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Mizukami K.,Kagoshima University | Kawamichi T.,A+ Network | Koie H.,Nihon University | Tamura S.,Tamura Animal Clinic | And 10 more authors.
The Scientific World Journal | Year: 2012

Neuronal ceroid lipofuscinosis (NCL) is an inherited, neurodegenerative lysosomal disease that causes premature death. The present study describes the clinical and molecular epidemiologic findings of NCL in Border Collies in Japan for 12 years, between 2000 and 2011. The number of affected dogs was surveyed, and their clinical characteristics were analyzed. In 4 kennels with affected dogs, the dogs were genotyped. The genetic relationships of all affected dogs and carriers identified were analyzed. The survey revealed 27 affected dogs, but there was a decreasing trend at the end of the study period. The clinical characteristics of these affected dogs were updated in detail. The genotyping survey demonstrated a high mutant allele frequency in examined kennels (34.8%). The pedigree analysis demonstrated that all affected dogs and carriers in Japan are related to some presumptive carriers imported from Oceania and having a common ancestor. The current high prevalence in Japan might be due to an overuse of these carriers by breeders without any knowledge of the disease. For NCL control and prevention, it is necessary to examine all breeding dogs, especially in kennels with a high prevalence. Such endeavors will reduce NCL prevalence and may already be contributing to the recent decreasing trend in Japan. © 2012 Keijiro Mizukami et al. Source


Kitahara G.,University of Miyazaki | Nambo Y.,Hidaka Training and Research Center | El-Sheikh Ali H.,University of Miyazaki | El-Sheikh Ali H.,Mansoura University | And 4 more authors.
Journal of Reproduction and Development | Year: 2012

This study was carried out to evaluate the blood profile and tissue expression of Anti-Müllerian hormone (AMH) as a biomarker for granulosa-theca cell tumors (GTCTs) in cattle. Five cases with unilateral ovarian GTCTs (GTCT group) were investigated in comparison to other groups of Japanese Black cows, which had either cystic ovarian disease (COD group, n=5), a functional corpus luteum on Days 9 to 11 of the estrous cycle (Day 0=estrus; CL group, n=13) or received superovulation treatment (SOT group, n=13). We used transrectal ultrasonography and measured plasma AMH, estradiol-17β (E 2), progesterone (P 4) and testosterone (T) levels. Moreover, GTCT tissues were collected and examined by immunohistochemical staining (IHC) for AMH. In the GTCT group, ultrasound images of GTCTs were variable and not definitive. However, the AMH level in the GTCT group (n=3, 58.1 ± 66.3 ng/ml) was significantly higher than in the COD, CL and SOT groups (0.1 ± 0.1 ng/ml for GTCT vs. COD, P<0.05; 0.2 ± 0.1 and 0.3 ± 0.2 ng/ml, respectively for GTCT vs. CL and SOT, P<0.01). The other hormonal levels in the GTCT group had no significant differences compared with the COD or SOT group. Neoplastic granulosa cells labeled with AMH antibody clearly demonstrated a variety of tissue patterns in all cases by IHC. To the best of our knowledge, this is the first study to investigate the blood profile and IHC of AMH in bovine GTCTs. Our findings indicate that AMH may be a novel biomarker to diagnose GTCTs in cattle. © 2012 by the Society for Reproduction and Development. Source


Ito K.,Nippon Veterinary and Life Science University | Kobayashi M.,Nippon Veterinary and Life Science University | Kuroki S.,Nippon Veterinary and Life Science University | Sasaki Y.,Nippon Veterinary and Life Science University | And 12 more authors.
Veterinary Journal | Year: 2013

Canine malignant melanomas are highly aggressive and fatal neoplasms. In the present report, 21 drugs that target specific signalling pathways were screened for their growth inhibitory activity on three canine malignant melanoma cell lines. The proteasome inhibitor bortezomib inhibited the growth of these cell lines. The growth inhibitory properties of bortezomib were then examined using nine canine malignant melanoma cell lines. Bortezomib demonstrated potent growth inhibitory activity in all cell lines with calculated IC50 values of 3.5-5.6. nM.Because suppression of the NF-κB pathway by preventing proteasomic degradation of IκB is an important mechanism of the anti-tumour activity of bortezomib, the activation status of and the effect of bortezomib on the NF-κB pathway were examined using a canine malignant melanoma cell line, CMM-1. The NF-κB pathway was constitutively activated in CMM-1 cells and bortezomib efficiently suppressed this activated pathway. Using a CMM-1 xenograft mouse model, bortezomib also significantly inhibited tumour growth via suppression of tumour cell proliferation.Collectively, these findings suggest that bortezomib has growth inhibitory activity against canine malignant melanomas potentially through suppression of the constitutively activated NF-κB pathway. Targeted therapy using bortezomib could therefore be beneficial in the management of canine malignant melanomas. © 2013 Elsevier Ltd. Source


Ito K.,Nippon Veterinary and Life Science University | Kuroki S.,Nippon Veterinary and Life Science University | Kobayashi M.,Nippon Veterinary and Life Science University | Ono K.,Nippon Veterinary and Life Science University | And 3 more authors.
Veterinary Journal | Year: 2013

Canine histiocytic sarcoma (HS) is an aggressive and fatal neoplasm that has a high recurrence rate and metastatic nature. In the present report, compounds were screened for their growth inhibitory activity in two HS cell lines using a chemical library known to target specific signalling pathways. Among 171 compounds screened, dasatinib, which targets several types of kinases, clearly inhibited cell growth in one of the two HS lines. The growth inhibitory properties of dasatinib were then examined using six HS cell lines and MDCK cells. Dasatinib demonstrated potent growth inhibitory activity against four HS cell lines with calculated IC50 values of 5.4-54.5. nM, while the IC50 values in the other cell lines were in the micromolar range. In conclusion, a kinase enzyme targeted by dasatinib appears to be crucial for growth in some subsets of HS and the on-target activity of dasatinib could underlie the marked growth inhibition in HS cells. © 2012 Elsevier Ltd. Source


Hirose N.,University of Tokyo | Uchida K.,University of Tokyo | Matsunaga S.,Japan Animal Referral Medical Center | Chambers J.K.,University of Tokyo | Nakayama H.,University of Tokyo
Journal of Veterinary Medical Science | Year: 2015

C horoid plexus tumor (CPT) is a primary intracranial neoplasm of the choroid plexus epithelium in the central nervous system. In the current World Health Organization classification, CPT is classified into two categories; choroid plexus papilloma (CPP) and carcinoma (CPC). In the present study, we investigated immunohistochemical expressions of N-cadherin, E-cadherin and β-catenin in 5 canine CPT cases (1 disseminated CPC, 2 CPCs and 2 CPPs). One CPP case was positive for N-cadherin and β-catenin, but negative for E-cadherin. The disseminated CPC case was positive for E-cadherin and β-catenin, but negative for N-cadherin. The other cases were positive for the three molecules examined. These results suggest that loss of the N-cadherin expression might associate with the spreading of CPC cells. ©2015 The Japanese Society of Veterinary Science. Source

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