Manganese Porphyrin, MnTE-2-PyP5+, Enhances Chemotherapeutic Response in Hematologic Malignancies

Persistent Link:
http://hdl.handle.net/10150/626138
Title:
Manganese Porphyrin, MnTE-2-PyP5+, Enhances Chemotherapeutic Response in Hematologic Malignancies
Author:
Jaramillo, Melba Concepcion Corrales
Issue Date:
2017
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Embargo:
Release after 19-Oct-2018
Abstract:
The prognosis for multiple myeloma (MM) and the activated B-cell subtype of diffuse large B-cell lymphoma (ABC DLBCL) is poor. Gene expression profiling studies have identified that the transcription factor, nuclear factor kappa B (NF-κB) is overexpressed and confers a poor prognosis in MM and ABC DLBCL. NF-κB regulates the transcription of genes involved in cell proliferation and survival. Thus, several groups have tried to identify and/or develop agents that target NF-κB to improve therapy and patient prognosis for MM and ABC DLBCL. Our laboratory has shown that the manganese porphyrin MnTE-2-PyP5+ inhibits NF-κB in a murine lymphoma cell culture model and enhances tumor cell death in combination with dexamethasone and cyclophosphamide, two agents that are routinely used to treat these neoplasms. MnTE-2-PyP5+ inhibits NF-κB by glutathionylating p65, a member of the NF-κB family. The objective of the following studies was to determine whether MnTE-2-PyP5+ enhances the chemotherapeutic response in human MM and ABC DLBCL cells that overexpress and depend on NF-κB for survival. The following studies demonstrate that MnTE-2-PyP5+ glutathionylates and inhibits NF-κB in human MM and ABC DLBCL cells. MnTE-2-PyP5+ also synergizes with several MM and DLBCL chemotherapeutics, including dexamethasone, cyclophosphamide, vincristine and bortezomib to enhance cell death. The data from these human cell lines will provide the basis for future studies to test MnTE-2-PyP5+ in animal models and for translating MnTE-2-PyP5+ to the clinic.
Type:
text; Electronic Thesis
Keywords:
chemotherapeutics; lymphoma; manganese porphyrins; multiple myeloma; redox biology
Degree Name:
M.S.
Degree Level:
masters
Degree Program:
Graduate College; Cellular and Molecular Medicine
Degree Grantor:
University of Arizona
Advisor:
Tome, Margaret E.; St. John, Paul

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleManganese Porphyrin, MnTE-2-PyP5+, Enhances Chemotherapeutic Response in Hematologic Malignanciesen_US
dc.creatorJaramillo, Melba Concepcion Corralesen
dc.contributor.authorJaramillo, Melba Concepcion Corralesen
dc.date.issued2017-
dc.publisherThe University of Arizona.en
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en
dc.description.releaseRelease after 19-Oct-2018en
dc.description.abstractThe prognosis for multiple myeloma (MM) and the activated B-cell subtype of diffuse large B-cell lymphoma (ABC DLBCL) is poor. Gene expression profiling studies have identified that the transcription factor, nuclear factor kappa B (NF-κB) is overexpressed and confers a poor prognosis in MM and ABC DLBCL. NF-κB regulates the transcription of genes involved in cell proliferation and survival. Thus, several groups have tried to identify and/or develop agents that target NF-κB to improve therapy and patient prognosis for MM and ABC DLBCL. Our laboratory has shown that the manganese porphyrin MnTE-2-PyP5+ inhibits NF-κB in a murine lymphoma cell culture model and enhances tumor cell death in combination with dexamethasone and cyclophosphamide, two agents that are routinely used to treat these neoplasms. MnTE-2-PyP5+ inhibits NF-κB by glutathionylating p65, a member of the NF-κB family. The objective of the following studies was to determine whether MnTE-2-PyP5+ enhances the chemotherapeutic response in human MM and ABC DLBCL cells that overexpress and depend on NF-κB for survival. The following studies demonstrate that MnTE-2-PyP5+ glutathionylates and inhibits NF-κB in human MM and ABC DLBCL cells. MnTE-2-PyP5+ also synergizes with several MM and DLBCL chemotherapeutics, including dexamethasone, cyclophosphamide, vincristine and bortezomib to enhance cell death. The data from these human cell lines will provide the basis for future studies to test MnTE-2-PyP5+ in animal models and for translating MnTE-2-PyP5+ to the clinic.en
dc.typetexten
dc.typeElectronic Thesisen
dc.subjectchemotherapeuticsen
dc.subjectlymphomaen
dc.subjectmanganese porphyrinsen
dc.subjectmultiple myelomaen
dc.subjectredox biologyen
thesis.degree.nameM.S.en
thesis.degree.levelmastersen
thesis.degree.disciplineGraduate Collegeen
thesis.degree.disciplineCellular and Molecular Medicineen
thesis.degree.grantorUniversity of Arizonaen
dc.contributor.advisorTome, Margaret E.en
dc.contributor.advisorSt. John, Paulen
dc.contributor.committeememberTome, Margaret E.en
dc.contributor.committeememberSt. John, Paulen
dc.contributor.committeememberBriehl, Margaret M.en
dc.contributor.committeememberZeng, Yien
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