Expression of ABC-transport proteins in canine mammary cancer: consequences for chemotherapy.

Intrinsic or acquired drug resistance is a major barrier for chemotherapy of cancer. Importantly, the presence of ATP-binding cassette, ABC-transport proteins in tumour cells circumvents an intracellular accumulation of chemotherapeutic drugs. In this study, 103 canine mammary tumour probes were investigated for mRNA expression of seven ABC-transporters by RT-PCR. All tumour samples expressed multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance protein (BCRP). MRP7 was detected in 97.1% of tumour probes, MRP3 in 96.1%, Pgp in 92.2%, MRP5 in 85.4% and MRP6 in 64.1%. More of the half of tumour samples (56.1%) expressed all of the examined ABC-transport proteins. Approximately one-third of the tumour samples (32.7%) were lacking in one transporter and only 11.2% possessed from three to five transporters. The canine transporter cBCRP was functionally analysed in stable transfected Madin-Darby canine kidney-II cells using an MTT viability test. cBCRP transfected cells showed a 5.4-fold resistance to 10 microm doxorubicin. Cell survival in the presence of methotrexate was not affected by cBCRP. In conclusion, absence of efficiency of chemotherapy of canine mammary cancer can be caused by expression of seven various ABC-transport proteins. Because cBCRP is expressed in all examined tumour probes and induces resistance to doxorubicin, the application of doxorubicin for treatment of canine mammary is inappropriate.

Investigation of the local expression of the relaxin system in canine mammary tumours.

While mammary tumours are the main reasons of death in bitches, early detection of tumours and metastases is crucial for survival of affected dogs. Invasiveness and angiogenesis, which are important processes of tumour growth and spreading, require connective tissue remodelling. This process is dominantly mediated by matrix metalloproteinases (MMP), which are well known to be positively regulated by relaxin (RLX) in various tissues, including human breast cancer. So far, the presence of RLX and its receptor RXFP-1 as well as their linkage with MMP in canine mammary tumours (CMT) is completely unknown. In the first part of the present study, concentrations of RLX, oestradiol and progesterone from plasma samples of bitches with CMT were compared with clinical and survival data to investigate the predictive value of these hormones. In the second part, the expressions of RLX, RXFP-1 and MMP-2, -9 and -13 were examined by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in 31 CMT samples. Finally, relationships of systemic plasma RLX or locally expressed RLX with expression of MMP in CMT were analyzed for the first time. Comparison of hormone concentrations in 93 bitches in terms of benign or malignant nature of the CMT, lung metastases, recidivation and 12-month survival discovered no significances. The expressions of RLX, RXFP-1 and MMP were independent from plasma RLX, but expressions of local RLX and RXFP-1 showed a strong correlation (p = 0.00004, r = 0.671) as well as RXFP-1 and MMP-2 (p = 0.009, r = 0.463), indicating a possible significant role of the locally produced RLX in CMT pathogenesis as an inducer of connective tissue remodelling.

Prolonged foetal retention in a bitch resulting in trichogranulomatuous panmetritis and re-establishment of fertility after unilateral ovariohysterectomy.

This case report describes the clinical course, the diagnostic and therapeutic management as well as histopathological findings in a case of foetal retention for about 5 months in a 5-year-old Boxer. Clinical symptoms included mucosanguinous vaginal discharge and a firm ovoid mass of about duck egg size palpable in mid abdomen. Sonographic examination was not suitable to visualize uterine contents, while radiography revealed a conglomeration of foetal bones focally visible in the right uterine horn, which was surgically removed together with the ipsilateral ovary in order to maintain the fertility of the bitch. After lancing the uterine wall the osseous skeleton as well as parts of hairy skin and muscles of the foetus attaching the uterine wall were detected. Histologically a unilateral necrotizing panmetritis with almost complete destruction of the endometrial structures was diagnosed. Furthermore, the endometrium, the myometrium as well as the serosa revealed a severe trichogranulomatuous inflammation with numerous foetal hairs visible within the inflammatory alterations. After treatment of the bitch with prostaglandin F(2alpha) and an antibiotic agent she became pregnant in the second heat after surgery and gave birth to two healthy puppies. This is the first report on foetal retention for several months followed by unilateral ovariohysterectomy with subsequent recovery of fertility. Furthermore, this case report describes for the first time the histomorphological diagnosis of a unilateral trichogranulomatuous panmetritis in a bitch.

Changes in the spleen and liver of pregnant sows and full-term piglets after feeding diets naturally contaminated with deoxynivalenol and zearalenone.

Wheat contaminated naturally with the Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) was fed to pregnant Landrace sows for 35days. On day 110, caesarean section was carried out, the offspring were killed immediately after birth, and their livers and spleens examined. At necropsy there were no macroscopic lesions observed in any organ of either sows or piglets. Histopathological evaluation of tissues from sows of the treated group revealed changes in liver and spleen tissues, whereas no significant changes were observed in these tissues in their piglets. Liver damage, as measured by prominent elevated transaminase activities, was not detected in the serum of the sows. In pregnant sows there were individual variations in sensitivity to the Fusarium toxins. In conclusion, it can be assumed that there are no adverse effects on the liver and spleen of full-term piglets when their mothers consumed diets containing up to 9570 and 358mug DON/ZON per kg diet.

Primary and secondary heart tumours in dogs and cats.

Primary and secondary neoplasms of the canine and feline heart are uncommon. During a 2-year period, 83 dogs suffering from primary cardiac (n=11), extracardiac benign (n=6) or malignant (n=66) tumours and 30 cats with primary cardiac (n=1) or extracardiac (n=29) malignant tumours were examined. Echocardiography revealed four cases of primary cardiac neoplasms in dogs, but secondary heart tumours were not detected. After necropsy, tissue samples from the heart and tumours were examined histologically and immunohistochemically. In dogs, primary neoplasms included seven haemangiosarcomas, two chemodectomas, one rhabdomyosarcoma, and one neurofibrosarcoma. In 24 of 66 dogs examined, metastases of extracardiac neoplasms were found in the heart (15 carcinomas, six malignant lymphomas, three haemangiosarcomas). In cats, one case of primary haemangiosarcoma of the pericardium and five cases of secondary cardiac tumours (two malignant lymphomas, three carcinomas) occurred. Cardiac neoplasms in cats were not identified clinically but were detected by detailed gross sectioning of the heart (n=2) or histopathological examinations (n=3). This study showed an unexpectedly high number (36%) of dogs with cardiac metastases.

High-dose-rate brachytherapy for intranasal tumours in dogs: results of a pilot study.

This prospective study describes the feasibility and toxicity of (192)Iridium high-dose-rate (HDR) brachytherapy as an alternative strategy for the treatment of canine intranasal tumours. Fifteen dogs with malignant intranasal tumours were treated twice weekly using a hypofractionated protocol with eight fractions, 5 Gy per fraction, resulting in a total dose of 40 Gy. Acute and chronic adverse side-effects appeared to be rare. Only 7% of the acute side-effects and 5% of the chronic were classified as severe (grade 3). Eight dogs showed clinical complete remission, and five dogs had partial remission, with a resolution of tumour-related symptoms. Magnetic resonance imaging showed a reduced tumour mass in 12 cases. Median survival time was 17 months (range 4-48 months), with four dogs (three without disease) still alive. Median time to recurrence of these dogs was 14 months. In nine dogs, progression or recurrence of the tumour was the cause of death. This study suggests that HDR brachytherapy is feasible and well tolerated.

Cowpox virus infection associated with a streptococcal septicaemia in a foal.

Cowpox virus infection associated with a streptococcal septicaemia was diagnosed in a weak German Warmblood filly, born 29 days prematurely, and humanely destroyed on the sixth day of life. At necropsy, ulcerative lesions in the alimentary tract, colitis, polyarthritis and nephritis were observed. Transmission electron microscopical examination of specimens from ulcerative lesions revealed typical orthopox virions. Cowpox virus was unequivocally identified by virological and molecular-biological methods.

Functional pathology of the ovaries and uteri of premature female piglets exposed to distinct amounts of zearalenone.

The objective of this study was to investigate the effects of four different concentrations (groups II-V) of orally administered zearalenone (ZON) over a feeding period of 35 days on parts of the genital tract of 75 day-old female piglets in comparison to a control group (I). In order to determine possible dose related characteristics for a ZON intoxication in ovaries and uteri, histomorphological (HE and Azan stained slides) and immunohistochemical methods [expression patterns of estrogen (ER) and progesterone (PR) receptor, proliferating cell nuclear antigen (PCNA)] were carried out. Using these methods, there were no obvious (immuno-) histomorphological differences within the treatment groups or in comparison to the control group. Nevertheless, compared to the group I, statistical analyses of all parameters investigated revealed significance only in the increased mitotic activity of muscle cells in the uterinelamina muscularis in treatment group V.

An oral choristoma in a foal resembling hairy polyp in humans.

A neonatal foal was presented with a 6.5-cm pedunculated mass arising from the upper deciduous incisors. The distal end was soft and covered by haired skin, whereas the proximal end was firm, covered with mucosal epithelium, and at the point of transection contained a fully developed tooth. Microscopically, the mass was covered by epidermis and mucosal epithelium and the remaining portion of the mass consisted of mature collagen, nonneoplastic fat and smooth muscle, and a single tooth within a bony socket. The mass is consistent with an oral choristoma and has features similar to those described for hairy polyp in humans.