Master of Science / Department of Anatomy and Physiology / Deryl L. Troyer / There is renewed interest in magnetic hyperthermia as a treatment modality for cancer, especially when it is combined with other more traditional therapeutic approaches, such as the co-delivery of anticancer drugs or photodynamic therapy. The influence of bimagnetic nanoparticles (MNPs) combined with short external alternating magnetic field (AMF) exposure on the growth of subcutaneous mouse melanomas (B16-F10) was evaluated. Bimagnetic Fe/Fe3O4 core/shell nanoparticles were designed for cancer targeting after intratumoral or intravenous administration. Their inorganic center was protected against rapid biocorrosion by organic dopamine-oligoethylene glycol ligands. TCPP (4-tetracarboxyphenyl porphyrin) units were attached to the dopamine-oligoethylene glycol ligands. The magnetic hyperthermia results obtained after intratumoral injection indicated that micromolar concentrations of iron given within the modified core-shell Fe/Fe3O4 nanoparticles caused a significant anti-tumor effect on murine B16-F10 melanoma with three short 10-minute AMF exposures. There is a decrease in tumor size after intravenous administration of the MNPs followed by three consecutive days of AMF exposure. These results indicate that intratumoral administration of surface-modified MNPs can attenuate mouse melanoma after AMF exposure. Moreover, intravenous administration of these MNPs followed by AMF exposure attenuates melanomas, indicating that adequate amounts of TCPP-labeled stealth Fe/Fe3O4 nanoparticles can accumulate in murine melanoma after systemic delivery to allow effective magnetic hyperthermic therapy in a rodent tumor mode.

Over four years from 2002 to 2006, a series of concomitant studies were undertaken to explore the complications and outcomes of skin cancer surgery. Specifically: 1. Through prospective studies, to identify risk factors for bleeding and infectious complications following skin surgery. 2. To determine through a randomized controlled trial whether mupirocin ointment versus paraffin ointment versus no ointment on a wound following skin closure affords the patient benefit. 3. To determine whether patients are at increased post operative bleeding risk should they remain on warfarin and / or aspirin prior to skin surgery. 4. To develop and then trial a novel approach (reducing opposed multilobed [ROM] flap) for below knee wound closures that may reduce the incidence of skin surgery complications on the leg and foot. 5. To investigate whether patients who suffer surgical complications are less likely to be satisfied with the service provision.

Master of Science / Department of Animal Sciences and Industry / Timothy G. Rozell / Follicle stimulating hormone (FSH) is known as the key hormone capable of causing proliferation of granulosa cells in the ovary. The classical receptor belongs to the G protein-coupled superfamily and is designated FSHR-1. A variant in the FSH receptor has been shown to be functional in mouse ovaries. The variant receptor is designated as FSHR-3, and when bound by FSH activates a pathway that shares similar characteristics to the growth factor type I receptor pathway, with no increase in cAMP. The FSHR-3 variant activates MAPK upon binding to FSH, and causes proliferation of cells on which it is known to be expressed. For example ID8 mouse ovarian surface epithelium cells (MOSEC), a cell line that when introduced in immunocompetent mice causes tumors similar to human ovarian cancer and which also express FSHR-3, proliferated in response to FSH. The present study explored the potential for decreasing expression of FSHR-3 protein. The RNA interference (RNAi) technique was used to insert small inhibitory RNA(siRNA) segments corresponding specifically to the R3 variant of the FSH receptor in ID8 MOSEC. Transfected cells were lysed and FSHR-3 protein was visualized using SDS Page and Western blotting analysis. A reduction in expression of FSHR-3 was observed in two of the transfection groups, with the greatest down-regulation of FSHR-3 being 30.1%. From these preliminary results we conclude that the FSHR-3 is expressed on ID8 cells, and that siRNA may be useful to reduce its expression. Thus, it may be possible to slow the growth of FSH-responsive tumors using siRNA to target the FSHR-3 receptor.