Comprehensive Analysis of the Tumour Immune Microenvironment in Canine Urothelial Carcinoma Reveals Immunosuppressive Mechanisms Induced by the COX-Prostanoid Cascade.

A comprehensive understanding of the tumour immune microenvironment (TIME) is essential for advancing precision medicine and identifying potential therapeutic targets. This study focused on canine urothelial carcinoma (cUC) recognised for its high sensitivity to cyclooxygenase (COX) inhibitors. Using immunohistochemical techniques, we quantified the infiltration of seven immune cell populations within cUC tumour tissue to identify clinicopathological features that characterise the TIME in cUC.

Perimenopausal and Menopausal Mammary Glands In A 4-Vinylcyclohexene Diepoxide Mouse Model.

As both perimenopausal and menopausal periods are recognized critical windows of susceptibility for breast carcinogenesis, development of a physiologically relevant model has been warranted. The traditional ovariectomy model causes instant removal of the entire hormonal repertoire produced by the ovary, which does not accurately approximate human natural menopause with gradual transition. Here, we characterized the mammary glands of 4-vinylcyclohexene diepoxide (VCD)-treated animals at different time points, revealing that the model can provide the mammary glands with both perimenopausal and menopausal states.

Molecular features of luminal breast cancer defined through spatial and single-cell transcriptomics.

Background: Intratumour heterogeneity is a hallmark of most solid tumours, including breast cancers. We applied spatial transcriptomics and single-cell RNA-sequencing on patient-derived xenografts (PDXs) to profile spatially resolved cell populations within oestrogen receptor-positive (ER ) breast cancer and to elucidate their importance in oestrogen-dependent tumour growth.

Methods: Two PDXs of 'ER-high' breast cancers with opposite oestrogen-mediated growth responses were investigated: oestrogen-suppressed GS3 (80-100% ER) and oestrogen-dependent SC31 (40-90% ER) models.

Pan-tumour analysis of COX-2 expression in dogs.

Cyclooxgenase-2 (COX-2) is associated with inflammatory microenvironment and tumour progression. COX-2 expression was reported in canine tumours, and anti-COX treatment showed therapeutic effects in selected tumour types. Currently, direct comparisons between different tumour types or reports were impossible due to varying evaluation protocols.

Phenotypic and molecular characterization of novel pulmonary adenocarcinoma cell lines established from a dog.

Canine pulmonary adenocarcinoma (PAC) resembles human lung tumors in never-smokers, but it is rarer than human pulmonary adenocarcinoma. Therefore, research on canine PAC is challenging. In the present study, we successfully established various novel canine PAC cell lines from a single lesion in a dog, including two parent cell lines and fourteen cloned cell lines, and characterized their cellular properties in vitro.

Identification and characterization of a proliferative cell population in estrogen receptor-positive metastatic breast cancer through spatial and single-cell transcriptomics.

Background: Intratumor heterogeneity is a hallmark of most solid tumors, including breast cancers. We applied spatial transcriptomics and single-cell RNA-sequencing technologies to profile spatially resolved cell populations within estrogen receptor-positive (ER ) metastatic breast cancers and elucidate their importance in estrogen-dependent tumor growth.

Methods: Spatial transcriptomics and single-cell RNA-sequencing were performed on two patient-derived xenografts (PDXs) of "ER-high" metastatic breast cancers with opposite estrogen-mediated growth responses: estrogen-suppressed GS3 (80-100% ER) and estrogen-stimulated SC31 (30-75% ER) models.

Expression profile of immunoregulatory factors in canine tumors.

Cancers utilize a variety of molecules to escape host immune responses. Better understanding the immune environment surrounding cancer may facilitate application of innovative cancer immunotherapies, such as immune checkpoint inhibitors, to dogs as well as humans. In this study, we screened the expression of 20 immune regulatory molecules in diverse canine tumors (n = 59).

Assessment of changes in blood pancreatic lipase activities using FDC-v-LIP in dogs that underwent various surgical procedures.

Objective: To describe the perioperative changes in blood pancreatic lipase activity and explore the contributing clinical factors associated with these changes.

Design: Prospective observational study.

Setting: University teaching hospital.

Single-Cell Transcriptomics Identifies Heterogeneity of Mouse Mammary Gland Fibroblasts With Distinct Functions, Estrogen Responses, Differentiation Processes, and Crosstalks With Epithelium.

Fibroblasts have been shown to be one of the essential players for mammary gland organization. Here, we identify two major types of mouse mammary gland fibroblasts through single-cell RNA sequencing analysis: fibroblasts and fibroblasts. Each population exhibits unique functional characteristics as well as discrete localization in normal mouse mammary glands.

Influence of Estrogen Treatment on and Cells in ER Breast Cancer: Insights from Single-Cell Analysis of Patient-Derived Xenograft Models.

A 100% ER positivity is not required for an endocrine therapy response. Furthermore, while estrogen typically promotes the progression of hormone-dependent breast cancer via the activation of estrogen receptor (ER)-α, estrogen-induced tumor suppression in ER breast cancer has been clinically observed. With the success in establishing estrogen-stimulated (SC31) and estrogen-suppressed (GS3) patient-derived xenograft (PDX) models, single-cell RNA sequencing analysis was performed to determine the impact of estrogen on and tumor cells.

Optimization of SPIO Injection for Sentinel Lymph Node Dissection in a Rat Model.

The magnetic technique, consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node dissection (SLND) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron dose, dilution, time course and massaging) were evaluated to optimize magnetic tracer uptake in the sentinel lymph nodes (SLN) in a rat hindleg model. 202 successful SLNDs were performed.

Mammary cell gene expression atlas links epithelial cell remodeling events to breast carcinogenesis.

The female mammary epithelium undergoes reorganization during development, pregnancy, and menopause, linking higher risk with breast cancer development. To characterize these periods of complex remodeling, here we report integrated 50 K mouse and 24 K human mammary epithelial cell atlases obtained by single-cell RNA sequencing, which covers most lifetime stages. Our results indicate a putative trajectory that originates from embryonic mammary stem cells which differentiates into three epithelial lineages (basal, luminal hormone-sensing, and luminal alveolar), presumably arising from unipotent progenitors in postnatal glands.

Functional characterization of androgen receptor in two patient-derived xenograft models of triple negative breast cancer.

Extensive efforts, through cell line-based models, have been made to characterize the androgen receptor (AR) signaling pathway in triple-negative breast cancer (TNBC). However, these efforts have not yet reached a consensus with regards to the mechanism of AR in TNBC. Considering that patient-derived xenografts (PDXs) are more appropriate than cell line-based models for recapitulating the structural and molecular features of a patient's tumor, we have identified and molecularly characterized two new AR-positive TNBC PDX models and assessed the impacts of AR agonist [dihydrotestosterone (DHT)] and antagonist (enzalutamide) on tumor growth and gene expression profiles by utilizing immunohistochemistry, western blots, and RNA-Seq analyses.

Author Correction: Aberrant expression of the COX2/PGE axis is induced by activation of the RAF/MEK/ERK pathway in BRAF canine urothelial carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Spindle assembly checkpoint competence in aneuploid canine malignant melanoma cell lines.

The spindle assembly checkpoint (SAC) is a surveillance mechanism that prevents unequal segregation of chromosomes during mitosis. Abnormalities in the SAC are associated with chromosome instability and resultant aneuploidy. This study was performed to evaluate the SAC competence in canine malignant melanoma (CMM) using four aneuploid cell lines (CMeC1, CMeC2, KMeC, and LMeC).

Aberrant expression of the COX2/PGE axis is induced by activation of the RAF/MEK/ERK pathway in BRAF canine urothelial carcinoma.

Cancer-promoting inflammation is an important event in cancer development. Canine urothelial carcinoma (cUC) overexpresses prostaglandin E (PGE) and has a unique sensitivity to cyclooxygenase 2 (COX2)-inhibiting therapy. In addition, majority of cUC harbour BRAF mutation.

PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma.

Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed. It is also known to be linked with several aspects of tumor malignancy in some types of human tumors, including invasion, metastasis, and cancer stemness. However, there are few reports on the expression of dog PDPN (dPDPN) in canine tumors, and the association between dPDPN and tumor malignancy has not been elucidated.

Overexpression of human epidermal growth factor receptor 2 in canine primary lung cancer.

Human epidermal growth factor receptor 2 (HER2) overexpression has been reported in various human cancers. HER2-targeted therapies showed clinical responses in humans with HER2-positive tumors. The incidence of canine primary lung cancer (cPLC) is increasing, but there are no effective systemic therapies for dogs with late-stage cPLC.

Environmental Carcinogenesis at the Single-Cell Level.

Elucidating the mechanisms behind how exposure to environmental chemicals can lead to cancer is not easy due to the complex natures of these compounds and the challenges to establish biologically relevant experimental models to study them. Environmental chemicals often present selective mechanisms of action on different cell types and can be involved in the modulation of targeted cells and their microenvironment, including immune cells. Currently, the limitations of traditional epidemiologic correlation analyses, cell-based assays, and animal models are that they are unable to comprehensively examine cellular heterogeneity and the tissue-selective influences.

Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland.

Menopause is a critical window of susceptibility for its sensitivity to endocrine disrupting chemicals due to the decline of endogenous estrogen. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). As flame retardants in household products, PBDEs are widely detected in human serum.

Copy Number Aberration in Canine Urothelial Carcinoma Detected by a Digital Polymerase Chain Reaction Assay.

Urothelial carcinoma (UC) is the most common tumor affecting the urinary bladder of dogs. Protein overexpression of ErbB2 (the canine homolog of HER2) has been observed in dogs with UC. However, no study regarding copy number aberration (CNA) is reported in dogs with UC.

Immunohistochemical evaluation of HER2 expression in canine thyroid carcinoma.

The human epidermal growth factor receptor 2 (HER2) is expressed in various human cancers including thyroid cancers (TC) and is used as a diagnostic marker and therapeutic target. Canine TC (cTC), the most common endocrine malignancy in dogs, shows a high metastasis rate, and HER2-targeted therapy could be a candidate for treatment. Here, we immunohistochemically evaluated HER2 expression in 21 paraffin-embedded cTC tissues and scored the degree of expression based on intensity and positivity (score: 0-3+).

YM155 enhances the cytotoxic activity of etoposide against canine osteosarcoma cells.

Canine osteosarcoma (OSA) is an aggressive and highly malignant primary bone tumor. Its poor survival outcome remains problematic despite recent advances in anti-cancer therapy, therefore highlighting the need for alternative treatment options or drug repositioning. The aim of this study was to determine if YM155, a small-molecule survivin inhibitor, potentiates the chemotherapeutic efficacy of etoposide against canine OSA in vitro and in vivo.

Anti-tumor effects of the histone deacetylase inhibitor vorinostat on canine urothelial carcinoma cells.

Canine urothelial carcinoma (cUC) is the most common tumor of the lower urinary tract in dogs. Although chemotherapy and radical surgery have improved the overall survival, most dogs with cUC succumb to metastasis or recurrence. Therefore, the development of an effective systematic therapy is warranted.