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Journal of Veterinary Internal Medicine May 2020Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery.
BACKGROUND
Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery.
OBJECTIVES
To investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor-infiltrating regulatory T cells (Tregs), and intratumoral hypoxia.
ANIMALS
Ninety-two client-owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma.
METHODS
Retrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor-2 (VEGFR2) and the number of Foxp3 Tregs and hypoxia-inducible factor (HIF)-1α cells in tumor tissues sampled at the first and second (recurrence) surgeries.
RESULTS
Median TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65-0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF-1α cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries.
CONCLUSIONS AND CLINICAL IMPORTANCE
Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.
Topics: Adenocarcinoma; Animals; Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Dog Diseases; Dogs; Female; Indoles; Male; Neoplasm Recurrence, Local; Neoplasms; Pyrroles; Retrospective Studies; Treatment Outcome; Tumor Microenvironment; Vascular Endothelial Growth Factor Receptor-2
PubMed: 32267594
DOI: 10.1111/jvim.15768 -
Journal of Veterinary Internal Medicine Mar 2020There is no widely accepted standard medical treatment for apocrine gland anal sac adenocarcinoma (AGASACA) in dogs. Targeted agents such as toceranib may be effective...
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.
Topics: Adenocarcinoma; Anal Gland Neoplasms; Anal Sacs; Animals; Apocrine Glands; Disease-Free Survival; Dog Diseases; Dogs; Female; Indoles; Male; Pyrroles; Retrospective Studies; Treatment Outcome; Wisconsin
PubMed: 31977135
DOI: 10.1111/jvim.15706 -
Animals : An Open Access Journal From... Dec 2021Limited data are available on canine and feline non-neoplastic anal sac disease. Therefore, the aim of this study was to obtain observational data on the incidence,...
Limited data are available on canine and feline non-neoplastic anal sac disease. Therefore, the aim of this study was to obtain observational data on the incidence, predisposing factors, diagnosis, treatment, and recurrence rate of canine and feline anal sac disease. To this end, a questionnaire was distributed among veterinarians. The incidence of non-neoplastic anal sac disease was estimated at 15.7% in dogs and 0.4% in cats. Predisposing factors were diarrhea, skin problems, several dog breeds, and particularly small breed dogs, male cats, British shorthairs, and obesity in dogs. Diagnosis was made based on the presence of clinical signs and characteristics of the anal sac content. Manual expression and treating any potential underlying disease were the most important treatments for all three types of non-neoplastic anal sac disease. Anal sacculectomy was performed in refractory cases. The most recurrent anal sac disease condition was impaction. Diagnosis of anal sac disease should be based on clinical signs and rectal examination, as the evaluation of the anal sac content is not reliable. Surgical outcomes of anal sacculectomy can be improved when surgery is performed after medical management. Future studies should investigate these findings in prospective trials.
PubMed: 35011201
DOI: 10.3390/ani12010095 -
Scientific Reports Jul 2023Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned... (Comparative Study)
Comparative Study
Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned dogs from 96 breeds with 23 common tumor types, including those whose mutation profile are unknown (anal sac carcinoma and neuroendocrine carcinoma) or understudied (thyroid carcinoma, soft tissue sarcoma and hepatocellular carcinoma). We discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. As in human cancer, TP53 is the most commonly mutated gene, detected in 22.5% of canine tumors overall. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E (equivalent of V600E in humans) in urothelial carcinoma. Our findings better position canines as a translational model of human cancer to investigate a wide spectrum of targeted therapies.
Topics: Animals; Dogs; Oncogene Proteins; Mutation; Neoplasms; Humans; Antineoplastic Agents
PubMed: 37414794
DOI: 10.1038/s41598-023-37505-2 -
Veterinary Dermatology Oct 2022Little information has been published regarding treatment of canine anal sacculitis (AS).
BACKGROUND
Little information has been published regarding treatment of canine anal sacculitis (AS).
OBJECTIVES
Primary objective: determine the outcomes of AS local treatment at the referral dermatology service of the authors' institution.
SECONDARY OBJECTIVE
determine signalment, body condition score (BCS), stool quality and comorbidities associated with AS.
ANIMALS
Thirty-three dogs with AS presented to the referral dermatology service between 1 January 2010 and 31 March 2021.
MATERIALS AND METHODS
An electronic medical record search was conducted. Information regarding sex, breed, age at disease onset, weight, BCS, stool quality, comorbidities, treatment and treatment outcome were collected. Treatment outcome was categorised as "resolved clinically", "clinical signs resolved per owner", "did not complete treatment" or "failed". Dogs were excluded if seen by another service, not treated for AS, or if perianal sinuses (fistulae), anal sac masses, or anal sac abscesses were identified.
RESULTS
Nineteen dogs were male and 14 female. Twenty-four breeds were included. Average age at disease onset was 4.4 years. Average BCS was 5.8 of 9. Stool quality was "poor" in seven of 33 and normal in 23 of 33 cases. Atopic dermatitis was the most common comorbidity (12 of 33). Treatment typically consisted of anal sac flushing with saline followed by infusion using a commercially available steroid/antibiotic/antifungal ointment. Treatment was repeated on average 2.9 times. Resolution of AS was obtained in 24 of 33 cases, clinical signs resolved per owner in four of 33, five of 33 cases did not complete treatment, and no cases failed treatment.
CONCLUSIONS AND CLINICAL RELEVANCE
Local treatment with flushing and infusion is effective for treating AS in dogs.
Topics: Anal Sacs; Animals; Dermatitis, Atopic; Dog Diseases; Dogs; Female; Male; Rectal Fistula; Retrospective Studies
PubMed: 35866443
DOI: 10.1111/vde.13102 -
Canadian Journal of Veterinary Research... Jan 2021The aim of the present study was to characterize the bacterial microbiota of anal sacs in healthy dogs using NGS. Swabs were used to sample the rectum and secretions...
The aim of the present study was to characterize the bacterial microbiota of anal sacs in healthy dogs using NGS. Swabs were used to sample the rectum and secretions from each anal sac in 15 healthy dogs. DNA was extracted from swabs and the V4 hypervariable region of the 16S rRNA gene was amplified and sequenced with Illumina MiSeq. Overall, 14 different bacterial phyla were identified in the rectum and in both anal sacs, the 5 main ones being Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria. The rectum had higher microbial diversity and richness than the left and right anal sacs. Community membership and structure significantly differed between the rectum and both anal sacs, but not between the right and the left anal sacs. This study showed that the diversity and richness of the bacterial microbiota of the anal sacs in dogs is greater than what has been reported in previous studies with culture-based methods. In conclusion, the bacterial microbiota of the anal sacs in dogs varies between individuals and differs from the rectal bacterial microbiota.
Topics: Anal Sacs; Animals; Bacteria; DNA, Bacterial; Dogs; Microbiota; RNA, Bacterial; RNA, Ribosomal, 16S; Rectum
PubMed: 33390648
DOI: No ID Found -
Cancers Dec 2022Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant...
Canine apocrine gland anal sac adenocarcinoma (AGASACA) is an aggressive canine tumor originating from the anal sac glands. Surgical resection, with or without adjuvant chemotherapy, represents the standard of care for this tumor, but the outcome is generally poor, particularly for tumors diagnosed at an advanced stage. For this reason, novel treatment options are warranted, and a few recent reports have suggested the activation of the immune checkpoint axis in canine AGASACA. In our study, we developed canine-specific monoclonal antibodies targeting PD-1 and PD-L1. A total of 41 AGASACAs with complete clinical and follow-up information were then analyzed by immunohistochemistry for the expression of the two checkpoint molecules (PD-L1 and PD-1) and the presence of tumor-infiltrating lymphocytes (CD3 and CD20), which were evaluated within the tumor bulk (intratumor) and in the surrounding stroma (peritumor). Seventeen AGASACAs (42%) expressed PD-L1 in a range between 5% and 95%. The intratumor lymphocytes were predominantly CD3+ T-cells and were positively correlated with the number of PD-1+ intratumor lymphocytes ( = 0.36; 0.02). The peritumor lymphocytes were a mixture of CD3+ and CD20+ cells with variable PD-1 expression (range 0-50%). PD-L1 expression negatively affected survival only in the subgroup of dogs treated with surgery alone ( 14; 576 vs. 235 days). The presence of a heterogeneous lymphocytic infiltrate and the expression of PD-1 and PD-L1 molecules support the relevance of the immune microenvironment in canine AGASACAs and the potential value of immune checkpoints as promising therapeutic targets.
PubMed: 36551672
DOI: 10.3390/cancers14246188 -
Veterinary Research Forum : An... 2023Volatile compounds of anal sac secretions are odorant chemicals used across the carnivores for social communication such as identifying individuals and group membership....
Volatile compounds of anal sac secretions are odorant chemicals used across the carnivores for social communication such as identifying individuals and group membership. Odor profiles taken from expressed anal sac secretions of some species of carnivores have been detected in previous studies. In this study, the volatile compounds of anal sac secretions between five male and five female domestic dogs () were compared. Volatile chemicals were extracted, separated, and analyzed by gas chromatography-mass spectrometry with solid-phase micro-extraction and identified from their electron ionization mass spectra and Kovats retention indices. The results showed the presence of various types of compounds including organic fatty acids, ketones, aldehydes, esters, and alcohols in the anal sac secretions of dogs. Greater amounts of diversity and esters, and lower amounts of alcohols were detected in the anal sac secretions of females compared to males. This was accompanied by finding citrate and acetic acid ester only in the females. Furthermore, presence of some sex-specific organic compounds like dimethylcyclopentyl ethanone indicates that the volatile profiles of anal sac secretions in 10 domestic dogs are differentiated by host sex.
PubMed: 37033781
DOI: 10.30466/vrf.2023.1983063.3714 -
Animals : An Open Access Journal From... Jun 2021Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the...
Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear.
PubMed: 34199347
DOI: 10.3390/ani11061649 -
BMC Ecology and Evolution Sep 2021Chemical communication is an important aspect of the behavioural ecology of a wide range of mammals. In dogs and other carnivores, anal sac glands are thought to convey...
BACKGROUND
Chemical communication is an important aspect of the behavioural ecology of a wide range of mammals. In dogs and other carnivores, anal sac glands are thought to convey information to conspecifics by secreting a pallet of small volatile molecules produced by symbiotic bacteria. Because these glands are unique to carnivores, it is unclear how their secretions relate to those of other placental mammals that make use of different tissues and secretions for chemical communication. Here we analyse the anal sac glands of domestic dogs to verify the secretion of proteins and infer their evolutionary relationship to those involved in the chemical communication of non-carnivoran mammals.
RESULTS
Proteomic analysis of anal sac gland secretions of 17 dogs revealed the consistently abundant presence of three related proteins. Homology searches against online databases indicate that these proteins are evolutionary related to 'odorant binding proteins' (OBPs) found in a wide range of mammalian secretions and known to contribute to chemical communication. Screening of the dog's genome sequence show that the newly discovered OBPs are encoded by a single cluster of three genes in the pseudoautosomal region of the X-chromosome. Comparative genomic screening indicates that the same locus is shared by a wide range of placental mammals and that it originated at least before the radiation of extant placental orders. Phylogenetic analyses suggest a dynamic evolution of gene duplication and loss, resulting in large gene clusters in some placental taxa and recurrent loss of this locus in others. The homology of OBPs in canid anal sac glands and those found in other mammalian secretions implies that these proteins maintained a function in chemical communication throughout mammalian evolutionary history by multiple shifts in expression between secretory tissues involved in signal release and nasal mucosa involved in signal reception.
CONCLUSIONS
Our study elucidates a poorly understood part of the biology of a species that lives in close association with humans. In addition, it shows that the protein repertoire underlying chemical communication in mammals is more evolutionarily stable than the variation of involved glands and tissues would suggest.
Topics: Anal Sacs; Animals; Carrier Proteins; Dogs; Female; Mammals; Odorants; Proteomics
PubMed: 34565329
DOI: 10.1186/s12862-021-01910-w