Anatomy, Histology, and Physiology of the Canine Prostate Gland

The prostate gland is the only male accessory gland in dogs and is responsible for secreting the prostatic fluid. Morphologically, the canine prostate gland lacks differentiation into zones, presenting a uniform parenchyma along the longitudinal axis. The luminal epithelial cells secrete a liquid rich in calcium, citric acid, simple sugars, and different enzymes as a component of the seminal plasma. Since the prostatic diseases are very common in small animal practice, there are many information regarding mechanisms of the different prostatic conditions and lack of information regarding the anatomy, histology, and physiology of the canine prostate gland. Thus, this chapter aims to meticulously describe the anatomy, histology, and physiology of the canine prostate gland

Effects of Lapatinib on HER2-Positive and HER2-Negative Canine Mammary Carcinoma Cells Cultured In Vitro

HER2 is a prognostic and predictive marker widely used in breast cancer. Lapatinib is a tyrosine kinase inhibitor that works by blocking the phosphorylation of the receptor HER2. Its use is related to relatively good results in the treatment of women with HER2+ breast cancer. Thus, this study aimed to verify the effects of lapatinib on four canine primary mammary gland carcinoma cell cultures and two paired metastatic cell cultures. Cultures were treated with lapatinib at concentrations of 100, 500, 1000 and 3000 nM for 24 h and the 50% inhibitory concentration (IC50) for each cell culture was determined. In addition, a transwell assay was performed to assess the ability of lapatinib to inhibit cell migration. Furthermore, we verified HER2 expression by RT-qPCR analysis of cell cultures and formalin-fixed paraffin-embedded tissues from samples corresponding to those used in cell culture. Lapatinib was able to inhibit cell proliferation in all cell cultures, but it was not able to inhibit migration in all cell cultures. The higher the expression of HER2 in a culture, the more sensitive the culture was to treatment. This relationship may be an indication that the expression of HER2 may be a predictive factor and opens a new perspective for the treatment of primary and metastatic mammary gland cancer

Controlled Drug Delivery Vehicles in Veterinary Oncology: State-of-the-Art and Future Directions

Controlled drug delivery systems can be used to carry several anticancer agents, including classical chemotherapeutic agents such as doxorubicin, paclitaxel or cisplatin, and are also used for the encapsulation of tyrosine kinase inhibitors and monoclonal antibodies. Usually, the controlled systems are used to decrease drug toxicity, increase local drug concentration or target specific organs or systems. In dogs, liposomal doxorubicin is the most known controlled drug delivery vehicle in veterinary medicine. However, several antitumor drugs can be encapsulated within these systems. Since the delivery vehicles are a relatively new topic in veterinary oncology, this review aims to discuss the current knowledge regarding the controlled drug delivery vehicles and discuss the current challenges and future direction of its use in veterinary oncology

Lapatinib antitumor effect is associated with PI3K and MAPK pathway: An analysis in human and canine prostate cancer cells.

The aberrant activation of HER2 has a pivotal role in bone metastasis implantation and progression in several tumor types, including prostate cancer (PC). Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Although HER2 overexpression has been reported in PC, anti-HER2 therapy response has revealed conflicting results. We investigated the potential of lapatinib in inhibiting cell migration and inducing apoptosis in two human (LNCaP and PC3) and two canine PC cell lines (PC1 and PC2). Cell migration and apoptosis were evaluated by Annexin V/PI analysis after lapatinib treatment. The transcriptome analysis of all cell lines before and after treatment with lapatinib was also performed. We found increased apoptosis and migration inhibition in LNCaP cells (androgen-sensitive cell line), while PC1, PC2, and PC3 cells showed no alterations after the treatment. The transcriptome analysis of LNCaP and PC3 cell lines showed 158 dysregulated transcripts in common, while PC1 and PC2 cell lines presented 82. At the doses of lapatinib used, we observed transcriptional modifications in all cell lines. PI3K/AKT/mTOR pathway were enriched in human PC cells, while canine PC cells showed enrichment of tyrosine kinase antitumor response and HER2-related pathways. In canine PC cells, the apoptosis failed after lapatinib treatment, possibly due to the downregulation of MAPK genes. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective antitumor response and clinical benefits to PC patients

A Comparative in Silico Analysis of CD24’s Prognostic Value in Human and Canine Prostate Cancer

CD24 is a cell surface molecule anchored by glycosyl-phosphatidyl-inositol and expressed by different human cancers, including prostate cancer (PC). Some studies have demonstrated that CD24 expression is associated with poor patient outcome; however, few studies have investigated CD24 expression in spontaneous animal models of human PC, such as canine PC. This study aimed to evaluate the expression of CD24 in human PC using the in silico analysis of the data obtained from The Cancer Genome Atlas (TCGA) and comparing it with the previously published prostatic canine transcriptome data. In addition, CD24 expression was confirmed by immunohistochemistry in an independent cohort of canine prostatic samples and its prognostic significance assessed. The systematic review identified 10 publications fitting with the inclusion criteria of this study. Of the 10 manuscripts, 5 demonstrated a direct correlation between CD24 overexpression and patient prognoses. CD24 expression was also associated with PSA relapse (2/5) and tumor progression (1/5). However, the in silico analysis did not validate CD24 as a prognostic factor of human PC. Regarding canine PC, 10 out of 30 normal prostates and 27 out of 40 PC samples were positive for CD24. As in humans, there was no association with overall survival. Overall, our results demonstrated a significant CD24 overexpression in human and canine prostate cancer, although its prognostic value may be questionable. However, tumors overexpressing CD24 may be a reliable model for new target therapies and dogs could be used of a unique preclinical model for these studies

Deregulation of VEGFR-2 and PDGFR Expression and Microvascular Density in a Triple-Negative Model of Canine Malignant Mammary Tumors with Lymph Node or Lung Metastasis

Canine mammary tumors (CMT) represent the most common cancer in noncastrated female dogs. Interestingly, triple-negative tumors are the most common molecular subtype in female dogs. In this study, we proposed to evaluate the expression of vascular endothelial growth factor receptor 2 (VEGFR-2), Platelet-derived growth factor receptor (PDGFR), and microvascular density (MVD) in a group of metastatic and nonmetastatic triple-negative CMT and compare the expression based on clinical parameters. Twenty-six female dogs with triple-negative mammary tumors were divided into three groups: nonmetastatic tumors (NMT) (n = 11), tumors with lymph node metastasis (LNM) (n = 10), and tumors with lung metastasis (LM) (n = 5). We observed increased VEGFR-2 expression in LNM compared with NMT and a positive correlation between tumor grade and VEGFR-2 expression. A positive correlation was noted between VEGFR-2 and PDGFR expression. Regarding microvascular density (MVD), we identified a higher number of vessels in primary tumors with lymph node metastasis and lung metastasis compared with tumors with no metastasis. The primary tumors with lung metastasis exhibited an increased MVD compared with carcinoma with lymph node metastasis. Overall, our results suggest a deregulation of VEGFR-2 and PDGFR and high MVD in metastatic tumors, indicating a role for angiogenesis in tumor progression