title: Cationic liposome-mediated E1A gene transfer to human breast and ovarian cancer cells and its biologic effects: a phase I clinical trial.
abstract: OBJECTIVE
  Preclinical studies have demonstrated that the adenovirus type 5 E1A gene is associated with antitumor activities by transcriptional repression of HER-2/neu and induction of apoptosis. Indeed, E1A gene therapy is known to induce regression of HER-2/neu-overexpressing breast and ovarian cancers in nude mice. Therefore, we evaluated the feasibility of intracavitary injection of E1A gene complexed with DC-Chol cationic liposome (DCC-E1A) in patients with both HER-2/neu-overexpressing and low HER-2/neu-expressing breast and ovarian cancers in a phase I clinical trial.
  
  
  METHODS
  An E1A gene complexed with DCC-E1A cationic liposome was injected once a week into the thoracic or peritoneal cavity of 18 patients with advanced cancer of the breast (n = 6) or ovary (n = 12).
  
  
  RESULTS
  E1A gene expression in tumor cells was detected by immunohistochemical staining and reverse transcriptase-polymerase chain reaction. This E1A gene expression was accompanied by HER-2/neu downregulation, increased apoptosis, and reduced proliferation. The most common treatment-related toxicities were fever, nausea, vomiting, and/or discomfort at the injection sites.
  
  
  CONCLUSIONS
  These results argue for the feasibility of intracavitary DCC-E1A administration, provide a clear proof of preclinical concept, and warrant phase II trials to determine the antitumor activity of the E1A gene.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. ghorto@notes.mdacc.tmc.edu
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
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authors.initials: NT
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authors.forename: W
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authors.lastname: Xia
authors.forename: S
authors.initials: S
authors.lastname: Zhang
authors.forename: J K
authors.initials: JK
authors.lastname: Wolf
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authors.initials: JB
authors.lastname: Putnam
authors.forename: P L
authors.initials: PL
authors.lastname: Weiden
authors.forename: J S
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authors.lastname: Willey
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authors.lastname: Carey
authors.forename: D L
authors.initials: DL
authors.lastname: Branham
authors.forename: J Y
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authors.lastname: Payne
authors.forename: S D
authors.initials: SD
authors.lastname: Tucker
authors.forename: C
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authors.lastname: Bartholomeusz
authors.forename: R G
authors.initials: RG
authors.lastname: Kilbourn
authors.forename: R L
authors.initials: RL
authors.lastname: De Jager
authors.forename: N
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authors.lastname: Sneige
authors.forename: R L
authors.initials: RL
authors.lastname: Katz
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authors.lastname: Anklesaria
authors.forename: N K
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authors.lastname: Ibrahim
authors.forename: J L
authors.initials: JL
authors.lastname: Murray
authors.forename: R L
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authors.lastname: Theriault
authors.forename: V
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authors.lastname: Valero
authors.forename: D M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: M W
authors.initials: MW
authors.lastname: Bevers
authors.forename: L
authors.initials: L
authors.lastname: Huang
authors.forename: G
authors.initials: G
authors.lastname: Lopez-Berestein
authors.forename: M C
authors.initials: MC
authors.lastname: Hung
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002784:Cholesterol / Q000031:analogs & derivatives; D016207:Cytokines / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D022761:Gene Transfer, Horizontal; D018734:Genes, erbB-2; D015316:Genetic Therapy; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007267:Injections; D019394:Ki-67 Antigen; D008081:Liposomes; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D010529:Peritoneal Cavity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013909:Thorax; D014407:Tumor Cells, Cultured
chemical_list: D017500:Adenovirus E1A Proteins; D016207:Cytokines; D019394:Ki-67 Antigen; D008081:Liposomes; C070648:3-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol; D002784:Cholesterol