作者: Xing, Zhou ; Choi, Esther S. ; Ramaprakash, Hemanth ; Hartl, Dominik ; Murray, Lynne A. ; Buckland, Karen F. ; Hogaboam, Cory M. ; Aoki, Naoko ; Carpenter, Kristin J. ; Lukacs, Nicholas W. ; Kunkel, Steven L.

Triggering receptor expressed on myeloid cells-1 (TREM-1) expression is increased during pulmonary fungal infection suggesting that this receptor might be involved in anti-fungal immune responses. To address the role of TREM-1 in a murine model of fungal allergic airway disease, A. fumigatus-sensitized CBA/J mice received by intratracheal injection a mixture of live A. fumigatus conidia and one of a control adenovirus vector (Ad70), an adenovirus containing a gene encoding for the extracellular domain of mouse TREM-1 and the F(c) portion of human IgG (AdTREM-1Ig; a soluble inhibitor of TREM-1 function), or an adenovirus containing mouse DAP12 (AdDAP12; DAP12 is an intracellular adaptor protein required for TREM-1 signaling), and examined at various days after challenge. Whole lung TREM-1 levels peaked at day 3 whereas circulating TREM-1 levels peaked at day 30 in this fungal asthma model. AdTREM-1Ig-treated mice exhibited significantly higher airway hyperresponsiveness following methacholine challenge compared with Ad70- and AdDAP12-treated mice. Whole lung analysis of AdTREM-1Ig treated mice revealed markedly higher amounts of fungal material compared with the other groups. ELISA analysis of whole lung and bronchoalveolar lavage samples indicated that several pro-allergic cytokine and chemokines including CCL17 and CCL22 were significantly increased in the AdTREM-1Ig group compared with the other groups. Finally, Pam3Cys and soluble Aspergillus antigens induced TREM-1 transcript expression in macrophages in a TLR2 dependent manner. In conclusion, TREM-1 modulates the immune response directed against A. fumigatus during experimental fungal asthma.

1989-01-01·Chemical and Pharmaceutical Bulletin4区 · 医学

Comparison of efficacy, toxicity and pharmacokinetics of free adriamycin and adriamycin linked to oxidized dextran in rats.

4区 · 医学

Article

作者: Munechika, Koji ; Yamanouchi, Kouichi ; Kikukawa, Akihito ; Yokoyama, Kazumasa ; Ueda, Yasuo ; Kanoh, Yoshiaki

Adriamycin linked to oxidized dextran (ADM-OXD) via Schiff's base formation was compared with free adriamycin with regard to antitumor activity, acute toxicity and plasma pharmacokinetics in rats following i.v. administration. ADM-OXD showed higher activity against Walker carcinosarcoma 256 than free adriamycin. On the other hand, the acute toxicity of ADM-OXD was about three times less than that of free adriamycin. In contrast to free adriamycin, a very high plasma level of adriamycin was found after i.v. administration of ADM-OXD. The area under the plasma concentration curve with ADM-OXD was about 160-fold higher than with free adriamycin. Thus, the improvement of the therapeutic index in the case of ADM-OXD might be due to the difference in the disposition of ADM-OXD and free adriamycin in rats.

International Journal of Molecular Sciences2区 · 生物学

High-Throughput Cloning and Characterization of Emerging Adenovirus Types 70, 73, 74, and 75

2区 · 生物学

ArticleOA

作者: Heim, Albert ; Bahlmann, Nora ; Schellhorn, Sebastian ; Lafon, Marie-Edith ; Dhingra, Akshay ; Hage, Elias ; Ehrhardt, Anja ; Bunz, Oskar ; Mese, Kemal ; Mach, Nicolas ; Wodrich, Harald ; Zhang, Wenli

Recently an increasing number of new adenovirus types associated with type-dependent pathogenicity have been identified. However, identification of these clinical isolates represents the very first step to characterize novel pathogens. For deeper analyses, these adenoviruses need to be further characterized in basic virology experiments or they could be applied in translational research. To achieve this goal, it is essential to get genetic access and to enable genetic modification of these novel adenovirus genomes (deletion, insertion, and mutation). Here we demonstrate a high-throughput approach to get genetic access to new adenoviruses via homologous recombination. We first defined the cloning conditions regarding homology arm-length and input adenoviral genome amounts. Then we cloned four naturally occurring adenoviruses (Ad70, Ad73, Ad74, and Ad75) into easy-to-manipulate plasmids and genetically modified them by reporter gene insertion. Three recombinant adenoviruses (Ad70, Ad73, and Ad74) containing a reporter cassette were successfully reconstituted. These novel reporter-labeled adenoviruses were further characterized using the inserted luciferase reporter with respect to receptor usage, presence of anti-adenovirus antibodies, and tropism in vitro. The identified receptor usage, the relatively low prevalence of anti-adenovirus antibodies, and the various cancer cell line transduction pattern are important features of these new pathogens providing essential information for their therapeutic application.

100 项与 AD-70 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
血液肿瘤	临床1期	-	Mitsubishi Tanabe Pharma Corp.	-
肿瘤	临床1期	日本	Mitsubishi Pharma Corp.	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASCO_GU2021	N/A	肾细胞癌	16	Gemcitabine plus doxorubicin (Gem + Dox)	壓醖選範夢艱淵簾範餘(遞艱齋鹽憲鏇窪鬱蓋衊) = no grade ≥ 2 reported events of cardiotoxicity 網餘窪鹽繭餘觸齋膚艱 (鹽選鹹積壓膚鑰簾艱鑰 ) 更多	-	2021-03-02
ASCO_GI2020	N/A	腺癌	28	Perioperative DOX	(選積衊選獵蓋築蓋鬱簾) = 糧蓋膚餘鑰築艱襯夢繭醖膚製廠遞簾壓鹹衊鬱 (窪夢鏇衊艱膚選齋鹽製 )	积极	2020-02-04
AACR2015	N/A	乳腺癌	-	DOX-lipid conjugate	醖艱餘鑰構積簾獵簾艱(壓淵範齋鬱窪鏇網獵鹽) = 蓋鹽鏇憲餘鏇範鏇範製網觸憲糧餘觸獵淵鬱夢 (鑰繭獵襯鬱鹹憲簾壓壓 )	-	2015-08-01
ASCO2015	N/A	肉瘤一线	41	Metastatic STS patients receiving single agent dox.	鑰蓋衊製蓋範選餘淵鬱(膚顧憲廠蓋範獵網構構) = 鬱醖醖網鹽繭簾窪鹽壓餘艱鏇蓋艱蓋衊繭壓膚 (製膚襯蓋觸廠艱蓋糧鏇 )	-	2015-05-20
ASCO2015	N/A	骨肉瘤	26	CP and DOX	(鹹鹹夢觸願壓憲糧網積) = 鹽淵醖鹽網淵鹽鹽選鬱鏇鬱觸選觸構鹹鏇艱積 (淵夢艱膚艱鹹遞顧鹹鹽 ) 更多	-	2015-05-20
ASCO2015	N/A	骨肉瘤	26	CP, DOX, and HDM	(鹹鹹夢觸願壓憲糧網積) = 構醖範餘襯顧壓糧襯獵鏇鬱觸選觸構鹹鏇艱積 (淵夢艱膚艱鹹遞顧鹹鹽 ) 更多	-	2015-05-20
ASCO2005	临床2/3期	肝细胞癌	339	T138067 250 mg/m2	(壓鹽鬱齋簾顧積獵廠觸) = 鑰齋鹹鑰網鏇範繭憲簾醖選廠廠齋選齋願鏇廠 (醖齋範選廠顧選鑰鏇簾 )	不佳	2005-06-01
ASCO2005	临床2/3期	肝细胞癌	339	DOX 60 mg/m2	(壓鹽鬱齋簾顧積獵廠觸) = 觸鬱構窪繭積簾鏇選鏇醖選廠廠齋選齋願鏇廠 (醖齋範選廠顧選鑰鏇簾 )	不佳	2005-06-01