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Molecular diagnosis and treatment for esophageal carcinoma with p53
Authors:Hideaki Shimada  Takenori Ochiai
Affiliation:(1) Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
Abstract:We reviewed molecular diagnosis and molecular treatment using p53 as a target for esophageal squamous cell carcinoma (SCC). First, we analyzed serum p53 antibodies (s-p53 Abs) in patients with esophageal SCC. Positive rate was 31% in all patients analyzed (n = 292) and 23% in stage I patients (cTNM/UICC stages) (n = 48). Presence of s-p53 Abs was significantly associated with p53 protein overexpression in resected tumor specimens. Seropositive patients were more likely to be resistant to chemoradiation and had a worse prognosis than seronegative patients. Second, we performed a clinical study of p53 gene therapy in 10 patients with unresectable chemoradiation-resistant esophageal SCC. In 9 patients, stability of the local tumor was achieved. No serious adverse events related to Ad5CMV-p53 have occurred in these patients, and the trial was safely conducted. Thus, intratumoral injection of Ad5CMV-p53 is safe, feasible, and biologically active when administered in multiple doses to patients with esophageal cancer. Observations from these clinical studies indicate that p53 is a useful molecular target in the diagnosis and treatment of esophageal SCC. Proceeding of a symposium at the 60th annual meeting of the Japan Esophageal Society: “Clinical aspects of molecular biology for the diagnosis and treatment of esophageal carcinoma.”
Keywords:p53  Gene therapy  Esophageal cancer  Serum p53 antibody
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