Phorbol 12,13 dibutyrate behaves in a tumor-inhibitory manner in esophageal adenocarcinoma cell lines.

Esophageal cancer is an extremely lethal human disease. Relatively little is known about the molecular mechanisms leading to esophageal cancers, nor the signaling pathways activated to maintain and augment the tumor growth. Esophageal cancer cell lines were evaluated to assess the effect of phorbol 12,13 dibutyrate on protein kinase C activity, indirectly using protein kinase D (formerly known as protein kinase C-µ), Akt activity, and cell proliferation. Treatment of esophageal cancer cell lines with the phorbol ester phorbol 12,13 dibutyrate led to a rapid and dramatic increase in the activation of protein kinase D. In addition, administration of phorbol 12,13 dibutyrate also decreased the phosphorylation of Akt. Interestingly, in the OE19 esophageal adenocarcinoma cell line, treatment with phorbol 12,13 dibutyrate also led to inhibition of cell growth. All the phorbol ester effects observed were reversible by combined treatment with a protein kinase C inhibitor, implicating protein kinase C in the cells' response to the phorbol ester. Overall, these studies suggest that protein kinase D (e.g. protein kinase C-µ) may behave as a tumor suppressor in some esophageal cancer samples, serving to inhibit Akt activity and block cell growth.

The safety and usefulness of endoscopy for evaluation of the graft and anastomosis early after esophagectomy and reconstruction.

BACKGROUND: Although rare, graft ischemia and necrosis after esophagectomy is a devastating complication. The aim of this study was to review our experience with early endoscopy for evaluation of the graft and anastomosis after esophagectomy and reconstruction. METHODS: From a population of 479 patients who underwent esophagectomy during the years 1996-2003, we identified 102 patients who had endoscopy within 21 days of operation. RESULTS: Endoscopy was performed a median of 9 days after operation. Graft ischemia, anastomotic leak, or both were found in 63 of the 102 patients. Reoperation was necessary in 27% of these patients, including graft removal in nine patients. In 39 patients, endoscopy demonstrated a healthy graft; only one of these patients (2.6%) required reoperation. No patient with ischemia judged insufficient to warrant graft removal on initial endoscopy subsequently lost their graft. There were no complications or anastomotic injuries associated with early endoscopy. CONCLUSION: Endoscopy early after esophagectomy is safe and provides accurate and reliable identification of graft ischemia that can be used to guide the treatment of these patients.

Reproducible echocardiography in juvenile sheep and its application in the evaluation of a pulmonary valve homograft implant.

Increased use of the ovine animal model in cardiovascular surgical research has created a salient need for standardized echocardiography techniques. To demonstrate a reproducible image in this species and confirm the validity of echocardiography as a diagnostic tool, we implanted 10 sheep with a pulmonary valve homograft and monitored them through weekly echocardiographic examinations until 20 weeks after implantation. We obtained good images from the left cranial and the left caudal transducer windows without needing to sedate the animals. Sedated sheep yielded adequate views from the right apical window. Echocardiographic data on the implanted homografts (including functional capacity, presence of calcification, and hemodynamic information and measurements), completely agreed with the results of the post-explantation examinations.