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Pharmacology & Pharmacy 2012年第3期3卷 316-321页

作者： Yuta Takahashi Shizuyo Horiyama Yoko Kimoto noriko yoshikawa Masaru Kunitomo Satomi Kagota Kazumasa Shinozuka Kazuki Nakamura Analytical Center School of Pharmacy and Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan Department of Pharmacology School of Pharmacy and Pharmaceutical Sciences Mukogawa Women’s University Nishinomiya Japan Institute for Biosciences Mukogawa Women’s University Nishinomiya Japan

We investigated the effect of a nicotine-and tar-free cigarette smoke extract (CSE) using an experimental metastasis mouse model which was intravenously injected with B16-BL6 mouse melanoma cells. Three-hour pretreatment of cells with various concentrations of CSE (0, 0.1, 0.3, and 1%) dose-dependently reduced the number of lung metastatic nodules 14 days after tumor injection. To elucidate the mechanism of this anti-metastatic effect of CSE, we examined the invasion and migration activities of B16-BL6 cells pretreated with CSE for three hours in vitro. CSE significantly reduced the invasion of cells at 1% and the migration at 0.3% and 1%. Under the same pretreatment conditions, CSE had no effect on the proliferation of cells. These findings suggest that CSE contains some ingredients that suppress hematogenic lung metastasis via inhibition of the invasion and migration activities of mouse melanoma cells.

关键词： Cigarette Smoke Extract (CSE) Anti-Metastasis B16-BL6 Mouse Melanoma Cells Invasion Migration

<i>Cordyceps sinensis</i>Acts As an Adenosine A<sub>3</sub>Receptor Agonist on Mouse Melanoma and Lung Carcinoma Cells, and Human Fibrosarcoma and Colon Carcinoma Cells

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Pharmacology & Pharmacy 2011年第4期2卷 266-270页

作者： noriko yoshikawa Arisa Nishiuchi Erika Kubo Yu Yamaguchi Masaru Kunitomo Satomi Kagota Kazumasa Shinozuka Kazuki Nakamura 不详

Cordyceps sinensis, a parasitic fungus on the larva of Lapidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells and mouse Lewis lung carcinoma (LLC) cells was inhibited by cordycepin (3’-deoxyadenosine), an ingredient of Cordyceps sinensis, and its effect was antagonized by MRS1191, a selective adenosine A3 receptor (A3-R) antagonist although adenosine (up to 100 μM) had no effect on the growth of B16-BL6 and LLC cells. In this study, we investigated whether water extracts of Cordyceps sinensis (WECS) inhibit the growth of B16-BL6 cells, LLC cells, HT1080 human fibrosarcoma (HT1080) cells and CW-2 human colon carcinoma (CW-2) cells via their A3-R. As a result, the growth of all cell lines were potently inhibited by WECS (10 μg/mL) and the inhibitory effect of WECS was significantly antagonized by MRS1191 (1 μM). Furthermore, WECS included 2.34% w/w cordycepin and 0.12% w/w adenosine as components according to the HPLC- ECD system. In conclusion, WECS inhibited the proliferation of four cancer cell lines by stimulation of A3-R and the main component in WECS with anticancer action might be cordycepin instead of adenosine.

关键词： Cordyceps Sinensis Adenosine A3 Receptor Cordycepin HPLC-ECD

Virus-induced gene silencing and virusinduced flowering in strawberry(Fragaria×ananassa)using apple latent spherical virus vectors

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Horticulture Research 2019年第1期6卷 1428-1437页

作者： Chunjiang Li noriko Yamagishi Ichiro Kasajima Nobuyuki yoshikawa Faculty of Agriculture Iwate UniversityMorioka 3-18-8Iwate 020-8550Japan Agri-Innovation Research Center Iwate UniversityMorioka 3-18-8Iwate 020-8550Japan

Apple latent spherical virus(ALSV)vector is a convenient alternative to genetic transformation in horticultural plants,especially in species recalcitrant to genetic ***,an RNA virus,can infect a wide variety of plant species including major horticultural plants without inducing ***,methodologies were developed for infection of ALSV vectors to strawberry seedlings and plantlets cultured in vitro.A seed-propagated F1 hybrid strawberry cultivar'Yotsuboshi'was aseptically grown on half-strength Murashige–Skoog medium for 1 month and true leaves were inoculated with an ALSV RNA preparation by particle *** vector infection rates varied from 58 to 100%according to the insertion sequences,in‘Yotsuboshi’***(‘Dover’)propagated in vitro could also be infected with ALSV vector at a similar infection *** virus-induced gene silencing(VIGS),we prepared an ALSV vector carrying a 201 nucleotide segment of the strawberry phytoene desaturase gene.‘Yotsuboshi’and‘Dover’plants infected by this vector generated completely white leaves at fifth or sixth true leaves and *** virus-induced flowering(VIF),we used an ALSV vector expressing the Arabidopsis thaliana flowering locus T *** seedlings infected by this vector started to flower from about 2 months post inoculation and bore fruits with viable *** ALSV vector was no longer detected in any of the seedlings from early-flowered ***,the ALSV vector may be beneficial for examination of gene functions by VIGS in strawberry,and VIF using ALSV vector constitutes an effective new plant breeding technique for the promotion of cross-breeding in strawberry.

关键词： straw breeding Fragaria

Embryonic stem cells develop into hepatocytes after intrasplenic transplantation in CCl_4-treated mice

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World Journal of Gastroenterology 2007年第6期13卷 866-873页

作者： Kei Moriya Masahide yoshikawa Ko Saito Yukiteru Ouji Mariko Nishiofuku noriko Hayashi Shigeaki Ishizaka Hiroshi Fukui Division of Hepatology Third Department of Internal Medicine Nara Medical University 840 Shijo-cho Kashihara Nara 634-8521 Japan Division of Developmental Biology Department of Parasitology Nara Medical University 840 Shijo-cho Kashihara Nara 634-8521 Japan

AIM： To transplant undifferentiated embryonic stem （ES） cells into the spleens of carbon tetrachloride （CCl4）-treated mice to determine their ability to differentiate into hepatocytes in the liver. METHODS： CCh, 0.5 mL/kg body weight, was injected into the peritoneum of C57BL/6 mice twice a week for 5 wk. In group 1 （n = 12）, 1 × 10^5 undifferentiated ES cells （0.1 mL of 1 × 10^6/mL solution）, genetically labeled with GFP, were transplanted into the spleens 1 d after the second injection. Group 2 mice （n = 12） were injected with 0.2 mL of saline twice a week, instead of CCh, and the same amount of ES cells was transplanted into the spleens. Group 3 mice （n = 6） were treated with CCh and injected with 0.1 mL of saline into the spleen, instead of ES cells. Histochemical analyses of the livers were performed on post-transplantation d （PD） 10, 20, and 30. RESULTS： Considerable numbers of GFP-immunopositive cells were found in the periportal regions in group 1 mice （CCh-treated） on PD 10, however, not in those untreated with CCh （group 2）. The GFP-positive cells were also immunopositive for albumin （ALB）, alpha-1 antitrypsin, cytokeratin 18, and hepatocyte nuclear factor 4 alpha on PD 20. Interestingly, most of the GFP-positive cells were immunopositive for DLK, a hepatoblast marker, on PD 10. Although very few ES-derived cells were demonstrated immunohistologically in the livers of group 1 mice on PD 30, improvements in liver fibrosis were observed. Unexpectedly, liver tumor formation was not observed in any of the mice that received ES cell transplantation during the experimental period CONCLUSION： Undifferentiated ES cells developed into hepatocyte-like cells with appropriate integration into tissue, without uncontrolled cell growth.

关键词： Embryonic stem cells Hepatic differentiation Intrasplenic transplantation Carbon tetrachloride

Liver injury after aluminum potassium sulfate and tannic acid treatment of hemorrhoids

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World Journal of Gastroenterology 2017年第27期23卷 5034-5040页

作者： Kenichi yoshikawa Reimi Kawashima Yuki Hirose Keiko Shibata Takafumi Akasu noriko Hagiwara Takeharu Yokota Nami Imai Akira Iwaku Go Kobayashi Hirohiko Kobayashi Akiyoshi Kinoshita Nao Fushiya Hiroyuki Kijima Kazuhiko Koike Masayuki Saruta Division of Gastroenterology and Hepatology Internal Medicinethe Jikei University Daisan Hospital Division of Gastroenterology and Hepatology Internal Medicinethe Jikei University School of Medicine

We are reporting a rare case of acute liver injury that developed after an internal hemorrhoid treatment with the aluminum potassium sulfate and tannic acid(ALTA) regimen. A 41-year-old man developed a fever and liver injury after undergoing internal hemorrhoid treatment with a submucosal injection of ALTA with lidocaine. The acute liver injury was classified clinically as hepatocellular and pathologically as cholestastic. We could not classify the mechanism of injury. High eosinophil and immunoglobulin E levels characterized the injury,and a drug lymphocyte stimulation test was negative on postoperative day 25. Fluid replacement for two weeks after hospitalization improved the liver injury. ALTA therapy involves injecting chemicals into the submucosa,from the rectum to the anus,and this is the first description of a case that developed a severe liver disorder after this treatment; hence,an analysis of future cases as they accumulate is desirable.

关键词： Aluminum potassium sulfate and tannic acid injection Aluminum potassium sulfate and tannic acid therapy Rectal submucosal injection Drug-induced lymphocyte stimulation test Drug-induced liver injury

Promoted differentiation of cynomolgus monkey ES cells into hepatocyte-like cells by co-culture with mouse fetal liver-derived cells

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World Journal of Gastroenterology 2006年第42期12卷 6818-6827页

作者： Ko Saito Masahide yoshikawa Yukiteru Ouji Kei Moriya Mariko Nishiofuku Shigehiko Ueda noriko Hayashi Shigeaki Ishizaka Hiroshi Fukui Department of Gastroenterology and Hepatology Nara Medical University Kashihara Nara Japan Division of Developmental Biology Department of Parasitology Nara Medical University Kashihara Nara Japan

AIM: To explore whether a co-culture of cynomolgus monkey embryonic stem (cES) cells with embryonic liver cells could promote their differentiation into hepatocytes. METHODS: Mouse fetal liver-derived cells (MFLCs) were prepared as adherent cells from mouse embryos on embryonic d (ED) 14, after which undifferentiated cES cells were co-cultured with MFLCs. The induction of cES cells along a hepatic lineage was examined in MFLC- assisted differentiation, spontaneous differentiation, and growth factors (GF) and chemicals-induced differentiations (GF-induced differentiation) using retinoic acid, leukemia inhibitory factor (LIF), FGF2, FGF4, hepatocyte growth factor (HGF), oncostatin M (OSM), and dexamethasone. RESULTS: The mRNA expression of α-fetoprotein, albumin (ALB), α-1-antitrypsin, and hepatocyte nuclear factor 4α was observed earlier in the differentiating cES cells co-cultured with MFLCs, as compared to cES cells undergoing spontaneous differentiation and those subjected to GF-induced differentiation. The expression of cytochrome P450 7a1, a possible marker for embryonic endoderm-derived mature hepatocytes, was only observed in cES cells that had differentiated in a co-culture with MFLCs. Further, the disappearance of Oct3/4, a representative marker of an undifferentiated state, was noted in cells co-cultured with MFLCs, but not in those undergoing spontaneous or GF-induced differentiation. Immunocytochemical analysis revealed an increased ratio of ALB-immunopositive cells among cES cells co-cultured with MFLCs, while glycogen storageand urea synthesis were also demonstrated. CONCLUSION: MFLCs showed an ability to induce cES cells to differentiate toward hepatocytes. The co-culture system with MFLCs is a useful method for induction of hepatocyte-like cells from undifferentiated cES cells.

关键词： Primate embryonic stem cells Fetal liver Hepatic differentiation Co-culture

Endoscopic submucosal dissection in a patient with esophageal adenoid cystic carcinoma

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World Journal of Gastroenterology 2017年第45期23卷 8097-8103页

作者： Kenichi yoshikawa Akiyoshi Kinoshita Yuki Hirose Keiko Shibata Takafumi Akasu noriko Hagiwara Takeharu Yokota Nami Imai Akira Iwaku Go Kobayashi Hirohiko Kobayashi Nao Fushiya Hiroyuki Kijima Kazuhiko Koike Haruka Kaneyama Keiichi Ikeda Masayuki Saruta Division of Gastroenterology and Hepatology Internal MedicineJikei University Daisan Hospital Department of Endoscopy Jikei University Daisan Hospital Division of Gastroenterology and Hepatology Internal MedicineJikei University School of Medicine

We report the first use of endoscopic submucosal dissection(ESD) for the treatment of a patient with adenoid cystic carcinoma of the esophagus(EACC). An 82-year-old woman visited our hospital for evaluation of an esophageal submucosal tumor. Endoscopic examination showed a submucosal tumor in the middle third of the esophagus. The lesion partially stained with Lugol's solution,and narrow band imaging with magnification showed intrapapillary capillary loops with mild dilatation and a divergence of caliber in the center of the lesion. Endoscopic ultrasound imaging revealed a solid 8 mm × 4.2 mm tumor,primarily involving the second and third layers of the esophagus. A preoperative biopsy was non-diagnostic. ESD was performed to resect the lesion,an 8 mm submucosal tumor. Immunohistologically,tumor cells differentiating into ductal epithelium and myoepithelium were observed,and the tissue type was adenoid cystic carcinoma. There was no evidence of esophageal wall,vertical stump or horizontal margin invasion with p T1 b-SM2 staining(1800 μm from the muscularis mucosa). Further studies are needed to assess the use of ESD for the treatment of patients with EACC.

关键词： Adenoid cystic carcinoma of esophagus Endoscope Ultrasound Esophageal Tumor Endoscopic submucosal dissection

Impairment of autophagic signaling in murine forebrain disrupts GABAA receptor trafficking leading to excitatoryinhibitory imbalance and ASD-like behaviours

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Impairment of autophagic signaling in murine forebrain disru...