Prognostic impact of neoadjuvant aglepristone treatment in clinicopathological parameters of progesterone receptor‐positive canine mammary carcinomas

Guil‐Luna, Silvia; Millán, Y.; Andrés, J.; Rollón, E.; Domingo, V.; García-Macías, J.; Sánchez-Céspedes, R.; Mulas, J. Martı́n de las

doi:10.1111/vco.12175

Cited by 14 publications

(7 citation statements)

References 32 publications

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“…These apparent antiproliferative and/or pro-apoptotic activities of antigestagens in P4 responsive tissues might be responsible for the positive effects of the use of mifepristone in adjuvant therapy of some human disorders, e.g., breast cancer and endometriosis [ 50 , 51 ]. Accordingly, in dogs, positive effects of aglepristone in the clinical management of vaginal tumors and mammary carcinomas were reported, e.g., by decreasing their size [ 52 , 53 , 54 ]. Thus, in the placenta, a decreased viability of decidual cells, associated with the modulation of PCNA and a-CASP3, and disruption of cellular adhesion, as suggested by decreased expression of CX43, might represent important mechanisms in the antigestagen-induced termination of pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Antigestagens Mediate the Expression of Decidualization Markers, Extracellular Matrix Factors and Connexin 43 in Decidualized Dog Uterine Stromal (DUS) Cells

Kazemian

Pereira

Hoffmann

et al. 2022

Animals

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Feto-maternal communication in the dog involves the differentiation of stromal cells into decidual cells. As the only placental cells expressing the nuclear progesterone (P4) receptor (PGR), decidual cells play crucial roles in the maintenance and termination of pregnancy. Accordingly, to investigate possible PGR-mediated mechanisms in canine decidual cells, in vitro decidualized dog uterine stromal (DUS) cells were treated with functional PGR-blockers, mifepristone and aglepristone. Effects on decidualization markers, epithelial and mesenchymal factors, and markers of cellular viability were assessed. Decidualization increased the expression of PTGES, PGR, IGF1, and PRLR, along with ECM1, COL4 and CX43, but downregulated IGF2. DUS cells retained their mesenchymal character, and the expression of COL4 indicated the mesenchymal-epithelial transformation. Antigestagen treatment decreased the availability of PTGES, PRLR, IGF1 and PGR. Furthermore, antigestagens decreased the mRNA and protein expression of CX43, and transcriptional levels of ECM1 and COL4. Additionally, antigestagens increased levels of activated-CASP3 (a proapoptotic factor), associated with lowered levels of PCNA (a proliferation marker). These data reveal important aspects of the functional involvement of PGR in canine decidual cells, regarding the expression of decidualization markers and acquisition of epithelial-like characteristics. Some of these mechanisms may be crucial for the maintenance and/or termination of canine pregnancy.

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Section: Discussionmentioning

confidence: 99%

Antigestagens Mediate the Expression of Decidualization Markers, Extracellular Matrix Factors and Connexin 43 in Decidualized Dog Uterine Stromal (DUS) Cells

Kazemian

Pereira

Hoffmann

et al. 2022

Animals

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“…Canine mammary tumours have been suggested as a potential suitable model for studies in human breast cancer research due to the great number of similarities between them . Both human and canine mammary gland are hormone dependent; that is, they are strongly influenced by ovarian hormones, mainly oestrogen (E) and progesterone (P), which act through binding to its E receptor (ER) and P receptor (PR), respectively, and they are traditional prognostic and predictive factors in both species …”

Section: Introductionmentioning

confidence: 99%

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors

Sánchez-Céspedes

Fernández-Martínez

Raya

et al. 2017

Vet Comparative Oncology

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The vitamin D receptor (VDR) belongs to the nuclear class II receptor family. VDR is a ligand transcription factor and mediates the actions of calcitriol, the active product of vitamin D synthesis. Nowadays, it is known that the biological actions of calcitriol include the capacity to modulate cancer features, such as proliferation and differentiation, apoptosis, angiogenesis, invasion and metastasis. VDR expression has been demonstrated in human breast cancer and vitamin D has emerged as a promising targeted therapy. We analyse the VDR expression in normal and neoplastic canine mammary tissue samples and its relationship with clinicopathological parameters and progesterone/oestrogens receptors (PR/ER). Expression of VDR, Ki67 (to evaluate the proliferation index, PI), PR and ER was assessed in 50 mammary gland tissue samples from 41 female dogs by immunohistochemistry. VDR-positive staining was found in the nuclei of both myoepithelial and luminal epithelial cell layers. VDR expression was higher in normal mammary tissue (37/37 cases, 100%) then followed by benign tumours (6/15 cases, 40%) and malignant tumours (9/34 cases, 26.5%) (P = .001). Female dogs aged ≥10 years had lower VDR expression compared with dogs younger (P = .017). Relationship between VDR and breed, number of tumours, tumour size, histologic subtype, histologic grade of malignancy, PI and PR and ER expression was not observed. Studies with more samples are necessary to further evaluate the possible role of VDR in the biological behaviour of canine mammary tumours, and to corroborate the possibility to use the dog as model for human breast cancer.

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“…The potential predictive value of immunohistochemical PR receptor determination in canine mammary carcinomas was demonstrated in studies of the PR antagonist aglepristone. A neoadjuvant aglepristone treatment increased the disease-free period in animals with tumors expressing the PR receptor [27]. Experimental studies on receptor expression in neoplastic tissues were also performed in animal species other than dogs.…”

Section: Discussionmentioning

confidence: 99%

Androgen and Estrogen Receptor Expression in Different Types of Perianal Gland Tumors in Male Dogs

Brodzki

Łopuszyński

Millán

et al. 2021

Animals

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Perianal gland tumors are modified sebaceous glands present in the skin of the perianal region in the dog. Hormonal stimulation may induce hyperplasia of the perianal glands or their neoplastic progression. The presence of androgen (AR) and estrogen (ER) receptors have been demonstrated both in normal perianal glands as well as in perianal tumors. The aim of the study was an immunohistochemical assessment of the expression of estrogen and androgen receptors in perianal gland tumors in dogs as an applicatory marker for antihormonal treatment. Biopsy samples of perianal masses were collected from 41 male dogs. A histopathological examination revealed 24 adenomas, 12 epitheliomas and five carcinomas. The immunohistochemical staining showed a mainly nuclear expression of AR and ER in the neoplastic cells. Both the androgen and estrogen receptors were expressed in adenoma, epithelioma and carcinoma cases; however, the highest expression of the receptors was stated in the adenoma and epithelioma. In the case of the carcinoma, the expression of sex hormone receptors was very weak. The differences of the number of cells expressing AR and ER as well as the observed differentiated intensity of staining in the studies demonstrated that the determination of the expression of the sex hormone receptors may be useful to elaborate a diagnostic and therapeutic algorithm.

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Prognostic impact of neoadjuvant aglepristone treatment in clinicopathological parameters of progesterone receptor‐positive canine mammary carcinomas

Cited by 14 publications

References 32 publications

Antigestagens Mediate the Expression of Decidualization Markers, Extracellular Matrix Factors and Connexin 43 in Decidualized Dog Uterine Stromal (DUS) Cells

Antigestagens Mediate the Expression of Decidualization Markers, Extracellular Matrix Factors and Connexin 43 in Decidualized Dog Uterine Stromal (DUS) Cells

Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors

Androgen and Estrogen Receptor Expression in Different Types of Perianal Gland Tumors in Male Dogs

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