A Translational Study Evaluating the Uses of Diagnostic and Therapeutic Practices Established in Human Malignant Melanoma in Equine Malignant Melanoma

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dc.contributor.authorMoore, Jenna Shereeen
dc.contributor.committeechairRobertson, John L.en
dc.contributor.committeememberBuechner-Maxwell, Virginia A.en
dc.contributor.committeememberFurr, Martin O.en
dc.contributor.committeememberCrisman, Mark V.en
dc.contributor.committeememberShaw, Edward Gusen
dc.contributor.departmentVeterinary Medicineen
dc.date.accessioned2014-11-23T07:00:20Zen
dc.date.available2014-11-23T07:00:20Zen
dc.date.issued2013-05-31en
dc.description.abstractMalignant melanoma is a neoplasm of melanocytes. It typically originates in skin, but may metastasize to other body systems. It is a relatively common neoplasm in both humans and horses, with striking similarities across both species. Heritable genetic factors associated with melanoma have been identified in both human malignant melanoma (HMM) and equine malignant melanoma (EMM). This work investigates similarities and differences of EMM and HMM through comparative protein expression using immunohistochemical staining. Nestin, Pax-3/7, B-Raf, and SOX-10 are commonly expressed in HMM tissues. Expression of these proteins is not noted in normal human melanocytes, is associated with decreased melanocytic differentiation, and with increased proliferation leading to tumorigenesis. My findings demonstrate similar expression of these proteins in EMM. Aberrant protein expression patterns may signal underlying genetic mutations. Similar abnormal expression patterns suggest that EMM and HMM may share common genetic abnormalities. Treatment of malignant melanoma presents similar challenges in both horses and humans. In general, early stages of the disease can be successfully treated with surgical excision; however, advanced stages of EMM and HMM are often refractory. Therefore, development of novel therapies for advanced stages of melanoma is essential in both species, with the horse representing a useful model for this process. One novel therapy, frankincense oil (FO) is a resin distillate from trees of the genus Boswellia. Studies have demonstrated cytostatic and apoptotic-modulating properties of FO in various human cancer cell lines. No studies have evaluated FO as a therapy for skin neoplasms. In my work, the apoptotic properties of FO from Boswellia frereana were verified in a HMM cell line (SK-Mel-5). The cytotoxicity and therapeutic efficacy of FO were also studied by evaluating the effects of FO in cases of perianal EMM. FO was found to be consistently cytotoxic when injected directly into EMM tumors, but largely inconsequential when applied topically. FO was found to substantially decrease the size of injected masses. These findings suggest that FO could be useful for debulking large masses in late stage dermal EMM. The combined results of these studies support further investigation of EMM as a translational model for HMM.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:1115en
dc.identifier.urihttp://hdl.handle.net/10919/50923en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectEquine melanomaen
dc.subjectMalignant Melanomaen
dc.subjectFrankincense oilen
dc.subjectBoswelliaen
dc.titleA Translational Study Evaluating the Uses of Diagnostic and Therapeutic Practices Established in Human Malignant Melanoma in Equine Malignant Melanomaen
dc.typeDissertationen
thesis.degree.disciplineBiomedical and Veterinary Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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