Expression of Phosphorylated Signal Transducer and Activator of Transcription 3 and its Prognostic Significance in Canine Anal Sac Adenocarcinoma

Mosca, Andrea; Restif, Olivier; Dobson, Jerome E.; Hughes, Katherine

doi:10.1016/j.jcpa.2020.11.002

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…Prognostic factors for canine AGASACA have been reported to include tumor and lymph node size, histologic pattern, necrosis, and lymph vascular invasion [12][13][14][15]. In addition, increased expression of Ki67, nuclear accumulation of p53, overexpression of p63, and vascular endothelial growth factor can be diagnostic indicators of AGASACA [16].…”

Section: Introductionmentioning

confidence: 99%

Establishment of an experimental model of canine apocrine gland anal sac adenocarcinoma organoid culture using a three-dimensional culture method

Nagashima,

Yamamoto,

Elbadawy

et al. 2024

Preprint

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Canine apocrine gland anal sac adenocarcinoma (AGASACA) is a rare, malignant tumor in dogs. To date, few cell lines are available and used to establish the current treatment protocols. Organoids are three-dimensional cell cultures derived mainly from stem cells and can reproduce tissueʼs epithelial structure, function, and genetics, and thus, of great promise in precision medicine. In the current investigation, 6 AGASACA organoids were developed from surgically removed tissues of AGASACA-affected dogs and analyzed for comparison with the original tissues. AGASACA organoids were successfully generated from all cases and were CK7 positive and CK20 negative, consistent with previous reports in dogs and humans. Electron microscopic images of AGASACA organoids showed organelles, including numerous granules and fat droplets that characterize apocrine gland cells. In addition, treatment of the AGASACA organoids with carboplatin, mitoxantrone, toceranib, and lapatinib revealed different sensitivity among lineages, with lapatinib, in particular, being divided into sensitive and resistant lineages. In contrast, toceranib showed generally high efficacy in all organoids. In conclusion, our established AGASACA organoids have the potential to be an experimental tool for the development of novel therapies for canine and human apocrine gland adenocarcinoma.

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Section: Introductionmentioning

confidence: 99%

Establishment of an experimental model of canine apocrine gland anal sac adenocarcinoma organoid culture using a three-dimensional culture method

Nagashima,

Yamamoto,

Elbadawy

et al. 2024

Preprint

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“…The median survival time ranges from one to two years, depending on the clinical stage [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. The prognostic factors include regional lymph node metastasis at the time of diagnosis, tumor and regional lymph node size, histological pattern, necrosis, and lymphovascular invasion [ 14 , 15 , 16 , 17 , 18 ]. Conversely, the prognostic significance of hypercalcemia remains controversial, and the Ki67 proliferation index does not demonstrate prognostic value [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Monoclonal Antibodies Targeting Canine PD-L1 and PD-1 and Their Clinical Relevance in Canine Apocrine Gland Anal Sac Adenocarcinoma

Minoli

Licenziato

Kocikowski

et al. 2022

Cancers

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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 (ρ = 0.36; p = 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 (n = 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.

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“…Although abnormalities in STAT activity have been extensively investigated in various human malignancies, veterinary research has mainly focused on investigating STAT3 expression in canine and feline mammary tumors, canine anal sac carcinoma, canine diffuse large B-cell lymphoma, feline oral squamous cell carcinoma, and feline injection-site fibrosarcoma [ 1 , 5 , 29 , 35 , 36 , 37 , 38 , 39 ]. Given the similar features shared between feline mammary tumors and human breast cancers, it is essential to investigate the involvement of STAT3 and STAT5a in feline mammary tumors [ 6 , 11 , 58 ].…”

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confidence: 99%

Reduction of phosphorylated signal transducer and activator of transcription-5 expression in feline mammary carcinoma

OWAKI,

MURAKAMI,

KATO

et al. 2024

The Journal of Veterinary Medical Science

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Signal transducers and activators of transcription (STAT) is a family of transcription factors involved in various normal physiological cellular processes. Moreover, STATs have been recently identified as novel therapeutic targets for various human tumors. STAT3, STAT5a, and STAT6 have been suggested to be involved in tumorigenesis in human breast cancer. Owing to the similarity between feline mammary carcinomas (FMCs) and human breast cancers, these factors may play an important role in FMCs. However, studies on the expression of STATs in animal tumors are limited.Therefore, in this study, we aimed to characterize the expression of total STAT5 (tSTAT5) and phosphorylated STAT5 (pSTAT5) in FMCs, feline mammary adenomas, non-neoplastic proliferative mammary gland lesions, and normal feline mammary glands using immunohistochemistry. High expression of tSTAT5 was observed in the cytoplasm of all the samples assessed in this study.Moreover, high expression of tSTAT5 was observed in the nucleus; however, its levels varied depending on the lesion. The percentage of pSTAT5-nuclear positive cells varied among normal feline mammary glands (40.1 ± 25.1%), and non-neoplastic lesions, including mammary hyperplasia (43.2 ± 28.6%) and fibroadenomatous changes (18.0 ± 13.6%). Moreover, the percentage of pSTAT5-nuclearpositive cells in feline mammary adenomas was 24.5 ± 19.2%, which was significantly reduced in feline mammary carcinomas (2.4 ± 5.6%), regardless of histopathological subtype. This study suggests that decreased STAT5 activity may be involved in the development and malignant progression of feline mammary carcinomas.

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Expression of Phosphorylated Signal Transducer and Activator of Transcription 3 and its Prognostic Significance in Canine Anal Sac Adenocarcinoma

Cited by 5 publications

References 29 publications

Establishment of an experimental model of canine apocrine gland anal sac adenocarcinoma organoid culture using a three-dimensional culture method

Establishment of an experimental model of canine apocrine gland anal sac adenocarcinoma organoid culture using a three-dimensional culture method

Development of Monoclonal Antibodies Targeting Canine PD-L1 and PD-1 and Their Clinical Relevance in Canine Apocrine Gland Anal Sac Adenocarcinoma

Reduction of phosphorylated signal transducer and activator of transcription-5 expression in feline mammary carcinoma

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