell viability. A high-content screening (HCS) was conducted to identify hit compounds. This screening measured neurite outgrowth, a phenotypic change which has been described as a marker of differentiation in neuroblastoma cell lines. From this screening, three hits that induced the desired changes in cancer cells were identified. In this work, we present analogues of a hit compound synthesized to increase potency. Currently, the mechanism of induced differentiation is unclear. However, by use of a Structure-Activity Relationship (SAR) study, the pharmacophore of the hit compound has begun to be elucidated. Understanding the chemical groups necessary for activity can give rise to more potent compounds as well as assist in future mode of action studies. Cell viability assays along with neurite outgrowth induced by the analogues of the hit compound are presented here to demonstrate the optimization of the compound potency in the BE(2)-C cell line."],"dc:format":["Text"],"dc:format.medium":["1 file (.pdf)"],"dc:identifier.uri":["https://hdl.handle.net/10877/15807"],"dc:language.iso":["en"],"dc:subject":["organic chemistry","medicinal chemistry","structure-activity relationship","neuroblastoma"],"dc:title":["Novel Neuroblastoma Differentiating Agents"],"dc:type":["Thesis"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Masters"],"thesis:degree_name":["Master of Science"],"thesis:institution_name":["Texas State University"]},"updated_at":"2026-07-27T21:22:34Z"}