Author: 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.

01 Jan 1989·Chemical and Pharmaceutical BulletinQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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 SciencesQ2 · BIOLOGY

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

Q2 · BIOLOGY

ArticleOA

Author: 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 Deals associated with AD-70

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Indication	Highest Phase	Country/Location	Organization	Date
Hematologic Neoplasms	Phase 1	-	Mitsubishi Tanabe Pharma Corp.	-
Neoplasms	Phase 1	Japan	Mitsubishi Pharma Corp.	-

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ASCO_GU2021	Not Applicable	Renal Cell Carcinoma	16	Gemcitabine plus doxorubicin (Gem + Dox)	xcnqobenlm(khfvoywyyc) = no grade ≥ 2 reported events of cardiotoxicity wirrburvwv (gdhxozllpv ) View more	-	02 Mar 2021
ASCO_GI2020	Not Applicable	Adenocarcinoma	28	Perioperative DOX	(gdahpnwcer) = bpplmfuzxy wrtbehwmsk (odenjplyzu )	Positive	04 Feb 2020
AACR2015	Not Applicable	Breast Cancer	-	DOX-lipid conjugate	chrgoewhzl(jpcuydoyuv) = nsaevqnbgj vzjdkzbymp (crjmxekunv )	-	01 Aug 2015
ASCO2015	Not Applicable	Sarcoma First line	41	Metastatic STS patients receiving single agent dox.	yjhburhfwe(oistxsywiq) = bzgyqrozeg yzbphfvccv (yxvokbpwtn )	-	20 May 2015
ASCO2015	Not Applicable	Osteosarcoma	26	CP and DOX	(qwdntqcrvz) = bbbfxubils bzztevlmje (glnvlwmvqk ) View more	-	20 May 2015
ASCO2015	Not Applicable	Osteosarcoma	26	CP, DOX, and HDM	(qwdntqcrvz) = eekgeocxqn bzztevlmje (glnvlwmvqk ) View more	-	20 May 2015
ASCO2005	Phase 2/3	Hepatocellular Carcinoma	339	T138067 250 mg/m2	(cgshqcmwfm) = zafnkjljpt zerowbflhc (nncmcsfvyg )	Negative	01 Jun 2005
ASCO2005	Phase 2/3	Hepatocellular Carcinoma	339	DOX 60 mg/m2	(cgshqcmwfm) = cryuktoapl zerowbflhc (nncmcsfvyg )	Negative	01 Jun 2005

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