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1.
J Vet Intern Med ; 34(2): 873-881, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31977135

ABSTRACT

BACKGROUND: There is no widely accepted standard medical treatment for apocrine gland anal sac adenocarcinoma (AGASACA) in dogs. Targeted agents such as toceranib may be effective in treatment of AGASACA, but the number of clinical reports investigating its efficacy is limited. HYPOTHESIS/AIM: To evaluate the efficacy of toceranib treatment of AGASACA in dogs, and to assess prognostic factors in the study population. Our hypothesis was that toceranib would provide a clinical benefit in the treatment of dogs with AGASACA. ANIMALS: Thirty-six client-owned dogs with either a cytologic or histologic diagnosis of AGASACA that were treated with toceranib alone or in combination with surgery, nonconcurrent chemotherapy or both. METHODS: Retrospective study. RESULT: The median progression-free survival (PFS) and overall survival time (OST) for the study population was 313 days and 827 days, respectively. A clinical benefit from toceranib treatment was observed in 69% of dogs, with 20.7% of dogs experiencing partial response and 48.3% of dogs experiencing stable disease. Dogs that responded to toceranib treatment had significantly prolonged PFS and OST. Hypercalcemia was a negative prognostic factor for clinical outcomes. CONCLUSIONS: Toceranib is effective in the treatment of AGASACA in dogs. Prospective, controlled clinical trials are needed to determine the efficacy of toceranib in comparison to other treatment protocols for dogs with AGASACA.


Subject(s)
Adenocarcinoma/veterinary , Anal Gland Neoplasms/drug therapy , Anal Sacs , Apocrine Glands , Dog Diseases/drug therapy , Indoles/therapeutic use , Pyrroles/therapeutic use , Adenocarcinoma/drug therapy , Anal Gland Neoplasms/mortality , Animals , Disease-Free Survival , Dog Diseases/mortality , Dogs , Female , Indoles/administration & dosage , Male , Pyrroles/administration & dosage , Retrospective Studies , Treatment Outcome , Wisconsin
2.
PLoS One ; 9(12): e113959, 2014.
Article in English | MEDLINE | ID: mdl-25536054

ABSTRACT

Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRPα and CGRPß. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton. However, the functional role of the nervous system in the response of bone to mechanical loading is unclear. We used the ulna end-loading model to induce an adaptive modeling response in CGRPα and CGRPß knockout mouse lines and their respective wildtype controls. For each knockout mouse line, groups of mice were treated with cyclic loading or sham-loading of the right ulna. A third group of mice received brachial plexus anesthesia (BPA) of the loaded limb before mechanical loading. Fluorochrome labels were administered at the time of loading and 7 days later. Ten days after loading, bone responses were quantified morphometrically. We hypothesized that CGRP signaling is required for normal mechanosensing and associated load-induced bone formation. We found that mechanically-induced activation of periosteal mineralizing surface in mice and associated blocking with BPA were eliminated by knockout of CGRPα signaling. This effect was not evident in CGRPß knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRPα deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRPα-dependent in vivo. This suggests that release of CGRP from sensory peptidergic fibers in periosteum and bone has a functional role in load-induced bone formation.


Subject(s)
Adaptation, Physiological , Bone and Bones/physiology , Calcitonin Gene-Related Peptide/metabolism , Analysis of Variance , Animals , Biomechanical Phenomena , Bone Density , Calcification, Physiologic , Fluorescent Dyes/metabolism , Mice, Inbred C57BL , Mice, Knockout , Osteogenesis , Periosteum/physiology , Signal Transduction , Ulna/physiology , Weight-Bearing/physiology
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