Aberrant E-cadherin, beta-catenin, and glial fibrillary acidic protein (GFAP) expression in canine choroid plexus tumors

Expression of E-cadherin and beta-catenin has been widely studied in various human and canine epithelial tumors and has been correlated with dedifferentiation, invasiveness, and metastasis. Choroid plexus tumors (CPTs) are of epithelial origin, and the most important prognostic factor in human medicine is the tumor grade. Limited information is available regarding E-cadherin and beta-catenin expression in human CPTs, and no information is found in the veterinary literature. In the current study, 42 canine CPTs (19 choroid plexus papillomas and 23 choroid plexus carcinomas) were retrospectively reviewed, and the intensity and cellular staining pattern of E-cadherin and beta-catenin were correlated with histological features, paying special attention to grade, invasion, and metastasis. In addition, cytokeratin and glial fibrillary acidic protein (GFAP) antibodies were evaluated as markers for canine CPTs. It was found that loss of E-cadherin and beta-catenin expression was uncommon in canine CPTs. Rather, membranous expression of both molecules was increased in CPTs compared to normal choroid plexus (NCP), regardless of tumor grade. Additionally, aberrant cytoplasmic or nuclear expression of both E-cadherin and beta-catenin was often observed in CPTs. GFAP was frequently expressed in CPTs in contrast to NCP. None of these parameters were correlated with malignancy, and therefore, do not appear to be useful for prognostic information. Nevertheless, a panel of antibodies including E-cadherin and GFAP might be useful to support the diagnosis of CPTs and help to differentiate them from other tumors, such as ependymomas and metastatic epithelial tumors.

The Swiss Canine Cancer Registry: a retrospective study on the occurrence of tumours in dogs in Switzerland from 1955 to 2008

Diagnostic records are a key feature of any cancer epidemiology, prevention or control strategy for man and animals. Therefore, the information stored in human and animal cancer registries is essential for undertaking comparative epidemiological, pathogenic and therapeutic research. This study presents the Swiss Canine Cancer Registry, containing case data compiled between 1955 and 2008. The data consist of pathology diagnostic records issued by three veterinary diagnostic laboratories in Switzerland. The tumours were classified according to the guidelines of the International Classification of Oncology for Humans on the basis of tumour type, malignancy and body location. The dogs were classified according to breed, age, sex, neuter status and place of residence. The diagnostic data were correlated with data on the Swiss general dog population and the incidence of cancer in dogs was thus investigated. A total of 67,943 tumours were diagnosed in 121,963 dogs and 47.07% of these were malignant. The most common tumour location was the skin (37.05%), followed by mammary glands (23.55%) and soft tissue (13.66%). The most common tumour diagnoses were epithelial (38.45%), mesenchymal (35.10%) and lymphoid tumours (13.23%). The results are compared with data in other canine registries and similarities in tumour distribution and incidence are noted. It is hoped that this study will mark the beginning of continuous registration of dog tumours in Switzerland, which, in turn, will serve as a reference for research in the fields of animal and human oncology.

Expression, localization, and functional model of cholesterol transporters in lactating and nonlactating mammary tissues of murine, bovine, and human origin

Members of the ATP-binding cassette (ABC) transporters play a pivotal role in cellular lipid efflux. To identify candidate cholesterol transporters implicated in lipid homeostasis and mammary gland (MG) physiology, we compared expression and localization of ABCA1, ABCG1, and ABCA7 and their regulatory genes in mammary tissues of different species during the pregnancy-lactation cycle. Murine and bovine mammary glands (MGs) were investigated during different functional stages. The abundance of mRNAs was determined by quantitative RT-PCR. Furthermore, transporter proteins were localized in murine, bovine, and human MGs by immunohistochemistry. In the murine MG, ABCA1 mRNA abundance was elevated during nonlactating compared with lactating stages, whereas ABCA7 and ABCA1 mRNA profiles were not altered. In the bovine MG, ABCA1, ABCG1, and ABCA7 mRNAs abundances were increased during nonlactating stages compared with lactation. Furthermore, associations between mRNA levels of transporters and their regulatory genes LXRalpha, PPARgamma, and SREBPs were found. ABCA1, ABCG1, and ABCA7 proteins were localized in glandular MG epithelial cells (MEC) during lactation, whereas during nonlactating stages, depending on species, the proteins showed distinct localization patterns in MEC and adipocytes. Our results demonstrate that ABCA1, ABCG1, and ABCA7 are differentially expressed between lactation and nonlactating stages and in association with regulatory genes. Combined expression and localization data suggest that the selected cholesterol transporters are universal MG transporters involved in transport and storage of cholesterol and in lipid homeostasis of MEC. Because of the species-specific expression patterns of transporters in mammary tissue, mechanisms of cholesterol homeostasis seem to be differentially regulated between species.

Prognostic significance of apoptotic cell death in bladder cancer: a tissue microarray study on 179 urothelial carcinomas from cystectomy specimens

To assess the prognostic significance of apoptosis related markers in bladder cancer.

The mammary gland vasculature revisited

Concomitant with the extensive growth and differentiation of the mammary epithelium during pregnancy and lactation, and epithelial involution after weaning, the vasculature of the mammary gland undergoes repeated cycles of expansion and regression. Vascular expansion is effected by sprouting angiogenesis, intussusception and conceivably also vasculogenesis. The capacity of the epithelial cells to stimulate vascular growth and differentiation is dependent on the constellation of systemic and local hormones and growth factors as well as the changing demands for oxygenation and nutrient supply. This results in the release of angiogenic factors which stimulate endothelial cell growth and regulate vascular architecture. In contrast to the angiogenic phase of the mammary gland cycle, little is known about the control of vascular regression although this would possibly offer new insights into therapeutic possibilities against breast cancer. In this review we summarize knowledge regarding the mechanisms regulating the vasculature of the mammary gland and delineate the importance of the vasculature in the attainment of organ function. In addition, we discuss the angiogenic mechanisms observed during mammary carcinogenesis and their consequences for breast cancer therapy.

Preponderance of cells with stem cell characteristics in metastasising mouse mammary tumours induced by deregulated EphB4 and ephrin-B2 expression

We have previously shown that EphB4 and ephrin-B2 are differentially expressed in the mammary gland and that their deregulated expression in the mammary epithelium of transgenic mice leads to perturbations of the mammary parenchyma and vasculature. In addition, overexpression of EphB4 and expression of a truncated ephrin-B2 mutant, capable of receptor stimulation but incapable of reverse signalling, confers a metastasising phenotype on NeuT initiated mouse mammary tumours. We have taken advantage of this transgenic tumour model to compare stem cell characteristics between the non-metastasising and metastasising mammary tumours. We analysed the expression of the proliferation attenuating p21(waf) gene, which was significantly increased in the metastasising tumours. Moreover, we compared the expression of CK-19, Sca-1, CD24 and CD49f as markers for progenitor cells exhibiting a decreasing differentiation grade. Sca-1 expressing cells were the earliest progenitors detected in the non-metastasising NeuT induced tumours. The metastasising NeuT/EphB4 tumours were enriched in CD24 expressing cells, whereas the metastasising NeuT/truncated ephrin-B2 tumours contained in addition significant amounts of CD49f expressing cells. The same cell populations were also enriched in mammary glands of single transgenic MMTV-EphB4 and MMTV-truncated ephrin-B2 females indicating that deregulated EphB4-ephrin-B2 signalling interferes with the homeostasis of the stem/progenitor cell pool before tumour formation is initiated. Since the same cell populations are enriched in the normal tissue, primary mammary tumours and metastases we conclude that these progenitor cells were the origin of tumour formation and that this change in the tumour origin has led to the acquisition of the metastatic tumour phenotype.

Polyunsaturated fatty acid-enriched diets used for the treatment of canine chronic enteropathies decrease the abundance of selected genes of cholesterol homeostasis

Lipids are important for cell function and survival, but abnormal concentrations may lead to various diseases. Cholesterol homeostasis is greatly dependent on the active transport by membrane proteins, whose activities coordinate lipid status with cellular function. Intestinal Niemann-Pick C1-Like 1 protein (NPC1L1) and scavenger receptor B1 (SR-B1) participate in the uptake of extracellular cholesterol, whereas ATP binding cassette A1 (ABCA1) mediates the efflux of excessive intracellular cholesterol. Caveolin-1 binds cholesterol and fatty acids (FA) and participates in cholesterol trafficking. Sterol response element binding protein-2 (SREBP-2) is a sensor that regulates intracellular cholesterol synthesis. Given that cholesterol is a constituent of chylomicrons, whose synthesis is enhanced with an increased FA supply, we tested the hypothesis that feeding polyunsaturated FA (PUFA)-enriched diets in treatment of canine chronic enteropathies alters the mRNA expression of genes involved in cholesterol homeostasis. Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we compared the mRNA abundance of NPC1L1, SR-B1, ABCA1, caveolin-1, and SREBP-2 in duodenal mucosal biopsies of dogs with food-responsive diarrhea (FRD; n=14) and inflammatory bowel disease (IBD; n=7) before and after treatment with cholesterol-free PUFA-enriched diets and in healthy controls (n=14). The abundance of caveolin-1, ABCA1, and SREBP-2 were altered by PUFA-enriched diets (P<0.05), whereas that of NPC1L1 and SR-B1 mRNA remained unchanged. The gene expression of caveolin-1, ABCA1, and SREBP-2 was down-regulated (P<0.05) by PUFA-enriched diets in IBD dogs only. Our results suggest that feeding PUFA-enriched diets may alter cholesterol homeostasis in duodenal mucosal cells of dogs suffering from IBD.

Long-term effectiveness of canine-to-canine bonded flexible spiral wire lingual retainers

The flexible spiral wire (FSW) canine-to-canine lingual retainer bonded to all 6 anterior teeth is a frequently used type of mandibular fixed retainer. This study aimed to assess the long-term effectiveness of FSW canine-to-canine lingual retainers in maintaining the alignment of the mandibular anterior teeth after orthodontic treatment.

Influence of a machined collar on crestal bone changes around titanium implants: a histometric study in the canine mandible

It has been shown that peri-implant crestal bone reactions are influenced by both a rough-smooth implant border in one-piece, non-submerged, as well as an interface (microgap [MG] between implant/abutment) in two-piece butt-joint, submerged and non-submerged implants being placed at different levels in relation to the crest of the bone. According to standard surgical procedures, the rough-smooth implant border for implants with a smooth collar should be aligned with the crest of the bone exhibiting a smooth collar adjacent to peri-implant soft tissues. No data, however, are available for implants exhibiting a sandblasted, large-grit and acid-etched (SLA) surface all the way to the top of a non-submerged implant. Thus, the purpose of this study is to histometrically examine crestal bone changes around machined versus SLA-surfaced implant collars in a side-by-side comparison.

Identification of ABCA1 and ABCG1 in milk fat globules and mammary cells--implications for milk cholesterol secretion

The ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 play an important role in cellular cholesterol homeostasis, but their function in mammary gland (MG) tissue remains elusive. A bovine MG model that allows repeated MG sampling in identical animals at different functional stages was used to test whether 1) ABCA1 and ABCG1 protein expression and subcellular localization in mammary epithelial cells (MEC) change during the pregnancy-lactation cycle, and 2) these 2 proteins were present in milk fat globules (MFG). Expression and localization in MEC were investigated in bovine MG tissues at the end of lactation, during the dry period (DP), and early lactation using immunohistochemical and immunofluorescence approaches. The presence of ABCA1 and ABCG1 in MFG isolated from fresh milk was determined by immunofluorescence. The ABCA1 protein expression in MEC, expressed as arbitrary units, was higher during the end of lactation (12.2±0.24) and the DP (12.5±0.22) as compared with during early lactation (10.2±0.65). In contrast, no significant change in ABCG1 expression existed between the stages. Throughout the cycle, ABCA1 and ABCG1 were detected in the apical (41.9±24.8 and 49.0±4.96% of cows, respectively), basal (56.2±28.1 and 54.6±7.78% of cows, respectively), or entire cytoplasm (56.8±13.4 and 61.6±14.4% of cows, respectively) of MEC, or showed combined localization. Unlike ABCG1, ABCA1 was absent at the apical aspect of MEC during early lactation. Immunolabeling experiments revealed the presence of ABCA1 and ABCG1 in MFG membranes. Findings suggest a differential, functional stage-dependent role of ABCA1 and ABCG1 in cholesterol homeostasis of the MG epithelium. The presence of ABCA1 and ABCG1 in MFG membranes suggests that these proteins are involved in cholesterol exchange between MEC and alveolar milk.

Poorly differentiated thyroid carcinomas: how much poorly differentiated is needed?

Poorly differentiated (PD) carcinomas of the thyroid are conceptually situated between well-differentiated (papillary or follicular) carcinomas and anaplastic thyroid carcinomas. Although the morphologic criteria for PD tumors are well defined, it is not clear how much of a PD area besides a well-differentiated component in a given tumor is required to allow such a diagnosis.

Percutaneous radiofrequency ablation of virtual tumours in canine kidney using Global Positioning System-like technology

What's known on the subject? And what does the study add? We have previously shown that percutaneous radiofrequency ablation guided by image-fusion technology allows for precise needle placement with real time ultrasound superimposed with pre-loaded imaging, removing the need for real-time CT or MR guidance. Emerging technology also allows real-time tracking of a treatment needle within an organ in a virtually created 3D format. To our knowledge, this is the first study utilising a sophisticated ultrasound-based navigation system that uses both image-fusion and real-time probe-tracking technologies for in-vivo renal ablative intervention.

Deregulated ephrin-B2 signaling in mammary epithelial cells alters the stem cell compartment and interferes with the epithelial differentiation pathway

Cancer most probably originates from stem/progenitor cells and exhibits a similar cell hierarchy as normal tissues. Moreover, there is growing evidence that only the stem cells are capable of metastasis formation. We have previously shown that overexpression of a dominant negative ephrin-B2 mutant interferes with mammary gland differentiation and confers a metastatic phenotype to NeuT-induced mammary tumors with an increase in cells with stem/progenitor characteristics. To investigate the role of ephrin-B2 in the control of the mammary stem cell niche, we analyzed the mammary stem and progenitor cell populations in transgenic mice overexpressing the mutant ephrin-B2. Quantification by FACS analysis revealed a significant increase of cells in the basal/alveolar cell-, the bi-potent progenitor- and the stem cell-enriched fractions. Moreover, the supposed precursors of estrogen receptor-positive cells were elevated in the stem cell-enriched fraction. In contrast, the epithelium from transgenic mice overexpressing the native ephrin-B2 gene showed an augmentation of the luminal cell- and the bi-potent progenitor-enriched fractions. Repopulation assays revealed that the epithelial cells of truncated ephrin-B2 transgenic epithelial cells have a higher regeneration capacity than those of controls and of native ephrin-B2 transgenic mice, confirming the augmentation of stem cells. Morphologically, these outgrowths exhibited impaired basal/luminal compartmentalization and epithelial polarization. These results demonstrate that deregulated ephrin-B2 expression interferes with the regulation of the stem cell niche and leads to a shift of the differentiation pathway and may thereby contribute to the acquisition of the metastatic phenotype long before carcinogenic growth becomes apparent.