title: Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy.
abstract: BACKGROUND
  The mda-7 gene (melanoma differentiation associated gene-7) is a novel tumor suppressor gene. The anti-proliferative activity of MDA-7 has been previously reported. In this report, we analyze the anti-tumor efficacy of Ad-mda7 in a broad spectrum of cancer lines.
  
  
  METHODS
  Ad-mda7-transduced cancer or normal cell lines were assayed for cell proliferation (tritiated thymidine incorporation assay, Alamar blue assay, and trypan-blue exclusion assay), apoptosis (TUNEL, and Annexin V staining visualized by fluorescent microscopy or FACs analysis), and cell cycle regulation (Propidium Iodide staining and FACs analysis).
  
  
  RESULTS
  Ad-mda7 treatment of tumor cells resulted in growth inhibition and apoptosis in a temporal and dose-dependent manner. The anti-tumor effects were independent of the genomic status of p53, RB, p16, ras, bax, and caspase 3 in these cells. In addition, normal cell lines did not show inhibition of proliferation or apoptotic response to Ad-mda7. Moreover, Ad-mda7-transduced cancer cells secreted a soluble form of MDA-7 protein. Thus, Ad-mda7 may represent a novel gene-therapeutic agent for the treatment of a variety of cancers.
  
  
  CONCLUSIONS
  The potent and selective killing activity of Ad-mda7 in cancer cells but not in normal cells makes this vector a potential candidate for cancer gene therapy.
authors.affiliation: Introgen Therapeutics Inc, Houston, TX 77030, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Mhashilkar
authors.forename: R D
authors.initials: RD
authors.lastname: Schrock
authors.forename: M
authors.initials: M
authors.lastname: Hindi
authors.forename: J
authors.initials: J
authors.lastname: Liao
authors.forename: K
authors.initials: K
authors.lastname: Sieger
authors.forename: F
authors.initials: F
authors.lastname: Kourouma
authors.forename: X H
authors.initials: XH
authors.lastname: Zou-Yang
authors.forename: E
authors.initials: E
authors.lastname: Onishi
authors.forename: O
authors.initials: O
authors.lastname: Takh
authors.forename: T S
authors.initials: TS
authors.lastname: Vedvick
authors.forename: G
authors.initials: G
authors.lastname: Fanger
authors.forename: L
authors.initials: L
authors.lastname: Stewart
authors.forename: G J
authors.initials: GJ
authors.lastname: Watson
authors.forename: D
authors.initials: D
authors.lastname: Snary
authors.forename: P B
authors.initials: PB
authors.lastname: Fisher
authors.forename: T
authors.initials: T
authors.lastname: Saeki
authors.forename: J A
authors.initials: JA
authors.lastname: Roth
authors.forename: R
authors.initials: R
authors.lastname: Ramesh
authors.forename: S
authors.initials: S
authors.lastname: Chada
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D017304:Annexin A5 / Q000378:metabolism; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002469:Cell Separation; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D004396:Coloring Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005091:Exons; D005434:Flow Cytometry; D016147:Genes, Tumor Suppressor / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006133:Growth Substances / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007378:Interleukins; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000628:therapy*; D010078:Oxazines; D011419:Propidium / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D014343:Trypan Blue / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014966:Xanthenes; D000099180:Interleukin-24
chemical_list: D017304:Annexin A5; D004396:Coloring Agents; D006133:Growth Substances; D007378:Interleukins; D010078:Oxazines; D011419:Propidium; D013936:Thymidine; D014343:Trypan Blue; D014966:Xanthenes; D000099180:Interleukin-24; C005843:resazurin