Apoptosis associated with esophageal adenocarcinoma: influence of photodynamic therapy

Tumor cell death in vitro by photodynamic therapy (PDT) has been related to the induction of apoptosis, We measured and compared changes in apoptosis and caspase 3 activity, an effector of apoptosis, in normal and neoplastic esophageal tissues during PDT, Apoptosis index, caspase 3 cleavage activity , pro-caspase 3, p53, and bcl-2 levels were measured in normal and neoplast ic tissues of patients with esophageal adenocarcinoma before, during, and a fter PDT with Photofrin. The apoptotic index was greater in carcinoma tissu e compared to adjacent normal tissues. In concert, pro-caspase 3 immunoreac tivity was absent and caspase 3-like cleavage activity was over 30-fold gre ater in carcinoma tissue compared to normal esophageal tissues. These param eters were unaffected by PDT. Variable changes in bcl-2 and p53 immunoreact ivity were noted in normal and carcinoma tissues during PDT, Greater levels of apoptosis and caspase 3 activity are hallmarks of esophageal adenocarci noma compared to normal esophageal tissue. These differences were unaffecte d by PDT. This may be due to the fact that tissues were obtained 72 h post- PDT therapy. Changes in these parameters may have occurred early after PDT therapy. An assessment of apoptosis and caspase 3 activity prior to 72 h po st-PDT may provide further insight into the mechanism involved, although no sustained effects on these parameters by PDT were noted. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.