title: Examination of the optimal condition on the in vitro sensitivity to telomelysin in head and neck cancer cell lines.
abstract: OBJECTIVE
  Telomelysin (OBP-301) is a telomerase-specific replication-competent adenovirus with a human telomerase reverse transcriptase (hTERT) promoter. Telomelysin has a strong antitumor effect on a variety of cancers, including head and neck squamous cell carcinoma (HNSCC), and combining telomelysin treatment with paclitaxel or cisplatin enhances the antitumor effect on HNSCC. In the present study, we investigated the relationship between the antitumor activity of telomelysin and tumor cell doubling time(DT), S-phase fraction, and E1A expression. We also investigated whether the antitumor effects of OBP-301-resistant tumor cells are enhanced by cisplatin, paclitaxel, or streptolysin O.
  
  
  METHODS
  The tumor cell DT of 17 human HNSCC cell lines was examined. Antitumor activities of telomelysin (OBP-301) for each HNSCC cell line were examined by MTT assay. Cell cycle analysis was conducted by flowcytometry. E1A gene expressions after infection with telomelysin, hTERT, CAR (Cocksackie Adenovirus Receptor), and c-Myc were examined by quantitative PCR, and E1A expressions were examined again after pretreatment with cisplatin, paclitaxel, or streptolysin O. Correlations were analyzed by Spearman's correlation coefficient.
  
  
  RESULTS
  There was a significant relationship between telomelysin sensitivity and DT, S-phase fraction and early E1A expression, and pretreatment with cisplatin, paclitaxel, and streptolysin O increased infectivity of telomelysin-resistant HNSCC cell lines.
  
  
  CONCLUSIONS
  These findings are useful for advancing clinical trials, and suggest that adjuvant telomelysin treatment would be effective even in telomelysin-resistant HNSCC cell lines.
authors.affiliation: Department of Biology and Function in the Head and Neck, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Japan. t076024e@yokohama-cu.ac.jp
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sakakibara
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tsukuda
authors.forename: Norio
authors.initials: N
authors.lastname: Kondo
authors.forename: Yukari
authors.initials: Y
authors.lastname: Ishiguro
authors.forename: Machiko
authors.initials: M
authors.lastname: Kimura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fujita
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000257:Adenoviridae Infections; D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001426:Bacterial Proteins / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018307:Neoplasms, Squamous Cell / Q000378:metabolism / Q000473:pathology; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics; D016196:S Phase / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D013301:Streptolysins / Q000494:pharmacology; D019098:Telomerase / Q000235:genetics
chemical_list: D017500:Adenovirus E1A Proteins; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001426:Bacterial Proteins; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D012333:RNA, Messenger; D011991:Receptors, Virus; D013301:Streptolysins; C025964:streptolysin O; C509186:TERT protein, human; D019098:Telomerase; D017239:Paclitaxel; D002945:Cisplatin