ORCID Profile
0000-0002-8914-7767
Current Organisation
Colorado State University
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Publisher: Wiley
Date: 08-07-2016
DOI: 10.1111/VCO.12101
Abstract: 25-hydroxyvitamin D (25(OH)D) is important in bone health as well as many diseases including cancer. Supplementation may increase responsiveness of cancer cells to chemotherapy. Serum 25(OH)D, intact parathyroid hormone (iPTH) and canine C-reactive protein (c-CRP) were measured in healthy dogs and dogs with haemoabdomen. Regression analysis determined optimal 25(OH)D concentrations. In healthy dogs (n = 282), mean iPTH concentrations correlated inversely (r(2) = 0.88, P 150 ng mL(-1) . Relative risk of cancer increased with decreasing 25(OH)D concentrations [RR = 3.9 for 25(OH)D below 40 ng mL(-1) (P = 0.0001)]. Serum 25(OH)D concentrations in dogs vary widely, and are influenced by dietary VitD content. Serum vitD measurement can identify dogs for which supplementation may improve health and response to cancer therapy.
Publisher: American Chemical Society
Date: 2010
Publisher: Public Library of Science (PLoS)
Date: 06-09-2018
Publisher: Wiley
Date: 20-10-2012
DOI: 10.1111/J.1476-5829.2011.00298.X
Abstract: Thymidine kinase 1 (TK1) is a soluble biomarker associated with DNA synthesis. This prospective study evaluated serum TK1 activity in dogs presenting with hemoabdomen and a splenic mass. An ELISA using azidothymidine as a substrate was used to evaluate TK1 activity. Sixty-two dogs with hemoabdomen and 15 normal controls were studied. Serum TK1 activity was significantly higher in dogs with hemangiosarcoma (HSA) than in normal dogs (mean ± SEM = 17.0 ± 5.0 and 2.01 ± 0.6, respectively), but not dogs with benign disease (mean ± SEM = 10.0 ± 3.3). Using a cut-off of 6.55 U/L, TK activity demonstrated a sensitivity of 0.52, specificity of 0.93, positive predictive value of 0.94 and negative predictive value of 0.48 for distinguishing HSA versus normal. When interval thresholds of 7.95 U/L were used together, diagnostic utility was increased. Serum TK1 evaluation may help to discriminate between benign disease and HSA in dogs with hemoabdomen and a splenic mass.
Publisher: SAGE Publications
Date: 27-07-2010
Abstract: There is an increasing need for more accurate prognostic and predictive markers in veterinary oncology because of an increasing number of treatment options, the increased financial costs associated with treatment, and the emotional stress experienced by owners in association with the disease and its treatment. Numerous studies have evaluated potential prognostic and predictive markers for veterinary neoplastic diseases, but there are no established guidelines or standards for the conduct and reporting of prognostic studies in veterinary medicine. This lack of standardization has made the evaluation and comparison of studies difficult. Most important, translating these results to clinical applications is problematic. To address this issue, the American College of Veterinary Pathologists' Oncology Committee organized an initiative to establish guidelines for the conduct and reporting of prognostic studies in veterinary oncology. The goal of this initiative is to increase the quality and standardization of veterinary prognostic studies to facilitate independent evaluation, validation, comparison, and implementation of study results. This article represents a consensus statement on the conduct and reporting of prognostic studies in veterinary oncology from veterinary pathologists and oncologists from around the world. These guidelines should be considered a recommendation based on the current state of knowledge in the field, and they will need to be continually reevaluated and revised as the field of veterinary oncology continues to progress. As mentioned, these guidelines were developed through an initiative of the American College of Veterinary Pathologists' Oncology Committee, and they have been reviewed and endorsed by the World Small Animal Veterinary Association.
Publisher: American Veterinary Medical Association (AVMA)
Date: 15-01-2019
Abstract: OBJECTIVE To evaluate effects of substituting mitoxantrone for doxorubicin in a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapeutic protocol for first-line treatment of dogs with multicentric intermediate- to large-cell lymphoma. DESIGN Retrospective cohort study. ANIMALS 44 dogs treated with cyclophosphamide, mitoxantrone, vincristine, and prednisone (CMOP) and 51 dogs treated with CHOP at 12 referral institutions. PROCEDURES Medical records were reviewed to determine response to treatment, progression-free survival time, and overall survival time. For dogs treated with CMOP, adverse events were also recorded. RESULTS All 44 (100%) dogs treated with CMOP and 37 of 38 (97.4%) dogs treated with CHOP had a complete or partial response. Median progression-free survival time for dogs treated with CMOP was 165 days (95% confidence interval [CI], 143 to 187 days), and median overall survival time was 234 days (95% CI, 165 to 303 days). For dogs treated with CHOP, median progression-free survival time was 208 days (95% CI, 122 to 294 days), and median overall survival time was 348 days (95% CI, 287 to 409 days). Progression-free and overall survival times were not significantly different between groups. Overall, 9 of the 44 (20%) dogs treated with CMOP had adverse events likely or probably related to mitoxantrone, but all of these adverse events were mild. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that mitoxantrone may be a reasonable substitution in a CHOP protocol for treatment of dogs with multicentric intermediate- to large-cell lymphoma when doxorubicin is contraindicated.
Publisher: American Chemical Society (ACS)
Date: 07-05-2009
DOI: 10.1021/LA900730B
Abstract: A novel surface modification technique was employed to produce a polymer modified positive contrast agent nanoparticle through attachment of well-defined homopolymers synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. A range of RAFT homopolymers including poly[N-(2-hydroxypropyl)methacrylamide], poly(N-isopropylacrylamide), polystyrene, poly(2-(dimethylamino)ethyl acrylate), poly(((poly)ethylene glycol) methyl ether acrylate), and poly(acrylic acid) were synthesized and subsequently used to modify the surface of gadolinium (Gd) metal-organic framework (MOF) nanoparticles. Employment of a trithiocarbonate RAFT agent allowed for reduction of the polymer end groups under basic conditions to thiolates, providing a means of homopolymer attachment through vacant orbitals on the Gd3+ ions at the surface of the Gd MOF nanoparticles. Magnetic resonance imaging (MRI) confirmed the relaxivity rates of these novel polymer modified structures were easily tuned by changes in the molecular weight and chemical structures of the polymers. When a hydrophilic polymer was used for modification of the Gd MOF nanoparticles, an increase in molecular weight of the polymer provided a respective increase in the longitudinal relaxivity. These relaxivity values were significantly higher than both the unmodified Gd MOF nanoparticles and the clinically employed contrast agents, Magnevist and Multihance, which confirmed the construct's ability to be utilized as a positive contrast nanoparticle agent in MRI. Further characterization confirmed that increased hydrophobicity of the polymer coating on the Gd MOF nanoparticles yielded minimal changes in the longitudinal relaxivity properties but large increases in the transverse relaxivity properties in the MRI.
Publisher: American Chemical Society (ACS)
Date: 16-03-2009
DOI: 10.1021/BM900043E
Abstract: Novel nanoscale theragnostic devices were successfully prepared through attachment of well defined, multifunctional polymer chains to gadolinium (Gd) metal-organic framework (MOF) nanoparticles. Copolymers of poly(N-isopropylacrylamide)-co-poly(N-acryloxysuccinimide)-co-poly(fluorescein O-methacrylate) were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization. The succinimide functionality was utilized as a scaffold for attachment of both a therapeutic agent, such as methotrexate, and a targeting ligand, such as H-glycine-arginine-glycine-aspartate-serine-NH(2) peptide. Employment of a trithiocarbonate RAFT agent allowed for reduction of the polymer end groups to thiolates providing a means of copolymer attachment through vacant orbitals on the Gd(3+) ions at the surface of the Gd MOF nanoparticles. These versatile, nanoscale scaffolds were shown to be biocompatible and have cancer cell targeting, bimodal imaging, and disease treatment capabilities. This unique method provided a simple yet versatile route of producing polymer-nanoparticle theragnostic materials with an unprecedented degree of flexibility in the construct, potentially allowing for tunable loading capacities and spatial loading of targeting/treatment agents, while incorporating bimodal imaging capabilities through both magnetic resonance and fluorescence microscopy.
Publisher: Wiley
Date: 07-2010
Publisher: Wiley
Date: 29-10-2019
DOI: 10.1111/VCO.12533
Abstract: Osteosarcoma is the most common paediatric primary bone malignancy. The major cause of death in osteosarcoma is drug-resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin (AF). Moreover, studies have shown that AF significantly reduces pulmonary metastases in xenotransplant models. Here, we describe a phase I/II study of AF in canine osteosarcoma, a well-recognized spontaneous model of human osteosarcoma. We performed a single-arm multicentre pilot study of AF in combination with standard of care (SOC) ( utation + carboplatin). We recruited 40 dogs to the trial and used a historical SOC-only control group (n = 26). Dogs >15 kg received 9 mg AF q3d PO and dogs <15 kg received 6 mg q3d. Follow-up occurred over at least a 3-year period. Auranofin plus SOC improved overall survival (OS) (P = .036) in all dogs treated. The improved outcome was attributable entirely to improved OS in male dogs (P = .009). At the time of writing, 10 dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that AF improves OS in male dogs when combined with SOC. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery.
No related grants have been discovered for Douglas Thamm.