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1.
J Comp Pathol ; 169: 35-46, 2019 May.
Article in English | MEDLINE | ID: mdl-31159949

ABSTRACT

Canine urothelial carcinoma (UC) is the most common type of cancer of the lower urinary tract and tends to affect elderly neutered female dogs, with a high predisposition for Scottish terriers. Tumour stroma, inflammation and necrosis are poorly characterized in canine UC and their role as prognostic factors is unknown. The aims of this study were to (1) assess histologically 381 canine UCs, with emphasis on myxoid tumour stroma, inflammation and necrosis and (2) assess possible associations between these features and the available epidemiological data as well as bladder wall muscle invasion. In 103 of 381 (27%) cases, the stroma was mixed collagenous and myxoid (fibromyxoid), which was strongly associated with invasive growth of muscle (P <0.0001). Peritumoural and intratumoural inflammation was present in 308 of 345 (89%) and 287 of 381 (75%) cases, respectively, and was mostly mild and lymphoplasmacytic. One hundred and fifteen of the 381 (30%) cases showed a variable eosinophilic inflammation and 58 of 381 (15%) presented with formations of one or several lymphoid follicles. Twenty-four percent (91 of 381) of cases had tumour necrosis, which was typically mild. In 83 of 91 (91%) cases, the necrosis was comedo-like. Moderate to severe tumour necrosis was associated with the presence of moderate to predominant fibromyxoid tumour stroma (P <0.02). The results of this study indicate that fibromyxoid stroma is common in canine UC and is a strong indicator for invasive growth of muscle, which is consistent with a poor prognosis. Based on histomorphology, tumour necrosis in canine UC is best described as comedonecrosis.


Subject(s)
Carcinoma, Transitional Cell/veterinary , Dog Diseases/pathology , Urinary Bladder Neoplasms/veterinary , Animals , Dogs , Tumor Microenvironment
2.
J Comp Pathol ; 163: 1-5, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30213367

ABSTRACT

Feline injection site sarcomas (FISS) were first described in the early 1990s. Despite extensive research, the pathogenesis of these tumours has not been elucidated conclusively. Their appearance and the marked increase in their incidence has been mainly connected to the injection of vaccines, and it is assumed that a chronic inflammatory reaction at the injection site triggers subsequent malignant transformation. The role of alum-based adjuvants has been discussed, but is controversial. The present study of the Swiss Feline Cancer Registry (SFCR) with data from 2009 to 2014 revealed a marked decrease of the incidence of fibrosarcomas compared with the previous observation period. Notably, this drop occurred after a non-adjuvanted feline leukaemia virus vaccine was introduced in Switzerland in 2007. This observation, together with the previous findings of the SFCR, further supports the notion that alum-adjuvanted vaccines are involved in the genesis of FISS and that non-adjuvanted vaccines might be safer for cats.


Subject(s)
Cat Diseases/pathology , Injection Site Reaction/veterinary , Sarcoma/veterinary , Soft Tissue Neoplasms/veterinary , Animals , Cats , Injection Site Reaction/pathology , Sarcoma/pathology , Soft Tissue Neoplasms/pathology , Switzerland
3.
J Comp Pathol ; 155(2-3): 156-170, 2016.
Article in English | MEDLINE | ID: mdl-27406312

ABSTRACT

This study is based on the Swiss Canine Cancer Registry, comprising 121,963 diagnostic records of dogs compiled between 1955 and 2008, in which 63,214 (51.83%) animals were diagnosed with tumour lesions through microscopical investigation. Adenoma/adenocarcinoma (n = 12,293, 18.09%) was the most frequent tumour diagnosis. Other common tumour diagnoses were: mast cell tumour (n = 4,415, 6.50%), lymphoma (n = 2,955, 4.35%), melanocytic tumours (n = 2,466, 3.63%), fibroma/fibrosarcoma (n = 2,309, 3.40%), haemangioma/haemangiosarcoma (n = 1,904, 2.80%), squamous cell carcinoma (n = 1,324, 1.95%) and osteoma/osteosarcoma (n = 842, 1.24%). The relative occurrence over time and the most common body locations of those tumour diagnoses are presented. Analyses of the influence of age, breed, body size, sex and neutering status on tumour development were carried out using multiple logistic regression. In certain breeds/breed categories the odds ratios (ORs) for particular tumours were outstandingly high: the boxer had higher ORs for mast cell tumour and haemangioma/haemangiosarcoma, as did the shepherd group for haemangioma/haemangiosarcoma, the schnauzer for squamous cell carcinoma and the rottweiler for osteoma/osteosarcoma. In small dogs, the risk of developing mammary tumours was three times higher than in large dogs. However, small dogs were less likely to be affected by many other tumour types (e.g. tumours of the skeletal system). Examination of the influence of sex and neutering status on tumour prevalence showed that the results depend on the examination method. In all sampling groups the risk for female dogs of developing adenoma/adenocarcinoma was higher than for male dogs. Females had a lower risk of developing haemangioma/haemangiosarcoma and squamous cell carcinoma than males. Neutered animals were at higher risk of developing specific tumours outside the genital organs than intact animals. The sample size allows detailed insight into the influences of age, breed, body size, sex and neutering status on canine tumour development. In many cases, the analysis confirms the findings of other authors. In some cases, the results are unique or contradict other studies, implying that further investigations are necessary.


Subject(s)
Dog Diseases/epidemiology , Dog Diseases/pathology , Neoplasms/veterinary , Registries , Animals , Dogs , Female , Male
4.
J Comp Pathol ; 154(2-3): 195-210, 2016.
Article in English | MEDLINE | ID: mdl-26922257

ABSTRACT

Cancer registries are valuable sources for epidemiological research investigating risk factors underlying different types of cancer incidence. The present study is based on the Swiss Feline Cancer Registry that comprises 51,322 feline patient records, compiled between 1965 and 2008. In these records, 18,375 tumours were reported. The study analyses the influence of sex, neutering status, breed, time and age on the development of the most common tumour types and on their locations, using a multiple logistic regression model. The largest differences between breeds were found in the development of fibrosarcomas and squamous cell carcinomas, as well as in the development of tumours in the skin/subcutis and mammary gland. Differences, although often small, in sex and neutering status were observed in most analyses. Tumours were more frequent in middle-aged and older cats. The sample size allowed detailed analyses of the influence of sex, neutering status, breed and age. Results of the study are mainly consistent with previous analyses; however, some results cannot be compared with the existing literature. Further investigations are necessary, since feline tumours have not been investigated in depth to date. More accurate comparisons would require the definition of international standards for animal cancer registries.


Subject(s)
Cat Diseases/epidemiology , Age Factors , Animals , Cats , Female , Incidence , Male , Registries , Risk Factors , Sex Factors
5.
Res Vet Sci ; 104: 126-35, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26850551

ABSTRACT

Dogs present with spontaneous neoplasms biologically similar to human cancers. Apoptotic pathways are deregulated during cancer genesis and progression and are important for therapy. We have assessed the degree of conservation of a set of canine Bcl-2 family members with the human and murine orthologs. To this end, seven complete canine open reading frames were cloned in this family, four of which are novel for the dog, their sequences were analyzed, and their functional interactions were studied in yeasts. We found a high degree of overall and domain sequence homology between canine and human proteins. It was slightly higher than between murine and human proteins. Functional interactions between canine pro-apoptotic Bax and Bak and anti-apoptotic Bcl-xL, Bcl-w, and Mcl-1 were recapitulated in yeasts. Our data provide support for the notion that systems based on canine-derived proteins might faithfully reproduce Bcl-2 family member interactions known from other species and establish the yeast as a useful tool for functional studies with canine proteins.


Subject(s)
Dogs/genetics , Open Reading Frames , Proto-Oncogene Proteins c-bcl-2/genetics , Animals , Cloning, Molecular , DNA, Complementary/genetics , DNA, Complementary/metabolism , Dogs/metabolism , Molecular Sequence Data , Organisms, Genetically Modified/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Saccharomyces cerevisiae/metabolism , Sequence Analysis, DNA
6.
Vet Pathol ; 53(1): 145-52, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26319779

ABSTRACT

Pancreatitis has been described in cats with diabetes mellitus, although the number of studies currently available is very limited. In addition, ketoacidosis has been hypothesized to be associated with pancreatitis in diabetic cats. The aims of the present study were to investigate whether diabetic cats have pancreatitis and to determine if pancreatitis is more frequent with ketoacidosis. Samples of pancreas were collected postmortem from 37 diabetic cats, including 15 with ketoacidosis, and 20 control cats matched for age, sex, breed, and body weight. Sections were stained with hematoxylin and eosin, double-labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/PCNA, and glucagon/Ki67, and single-labeled for Iba1. A previously proposed semiquantitative score was used to characterize pancreatitis, along with counts of inflammatory cells. Scores of pancreatitis and the number of neutrophils, macrophages, and lymphocytes in the exocrine pancreas did not differ between diabetic and control cats or between diabetic cats with and without ketoacidosis. Of note, PCNA-positive acinar cells were increased (P = .002) in diabetic cats, particularly near islets (P < .001). Ki67-positive acinar cells were increased only near islets (P = .038). Ketoacidosis was not linked to proliferation. The results suggest that histopathologic evidence of pancreatitis may not be more frequent in diabetic cats and that ketoacidosis may not be associated with it at the time of death. Augmented PCNA-positive acinar cells might indicate increased proliferation due to chronic pancreatitis. The reason behind the prevalent proliferation of acinar cells surrounding pancreatic islets deserves further investigation.


Subject(s)
Cat Diseases/pathology , Diabetes Mellitus/veterinary , Ketosis/veterinary , Pancreas, Exocrine/pathology , Pancreatitis/veterinary , Acinar Cells/pathology , Animals , Cat Diseases/metabolism , Cats , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Female , Glucagon/metabolism , Insulin/metabolism , Ketosis/metabolism , Ketosis/pathology , Male , Pancreas/metabolism , Pancreas/pathology , Pancreas, Exocrine/metabolism , Pancreatitis/metabolism , Pancreatitis/pathology
7.
Vet Pathol ; 53(1): 136-44, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26113611

ABSTRACT

Pancreatic amyloidosis and loss of α and ß cells have been shown to occur in cats with diabetes mellitus, although the number of studies currently available is very limited. Furthermore, it is not known whether pancreatic islet inflammation is a common feature. The aims of the present study were to characterize islet lesions and to investigate whether diabetic cats have inflammation of the pancreatic islets. Samples of pancreas were collected postmortem from 37 diabetic and 20 control cats matched for age, sex, breed, and body weight. Histologic sections were stained with hematoxylin and eosin and Congo red; double labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/proliferating cell nuclear antigen, and glucagon/Ki67; and single labeled for amylin and Iba1. Mean insulin-positive cross-sectional area was approximately 65% lower in diabetic than control cats (P = .009), while that of amylin and glucagon was similar. Surprisingly, amyloid deposition was similar between groups (P = .408). Proliferation of insulin- and glucagon-positive cells and the number of neutrophils, macrophages, and T (CD3) and B (CD20) lymphocytes in the islets did not differ. The presence of T and B lymphocytes combined tended to be more frequent in diabetic cats (n = 8 of 37; 21.6%) than control cats (n = 1 of 20; 5.0%). The results confirm previous observations that loss of ß cells but not α cells occurs in diabetic cats. Islet amyloidosis was present in diabetic cats but was not greater than in controls. A subset of diabetic cats had lymphocytic infiltration of the islets, which might be associated with ß-cell loss.


Subject(s)
Amyloidosis/veterinary , Cat Diseases/pathology , Diabetes Mellitus/veterinary , Insulin/metabolism , Islets of Langerhans/pathology , Amyloidosis/metabolism , Amyloidosis/pathology , Animals , Cat Diseases/metabolism , Cats , Diabetes Mellitus/metabolism , Diabetes Mellitus/pathology , Female , Glucagon/metabolism , Islet Amyloid Polypeptide/metabolism , Islets of Langerhans/metabolism , Male , Pancreas/metabolism , Pancreas/pathology
8.
J Comp Pathol ; 153(4): 266-77, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26422414

ABSTRACT

Cancer is one of the leading causes of death in companion animals. Information on the epidemiology of cancer is instrumental for veterinary practitioners in patient management; however, spontaneously arising tumours in companion animals also resemble those in man and can provide useful data in combating cancer. Veterinary cancer registries for cats are few in number and have often remained short-lived. This paper presents a retrospective study of tumours in cats in Switzerland from 1965 to 2008. Tumour diagnoses were coded according to topographical and morphological keys of the International Classification of Oncology for Humans (ICD-O-3). Correlations between breed, sex and age were then examined using a multiple logistic regression model. A total of 18,375 tumours were diagnosed in 51,322 cats. Of these, 14,759 (80.3%) tumours were malignant. Several breeds had significantly lower odds ratios for developing a tumour compared with European shorthair cats. The odds of a cat developing a tumour increased with age, up to the age of 16 years, and female cats had higher risk of developing a tumour compared with male cats. Skin (4,970; 27.05%) was the most frequent location for tumours, followed by connective tissue (3,498; 19.04%), unknown location (2,532; 13.78%) and female sexual organs (1,564; 8.51%). The most common tumour types were epithelial tumours (7,913; 43.06%), mesenchymal tumours (5,142; 27.98%) and lymphoid tumours (3,911; 21.28%).


Subject(s)
Cat Diseases/epidemiology , Neoplasms/veterinary , Registries , Animals , Cats , Neoplasms/epidemiology , Retrospective Studies , Switzerland
10.
J Comp Pathol ; 152(2-3): 161-71, 2015.
Article in English | MEDLINE | ID: mdl-25824119

ABSTRACT

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.


Subject(s)
Dog Diseases/epidemiology , Neoplasms/veterinary , Registries , Animals , Dogs , Neoplasms/epidemiology , Retrospective Studies , Switzerland/epidemiology
11.
Vet Pathol ; 51(6): 1143-50, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24565829

ABSTRACT

In humans, diabetes mellitus (DM) is an important cause of renal damage, with glomerular lesions being predominant. In cats, although diabetes is a common endocrinopathy, it is yet unknown whether it leads to renal damage. The aim of the study was to compare renal histologic features and parameters of renal function in diabetic cats against a control population matched for age, gender, breed, and body weight. Thirty-two diabetic and 20 control cats were included. Kidney sections from paraffin-embedded kidney samples were stained and examined with optical microscopy to identify glomerular, tubulointerstitial, and vascular lesions and to assess their frequency and severity. Serum creatinine and urea concentrations were also compared. Glomerular lesions were observed in 29 cats overall, with mesangial matrix increase being more common (19 cats). Tubulointerstitial lesions were observed in 42 cats, including lymphocytic infiltration (29), fibrosis (22), or tubular necrosis (21). Vascular lesions were observed in 5 cases. The frequency and severity of histologic lesions did not differ between diabetic and control cats; however, among diabetics, those that survived longer after diagnosis had more glomerular and vascular lesions. Serum creatinine and urea concentrations were similar between groups; in diabetic cats median creatinine was 109 µmol/l (range, 51-1200) and urea was 12 mmol/l (range, 4-63), and in controls creatinine was 126 µmol/l (range, 50-875) and urea 11 mmol/l (range, 3-80). The results suggest that DM in cats does not lead to microscopically detectable kidney lesions or clinically relevant renal dysfunction. The authors hypothesize that the short life expectancy of diabetic cats may be the main reason for the difference from human diabetics.


Subject(s)
Cat Diseases/pathology , Diabetes Mellitus/veterinary , Kidney Diseases/veterinary , Kidney/pathology , Animals , Case-Control Studies , Cats , Creatinine/blood , Diabetes Mellitus/pathology , Female , Glomerular Mesangium/pathology , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Male , Retrospective Studies , Urea/blood
12.
Parasitol Res ; 113(4): 1425-33, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24504600

ABSTRACT

Aelurostrongylus abstrusus parasitizes the respiratory tract and can heavily affect the breathing and general condition of cats. Experimental infections of six cats were initiated by intragastric administration with 100 or 800 third-stage larvae (L3) obtained from the terrestrial snail Helix aspersa. First-stage larvae were isolated from faecal samples after 35-41 days post infection (dpi) in five animals and until end of study (84 dpi) in two cats. Cough and respiratory sounds were observed starting from 28 to 41 dpi and dyspnoea and panting starting from 52 dpi. All cats had enlarged lymph nodes and, starting from 56 dpi, reduced body weight, and four cats showed intermittent reduced general condition with apathia and anorexia. Eosinophilia and leucocytosis partially with massive lymphocytosis, and occasional basophilia and monocytosis were observed. Mild anaemia was present in five cats, while alterations in coagulation parameters suggested stimulation of the coagulation cascade with increased consumption of coagulation factors (delayed PT, hypofibrinogenemia). Adult A. abstrusus specimens were isolated from the five patent cats at necropsy and all six cats showed pathological changes in the lungs, including disseminated inflammatory cell infiltrates, often associated with incorporated larvae and eggs. There was some degree of overlap between the severity and the inoculation doses. Infections starting from 100 L3 of A. abstrusus had an impact on the lung tissues and on the health of the cats, despite the presence of only mild haematological abnormalities. Due to the worldwide occurrence of feline lung worms, parasitic infections should be considered in the differential diagnosis of lung diseases regardless of the presence of clinical signs and larval excretion.


Subject(s)
Cat Diseases/pathology , Metastrongyloidea/isolation & purification , Strongylida Infections/veterinary , Animals , Cat Diseases/parasitology , Cats/parasitology , Feces/parasitology , Female , Larva , Lung/parasitology , Lung/pathology , Male , Respiratory Tract Diseases/parasitology , Respiratory Tract Diseases/pathology , Strongylida Infections/pathology
13.
Schweiz Arch Tierheilkd ; 155(4): 219-28, 2013 Apr.
Article in German | MEDLINE | ID: mdl-23531943

ABSTRACT

Aim of this study is to present a survey of the dog population and breed distribution in Switzerland from 1955 to 2008 as basis to realize a population based canine cancer register for Switzerland. The number of dogs rose from 309'000 in 1955 to approximately 500'000 in 2008 correlating with a parallel increase of human population. The ratio of dogs per 100 inhabitants remains stable. This ratio is lower in German speaking compared to French or Italian speaking Cantons. The variety and popularity of breeds changed from 1955 to 2008, "winners" are Labrador and Golden Retrievers, Yorkshire and Jack Russel Terriers. Less popular breeds over the years are German Sheherd dogs and Poodles.


Subject(s)
Dogs/classification , Animals , Demography , Population Growth , Switzerland
14.
Vet Pathol ; 50(5): 789-96, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23417166

ABSTRACT

The BH3-only protein Bad is a proapoptotic Bcl-2 family member that acts as a sensitizer in intrinsic apoptosis by inactivating antiapoptotic members through heterodimer formation. Bad has been shown to contribute to tumorigenesis, including lymphoma formation in humans and mice, through alteration in expression or functional status. Here, its immunohistochemical expression was analyzed in canine nonneoplastic and lymphoma tissues using tissue microarrays. Bad was expressed in the cytoplasm of a wide range of nonneoplastic tissues, especially epithelial cells. Nonneoplastic lymph nodes displayed weak immunostaining in the follicular germinal centers only. Immunoblotting supported these observations but also revealed presence of nonspecific labeling in some organs. Of 81 lymphomas, 29 (35.8%) displayed moderate to strong immunohistochemical Bad labeling, and a significant expression increase was found in lymphomas (especially B cell and double negative) compared to nonneoplastic lymph nodes. These findings warrant further investigations of the functional status, the involvement of partner proteins, and a possible impact of Bad on prognosis in canine lymphoma.


Subject(s)
Dog Diseases/metabolism , Lymphoma/veterinary , bcl-Associated Death Protein/metabolism , Animals , Blotting, Western/veterinary , Cytoplasm/metabolism , Dogs , Immunohistochemistry/veterinary , Lymph Nodes/metabolism , Lymphoma/metabolism , Microarray Analysis/veterinary
15.
Schweiz Arch Tierheilkd ; 153(11): 520-5, 2011 Nov.
Article in German | MEDLINE | ID: mdl-22045458

ABSTRACT

In 21 animals, chronic swelling on the lateral aspect of the stifle also known as «perigonitis¼, «stable-syndrome¼ or «bursitis bicipitalis femoris¼ were evaluated. Ultrasonography showed increased fluid in the distal subtendinous bursa of the biceps femoris muscle and structural changes in the tendons, muscles, subcutis and fasciae. Soft tissue swelling and an irregular contour of the lateral tibial condyle were typical signs on radiographs. Macroscopic changes were found at the insertion of the biceps femoris muscle, the distal subtendinous bursa of the biceps femoris muscle, the lateral collateral ligament of the stifle, the origin of muscles on the lateral femoral condyle and the lateral tibial condyle. They mainly consisted of tendon and muscle tissue necrosis with granulation tissue. Histology revealed areas of coagulation necrosis in tendons and ligaments, in which occasionally Onchocerca spp. were seen. The severity of lesions correlated well with the clinical signs, which were associated with a poor prognosis in advanced cases.


Subject(s)
Bursitis/veterinary , Cattle Diseases/pathology , Muscular Diseases/veterinary , Necrosis/veterinary , Stifle/pathology , Animals , Blood Chemical Analysis , Bursitis/complications , Bursitis/diagnosis , Bursitis/pathology , Cattle , Cattle Diseases/diagnosis , Female , Muscular Diseases/complications , Muscular Diseases/diagnosis , Muscular Diseases/pathology , Necrosis/complications , Necrosis/diagnosis , Necrosis/pathology , Tendons/pathology
16.
J Vet Intern Med ; 25(3): 518-23, 2011.
Article in English | MEDLINE | ID: mdl-21488964

ABSTRACT

BACKGROUND: Progesterone receptor (PR) antagonist aglepristone (RU534) has been used successfully for pregnancy termination and therapy of pyometra, vaginal tumors, and mammary hyperplasia in bitches and queens. All of these conditions share with canine mammary carcinomas the expression of PR. OBJECTIVES: To study the effect of RU534 on proliferation and apoptosis in canine mammary carcinomas in relation to PR expression. ANIMALS: Twenty-seven nonspayed bitches with mammary carcinomas were treated with either 2 doses of 20 mg/kg RU534 (n = 22, RU534-treated group) or oil placebo (n = 5, control group) on days 1 and 8. METHODS: Tumor samples were collected before (day 1) and after (day 15) treatment for immunohistochemistry. PR expression, proliferation index (PI), and apoptotic index (AI) were determined using antibodies against PR, Ki67, and cleaved lamin A/C antigens, respectively. The effect of treatment on these parameters was analyzed. RESULTS: Differential expression of PR between day 1 (59.1% PR-positive tumors) and day 15 (36.4% PR-positive tumors) was observed in RU534-treated tumors exclusively. After RU534 treatment, mean PI was significantly decreased in PR-positive but unchanged in PR-negative RU534-treated tumors. A reduction of ≥20% in PI was found in 61.5% of RU534-treated tumors with PR expression. Conversely, no effect on AI was observed after RU534 treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Neoadjuvant RU534 treatment had PR expression-related inhibiting effects on proliferation of canine mammary carcinoma cells.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma/veterinary , Dog Diseases/drug therapy , Estrenes/therapeutic use , Mammary Neoplasms, Animal/drug therapy , Receptors, Progesterone/metabolism , Animals , Carcinoma/drug therapy , Dogs , Female , Gene Expression Regulation, Neoplastic/drug effects , Receptors, Progesterone/genetics
17.
Endocrinology ; 152(3): 804-15, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21266508

ABSTRACT

Acute inflammation in humans is associated with transient insulin resistance (IR) and dyslipidemia. Chronic low-grade inflammation is a pathogenic component of IR and adipose tissue dysfunction in obesity-induced type 2 diabetes. Because feline diabetes closely resembles human type 2 diabetes, we studied whether lipopolysaccharide (LPS)-induced subacute inflammation, in the absence of obesity, is the potential primary cause of IR and metabolic disorders. Cats received increasing iv doses (10-1000 ng/kg(-1) · h(-1)) of LPS (n = 5) or saline (n = 5) for 10 d. Body temperature, proinflammatory and metabolic markers, and insulin sensitivity were measured daily. Tissue mRNA and protein expression were quantified on d 10. LPS infusion increased circulating and tissue markers of inflammation. Based on the homeostasis model assessment, endotoxemia induced transient IR and ß-cell dysfunction. At the whole-body level, IR reverted after the 10-d treatment; however, tissue-specific indications of IR were observed, such as down-regulation of adipose glucose transporter 4, hepatic peroxisome proliferative activated receptor-γ1 and -2, and muscle insulin receptor substrate-1. In adipose tissue, increased hormone-sensitive lipase activity led to reduced adipocyte size, concomitant with increased plasma and hepatic triglyceride content and decreased total and high-density lipoprotein cholesterol levels. Prolonged LPS-induced inflammation caused acute IR, followed by long-lasting tissue-specific dysfunctions of lipid-, glucose-, and insulin metabolism-related targets; this ultimately resulted in dyslipidemia but not whole-body IR. Endotoxemia in cats may provide a promising model to study the cross talk between metabolic and inflammatory responses in the development of adipose tissue dysfunction and IR.


Subject(s)
Adipose Tissue/physiopathology , Endotoxemia/metabolism , Inflammation/chemically induced , Lipid Metabolism/physiology , Lipoproteins/metabolism , Animals , Cats , Endotoxemia/chemically induced , Gene Expression Regulation , Insulin Resistance , Insulin-Secreting Cells , Lipopolysaccharides , Male
18.
Domest Anim Endocrinol ; 40(3): 155-64, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21194873

ABSTRACT

Adrenal necrosis has been reported as a complication of trilostane application in dogs with hyperadrenocorticism. One suspicion was that necrosis results from the increase of adrenocorticotropic hormone (ACTH) during trilostane therapy. The aim of the current study was to assess the effects of ACTH and trilostane on adrenal glands of rats. For experiment 1, 36 rats were divided into 6 groups. Groups 1.1 to 1.4 received ACTH in different doses (60, 40, 20, and 10 µg/d) infused subcutaneously with osmotic minipumps for 16 wk. Group 1.5 received saline, and group 1.6 received no therapy. For experiment 2, 24 rats were divided into 3 groups. Group 2.1 and 2.2 received 5 and 50 mg/kg trilostane/d orally mixed into chocolate pudding for 16 wk. Eight control rats received pudding alone. At the end of the experiments, adrenal glands were assessed for necrosis by histology and immunohistochemistry; levels of endogenous ACTH and nucleosomes were assessed in the blood. Rats treated with 60 µg ACTH/d showed more hemorrhage and vacuolization and increased numbers of apoptotic cells in the adrenal glands than rats treated with 20 or 10 µg ACTH/d, trilostane, or control rats. Rats treated with 60 µg ACTH/d had a higher amount of nucleosomes in the blood compared with rats treated with 10 µg ACTH/d, trilostane, or saline. We conclude that in healthy rats ACTH, but not trilostane, causes adrenal degeneration in a dose-dependent manner. Results of this study support the hypothesis that adrenal gland lesions seen in trilostane-treated dogs are caused by ACTH and not by trilostane.


Subject(s)
Adrenal Glands/drug effects , Adrenal Glands/pathology , Adrenocortical Hyperfunction/veterinary , Adrenocorticotropic Hormone/pharmacology , Apoptosis/physiology , Dihydrotestosterone/analogs & derivatives , Dog Diseases/pathology , Adrenocortical Hyperfunction/blood , Adrenocortical Hyperfunction/drug therapy , Adrenocortical Hyperfunction/physiopathology , Adrenocorticotropic Hormone/blood , Animals , Apoptosis/drug effects , Body Weight/physiology , Dihydrotestosterone/adverse effects , Dihydrotestosterone/pharmacology , Dog Diseases/drug therapy , Dogs , Enzyme Inhibitors/pharmacology , Immunohistochemistry , Male , Necrosis , Nucleosomes/physiology , Rats , Rats, Sprague-Dawley , Statistics, Nonparametric
19.
J Comp Pathol ; 142(4): 311-22, 2010 May.
Article in English | MEDLINE | ID: mdl-20116802

ABSTRACT

Survivin is a member of the family of proteins known as 'inhibitors of apoptosis proteins'. Survivin has a role in cellular decisions concerning division and survival and is frequently expressed in neoplastic cells. The aim of the present study was to investigate immunohistochemically the expression of survivin in normal canine tissues and in canine lymphoma. A representative range of fetal and adult normal tissues as well as biopsy samples from dogs with lymphoma were assembled in tissue arrays. The lymphomas were classified according to the revised Kiel and to the Revised European American Lymphoma-World Health Organization (REAL-WHO) schemes. Polyclonal and monoclonal antisera cross-reactive with canine survivin identified cytoplasmic expression of the molecule in a broad range of normal canine cells. The same reagents demonstrated cytoplasmic labelling of more than 5% of cells in all 83 lymphoma samples tested with polyclonal antiserum and in 67 of 82 (82%) of samples tested with monoclonal antiserum. Survivin was expressed by a wide range of canine lymphoma subtypes, but the expression of this molecule in normal canine tissues must be considered if novel therapies targeting survivin are applied to the management of canine lymphoma.


Subject(s)
Antigens, Neoplasm/genetics , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Animals , Apoptosis/genetics , Cytoplasm/genetics , Cytoplasm/metabolism , Dogs , Inhibitor of Apoptosis Proteins/genetics , Inhibitor of Apoptosis Proteins/metabolism , Lymphoma/genetics
20.
Horm Metab Res ; 42(5): 340-7, 2010 May.
Article in English | MEDLINE | ID: mdl-20162504

ABSTRACT

Obesity and hyperlipidemia are associated with impaired insulin sensitivity in human type 2 diabetes mellitus, possibly due to activation of a mild inflammatory response. Because obesity-induced insulin resistance predisposes cats to diabetes and because hyperlipidemia is a frequent concurrent finding, excess lipids may also impair insulin sensitivity in cats. Healthy cats (n=6) were infused with lipids (Lipovenoes 10%) for 10 days to clamp blood triglycerides at the approximate concentration of untreated feline diabetes (3-7 mmol/l). Controls received saline (n=5). On day 10, plasma adiponectin and proinflammatory markers were measured. Whole-body insulin sensitivity was calculated following an intravenous glucose tolerance test. Tissue mRNAs of glucose metabolism-related genes were quantified in subcutaneous and visceral fat, liver, and skeletal muscles. Accumulation of lipids was assessed in liver. At the termination of infusion, whole-body insulin sensitivity did not differ between groups. Compared to saline, cats infused with lipids had 50% higher plasma adiponectin and 2-3 times higher alpha(1)-acid glycoprotein and monocyte chemoattractant protein-1. Unexpectedly, lipid-infused cats had increased glucose transporter-4 (GLUT4) mRNA in the visceral fat, and increased peroxisome proliferative activated receptor-gamma2 (PPARgamma2) in subcutaneous fat; adiponectin expression was not affected in any tissue. Lipid-infused cats developed hepatic steatosis. Although hyperlipidemia induced systemic inflammation, whole-body insulin sensitivity was not impaired after 10 day infusion. Increased circulating adiponectin may have contributed to prevent insulin resistance, possibly by increasing GLUT4 and PPARgamma2 transcripts in fat depots.


Subject(s)
Glucose/metabolism , Hyperlipidemias/metabolism , Inflammation/genetics , Insulin Resistance/genetics , Adipose Tissue/pathology , Animals , Bacteremia/blood , Blood Glucose/metabolism , Blotting, Western , Cats , DNA Primers , Fatty Acids, Nonesterified/blood , Glucose Tolerance Test , Glucose Transporter Type 4/metabolism , Hyperlipidemias/pathology , Insulin/blood , Liver/pathology , Male , PPAR gamma/metabolism , RNA/biosynthesis , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction , Triglycerides/blood
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