Dataset Information

Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs.

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.

SUBMITTER: Heaton CM

PROVIDER: S-EPMC7096647 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs.

Heaton Caitlin M CM Fernandes Arthur F A AFA Jark Paulo C PC Pan Xuan X

Journal of veterinary internal medicine 20200124 2

<h4>Background</h4>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.<h4>Hypothesis/aim</h4>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 ...[more]

PMID: 31977135

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Project description:The apocrine sweat gland is a unique skin appendage in humans compared to mouse and chicken models. The absence of apocrine sweat glands in chicken and murine skin largely restrains further understanding of the complexity of human skin biology and skin diseases, like hircismus. Sheep may serve as an additional system for skin appendage investigation owing to the distributions and histological similarities between the apocrine sweat glands of sheep trunk skin and human armpit skin. To understand the molecular mechanisms underlying morphogenesis of apocrine sweat glands in sheepskin, transcriptome analyses were conducted to reveal 1631 differentially expressed genes that were mainly enriched in three functional groups (cellular component, molecular function and biological process), particularly in gland, epithelial, hair follicle and skin development. There were 7 Gene Ontology (GO) terms enriched in epithelial cell migration and morphogenesis of branching epithelium that were potentially correlated with the wool follicle peg elongation. An additional 5 GO terms were enriched in gland morphogenesis (20 genes), gland development (42 genes), salivary gland morphogenesis and development (8 genes), branching involved in salivary gland morphogenesis (6 genes) and mammary gland epithelial cell differentiation (4 genes). The enriched gland-related genes and two Kyoto Encyclopedia of Genes and Genomes pathway genes (WNT and TGF-β) were potentially involved in the induction of apocrine sweat glands. Genes named BMPR1A, BMP7, SMAD4, TGFB3, WIF1, and WNT10B were selected to validate transcript expression by qRT-PCR. Immunohistochemistry was performed to localize markers for hair follicle (SOX2), skin fibroblast (PDGFRB), stem cells (SOX9) and BMP signaling (SMAD5) in sheepskin. SOX2 and PDGFRB were absent in apocrine sweat glands. SOX9 and SMAD5 were both observed in precursor cells of apocrine sweat glands and later in gland ducts. These results combined with the upregulation of BMP signaling genes indicate that apocrine sweat glands were originated from outer root sheath of primary wool follicle and positively regulated by BMP signaling. This report established the primary network regulating early development of apocrine sweat glands in sheepskin and will facilitate the further understanding of histology and pathology of apocrine sweat glands in human and companion animal skin.

Dataset Information

Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs.

Background

Hypothesis/aim

Animals

Methods

Result

Conclusions

Publications

Evaluation of toceranib for treatment of apocrine gland anal sac adenocarcinoma in dogs.

Similar Datasets

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