Document Detail


E1A, E1B double-restricted adenovirus enhances the cytotoxicity and antitumor activity of gemcitabine to renal cell carcinoma.
MedLine Citation:
PMID:  21542972     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Our previous studies have demonstrated potent oncolysis efficacy of the E1A, E1B double-restricted replication-competent oncolytic adenovirus AxdAdB-3 for treatment of bladder cancer. Here, we reported the feasibility and efficacy of AxdAdB-3 alone, or in combination with gemcitabine for treating renal cell carcinoma.
METHODS: Cytopathic effects of AxdAdB-3 were evaluated in human renal cell carcinoma cell lines TOS-1, TOS-2, TOS-3, TOS-3LN, SMKT-R3, SMKT-R4 and ACHN, and in normal human renal proximal tubule epithelial cells (RPTEC). AxdAdB-3 induced down-regulation of the cell cycle was determined by flow cytometry. Combination therapies of AxdAdB-3 with gemcitabine were evaluated in vitro and in vivo on subcutaneous TOS-3LN tumors in a severe combined immunodeficiency disease (SCID) mouse model.
RESULTS: AxdAdB-3 was potently cytopathic against the tested most renal cell carcinoma cell lines including TOS-2, TOS-3, TOS-3LN, SMKT-R3 and SMKT-R4, while normal human RPTEC were not destroyed. AxdAdB-3 effectively induced cell cycle S-phase entry. Combined therapy of AxdAdB-3 with gemcitabine demonstrated stronger antitumor effects in vitro and in vivo compared with either AxdAdB-3 or gemcitabine alone.
CONCLUSION: AxdAdB-3 alone, or in combination with gemcitabine may be a promising strategy against renal cell carcinoma.
Authors:
Hua Wang; Makoto Satoh; Gui-Ping Chen; De-Chuan Li; Hirofumi Hamada; Yoichi Arai
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chinese medical journal     Volume:  124     ISSN:  0366-6999     ISO Abbreviation:  Chin. Med. J.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-05-05     Completed Date:  2011-09-30     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  7513795     Medline TA:  Chin Med J (Engl)     Country:  China    
Other Details:
Languages:  eng     Pagination:  1082-7     Citation Subset:  IM    
Affiliation:
Department of Urology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China. hwangua@yahoo.com.cn
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics,  metabolism,  physiology*
Adenovirus E1A Proteins / genetics*
Adenovirus E1B Proteins / genetics*
Animals
Antimetabolites, Antineoplastic / pharmacology*,  therapeutic use*
Carcinoma, Renal Cell / drug therapy*,  therapy*
Cell Cycle / drug effects,  genetics
Cell Line
Cell Line, Tumor
Cell Proliferation / drug effects
Coxsackie and Adenovirus Receptor-Like Membrane Protein
Deoxycytidine / analogs & derivatives*,  pharmacology,  therapeutic use
Flow Cytometry
Humans
Immunohistochemistry
Male
Mice
Mice, Inbred BALB C
Mice, SCID
Oncolytic Virotherapy
Receptors, Virus / genetics,  metabolism
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/9030425E11Rik protein, mouse; 0/Adenovirus E1A Proteins; 0/Adenovirus E1B Proteins; 0/Antimetabolites, Antineoplastic; 0/CLMP protein, human; 0/Coxsackie and Adenovirus Receptor-Like Membrane Protein; 0/Receptors, Virus; 951-77-9/Deoxycytidine; B76N6SBZ8R/gemcitabine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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