著者

Yui HIROSE Mona UCHIDA Masaya TSUBOI Takayuki NAKAGAWA Leo YAGA Shingo MAEDA Yasuyuki MOMOI Yugo KURIKI Mako KAMIYA Yasuteru URANO Tomohiro YONEZAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.22-0003, (Released:2022-03-07)

被引用文献数

3

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Since gamma-glutamyl transpeptidase (GGT) is highly and locally expressed in human breast cancer, a GGT-enzymatically activatable fluorescent probe, gamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG), has been developed to detect the human breast cancer area with high performance. In this study, GGT expression and the efficacy of gGlu-HMRG on visualization were investigated in canine mammary gland tumors (MGT). Seventeen non-fixed fresh-frozen MGT specimens and each peritumoral control tissue were utilized. The GGT mRNA levels were highly observed in the tumor specimens compared with the control. GGT immunostaining was mostly observed on the cell membrane and cytosol of the alveolar and duct mammary epithelium of MGT tissues. These signals were strongly positive in several cases while they were mild to not observed in other cases. When gGlu-HMRG solution was dropped to the non-fixed tissue pieces of MGT or control tissues, the fluorescence intensities (FIs) were measured using Maestro in-vivo imaging device. FIs in MGT tissues were significantly higher than each control tissue 20 min after treatment. Based on Youden index method said that the maximum sensitivity and specificity of FI was 82.4% and 82.4%. These findings suggest that GGT is highly expressed in several MGTs in dogs and gGlu-HMRG could visualize at least a part of MGT tissues in dogs. Nevertheless, it should be needed to assess the false-negative areas more carefully in canine than human cases.

著者

Satoshi KAMOTO Masahiro SHINADA Daiki KATO Masaya TSUBOI Sho YOSHIMOTO Ryohei YOSHITAKE Shotaro ETO Namiko IKEDA Yosuke TAKAHASHI Yuko HASHIMOTO James CHAMBERS Kazuyuki UCHIDA Shinji YAMADA Mika K. KANEKO Ryohei NISHIMURA Yukinari KATO Takayuki NAKAGAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.83, no.11, pp.1795-1799, 2021 (Released:2021-11-24)

参考文献数

37

被引用文献数

2

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Podoplanin is expressed in various human tumors where it promotes tumor progression, epithelial-mesenchymal transition, and distant metastasis. Podoplanin is also expressed in cancer-associated fibroblasts and induces tumor malignancy. The objective of this study was to evaluate podoplanin expression in various types of feline tumor tissues. Immunohistochemical analysis revealed that podoplanin was expressed in cells of 13/15 (87%) squamous cell carcinomas and 5/19 (26%) fibrosarcomas. Moreover, cancer-associated fibroblasts expressed podoplanin in most tumor types, including 18/21 (86%) mammary adenocarcinoma tissues. Our findings demonstrate that various types of feline tumor tissues expressed podoplanin, indicating the importance of the comparative aspects of podoplanin expression, which may be used as a novel research model for podoplanin biology.

著者

Namiko IKEDA Daiki KATO Masaya TSUBOI Ryohei YOSHITAKE Shotaro ETO Sho YOSHIMOTO Masahiro SHINADA Satoshi KAMOTO Yuko HASHIMOTO Yousuke TAKAHASHI James CHAMBERS Kazuyuki UCHIDA Ryohei NISHIMURA Takayuki NAKAGAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.21-0217, (Released:2021-10-22)

被引用文献数

1

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Cancer immunotherapy is a novel cancer treatment for canine tumors. Indoleamine 2,3-dioxygenase 1 (IDO1) is overexpressed in some human tumors and inhibits antitumor immunity. In this study, we comprehensively evaluated expression pattern of IDO1 and the nature of IDO1-expressing cells in canine normal and tumor tissues. In normal tissue samples, IDO1 expression was detected only in the lymph nodes, spleen, tonsil tissues, and colon tissues. In contrast, IDO1-positive tumor cells were observed in several tumor tissue types. This is the first study to evaluate IDO1 expression in canine normal and tumor tissues, and the results suggest that IDO1 is a promising target for novel cancer immunotherapy in dogs with tumors.

著者

Satoshi KAMOTO Masahiro SHINADA Daiki KATO Masaya TSUBOI Sho YOSHIMOTO Ryohei YOSHITAKE Shotaro ETO Namiko IKEDA Yosuke TAKAHASHI Yuko HASHIMOTO James CHAMBERS Kazuyuki UCHIDA Shinji YAMADA Mika K. KANEKO Ryohei NISHIMURA Yukinari KATO Takayuki NAKAGAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.20-0608, (Released:2021-10-18)

被引用文献数

2

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Podoplanin is expressed in various human tumors where it promotes tumor progression, epithelial-mesenchymal transition, and distant metastasis. Podoplanin is also expressed in cancer-associated fibroblasts and induces tumor malignancy. The objective of this study was to evaluate podoplanin expression in various types of feline tumor tissues. Immunohistochemical analysis revealed that podoplanin was expressed in cells of 13/15 (87%) squamous cell carcinomas and 5/19 (26%) fibrosarcomas. Moreover, cancer-associated fibroblasts expressed podoplanin in most tumor types, including 18/21 (86%) mammary adenocarcinoma tissues. Our findings demonstrate that various types of feline tumor tissues expressed podoplanin, indicating the importance of the comparative aspects of podoplanin expression, which may be used as a novel research model for podoplanin biology.

著者

Shinya Suzuki Mayako Uchida Yukio Suga Hideki Sugawara Hideya Kokubun Yoshihiro Uesawa Takayuki Nakagawa Hisamitsu Takase

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.7, pp.1164-1171, 2019-07-01 (Released:2019-07-01)

参考文献数

40

被引用文献数

2 12

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No nationwide study on polypharmacy in palliative care among Japanese community pharmacies has yet been conducted. We conducted an online questionnaire survey for community pharmacist members of The Japanese Society for Pharmaceutical Palliative Care and Sciences regarding their contributions to cancer patients who regularly used six or more drugs, including opioids, in service during the two-month period from October to November 2017. Of 579 community pharmacists, 83 responded to the survey (14.3%). Among them, 47.0 and 27.7% of respondents replied that more than 40% of opioid-using and non-using cancer patients were prescribed six or more regular medications, respectively. The proportion of patients with polypharmacy was marginally higher among opioid-using than non-using patients. Additionally, 31.3 and 22.9% of respondents replied that a low or moderate rate of opioid-using and non-using patients with polypharmacy received inappropriate prescriptions, respectively, including “unnecessary medications,” “adverse drug reactions” and “duplication of pharmacological effect.” The proportion of patients who received inappropriate prescriptions was significantly higher among opioid-using than non-using patients. Furthermore, 37.3 and 19.3% of respondents replied that pharmacist’s recommendations contributed to drug reduction in opioid-using and non-using patients with polypharmacy who received inappropriate prescriptions, respectively. The responders with higher confidence in palliative care showed more success rate for reducing inappropriate medications. Our findings suggest that opioid use can be associated with an increased risk of polypharmacy in cancer patients, and that recommendations by a population of community pharmacists can reduce inappropriate medications and improve adverse drug reactions in both opioid-using and non-using cancer patients with polypharmacy.

著者

Miko Kondo Shunsaku Nakagawa Satoru Orii Kotaro Itohara Mitsuhiro Sugimoto Tomohiro Omura Yuki Sato Satoshi Imai Atsushi Yonezawa Takayuki Nakagawa Kazuo Matsubara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.10, pp.1463-1468, 2020-10-01 (Released:2020-10-01)

参考文献数

34

被引用文献数

1

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Vancomycin is a glycopeptide antibiotic used for the treatment of Gram-positive infections. For adult patients, treatment with vancomycin requires effective therapeutic drug-monitoring (TDM) to achieve clinical outcomes and reduce the incidence of adverse effects. However, it remains still unclear whether the TDM with vancomycin is beneficial in yielding better clinical outcomes in pediatrics. The objective of our study was to evaluate whether the clinical response to treatment was associated with initial trough concentrations of vancomycin in pediatric patients. A retrospective observation study of 60 patients (age: 1 month–15 years) who had completed and qualified for analysis was conducted at Kyoto University Hospital. The response to treatment was assessed by the time to resolution of fever and time to 50% decline in C-reactive protein (CRP). In addition, we explored whether vancomycin trough level was associated with the baseline characteristics. Trend analysis showed that there were significant correlations between vancomycin trough level and age, body weight, estimated glomerular filtration rate, and serum albumin levels. The time to resolution of fever of the patients with higher initial trough level (≥ 5 µg/mL) was significantly lower than that of the patients with lower trough level (< 5 µg/mL). The higher vancomycin concentration tended to be associated with the shorter time to 50% decline in CRP. The findings suggest that initial trough concentration is important in achieving better outcomes with vancomycin treatment in pediatrics.

著者

Kentaro ENDO Naoki FUJITA Takayuki NAKAGAWA Ryohei NISHIMURA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.18-0551, (Released:2019-06-04)

被引用文献数

13

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Mesenchymal stem cells (MSCs) are proposed to be useful in cartilage regenerative medicine, however, canine MSCs have been reported to show poor chondrogenic capacity. Therefore, optimal conditions for chondrogenic differentiation should be determined by mimicking the developmental process. We have previously established novel and superior canine MSCs named bone marrow peri-adipocyte cells (BM-PACs) and the objective of this study was to evaluate the effects of growth factors required for in vivo chondrogenesis using canine BM-PACs. Spheroids of BM-PACs were cultured in chondrogenic medium containing 10 ng/ml transforming growth factor-β1 (TGF-β1) with or without 100 ng/ml bone morphogenetic protein-2 (BMP-2), 100 ng/ml growth differentiation factor-5 (GDF-5) or 100 ng/ml insulin-like growth factor-1 (IGF-1). Chondrogenic differentiation was evaluated by the quantification of glycosaminoglycan and Safranin O staining for proteoglycan production. The expression of cartilage matrix or hypertrophic gene/protein was also evaluated by qPCR and immunohistochemistry. Spheroids in all groups were strongly stained with Safranin O. Although BMP-2 significantly increased glycosaminoglycan production, Safranin O-negative outer layer was formed and the mRNA expression of COL10 relating to cartilage hypertrophy was also significantly upregulated (P<0.05). GDF-5 promoted the production of glycosaminoglycan and type II collagen without increasing COL10 mRNA expression. The supplementation of IGF-1 did not significantly affect cartilaginous and hypertrophic differentiation. Our results indicate that GDF-5 is a useful growth factor for the generation of articular cartilage from canine MSCs.

著者

Congyun Jin Yoshiaki Yao Atsushi Yonezawa Satoshi Imai Hiroki Yoshimatsu Yuki Otani Tomohiro Omura Shunsaku Nakagawa Takayuki Nakagawa Kazuo Matsubara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.11, pp.1990-1995, 2017-11-01 (Released:2017-11-01)

参考文献数

22

被引用文献数

13

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Riboflavin (vitamin B2) plays a role in various biochemical oxidation-reduction reactions. Flavin mononucleotide (FMN) and FAD, the biologically active forms, are made from riboflavin. Riboflavin transporters (RFVTs), RFVT1-3/Slc52a1-3, have been identified. However, the roles of human (h)RFVTs in FMN and FAD homeostasis have not yet been fully clarified. In this study, we assessed the contribution of each hRFVT to riboflavin, FMN and FAD uptake and efflux using in vitro studies. The transfection of hRFVTs increased cellular riboflavin concentrations. The uptake of riboflavin by human embryonic kidney cells transfected with hRFVTs was significantly increased, and the efflux was accelerated in a time-dependent manner. However, the uptake and efflux of FMN and FAD hardly changed. These results strongly suggest that riboflavin, rather than FMN or FAD, passes through plasma membranes via hRFVTs. Our findings could suggest that hRFVTs are involved in riboflavin homeostasis in the cells, and that FMN and FAD concentrations are regulated by riboflavin kinase and FAD synthase.

著者

Masaki MICHISHITA Aya OHTSUKA Rei NAKAHIRA Tsuyoshi TAJIMA Takayuki NAKAGAWA Nobuo SASAKI Toshiro ARAI Kimimasa TAKAHASHI

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.15-0550, (Released:2015-11-28)

被引用文献数

1 22

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Feline mammary carcinomas are characterized by rapid progression and metastases. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, proliferation and metastasis. The present study aimed to investigate the effects of a single drug therapy of bevacizumab on a xenograft model of feline mammary carcinoma expressing VEGF protein. Bevacizumab treatment suppressed tumor growth by inhibiting angiogenesis and enhancing apoptosis; however, it did not affect the tumor proliferation index. Thus, bevacizumab had anti-tumor effects on a xenograft model, and this may be useful for the treatment of feline mammary carcinoma.

著者

Di ZHANG Reina FUJIWARA Toshie ISERI Shotaro NAGAHAMA Kei KAKISHIMA Masatoshi KAMATA Manabu MOCHIZUKI Takayuki NAKAGAWA Nobuo SASAKI Ryohei NISHIMURA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.75, no.5, pp.663-666, 2013 (Released:2013-05-31)

参考文献数

16

被引用文献数

3 10

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The epidural distribution of iohexol (0.2 ml/kg) administered at thoracic vertebrae (Thoracic group) and lumbar vertebrae (Lumbar group) was compared by computed tomographic (CT) epidurography in dogs. The total spread of iohexol was similar between the 2 groups upon reaching a similar cranial level. The maximal CT values were higher at the C7/T1 and T4/T5 levels in Thoracic group, but they were higher at the T13/L1 and L4/L5 levels in Lumbar group (P<0.05). This result suggests that the distribution pattern of the drug administered epidurally at thoracic vertebrae and lumbar vertebrae is different in dogs.

著者

Kohei SAEKI Yoshifumi ENDO Kazuyuki UCHIDA Ryohei NISHIMURA Nobuo SASAKI Takayuki NAKAGAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.74, no.2, pp.227-230, 2012 (Released:2012-03-02)

参考文献数

34

被引用文献数

8 13

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The numbers of tumor infiltrating T lymphocytes, B lymphocytes and antigen presenting cells were evaluated in an immunohistochemical manner in 140 canine spontaneous mammary gland tumor (MGT) tissues. As a result, we found a statistically significant increase in the number of intratumoral T lymphocytes (23.2 ± 23.8) in the malignant MGT group (n=51) compared with the benign MGT group (14.0 ± 16.0, n=89; P<0.05). Moreover, the high T lymphocyte infiltration in the malignant group correlated with poor prognosis in multivariate analysis (P<0.05). This study indicated the relationship between increased infiltrating T lymphocytes and canine MGT malignancy.

著者

Shunsuke NOGUCHI Takashi MORI Yuki HOSHINO Nami YAMADA Takayuki NAKAGAWA Nobuo SASAKI Yukihiro AKAO Kohji MARUO

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.74, no.1, pp.1-8, 2012 (Released:2012-02-01)

参考文献数

20

被引用文献数

38 50

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MicroRNA-145 (miRNA-145; miR-145) is aberrantly expressed in most of human cancers and plays a significant role in carcinogenesis and cancer progression. In the current study, we focused on how miR-145 plays a role in canine and human malignant melanomas. MiR-145 was significantly downregulated in canine malignant melanoma tissues and canine melanoma cell lines, as well as human melanoma cell lines tested. The ectopic expression of miR-145 showed a significant growth inhibition in both canine and human melanoma cells tested, and the effect was achieved partly by suppressing c-MYC in canine melanoma LMeC and in human melanoma A2058 and Mewo cells. At the same time, a suppressive tendency on cell migration in canine melanoma KMeC cells and significant suppression of cell migration in human melanoma A2058 cells by suppressing FASCIN1 were also found. These findings suggest that miR-145 acts as a tumor suppressor in both canine and human malignant melanomas.

著者

Lobna MKAOUAR Yoshifumi ENDO He XI JUN Soo-Jung LEE Tassanee JAROENSONG Manabu MOCHIZUKI Kazuyuki UCHIDA Hiroyuki NAKAYAMA Nobuo SASAKI Takayuki NAKAGAWA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.1112250747, (Released:2012-01-05)

被引用文献数

4 5

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In this study, the nuclear expression of nuclear factor kappa B (NF-κB) in 48 tissues specimens from 25 canine spontaneous mammary gland tumor (MGT) patients were assessed by immunohistochemistry to compare their levels with clinical features, histological types, prognostic outcomes and proliferative activities, including the mitotic index (MI) and cylcinD1 expression. Twelve of eighteen (66.7%) malignant tumor tissues showed a nuclear staining greater than 10%, while benign tumor and hyperplastic tissues showed nuclear staining less than 10%. Higher nuclear expression of NF-κB was positively correlated with larger tumor size, lymph node metastasis and higher MI, however no correlation was observed with distant metastasis and cyclin D1 expression. Higher NF-κB nuclear expression correlated with shorter patient survival. These findings suggest that NF-κB is a useful prognostic factor for canine MGT patients.