Hirotaka Okamoto

Increased endothelial cell retraction and tumor cell invasion by soluble factors derived from pancreatic cancer cells

AbstractBackground: Tumor cells induce endothelial cell retraction before invasion. In pancreatic cancer cells, the factors affecting endothelial cell retraction are not well-understood. Methods: The activities of the endothelial cell retraction in conditioned media (CM) derived from three human pancreatic cancer cell lines, PSN-1, MiaPaca-2, and Capan-1, were measured for the amount of intercellular junctional transport of FITC dextran through an endothelial cell monolayer in a transwell cell culture system. Results: The CM derived from the three pancreatic cancer cells induced endothelial cell retraction. The endothelial cell retraction activity in the CM from PSN-1 cells was significantly higher than those from MiaPaca-2 and Capan-1 cells. The CM from PSN-1 cells enhanced both the adhesion and the invasion of MiaPaca-2 and Capan-1 cells. The factors with endothelial cell retraction activity in the CM from PSN-1 cells were characterized as heat-stable, trypsin-sensitive glycoproteins ranging from 10,000 to 50,000 in molecular weight, and were found both in heparinbound and unbound fractions. Conclusions: PSN-1 cells produced and secreted at least two factors inducing the endothelial cell retraction. The factors could play an important role in the establishment of invasion and metastasis of PSN-1 cells.

Down-regulation of focal adhesion kinase, pp125FAK , in endothelial cell retraction during tumor cell invasion

Although endothelial cell retraction is required before tumor cell invasion, its molecular mechanism still remains obscure. We previously demonstrated that conditioned medium (CM) derived from a human pan-creatic cancer cell line, PSN-1, induced endothelial cell retraction and facilitated tumor cell invasion. To investigate the molecular change of events in the transduction of extracellular signals during endothelial cell retraction, we examined the effect of the CM derived from PSN-1 cells on the tyrosine phosphorylation in endothelial cells. Immunoblot analyses revealed that the PSN-1 CM decreased tyrosine phosphorylation of a 120-130 kD protein, and induced the concomitant down-regulation of focal adhesion kinase, pp125FAK , dur-ing endothelial cell retraction in time- and dose-dependent fashions. These changes preceded endothelial cell retraction and were reversible after removal of the CM. Further quantitative densitometric analyses demon-strated that the extent of decrea se in tyrosine phosphorylated 120-130 kD protein during the endothelial cell retraction was likely to be proportional to that of the down-regulation of pp125FAK . A tyrosine phosphory-lated 120-130 kD protein immunoprecipitated by anti-phosphotyrosine antibody immunoreacted with anti-pp125FAK antibody. These results suggested that decreased amount of a tyrosine phosphorylated 120-130 kD protein probably due to the down-regulation of pp125FAK might be associated with the signal transduction pathway in the endothelial cells during their retraction. Furthermore, these findings were also observed in the CM from another four human cancer cell lines, suggesting the down-regulation of pp125FAK in endothelial cells during tumor cell invasion.

Traumatic Pancreatitis - Endoscopic and Surgical Management

Acute pancreatitis is inflammation of the pancreas that occurs suddenly and usually resolves in a few days with treatment. Acute pancreatitis can be a life-threatening illness with severe complications. The most common cause of acute pancreatitis is the presence of small gallstones that cause inflammation of the pancreas as they pass through the common bile duct. Chronic heavy alcohol use is also a common cause. Acute pancreatitis can occur within hours or as long as 2 days after consuming alcohol. Other causes of acute pancreatitis include abdominal trauma, medications, infections, tumors, and genetic abnormalities of the pancreas.

Feasibility and Validation of Single-Port Laparoscopic Surgery for Simple-Adhesive or Nonadhesive Ileus.

AbstractA single incisional laparoscopic surgery (SILS) approach is increasingly being used, taking advantage of the minimally invasive technique. The aim of this study was to evaluate the feasibility and the validation of SILS procedure for small bowel obstruction (SBO).Sixteen consecutive patients with SBO who underwent SILS release of ileus between April 2010 and March 2015 were compared with the conventional multiport laparoscopic treatment group of 16 patients matched for age, gender, and surgical procedure.Laparoscopic treatment was completed in a total of 14 patients in SILS group and 13 in multiport laparoscopic group. Two cases and 3 cases were converted to multiport laparoscopic surgery or open surgery. Eight patients with nonscar and nonadhesive ileus, such as internal hernia, obturator hernia, gallstone ileus, and intestinal invagination, were treated successfully in the laparoscopic procedure. There was no mortality in either of the groups. The mean procedural time was 105 minutes in the SILS group and 116 minutes in the multiport laparoscopic group. The mean amount of blood loss was not statistically different in either of groups (15 ml vs. 23 ml). Patients resumed oral intake after a mean of 2 days in the SILS and 3 days in the multiport groups with the statistically difference. The length of hospital stay was shorter in the SILS group (5 days vs. 7 days) with no statistically difference. Perioperative morbidity was seen in 2 patients in the SILS group and 3 patients in the multiport group.SILS approach has superior and/or similar perioperative outcomes to multiport approach for SBO. SILS release of ileus as an ultra-minimal invasion technique is feasible, effective, and offers benefits with cosmesis in simple adhesive or scar-less nonadhesive ileus patients.

Initial Japanese Experience of Laparoscopic Cholecystectomy using a New Robot-Assisted System

The object of this paper is to clarify the feasibility and safety of robot-assisted laparoscopic cholecystectomy. Acute or chronic cholecystitis is the most common disease in patients, caused by ch...