Role of Sialylglycoconjugate(s) in the Initial Phase of Metastasis of Liver-metastatic RAW117 Lymphoma Cells

To elucidate the early events of blood-borne metastasis under actual blood flow, real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117-P and liver-metastatic RAW117-H10 cells, was investigated using positron emission tomography (PET). Both types of cells accumulated in the liver immediately after injection via the portal vein, and were eliminated from the liver time-dependently. The elimination rate of RAW117-H10 cells, however, was slower than that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly with hepatic sinusoidal endothelium than the parental cells. This result correlated with the metastatic potential of these cells: RAW117-H10 cells metastasized in the liver to a greater extent than RAW117-P cells after injection via this route. To investigate the role of sialylglycoconjugates in the interaction of RAW117-H10 cells with the hepatic endothelium after injection via the portal vein, the trafficking of RAW117-H10 cells was examined after the cells had been treated with sialidase. The elimination rate of RAW117-H10 cells from liver was observed to be greatly accelerated by sialidase treatment. To elucidate what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl Lewis X did not differ significantly. These findings suggest that some sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important role in the initial interaction of RAW117-H10 cells with the hepatic endothelium, leading to metastasis.     

Role of sialylglycoconjugate(s) in the initial phase of metastasis of liver-metastatic RAW117 lymphoma cells.

To elucidate the early events of blood-borne metastasis under actual blood flow, real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117-P and liver-metastatic RAW117-H10 cells, was investigated using positron emission tomography (PET). Both types of cells accumulated in the liver immediately after injection via the portal vein, and were eliminated from the liver time-dependently. The elimination rate of RAW117-H10 cells, however, was slower than that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly with hepatic sinusoidal endothelium than the parental cells. This result correlated with the metastatic potential of these cells: RAW117-H10 cells metastasized in the liver to a greater extent than RAW117-P cells after injection via this route. To investigate the role of sialylglycoconjugates in the interaction of RAW117-H10 cells with the hepatic endothelium after injection via the portal vein, the trafficking of RAW117-H10 cells was examined after the cells had been treated with sialidase. The elimination rate of RAW117-H10 cells from liver was observed to be greatly accelerated by sialidase treatment. To elucidate what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl Lewis X did not differ significantly. These findings suggest that some sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important role in the initial interaction of RAW117-H10 cells with the hepatic endothelium, leading to metastasis.     

Usefulness of three-dimensional CT cholangiography for patients prior to laparoscopic cholecystectomy

PURPOSE: The aim of this study was to demonstrate three-dimensional biliary anatomy by using spiral CT scanning for patients prior to laparoscopic cholecystectomy. MATERIALS AND METHODS: We studied 22 patients (11 men, 11 women; mean age, 60 years) with preoperative imaging. All patients had normal serum bilirubin levels. Either 50 ml (in 10 cases) or 100 ml (in 12 cases) of meglumine iotroxate was infused intravenously over 30 minutes. Spiral CT scanning was started immediately after the infusion was finished. Volumetric data through the entire biliary tracts were obtained during one breath-hold. The data were reconstructed by using a maximum intensity projection algorithm and three-dimensional shaded surface rendering. RESULTS: In all patients, the anatomical relationship between the cystic duct and the common bile duct was clearly depicted, including one with junctional anomaly. The intrahepatic biliary ducts and the confluence of the hepatic ducts were displayed from all angles. The third or higher intrahepatic branches were delineated in 11 of the 12 (92%) patients with the use of 100 ml of the cholangiographic agent and in seven of the 10 (70%) with 50 ml. CONCLUSION: Three-dimensional CT cholangiography was able to provide adequate information about precise biliary anatomy.     

Review: Lutheran/B-CAM: A Laminin Receptor on Red Blood Cells and in Various Tissues

The Lutheran blood group glycoprotein (Lu), also known as basal cell adhesion molecule (B-CAM), is a transmembrane receptor with five immunoglobulin-like domains in its extracellular region; it is therefore classified as a member of the immunoglobulin (Ig) gene family. Lu/B-CAM is observed not only on red blood cells, but also on a subset of muscle and epithelial cells in various tissues. Recently, several groups have reported that Lu/B-CAM is a novel receptor for laminin α5. The laminin α5 chain is a component of the laminin-511 (α5β1γ1), -521 (α5β2γ1), and -523 (α5β2γ3) heterotrimers and is expressed throughout the mammalian body. We also have shown that Lu/B-CAM is co-localized with laminin α5 in various tissues. Although the biological role of Lu/B-CAM remains unclear, the specific binding of Lu/B-CAM to laminin α5 suggests that it plays an important role in developmental and physiological processes. It also is necessary to investigate further the interaction between Lu/B-CAM and laminin α5 in pathological processes, including sickle cell disease and cancer.     

Congenital hyperinsulinism: Global and Japanese perspectives

Over the past 20 years, there has been remarkable progress in the diagnosis and treatment of congenital hyperinsulinism (CHI). These advances have been supported by the understanding of the molecular mechanism and the development of diagnostic modalities to identify the focal form of ATP‐sensitive potassium channel CHI. Many patients with diazoxide‐unresponsive focal CHI have been cured by partial pancreatectomy without developing postsurgical diabetes mellitus. Important novel findings on the genetic basis of the other forms of CHI have also been obtained, and several novel medical treatments have been explored. However, the management of patients with CHI is still far from ideal. First, state‐of‐the‐art treatment is not widely available worldwide. Second, it appears that the management strategy needs to be adjusted according to the patient's ethnic group. Third, optimal management of patients with the diazoxide‐unresponsive, diffuse form of CHI is still insufficient and requires further improvement. In this review, we describe the current landscape of this disorder, discuss the racial disparity of CHI using Japanese patients as an example, and briefly note unanswered questions and unmet needs that should be addressed in the near future.     

A Novel Approach to Detecting Postpartum Hemorrhage Using Contrast-Enhanced Ultrasound

The aim of this study was to estimate the efficacy of contrast-enhanced ultrasound (CEUS) in detecting postpartum hemorrhage (PPH) after cesarean section. This is the first study of CEUS in obstetric hemorrhage. A total of 37 patients, operated at Nagoya University Hospital, underwent CEUS. We evaluated the findings of CEUS, which were qualitatively defined as positive when pooling or leakage of contrast agent was observed in the uterine cavity, by measuring the amount of bleeding during the first 4 h after cesarean section. The time–intensity curve patterns of leaked contrast agents were also analyzed for quantitative prediction of the amount of blood loss. Significant differences between the excessive hemorrhage (N = 7) and non-excessive hemorrhage groups (N = 30) were noted in the occurrence of positive CEUS (p = 0.011). Additionally, mean postpartum blood loss markedly increased in patients with a positive CEUS (p = 0.002). From a quantitative perspective, the time until leakage of contrast agents was detected correlated with the amount of bleeding, but the other characteristics of the time–intensity curve pattern did not provide valuable information. In conclusion, CEUS, which enables bedside assessment and rapid diagnosis, is a promising strategy for the detection of PPH.     

Biologics in combination with chemotherapy for gastric cancer: is this the answer?

Gastric cancer (GC) continues to be a significant problem worldwide and is the third leading cause of cancer death. Armamentarium to treat GC whether it is potentially curable or metastatic (incurable) has changed little over the last decades with only two new agents being approved (trastuzumab and ramucirumab). Many relatively healthy patients after second-line therapy have limited and generally ineffective options. The recent The Cancer Genome Atlas analysis has uncovered four genotypes of GC; however, it is not sufficient to change our treatment strategies and more work needs to be done. The popular front-line regimen containing a platinum compound and a fluoropyrimidine is widely used for drug development and has worked well globally. Thus, this combination appears suitable for adding a biologic agent. The search for new classes of cytotoxics has almost stopped, but it is clear that cytotoxic therapy continues to contribute and it is here to stay. Biologic agents that modulate the immune system of the host appear promising along with many other biologics that can potentially inhibit signaling pathways that are often employed by GC cells. We will briefly describe the efforts that have targeted EGFR, mTOR, angiogenesis and MET pathways.