Evidence That Transfer of Functional p53 Protein Results in Increased Apoptosis in Prostate Cancer
| Autor: | Christopher G. Wood, Kim Anh Do, E. Hossan, L. Clifton Stephens, Timothy J. McDonnell, Robert B. Evans, Christopher J. Logothetis, Xuemei Wang, James A. Merritt, Shawn Brisbay, Cindy Soto, Marc G. Jacobson, Patricia Troncoso, Curtis A. Pettaway, Karen Parker, Mitchell S. Steiner, Louis L. Pisters |
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| Rok vydání: | 2004 |
| Předmět: |
Male
Oncology Cancer Research medicine.medical_specialty Pathology Time Factors Genetic enhancement medicine.medical_treatment Genetic Vectors Apoptosis DNA Fragmentation Disease-Free Survival Adenoviridae Prostate cancer Prostate In Situ Nick-End Labeling Internal medicine medicine Humans Transgenes Aged Genitourinary system business.industry Prostatectomy Prostatic Neoplasms Genetic Therapy Middle Aged Genes p53 medicine.disease Immunohistochemistry Treatment Outcome medicine.anatomical_structure Disease Progression Tumor Suppressor Protein p53 business Immunostaining |
| Zdroj: | Clinical Cancer Research. 10:2587-2593 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-03-0388 |
| Popis: | Purpose: INGN 201 (Ad-p53) is a replication-defective adenoviral vector that encodes a wild-type p53 gene driven by the cytomegalovirus promoter. INGN 201 has been shown to have antitumoral activity against human prostate cancer cell lines. This study was undertaken to determine the safety of INGN 201 in patients with locally advanced prostate cancer, to assess transgene expression, and to evaluate antitumoral activity. Experimental Design: Our study included patients with clinical stage T3, T1c-T2a with Gleason score 8–10 disease, or T2a-T2b with Gleason score 7 disease and a prostate-specific antigen level >10 ng/ml. INGN 201 was administered by intraprostatic injection under ultrasonographic guidance. One course of INGN 201 was defined as three separate INGN 201 administrations 2 weeks apart. Biopsies at baseline and 24 h after the first administration were assessed for p53 protein by immunohistochemical staining and for apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Results: A total of 38 courses of INGN 201 gene therapy were administered to 30 patients, of whom 26 underwent radical prostatectomy. There were no grade 3 or 4 adverse events related to INGN 201 administration. Of the 11 patients with negative baseline immunostaining for p53 protein, 10 had positive p53 immunostaining after the first administration of INGN 201, and 8 had an increase in apoptotic cells by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. All 26 of the patients who underwent radical prostatectomy had significant residual viable prostate cancer, and 12 have experienced biochemical failure (median follow-up, 42 months). Conclusion: Intraprostatic INGN 201 gene therapy is safe and can reliably result in p53 protein production and apoptosis. |
| Databáze: | OpenAIRE |
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