Establishment of a BRAF V595E-mutant canine prostate cancer cell line and the antitumor effects of MEK inhibitors against canine prostate cancer     

Masanori Kobayashi  Moe Onozawa  Shiho Watanabe  Tomokazu Nagashima  Kyoichi Tamura  Yoshiaki Kubo  Akiko Ikeda  Kazuhiko Ochiai  Masaki Michishita  Makoto Bonkobara  Masato Kobayashi  Tatsuya Hori  Eiichi Kawakami 《Veterinary and comparative oncology》2023,21(2):221-230

Canine prostate cancer (cPCa) is a malignant neoplasm with no effective therapy. The BRAF V595E mutation, corresponding to the human BRAF V600E mutation, is found frequently in cPCa. Activating BRAF mutations are recognized as oncogenic drivers, and blockade of MAPK/ERK phosphorylation may be an effective therapeutic target against BRAF-mutated tumours. The aim of this study was to establish a novel cPCa cell line and to clarify the antitumor effects of MEK inhibitors on cPCa in vitro and in vivo. We established the novel CHP-2 cPCa cell line that was derived from the prostatic tissue of a cPCa patient. Sequencing of the canine BRAF gene in two cPCa cell lines revealed the presence of the BRAF V595E mutation. MEK inhibitors (trametinib, cobimetinib and mirdametinib) strongly suppressed cell proliferation in vitro, and trametinib showed the highest efficacy against cPCa cells with minimal cytotoxicity to non-cancer COPK cells. Furthermore, we orally administered 0.3 or 1.0 mg/kg trametinib to CHP-2 xenografted mice and examined its antitumor effects in vivo. Trametinib reduced tumour volume, decreased phosphorylated ERK levels, and lowered Ki-67 expression in xenografts in a dose-dependent manner. Although no clear adverse events were observed with administration, trametinib-treated xenografts showed osteogenesis that was independent of dosage. Our results indicate that trametinib induces cell cycle arrest by inhibiting ERK activation, resulting in cPCa tumour regression in a dose-dependent manner. MEK inhibitors, in addition to BRAF inhibitors, may be a targeted agent option for cPCa with the BRAF V595E mutation.  相似文献   

Molecular characterization of Rhipicephalus (Boophilus) microplus Bm86 homologue from Haemaphysalis longicornis ticks     

Liao M  Zhou J  Hatta T  Umemiya R  Miyoshi T  Tsuji N  Xuan X  Fujisaki K 《Veterinary parasitology》2007,146(1-2):148-157

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Mitochondrial dysfunction of in vitro grown rabbit oocytes results in preimplantation embryo arrest after activation     

Kanaya H  Hashimoto S  Teramura T  Morimoto Y  Matsumoto K  Saeki K  Iritani A  Hosoi Y 《The Journal of reproduction and development》2007,53(3):631-637

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Relationships between immunoglobulin and fat‐soluble vitamins in colostrum of Japanese Black multiparous cows          下载免费PDF全文

Mengdong Wang  Shuntaro Ikeda  Hidetugu Yoshioka  Hiroshi Nagase  Shoko Kitamura  Erina Itoyama  Hiroaki Murakami  Miki Sugimoto  Shinichi Kume 《Animal Science Journal》2015,86(7):673-678

Data from 19 Japanese Black multiparous cows were collected to clarify the relationships among immunoglobulin (Ig) G, IgA, β‐carotene, vitamin A and α‐tocopherol contents in colostrum of cows in order to evaluate the role of fat‐soluble vitamins on colostral IgG and IgA production. Mean colostral IgG was 141 mg/mL, ranging from 65 to 208 mg/mL, whereas mean colostral IgA was 8.7 mg/mL, ranging from 1.0 to 34.6 mg/mL. Colostral IgG increased with aging in multiparous cows. There were positive correlations between colostral IgG and colostral vitamin A or colostral α‐tocopherol in cows, and the higher adjusted R² was obtained in the prediction model of colostral IgG from age and colostral vitamin A. Colostral vitamin A was positively correlated with colostral β‐carotene or colostral α‐tocopherol in cows, but there were no relationships between colostral IgA and colostral IgG or colostral fat‐soluble vitamins. These results indicate that fat‐soluble vitamin contents in colostrum of cows may change in similar patterns and high colostral vitamin A is related with high colostral IgG.  相似文献   

Chordoma of the thoracic vertebrae in a Bengal tiger (Panthera tigris tigris)     

Mizuki KURAMOCHI  Takeshi IZAWA  Mayuka HORI  Kayo KUSUDA  Junichiro SHIMIZU  Toshie ISERI  Hideo AKIYOSHI  Fumihito OHASHI  Mitsuru KUWAMURA  Jyoji YAMATE 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(7):893-895

A 19-year-old female Bengal tiger (Panthera tigris tigris) was presented with hind limb weakness, ataxia and respiratory distress. Computed tomography revealed a mass between the left side of the T7 vertebra and the base of the left 7th rib. The tiger then died, and necropsy was performed. Grossly, the vertebral mass was 6 × 5.7 × 3 cm, and invaded the adjacent vertebral bone and compressed the T7 spinal cord. Histologically, the mass was composed of large, clear, vacuolated and polygonal cells with osteochondral matrix. Cellular and nuclear atypia were moderate. The vacuolated cells stained positively for cytokeratin and vimentin and negatively for S-100. Based on these findings, the present case was diagnosed as a vertebral chordoma; the first report in a tiger.  相似文献   

Heat shock decreases the embryonic quality of frozen-thawed bovine blastocysts produced in vitro     

Miyuki MORI  Takeshi HAYASHI  Yoshihiro ISOZAKI  Naoki TAKENOUCHI  Miki SAKATANI 《The Journal of reproduction and development》2015,61(5):423-429

In this study, the effect of heat shock on frozen-thawed blastocysts was evaluated using in vitro-produced (IVP) bovine embryos. In experiment 1, the effects of 6 h of heat shock at 41.0 C on fresh blastocysts were evaluated. HSPA1A expression as a reflection of stress was increased by heat shock (P < 0.05), but the expressions of the quality markers IFNT and POU5F1 were not affected. In experiment 2, frozen-thawed blastocysts were incubated at 38.5 C for 6 h (cryo-con) or exposed to heat shock at 41.0 C for 6 h (cryo-HS). Then, blastocysts were cultured at 38.5 C until 48 h after thawing (both conditions). Cryo-HS blastocysts exhibited a decreased recovery rate: HSPA1A expression was dramatically increased compared with that in fresh or cryo-con blastocysts at 6 h, and IFNT expression was decreased compared with that in cryo-con blastocysts at 6 h (both P < 0.05). Cryo-con blastocysts at 6 h also exhibited higher HSPA1A expression than fresh blastocysts (P < 0.05). At 48 h after thawing, the number of hatched blastocysts and blastocyst diameter were lower in cryo-HS blastocysts (P < 0.05). Cryo-con blastocysts showed lower POU5F1 levels at 48 h than fresh, cryo-con or cryo-HS blastocysts at 6 h (P < 0.05), but their POU5F1 levels were not different from those of cryo-HS blastocysts at 48 h. These results indicated that application of heat shock to frozen-thawed blastocysts was highly damaging. The increase in damage by the interaction of freezing-thawing and heat shock might be one reason for the low conception rate in frozen-thawed embryo transfer in summer.  相似文献   

Development of a programmable piggyback syringe pump and four-times-a-day injection regimen for superovulation in non-lactating Holstein cows     

Abdul Razaq IRSHAD  Taihei SASAKI  Tomoaki KUBO  Naoyuki ODASHIMA  Keiji KATANO  Takeshi OSAWA  Toru TAKAHASHI  Yoshiaki IZAIKE 《The Journal of reproduction and development》2015,61(5):485-488

The objectives of the present study were to develop a programmable piggyback syringe pump for bovine superovulation and to evaluate the effects of a four-times-a-day injection regimen using the pump. Non-lactating Holstein cows were treated with a total of 30 armour units of porcine FSH by injection four times a day with the pump (study, n = 9) or injection twice a day manually (control, n = 9) for four consecutive days from D10 of the estrous cycle. The pump-driven program successfully induced superovulation in all cows tested. The numbers of small (3– < 5 mm in diameter) and large (≥ 10 mm in diameter) follicles were greater in the study group on D11-13 and D14, respectively. There were fewer unovulated follicles detected on D21 (7 days after estrus) in the study group than in the control group (1.2 ± 0.4 and 3.2 ± 0.6, respectively).  相似文献   

Exploring quantitative trait loci for anthocyanin content in interspecific hybrid grape (Vitis labruscana × Vitis vinifera)     

Yusuke Ban  Nobuhito Mitani  Takeshi Hayashi  Akihiko Sato  Akifumi Azuma  Atsushi Kono  Shozo Kobayashi 《Euphytica》2014,198(1):101-114

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Genetic dissection of black grain rice by the development of a near isogenic line     

Hiroaki Maeda  Takuya Yamaguchi  Motoyasu Omoteno  Takeshi Takarada  Kenji Fujita  Kazumasa Murata  Yukihide Iyama  Yoichiro Kojima  Makiko Morikawa  Hidenobu Ozaki  Naoyuki Mukaino  Yoshinori Kidani  Takeshi Ebitani 《Breeding Science》2014,64(2):134-141

Rice (Oryza sativa L.) can produce black grains as well as white. In black rice, the pericarp of the grain accumulates anthocyanin, which has antioxidant activity and is beneficial to human health. We developed a black rice introgression line in the genetic background of Oryza sativa L. ‘Koshihikari’, which is a leading variety in Japan. We used Oryza sativa L. ‘Hong Xie Nuo’ as the donor parent and backcrossed with ‘Koshihikari’ four times, resulting in a near isogenic line (NIL) for black grains. A whole genome survey of the introgression line using DNA markers suggested that three regions, on chromosomes 1, 3 and 4 are associated with black pigmentation. The locus on chromosome 3 has not been identified previously. A mapping analysis with 546 F₂ plants derived from a cross between the black rice NIL and ‘Koshihikari’ was evaluated. The results indicated that all three loci are essential for black pigmentation. We named these loci Kala1, Kala3 and Kala4. The black rice NIL was evaluated for eating quality and general agronomic traits. The eating quality was greatly superior to that of ‘Okunomurasaki’, an existing black rice variety. The isogenicity of the black rice NIL to ‘Koshihikari’ was very high.  相似文献   

Identification of quantitative trait loci associated with boiled seed hardness in soybean     

Kaori Hirata  Ryoichi Masuda  Yasutaka Tsubokura  Takeshi Yasui  Tetsuya Yamada  Koji Takahashi  Taiko Nagaya  Takashi Sayama  Masao Ishimoto  Makita Hajika 《Breeding Science》2014,64(4):362-370

Boiled seed hardness is an important factor in the processing of soybean food products such as nimame and natto. Little information is available on the genetic basis for boiled seed hardness, despite the wide variation in this trait. DNA markers linked to the gene controlling this trait should be useful in soybean breeding programs because of the difficulty of its evaluation. In this report, quantitative trait locus (QTL) analysis was performed to reveal the genetic factors associated with boiled seed hardness using a recombinant inbred line population developed from a cross between two Japanese cultivars, ‘Natto-shoryu’ and ‘Hyoukei-kuro 3’, which differ largely in boiled seed hardness, which in ‘Natto-shoryu’ is about twice that of ‘Hyoukei-kuro 3’. Two significantly stable QTLs, qHbs3-1 and qHbs6-1, were identified on chromosomes 3 and 6, for which the ‘Hyoukei-kuro 3’ alleles contribute to decrease boiled seed hardness for both QTLs. qHbs3-1 also showed significant effects in progeny of a residual heterozygous line and in a different segregating population. Given its substantial effect on boiled seed hardness, SSR markers closely linked to qHbs3-1, such as BARCSOYSSR_03_0165 and BARCSOYSSR_03_0185, could be useful for marker-assisted selection in soybean breeding.  相似文献