Correlation between the expression of LAT1 in cancer cells and the potential efficacy of boron neutron capture therapy

Boron neutron capture therapy (BNCT) is a binary cancer therapy that involves boron administration and neutron irradiation. The nuclear reaction caused by the interaction of boron atom and neutron produces heavy particles with highly cytocidal effects and destruct tumor cells, which uptake the boron drug. p-Boronophenylalanine (BPA), an amino acid derivative, is used in BNCT. Tumor cells with increased nutrient requirements take up more BPA than normal tissues via the enhanced expression of LAT1, an amino acid transporter. The current study aimed to assess the correlation between the expression of LAT1 and the uptake capacity of BPA using genetically modified LAT1-deficient/enhanced cell lines. We conducted an in vitro study, SCC7 tumor cells wherein LAT1 expression was altered using CRISPR/Cas9 were used to assess BPA uptake capacity. Data from The Cancer Genome Atlas (TCGA) were used to examine the expression status of LAT1 in human tumor tissues, the potential impact of LAT1 expression on cancer prognosis and the potential cancer indications for BPA-based BNCT. We discovered that the strength of LAT1 expression strongly affected the BPA uptake ability of tumor cells. Among the histologic types, squamous cell carcinomas express high levels of LAT1 regardless of the primary tumor site. The higher LAT1 expression in tumors was associated with a higher expression of cell proliferation markers and poorer patient prognosis. Considering that BPA concentrate more in tumors with high LAT1 expression, the results suggest that BNCT is effective for cancers having poor prognosis with higher proliferative potential and nutritional requirements

Enhanced visualization of the portal vein system in superior mesenteric arterial portography using prostaglandin E1.

The portal vein system was clearly visualized in superior mesenteric arterial portography using prostaglandin E1. Angiographic examination was performed in 68 patients with various liver diseases during the 2 year period from 1980 to 1981. Twenty microgram of prostaglandin E1 was injected into the superior mesenteric artery 30 seconds before injection of 60 ml of contrast medium. The main portal vein was visualized in all of 68 cases. A high rate of success for visualization of the intrahepatic portal vein system by prostaglandin E1 was achieved. The first branches of the intrahepatic portal vein were visualized in 100% of the cases, the second branches in 82%, the third branches in 44%, and the fourth branches in 4% in the right portal vein system. In the left portal vein system, the first branches were visualized in 87%, the second branches in 41%, and the third branches in 3% of the cases. The intrahepatic portal vein system was more clearly visualized in females than in males (P less than 0.05). This procedure is simple, safe and useful for clear visualization of the portal vein system.</p

The Lifestyle of the Segmented Filamentous Bacterium: A Non-Culturable Gut-Associated Immunostimulating Microbe Inferred by Whole-Genome Sequencing

Numerous microbes inhabit the mammalian intestinal track and strongly impact host physiology; however, our understanding of this ecosystem remains limited owing to the high complexity of the microbial community and the presence of numerous non-culturable microbes. Segmented filamentous bacteria (SFBs), which are clostridia-related Gram-positive bacteria, are among such non-culturable populations and are well known for their unique morphology and tight attachment to intestinal epithelial cells. Recent studies have revealed that SFBs play crucial roles in the post-natal maturation of gut immune function, especially the induction of Th17 lymphocytes. Here, we report the complete genome sequence of mouse SFBs. The genome, which comprises a single circular chromosome of 1 620 005 bp, lacks genes for the biosynthesis of almost all amino acids, vitamins/cofactors and nucleotides, but contains a full set of genes for sporulation/germination and, unexpectedly, for chemotaxis/flagella-based motility. These findings suggest a triphasic lifestyle of the SFB, which comprises two types of vegetative (swimming and epicellular parasitic) phases and a dormant (spore) phase. Furthermore, SFBs encode four types of flagellin, three of which are recognized by Toll-like receptor 5 and could elicit the innate immune response. Our results reveal the non-culturability, lifestyle and immunostimulation mechanisms of SFBs and provide a genetic basis for the future development of the SFB cultivation and gene-manipulation techniques

Comparison of estimation methods of liver maximum removal rate of indocyanine green.

Three linear plots by which the liver's maximum removal rate (Rmax) of indocyanine green (ICG) and the Michaelis constant (Km) can be calculated were compared in a microcomputer simulation study. The widely-used Lineweaver-Burk plot (1/V vs. 1/S; V, ICG initial removal rate (mg/kg/min); S, ICG loading dose (mg/kg] presented the greatest bias and variance. There was no remarkable difference in bias between the S/V vs. S plot and the V vs. V/S plot, but the latter possessed a smaller variance. Therefore, the V vs. V/S plot was considered the best for estimating Rmax. The best combination of three ICG loading doses was 0.5, 2, and 5 mg/kg. This combination was selected by comparison of the Rmax estimated from three points with that estimated from six points (0.5, 1, 2, 3, 4 and 5 mg/kg).</p

Peritoneoscopy of the liver after abdominal surgery.

The incidence of intraperitoneal adhesion after abdominal surgery was studied. Peritoneoscopy was performed in 933 patients with liver diseases over the 6 year 5 month period from March 1974 to July 1980. Of the patients, 352 (37.7%) had undergone an abdominal operation, and intraperitoneal adhesion was detected in 205 (58.2%) of these patients. The liver was not observable in 5 out of 61 patients with adhesions after upper abdominal operations. Whereas, the liver was clearly observable in patients with lower abdominal operations in spite of adhesions. Out of the 581 patients without any abdominal operations, 30 patients (5.2%) had adhesions in the abdominal cavity, and 6 of them had extensive adhesions that partially obscured the observation of liver surface. In all patients, peritoneoscopy was performed without complications by avoiding the surgical scar for puncture sites and ensuring a free air lumen before trocar puncture.</p

Comparative diagnosis of alcoholic liver diseases by multivariate and histological analysis.

Sixty-seven cases of alcoholic liver disease were histologically classified into 4 groups: alcoholic liver cirrhosis (ALC), alcoholic hepatitis (AH), alcoholic liver fibrosis (ALF) and alcoholic fatty liver (AFL). They were statistically reclassified by the likelihood method using age, total alcohol intake, hepatomegaly and 12 liver function tests. A score table for likely diagnosis was constructed from the incidences of each range. The cases were re-evaluated using the score table, with an overall correct diagnosis rate of 73%. The best combination of 5 parameters included the indocyanine green plasma disappearance rate, total alcohol intake, cholesterol, choline esterase and glutamic oxaloacetic transaminase/glutamic pyruvic transaminase ratio. A correct diagnosis rate of 75% was attained using these 5 parameters, and 94% of patients were correctly diagnosed by the first or the second likelihood diagnosis. Differential diagnosis of alcoholic liver diseases was easily and confidently obtained with the likelihood score table.</p

Peritoneoscopy of alcoholic liver cirrhosis in comparison with non-alcoholic liver cirrhosis.

Peritoneoscopic findings of 39 patients with alcoholic liver cirrhosis (ALC) were compared with those of 95 patients with non-alcoholic liver cirrhosis (NALC). They were selected from 245 patients with liver cirrhosis subjected to peritoneoscopy in the 7 year period from 1975 to 1981. Out of the 95 NALC patients, 24 had hepatitis B surface antigen. The ALC patients had nodules which varied in size (61%), large depressions (69%), and a markedly rounded edge of the liver (33%) more often than NALC patients (18, 43 and 3%, respectively). Nodularity differed between the right and left lobes in ALC (41%) more often than in NALC (16%). Interstitial reddish markings and patchy nodules were, however, more frequent in NALC (51 and 28%, respectively) than in ALC (8 and 5%, respectively). Lymphatic vesicles were observed both in ALC (85%) and NALC (78%). In conclusion, the peritoneoscopic features which suggested ALC were the coexistence of nodules of various sizes, large depressions and a markedly dull edge of the liver. Interstitial reddish markings and patchy nodules were more indicative of NALC than ALC.</p

Effects of sake and bourbon on liver histopathology and function in rats.

Sake or bourbon (8g ethanol/kg body weight) was intragastrically administered to rats for 12 days. An equal dose of ethanol in water or an isocaloric glucose solution was administered to control groups. Food was withheld, but water freely provided. Neither mortality nor liver and body weights were different between the alcohol-treated groups. Glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were more elevated in the sake group than in the other groups. Additionally, liver fibrosis was more pronounced, and vacuole formation or steatosis was less in this group. These results suggest that sake is more fibrogenic. Some components other than ethanol, such as long-alkyl chain alcohols, may have been responsible for the differential histopathology.</p