title: p53 therapy in a patient with Li-Fraumeni syndrome.
abstract: Li-Fraumeni syndrome is an autosomal dominant disorder that greatly increases the risk of developing multiple types of cancer. The majority of Li-Fraumeni syndrome families contain germ-line mutations in the p53 tumor suppressor gene. We describe treatment of a refractory, progressive Li-Fraumeni syndrome embryonal carcinoma with a p53 therapy (Advexin) targeted to the underlying molecular defect of this syndrome. p53 treatment resulted in complete and durable remission of the injected lesion by fluorodeoxyglucose-positron emission tomography scans with improvement of tumor-related symptoms. With respect to molecular markers, the patient's tumor had abnormal p53 and expressed coxsackie adenovirus receptors with a low HDM2 and bcl-2 profile conducive for adenoviral p53 activity. p53 treatment resulted in the induction of cell cycle arrest and apoptosis documented by p21 and cleaved caspase-3 detection. Increased adenoviral antibody titers after repeated therapy did not inhibit adenoviral p53 activity or result in pathologic sequelae. Relationships between these clinical, radiographic, and molecular markers may prove useful in guiding future application of p53 tumor suppressor therapy.
authors.affiliation: Mary Crowley Medical Research Center, Baylor University Medical Center, 60th Floor, 1717 Main Street, Dallas, TX 75201, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Senzer
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Michael
authors.initials: M
authors.lastname: Nemunaitis
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lamont
authors.forename: Martin
authors.initials: M
authors.lastname: Gore
authors.forename: Hani
authors.initials: H
authors.lastname: Gabra
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Nayanta
authors.initials: N
authors.lastname: Sodha
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Lynch
authors.forename: Louis A
authors.initials: LA
authors.lastname: Zumstein
authors.forename: Kerstin B
authors.initials: KB
authors.lastname: Menander
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sobol
authors.forename: Sunil
authors.initials: S
authors.lastname: Chada
mesh_terms: D000328:Adult; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002648:Child; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D016158:Genes, p53; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D049268:Positron-Emission Tomography / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019788:Fluorodeoxyglucose F18; D053148:Caspase 3