Biomedical Sciences electronic theses and dissertations (MU)
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The items in this collection are the theses and dissertations written by students of the Department of Biomedical Sciences. Some items may be viewed only by members of the University of Missouri System and/or University of Missouri-Columbia. Click on one of the browse buttons above for a complete listing of the works.
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Item A retrospective evaluation of a single institution's use of toceranib for non-mast cell neoplasia(University of Missouri--Columbia, 2025) Sawyer, Kristin; Bryan, Jeffrey[EMBARGOED UNTIL 05/01/2026] Toceranib phosphate (Palladia) is a tyrosine kinase inhibitor with broad antitumor and antiangiogenic activity. Although initially approved for treating canine mast cell tumors, its off-label use for non-mast cell neoplasia has increased. This study retrospectively evaluates the clinical outcomes, response rates, and adverse events associated with toceranib treatment in canine patients with various non-mast cell neoplasms at a single institution over a 10-year period. Medical records of 246 dogs prescribed toceranib between 2011 and 2021 were reviewed. Data collected included signalment, tumor type, dosing regimen, prior treatments, best response to therapy, progression-free interval (PFI), and adverse events. Forty-two tumor types were identified, with metastatic osteosarcoma (OSA), thyroid carcinoma, apocrine gland anal sac adenocarcinoma (AGASACA), insulinoma, nasal carcinoma, and melanoma being most common. The median starting toceranib dose was 2.64 mg/kg (range: 1.83--3.16 mg/kg), and all dogs were treated on a Monday- Wednesday-Friday schedule. The objective response rate (complete or partial response) was low at 12.2%, while stable disease was the most common outcome and was observed in 48.3% of dogs. Median progression free interval for all patients was 145 days, but this number varied greatly by tumor type: metastatic OSA (67 days), AGASACA (189 days), thyroid carcinoma (427 days), insulinoma (233 days), nasal carcinoma (356 days), and melanoma (91 days). Hematologic and biochemical adverse events were uncommon and mostly mild. Anemia (21.5%), neutropenia (10.5%), and thrombocytopenia (7.3%) were the most frequent hematologic toxicities. Gastrointestinal adverse events occurred in 62.6% of patients, primarily diarrhea, inappetence, and vomiting, though most were mild and manageable with dose adjustments. Proteinuria developed in 13.4% of dogs. Treatment discontinuation due to adverse events was observed in 11.4% of cases. Despite its relatively low objective response rate, toceranib provided stable disease in many cases, potentially slowing tumor progression. However, response rates varied by tumor type, with nasal carcinoma demonstrating the highest objective response rate (23%) and metastatic osteosarcoma and melanoma among the lowest (9.5% and 9%, respectively). Compared to conventional chemotherapy, toceranib had a lower likelihood of inducing an objective tumor response for several tumors but offered prolonged disease stabilization in select cases. This study highlights the need for refined case selection when prescribing toceranib for non-mast cell neoplasia. While some tumor types, such as nasal carcinoma and thyroid carcinoma, appear to derive meaningful benefit, others show limited response. Given the potential for adverse events and the risk of treatment futility, further prospective studies are needed to optimize dosing regimens, combination therapies, and patient selection criteria.Item Therapeutic potential of tongue exercise on tongue force during swallowing in a rodent model of hypoglossal (XII) motor neuron loss(University of Missouri--Columbia, 2025) Oti, Grace; Nichols, Nicole L.; Lever, Teresa E.[EMBARGOED UNTIL 05/01/2026] Progressive loss of hypoglossal (XII) motor neurons results in tongue weakness as well as impaired swallowing and breathing, and is observed in neuromuscular disorders, e.g. amyotrophic lateral sclerosis (ALS). These deficits significantly diminish quality of life and increase the risk of malnutrition, dehydration, and aspiration pneumonia, yet targeted treatments remain unavailable. To explore potential therapies, we employed a rat model of XII axis degeneration using intralingual injections of cholera toxin B conjugated to saporin (CTB-SAP), which selectively targets XII motor neurons. Previous studies demonstrated that high-repetition, low-resistance tongue exercise improves tongue motility and lick force in this model. However, it remains unknown if tongue force (i.e., tongue strength) during swallowing is affected in CTB-SAP rats ± tongue exercise. Thus, this thesis aimed to develop a surgical protocol to apply superior laryngeal nerve (SLN) stimulation in rats to repetitively evoke swallowing while assessing maximum tongue force, allowing us to test the following two hypotheses: 1) CTB-SAP rats demonstrate decreased tongue force during swallowing vs. controls; and 2) tongue exercise mitigates these CTB-SAP-induced deficits. Adult male rats received intralingual CTB-SAP or control injections and were assigned to sham or exercise groups (n=9–11/group). Nine days later, swallows were evoked in anesthetized rats using SLN electrical stimulation across ascending and descending intensities (10–40 µA). Simultaneous tongue strain gauge recordings were used to assess swallowing function, where recordings were subsequently analyzed by a customized MATLAB code to quantify four outcome measures: total number of evoked swallows, swallow rate, inter-swallow interval, and average tongue force. Our results demonstrate that: 1) 30 µA and 40 µA stimuli evoked maximum tongue force during swallowing across all groups; 2) average tongue force during swallowing was reduced in CTB-SAP rats vs. controls, while all other swallowing metrics remained unaffected across groups; and 3) tongue exercise did not significantly improve any of the swallowing metrics. While no statistically significant differences were detected between the sham and exercise groups, there was an observable improvement in average tongue force for CTB-SAP + exercise rats compared to CTB-SAP + sham exercise rats which may be clinically relevant. In conclusion, this study optimized SLN stimulation as an effective method for assessing tongue strength during swallowing. Our collective findings confirm that intralingual injections of CTB-SAP induce deficits in tongue force during swallowing that may be mitigated by a high-repetition, low force tongue exercise paradigm, and highlight the translational potential of this model for exploring therapeutic strategies in ALS research.Item Evaluating peripheral leukocyte ratios to predict disease status and outcome in dogs with appendicular osteosarcoma(University of Missouri--Columbia, 2025) Olson, Katherine; Bryan, Jeffrey[EMBARGOED UNTIL 05/01/2026] This study investigates the prognostic significance of peripheral leukocyte ratios and myeloid-derived suppressor cells (MDSCs) in dogs with appendicular osteosarcoma, a highly immunogenic and aggressive cancer. Osteosarcoma develops similarly in humans and dogs and is associated with high rates of tumor progression and metastasis. Immune cell ratios, such as the lymphocyte-monocyte ratio (LMR), neutrophillymphocyte ratio (NLR), and eosinophil-lymphocyte ratio (ELR) have been explored in human oncology as potential biomarkers for cancer prognosis, though these have been less studied in veterinary oncology. MDSCs, immature myeloid cells involved in immune suppression and tumor progression, accumulate in both the peripheral circulation and tumor microenvironment in osteosarcoma patients and may correlate with disease stage. This study aimed to assess the relationship between leukocyte ratios and clinical outcomes in dogs treated with amputation and carboplatin chemotherapy. A retrospective study was conducted evaluating 136 dogs diagnosed with appendicular osteosarcoma from 2016 to 2022 at two veterinary institutions. The study analyzed medical records to examine the prognostic significance of leukocyte ratios (LMR, NLR, ELR), absolute monocyte count, and alkaline phosphatase (ALP) levels in relation to progression-free interval (PFI) and overall survival time (OST). Survival analysis was performed, and receiver operating characteristic (ROC) curves were used to identify cutoff values for these biomarkers. Additionally, a prospective cohort of dogs diagnosed between October 2022 and December 2024 was monitored for trends in MDSC levels, monocyte counts, LMR, and ALP during treatment. The median age of dogs at diagnosis was 8 years, and the most common tumor locations were the distal radius and proximal humerus. Elevated ALP levels were significantly associated with shorter PFI and OST. Proximal humerus tumors were associated with worse survival outcomes. Lymphocyte and monocyte counts did not show prognostic significance, but the LMR at diagnosis correlated with both PFI and OST. Dogs with an LMR below 2.81 had significantly shorter PFI (127.5 days vs. 190 days, p = 0.0003) and OST (198 days vs. 295 days, p = 0.0011) compared to those with higher LMR values. The NLR also correlated with PFI, with an NLR greater than 2.99 associated with shorter progression-free survival. In contrast, the ELR did not provide significant prognostic differentiation. Changes in LMR and NLR during treatment suggested their potential as biomarkers for monitoring disease status, especially in relation to metastatic disease. In the prospective cohort, three dogs were monitored for trends in monocyte count, LMR, and MDSC levels during chemotherapy. There was an interesting but inconsistent correlation between LMR and MDSC at various stages of treatment, but no consistent relationship observed. The two dogs in this cohort that developed metastatic disease had a higher relative population of polymorphonuclear MDSCs (pMDSCs) at diagnosis compared to the dog that was 15-months disease free, who had a higher relative population of circulating mononuclear MDSCs (mMDSCs). Further studies are warranted to evaluate the relationship between absolute MDSCs and LMR, as well as the relative circulating levels of pMDSCs and mMDSCs for their influence on prognosis and disease burden. This study highlights the prognostic value of peripheral leukocyte ratios, especially LMR and NLR, in dogs with appendicular osteosarcoma. These biomarkers were associated with disease status and may provide a non-invasive, cost-effective means of assessing prognosis. Further research is needed to refine their clinical applicability and to better understand the role of MDSCs as potential biomarkers for osteosarcoma progression and treatment response.Item Lattice Radiation Therapy (LRT) for macroscopic soft tissue sarcomas in dogs(University of Missouri--Columbia, 2025) Morales Coll, Valerie; Maitz, Charles[EMBARGOED UNTIL 05/01/2026] Soft tissue sarcomas (STS) are common tumors in dogs with many cross-species similarities existing between canine and human STS including pathologic and molecular features. Spatially fractionated radiotherapy, utilizing an intensity-modulated technique known as Lattice Radiation Therapy (LRT), enables the safe delivery of hypofractionated, dose-escalated treatment to large tumors and has been associated with the induction of immune responses. Seven dogs were prospectively randomized to receive either palliative radiation (n=3, 20 Gy in 5 daily fractions) or LRT (n=4, 20 Gy to 95% of the PTV with a simultaneous integrated boost of 66.7 Gy delivered every other day). Tumor biopsy was performed before the first dose of radiation therapy, and at the end of the final dose of radiation. The peripheral blood mononuclear cell was collected before the first dose of radiation therapy, and at the end of the final dose of radiation as well as 2-weeks post completion of treatment. Analysis of immune response within the tumor microenvironment will be analyzed using the Nanostring Canine IO panel. An overall response rate of 50% was noted in the LRT group. While no local tumor progression was observed in the LRT group, all 3 (100%) patients in the palliative RT had evidence of local tumor progression at 21-, 35- and 150-days post radiation. Median overall survival was 436 days in patients receiving LRT versus 194 days in the pRT cohort. These results suggest that LRT can be safely administered to canine patients with large macroscopic sarcomas and may confer improved local control and survival outcomes. Findings in gene expression in patients receiving LRT can be potentially correlated with important signaling pathways. Collectively these findings suggest dogs with naturally occurring tumors can serve as valuable translational models to bridge current gaps in our understanding and help accelerate clinical translation of Lattice approaches.Item The unstructured interstitial pattern in canine thorax radiography underestimates and may fail to identify respiratory disease compared to computed tomography(University of Missouri--Columbia, 2025) Baumgardner, Rachel; Reinero, Carol[EMBARGOED UNTIL 05/01/2026] In dogs, lung disease presenting with a radiographic unstructured interstitial pattern (UnIP) poses a diagnostic challenge due to varied clinical signs, non-specific differentials, and need for tissue sampling to confirm the pathologic process. The terminology describing patterns on thoracic radiography (TR) can be misleading in assuming an interstitial pattern implies disease of the pulmonary interstitium. Thoracic computed tomography (CT) is more likely to predict anatomic localization on a subgross level with robust evidence for CT patterns/subpatterns having corresponding histologic correlates in people. The study objective is to show that dogs with a UnIP on TR (1) have multiple CT patterns and subpatterns reflecting pathology beyond the interstitium and that (2) CT supports final definitive diagnoses encompassing more disorders than a UnIP on TR would imply. Thirty-six dogs with respiratory clinical signs, a UnIP on TR, thoracic CT, and additional tests to determine final diagnosis were retrospectively enrolled. Thoracic CT scans were assessed for presence or absence of four major CT patterns and 14 subpatterns. Final diagnoses were obtained by comprehensive evaluation of clinicopathologic abnormalities. Thoracic CT identified disease beyond the interstitium in all patients with a sole UnIP including large airway, small airway, and mixed airway/parenchyma disease. Mean (range) number of final diagnoses was 5 (1-13) with 33/36 (92%) dogs having >1 final diagnosis. Despite the classic paradigm for radiographic UnIP corresponding to interstitial disease, CT provides more comprehensive anatomic correlates, expanding the differential list for respiratory disease.