Role of Caspase-3, Phosphatidylinositol-3 Kinase (PI3K), and 3-methylhistidine (3-MH) in the Pathophysiology of Skeletal Muscle Loss in Weight-losing Pancreas Cancer Patients

OBJECTIVES:

• Compare levels of caspase-3 and phosphorylated Akt (pAkt) in the rectus abdominous muscle of patients with pancreatic cancer who are experiencing cachexia and are undergoing surgery for diagnosis or primary therapy with patients who have not lost weight and are undergoing abdominal surgery for nonmalignant conditions.
• Compare levels of urinary 3-methylhistidine (3-MH) in these patients.
• Evaluate possible correlations of caspase-3 activity, pAkt, and urinary 3-MH with early time to progression and subsequent lean body weight loss in patients with pancreatic cancer.
• Associate excretion of urinary 3-MH with higher levels of caspase-3 activity and pAkt to analyze the utility of 3-MH as a marker of skeletal muscle proteolysis.

OUTLINE: This is a pilot study.

During surgery, a muscle biopsy is performed and approximately 1 cm of rectus abdominous muscle is obtained for analysis. Caspase-3 activity and total/phosphorylated phosphatidylinositol-3 kinase and Akt are measured in muscle biopsies by western blot analysis. 3-methylhistidine activity is measured in urine samples.

After completion of study, patients with pancreatic cancer are followed postoperatively at 3 and 6 months.