著者

Yosuke AMAGAI Akane TANAKA Akira MATSUDA Kumiko OIDA Kyungsook JUNG Sho NISHIKAWA Hyosun JANG Saori ISHIZAKA Hiroshi MATSUDA

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.13-0025, (Released:2013-02-22)

被引用文献数

1 4

---

Myeloid cell leukemia sequence 1 (MCL1) is a potent antiapoptotic protein that plays a critical role in cell survival and drug resistance in various cancers. However, to the best of our knowledge, the role of MCL1 in mast cell tumors (MCTs) has not been investigated in dogs. Here, we detected increased MCL1 expression in MCT cell lines, regardless of the presence of a c-kit mutation. MCL1 expression increased when the cells were exposed to specific inhibitors of mitogen-activated protein kinase or Janus kinase-signaling pathways, thus protecting the cells from apoptosis, but not when KIT or phosphatidylinositol-3 kinase signaling cascades were inhibited. These results indicate that MCL1 expression may contribute to MCT survival and confer drug resistance.

著者

松田 緝 マツダ アキラ Akira Matsuda

雑誌

経済と経営

巻号頁・発行日

vol.20, no.1, pp.17-41, 1989-06

著者

Akira MATSUDA Ikki MITSUI Yuki SHIMIZU Teppei KANDA Akihiro OHNISHI Masahiro MIYABE Yoshiki ITOH

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.20-0179, (Released:2020-09-11)

被引用文献数

1

---

Little is known about the pathological roles of sebaceous glands in canine skin diseases, as most examinations have been conducted with cultured human sebaceous epithelial cell lines. To our knowledge, there is no available canine sebaceous epithelial cell line. The purpose of this study was to establish a canine sebaceous epithelial cell line and characterize it. An eyelid mass in a dog was surgically resected for treatment, and it was histologically diagnosed as sebaceous epithelioma. Collected tissue was conducted for culture, and the growing epithelial-like cells were passaged. The cells showed continuous proliferation for over 6 months. After 40 passages, the cells were named CMG-1. Lipid droplets in the cytoplasm of CMG-1 cells were confirmed by Oil Red O staining. As reported in studies with human sebaceous epithelial cell lines, lipogenesis in CMG-1 cells was promoted by linoleic acid, whereas TGF-β suppressed it. Additionally, real-time PCR revealed that the expression levels of chemokines and cytokines, including CCL-2, CCL-20, CXCL-10, TNF-α, IL-1α, IL-1β, and IL-8, were significantly increased in CMG-1 cells following treatment with lipopolysaccharide. In conclusion, we successfully established a new canine sebaceous epithelial cell line. Our data indicated that lipogenesis and inflammatory responses were quantitatively evaluable in this cell line. CMG-1 cells could be useful for the pathological analysis of sebaceous gland diseases in dogs.

著者

Yosuke AMAGAI Akane TANAKA Akira MATSUDA Kumiko OIDA Kyungsook JUNG Hiroshi MATSUDA

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.12-0540, (Released:2013-01-17)

被引用文献数

4 7 2

---

Mast cell tumors (MCTs) are the most common tumors in dogs, accounting for 16–21% of cutaneous tumors. Although several small molecule inhibitors, including imatinib mesylate, have been used for the treatment of MCTs, the response rate remains less than 50%. In this study, the effects of different selective signal inhibitors on MCT cell growth were evaluated using 4 different cell lines derived from dogs. We found that the phosphoinositide 3-kinase (PI3K) signaling pathway is crucial for the proliferation of MCT cells in the presence or absence of c-kit gene mutations. Here, we propose a novel therapeutic strategy to target the PI3K pathway for the treatment of canine MCTs.

著者

Akira MATSUDA Ikki MITSUI Yuki SHIMIZU Teppei KANDA Akihiro OHNISHI Masahiro MIYABE Yoshiki ITOH

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.82, no.11, pp.1577-1584, 2020 (Released:2020-11-12)

参考文献数

42

被引用文献数

1

---

Little is known about the pathological roles of sebaceous glands in canine skin diseases, as most examinations have been conducted with cultured human sebaceous epithelial cell lines. To our knowledge, there is no available canine sebaceous epithelial cell line. The purpose of this study was to establish a canine sebaceous epithelial cell line and characterize it. An eyelid mass in a dog was surgically resected for treatment, and it was histologically diagnosed as sebaceous epithelioma. Collected tissue was conducted for culture, and the growing epithelial-like cells were passaged. The cells showed continuous proliferation for over 6 months. After 40 passages, the cells were named CMG-1. Lipid droplets in the cytoplasm of CMG-1 cells were confirmed by Oil Red O staining. As reported in studies with human sebaceous epithelial cell lines, lipogenesis in CMG-1 cells was promoted by linoleic acid, whereas transforming growth factor-β (TGF-β) suppressed it. Additionally, real-time PCR revealed that the expression levels of chemokines and cytokines, including CC chemokine ligand (CCL)-2, CCL-20, CXCL-10, Tumor necrosis factor-α (TNF-α), Interleukin (IL)-1α, IL-1β, and IL-8, were significantly increased in CMG-1 cells following treatment with lipopolysaccharide. In conclusion, we successfully established a new canine sebaceous epithelial cell line. Our data indicated that lipogenesis and inflammatory responses were quantitatively evaluable in this cell line. CMG-1 cells could be useful for the pathological analysis of sebaceous gland diseases in dogs.

著者

YUKARI SUZUKI AKIRA MATSUDA TOHRU UEDA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.5, pp.1808-1811, 1987-05-25 (Released:2009-10-19)

参考文献数

7

被引用文献数

10 10

---

Oxidation of 6, 5'-cyclo-5'-deoxy-2', 3'-Ο-isopropylideneuridine with selenium dioxide gave the 5'-oxo derivative, which was converted to the 5'-ethoxycarbonylmethylidene derivative (3). Reduction of 3 afforded, after deprotection, the title compounds (6, R and S). The base-catalyzed epimerization of 6 at the 5'-position was observed, and the equilibrium was in favor of the (R) -epimer.

著者

吉村 祐一 / 上田 享 松田 彰 Akira MATSUDA

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.7, pp.1761-1769, 1992-07-25 (Released:2008-03-31)

参考文献数

49

被引用文献数

20 28

---

6, 1'-Propanouridine (10), a carbon-bridged cyclouridine fixed in the syn-conformation, was synthesized from D-fructose. Two additional carbon-units were introduced at the 1'-position of 1'-hydroxymethyl-O2, 2'-anhydrouridine 13 and inversion of the 2' hydroxyl group was achieved by sequential oxidation-reduction reactions. Finally, the spiro-carbon bridge was constructed by radical cyclization of the 1'-iodopropyl derivative of 5-chlorouridine. Dehydrochlorination followed by deprotection gave the desired 10. The circular dichroism (CD) spectrum of 10 showed a negative Cotton effect ([θ]=-6100) at the main absorption region, whereas 5'-O-tert-butyldimethylsilyl-2', 3'-O-isopropylidene-6, 1'-propanouridine (30) showed almost no Cotton band at the same absorption region. These results suggest that the critical region in which the CD Cotton effect changes from negative to positive is present in the syn region where 10 is located. Correlation of the magnitude and the direction of the sign of the CD Cotton effect and the torsion angle (χ) is also discussed.

著者

KATSUTOSHI TAKAHASHI HISAO EKIMOTO SHOKO AOYAGI AKIKO KOYU HIROSHI KURAMOCHI OSAMU YOSHIOKA AKIRA MATSUDA AKIO FUJII HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.32, no.1, pp.36-42, 1979 (Released:2006-04-12)

参考文献数

12

被引用文献数

30 31

---

Pepleomycin (PEP), 3-[(S)-1'-phenylethylamino]propylaminobleomycin has potent activity and is less pulmonary toxic than bleomycin (BLM). Biological activity and toxicity of the following degradation products of PEP have been studied in detail: the product of carbamoyl migration (ISO), the product of decarbamylation (DC), the product of ring closure of the side chain on the pyrimidine moiety (RC), the depyruvamide product (DP) and the product of an enzymatic inactivation (DA). These degradation products showed much lower activity than PEP in vitro: antimicrobial and anti-HeLa activities, inhibition of DNA synthesis in AH66 cells and the DNA strand cleavage. Acute toxicity and pulmonary toxicity were tested in mice. Results indicated much lower acute toxicity corresponding to the decreased in vitro activity when compared to PEP. DP and RC did not cause lung fibrosis in mice, while ISO and DC showed 1/2.6 and 1/5.7 degree of pulmonary toxicity, respectively, in comparison with PEP.

著者

Hisao EKIMOTO Kimihiko TAKADA Takao OHNUKI Katsutoshi TAKAHASHI Akira MATSUDA Tomohisa TAKITA Hamao UMEZAWA

出版者

SOCIETY FOR FREE RADICAL RESEARCH JAPAN

雑誌

Journal of Clinical Biochemistry and Nutrition (ISSN:09120009)

巻号頁・発行日

vol.2, no.1, pp.25-31, 1987 (Released:2010-02-25)

参考文献数

26

被引用文献数

7 11

---

Sensitivity to bleomycin-induced pulmonary fibrosis was tested in various strains of mice. Among the strains examined, ICR, C57BL/10(H-2b), and C3H/He(H-2k) mice were highly sensitive to the induced pulmonary fibrosis; C57BL/6(H-2b), DBA/2(H-2d), A/J(H-2a), B6C3F1 and BDF1 mice were moderately sensitive, and CBA/JN(H-2k), BALB/c(H-2d), CDF1 and CBF1 mice were less sensitive. In congenic mice, which differ from each other only in the H-2 locus, C57BL/10(H-2b) was highly sensitive; B10·D2(H-2d) was moderately sensitive; and B10·BR(H-2k) and B10·A(H-2a) were less sensitive. Thus, the sensitivity differed depending on the haplotype of the H-2 genes. Furthermore, non-H-2 genes also seemed to be involved in the sensitivity to the pulmonary fibrosis. There was no correlation between the sensitivity to pulmonary fibrosis and enzyme activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the lung tissues, but the levels of reducing agents such as ascorbic acid and tocopherol in the lungs were inversely correlated with the sensitivity to the pulmonary fibrosis, except in the case of BALB/c and its F1 mice.

著者

HISAO EKIMOTO HIROSHI KURAMOCHI KATSUTOSHI TAKAHASHI AKIRA MATSUDA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.33, no.4, pp.426-434, 1980 (Released:2006-04-12)

参考文献数

18

被引用文献数

21 22

---

The kinetics of the reaction of BLM-Fe(II)-O2 with DNA in the absence or presence of 2-mercaptoethanol (2-ME) were studied. The total number of bases released by BLM-Fe(II)-O2 in the presence of 2-ME increased about 6.5 times more than that in the absence of 2-ME in the reaction of 6 hours at 37°C. The molar ratios of the released bases ware little affected by the reaction time, temperature or 2-ME. Among the four bases, thymine was preferentially released. On the basis of a reaction scheme of BLM-Fe(II)-O2 with DNA, the equations were derived by the steady-state method. In the absence of 2-ME, the release of bases from DNA was dependent on the concentration of BLM-Fe(II)-O2, but independent of the concentration of DNA. In the presence of 2-ME, a biphasic reaction was observed; the first one is due to BLM-Fe (II) which originally existed and the second one is due to BLM-Fe(II) produced by the reduction of BLM-Fe(III) with 2-ME. In the second reaction, the rate of the release of bases from DNA was proportional to the concentration of BLM-Fe(II) and 2-ME, but inversely proportional to the concentration of DNA. The rate-determining step in the reaction of BLM-Fe(II)-O2 with DNA in the presence of 2-ME was found to be the reduction of BLM-Fe(III) to BLM-Fe(II). By these kinetic studies, the reaction of BLM-Fe(II)-O2 with DNA in the presence of 2-ME was elucidated to proceed in a catalytic fashion. Furthermore, the maximum number of bases released by BLM from DNA was one base per twelve to thirteen bases.

著者

HISAO EKIMOTO KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.38, no.8, pp.1077-1082, 1985 (Released:2006-04-19)

参考文献数

12

被引用文献数

25 34

---

Lipid peroxidation catalyzed by bleomycin (BLM)-metal complexes was studied in vitro using arachidonic acid as the substrate. Iron complexes of BLM caused extensive lipid peroxidation, but other metal complexes did not. The lipid peroxidation caused by the iron complexes was inhibited by antioxidants such as dl-α-tocopherol, ascorbic acid etc., but not by other scavengers of hydroxyl and superoxide radicals, and of singlet oxygen. Cyanide ion suppressed the lipid peroxidation caused by BLM-Fe(II), but did not suppress the peroxidation activity of BLM-Fe(III). The peroxidation activity of BLM-Fe(II) was lost instantly by pre-incubation of the complex at 37°C before mixing with arachidonic acid, but that of BLM-Fe(III) was not. These results indicate that the active form for the lipid peroxidation derived from BLM-Fe(II) differs from that of BLM-Fe(III).

著者

HISAO EKIMOTO MINAKO AIKAWA TAKAO OHNUKI KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.38, no.1, pp.94-98, 1985 (Released:2006-04-19)

参考文献数

16

被引用文献数

5 6

---

Pulmonary fibrosis in mice induced by peplomycin (PEP) was suppressed by administration of anti-inflammatory agents such as prednisolone and D-penicillamine during or after the administration of PEP. Pulmonary fibrosis was also suppressed by administration of cyclophosphamide, an immunosuppressive antitumor agent before, during or after the administration of PEP. The pulmonary fibrosis in athymic nude mice induced by PEP was less than that in normal mice. The low response in the nude mice was enhanced by transfer of thymocytes to the same level as that in the normal mice. This suggests that the immune system, especially thymus-dependent immunity, is involved in the pulmonary fibrosis induced by PEP.

著者

HISAO EKIMOTO KINIIHIKO TAKADA KATSUTOSHI TAKAHASHI AKIRA MATSUDA TOMOHISA TAKITA HAMAO UMEZAWA

出版者

JAPAN ANTIBIOTICS RESEARCH ASSOCIATION

雑誌

The Journal of Antibiotics (ISSN:00218820)

巻号頁・発行日

vol.37, no.6, pp.659-663, 1984 (Released:2006-04-19)

参考文献数

30

被引用文献数

7 5

---

The pulmonary fibrosis caused by peplomycin (PEP) was studied in terms of oxygen toxicity using ICR mice. When 16μg of PEP was administered intratracheally in mice after exposure to the air containing 75% O2 for 10 days, the pulmonary fibrosis was completely suppressed, while when mice were exposed to 75% O2 after the administration of PEP, the fibrosis was much severe than that of mice raised in atmospheric air. In 50% O2 similar oxygen effect was also observed, but it was weaker than that in 75% O2. In 90% O2 the oxygen toxicity was observed in mice without administration of PEP. When mice were exposed to 75% O2 the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which are relevant to the detoxication of active oxygen species, were not increased in the lung, but the levels of reducing agents such as glutathione and ascorbic acid, and high molecular substances having 1O2-scavenging activity were enhanced. The results suggest that these materials have some roles to decrease the pulmonary fibrosis caused by PEP.

著者

Yosuke AMAGAI Akane TANAKA Akira MATSUDA Kumiko OIDA Kyungsook JUNG Sho NISHIKAWA Hyosun JANG Saori ISHIZAKA Hiroshi MATSUDA

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.7, pp.971-974, 2013 (Released:2013-07-31)

参考文献数

25

被引用文献数

1 4

---

Myeloid cell leukemia sequence 1 (MCL1) is a potent antiapoptotic protein that plays a critical role in cell survival and drug resistance in various cancers. However, to the best of our knowledge, the role of MCL1 in mast cell tumors (MCTs) has not been investigated in dogs. Here, we detected increased MCL1 expression in MCT cell lines, regardless of the presence of a c-kit mutation. MCL1 expression increased when the cells were exposed to specific inhibitors of mitogen-activated protein kinase or Janus kinase-signaling pathways, thus protecting the cells from apoptosis, but not when KIT or phosphatidylinositol-3 kinase signaling cascades were inhibited. These results indicate that MCL1 expression may contribute to MCT survival and confer drug resistance.