p53 therapy in a patient with Li-Fraumeni syndrome
| Autor: | Louis A. Zumstein, Rosalind A. Eeles, Kerstin B. Menander, Frank J. Lynch, Hani Gabra, John Nemunaitis, Robert E. Sobol, Jeffrey P. Lamont, Nayanta Sodha, Sunil Chada, Martin Gore, Neil Senzer, Michael Nemunaitis |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Cancer Research Cell cycle checkpoint Apoptosis Li-Fraumeni Syndrome Embryonal carcinoma Lesion Refractory Fluorodeoxyglucose F18 medicine Humans Child Caspase 3 business.industry Antibody titer Cancer Genetic Therapy Middle Aged Genes p53 medicine.disease Pedigree Oncology Li–Fraumeni syndrome Positron-Emission Tomography Immunology Cancer research Female Tumor Suppressor Protein p53 medicine.symptom business |
| Zdroj: | Molecular Cancer Therapeutics. 6:1478-1482 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.mct-07-0125 |
| Popis: | 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. [Mol Cancer Ther 2007;6(5):1478–1482 |
| Databáze: | OpenAIRE |
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