Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.
Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have high recurrence rates. Immunostimulatory gene therapy is a promising approach in veterinary oncology. This phase I dose-escalation study was performed to determine toxicity and feasibility of gene therapy with feline granulocyte-macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas. Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative intratumoral injections followed by magnetofection were given. Four control cats received only surgical treatment. Adverse events were recorded and correlated according to the veterinary co-operative oncology group toxicity scale. An enzyme-linked immunosorbent assay was performed to detect plasma feGM-CSF concentrations. No significant treatment related toxicity was observed. Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA applied by magnetofection is safe and feasible for phase II testing.
Numerous investigations and reports have covered the potential negative effects of an excess of calcium (Ca) in the skeletal development of young dogs. However, it still remains unclear why not all puppies, particularly of larger breeds, develop clinical signs of skeletal disorders after an overexposure to Ca. This trial with the small Beagle breed and a larger Foxhound-crossbred dog (with an adult weight of around 35 kg) investigated the effects of Ca-excess on parameters of bone growth. The employed small breed is known for its chondrodystrophic predispositions, no such data are reported for the slender hound-type Foxhound-crossbred dogs. The Ca-supply had no influence on weight development and general health of the dogs. The measurements of bone lengths and widths in X-rays of the forearm of Beagles and Foxhound-crossbred dogs at 6 weeks of age, and again after a period of overexposure to Ca at about 27 weeks of age, revealed a growth-reducing influence only in Beagles, without influence on clinical parameters of skeletal health.
The objective of the study was to determine the effect of topical 0.5% tropicamide on intraocular pressure (IOP) in normotensive feline eyes. IOP was measured bilaterally in 70 clinically healthy cats and gonioscopy (and goniophotography) was performed. Thereafter, 50 cats were treated unilaterally with one drop of 0.5% tropicamide. The contralateral, left eye served as a control. In the placebo group consisting of 20 cats, one drop of physiologic saline solution was administered to the right eye. In all cats, IOP of both eyes was measured 30, 60 and 90 min after topical administration. After unilateral tropicamide application, IOP increased significantly both in the right and in the left eye. Maximum average IOP increase was observed at the control measurement performed 90 min after treatment, with an elevation of 3.8 +/- 4.2 mmHg in the right eye and 3.5 +/- 3.6 mmHg in the left eye. Maximum IOP increase after treatment was 18.0 mmHg in the treated eye and 17.0 mmHg in the left eye. Measurements made at 60 min after treatment revealed a significantly higher increase in IOP in the right eye as compared to the left eye (P60 < 0.05), whereas the differences between right and left eye in IOP increase were not significant at 30 and 90 min after mydriatic application (P30 = 0.123; P90 = 0.305). Although tropicamide-induced mydriasis was observed in the treated eye, the contralateral eye did not show any changes in pupillary function at any time. With increasing age of the cats, IOP increase was found to be more moderate, whereas the gender of the cats did not have any significant influence on IOP changes. In the 20 cats in the placebo group, no significant changes in IOP were observed. We conclude that topical 0.5% tropicamide causes a significant elevation of IOP in the treated and untreated eye in normal cats.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.