Glycosphingolipid GM2 Induces Invasiveness in Irradiation-tolerant Lung Cancer Cells.

Glycans, including glycosphingolipids, are broadly expressed in plasma membranes and play important roles in cell-cell interactions. Recently, it has been revealed that glycans participate in the regulation of malignant phenotypes of cancer cells, e.g. growth and invasion. However, their roles in irradiation-tolerant cancer cells have not yet been elucidated. In this study, we show that specific glycosphingolipids are highly expressed in invasive, irradiation-tolerant lung cancer cells. Particularly, the glycosphingolipid GM2 contributes to the development of an invasive phenotype in these lung cancer cells. Our results suggest that glycosphingolipids, including GM2, are implicated in the regulation of invasiveness in irradiation-tolerant lung cancer cells and may therefore serve as potential therapeutic targets for lung cancers following radiotherapy.Key words: glycosphingolipids, GM2, invasion, lung cancer cells, radiotherapy.

Full genome analysis of Philippine indigenous subgenotype IA hepatitis A virus strains from Japanese patients with imported acute hepatitis A.

AIM: Hepatitis A virus (HAV) is the most common cause of infectious hepatitis worldwide. Although hepatitis A cases imported from South-East Asian countries, including the Philippines, have been reported in Japan, the molecular epidemiological data have been limited for these HAV-endemic countries. METHODS: The full-length genomic sequences of HAV isolates were determined and subjected to the phylogenetic analyses. RESULTS: The HAV isolates (HA12-0796 and HA12-0938) obtained from two Japanese patients who developed acute hepatitis A in July 2012, 1 month after traveling to the Philippines, where they consumed undercooked shellfish, differed by only one nucleotide (nt) over the entire genome. These HAV isolates of genotype IA were 99.1-99.5% identical within 228-237 nt to those recovered from river water in the Philippines, suggesting that the HA12-0796 and HA12-0938 isolates represent HAV circulating in the Philippines. HAV isolates belonging to one of the two IA sublineages (IA-2) which were implicated in some of the mini-epidemics in 2010 in Japan are hypothesized to be connected with the Philippines. In support of this speculation, the present IA isolates (HA12-0796 and HA12-0938) shared 98.8% identity over the entire genome with one IA-2 isolate (HAJIH-Fukuo10) recovered from a Japanese female who developed a domestic HAV infection during the mini-epidemics. In the phylogenetic tree constructed based on the entire genome, these three isolates (HA12-0796, HA12-0938 and HAJIH-Fukuo10) segregated into a cluster with a bootstrap value of 100%. CONCLUSION: These results indicate that HAV isolates belonging to the IA-2 lineage might have been imported from the Philippines.

[Endoscopic treatment for hemorrhagic peptic ulcer in patients aged 70 years or more].

In this study on endoscopic hemostasis in patients aged 70 years or older with gastrointestinal ulcer bleeding, presence of shock, volume of transfusion over 6 units, and ulcer size over 3cm and solitary ulcer were significant risk factors for rebleeding. For 30-day mortality, concomitant disease and inpatient status were significant risk factors. Based on these results, we consider elderly patients with the above risk factors as high-risk patients for rebleeding or fatal outcome. The purpose of this study was to evaluate the efficacy of prevention of rebleeding such as by combined hemostatic methods and scheduled second-look endoscopy, and also to evaluate the offers of multidisciplinary approach such as interventional radiology for decreasing of mortality. Our conclusion is that we were able to reduce rebleeding rate and mortality after endoscopic hemostasis in high-risk patients and implement strategy to provide more careful endoscopic management with a multidisciplinary approach.

[NSAID and its effect on prostaglandin].

Recently, the use of non-steroidal anti-inflammatory drug(NSAID) as an anti-inflammatory analgesic and antithrombotic has increased with the general aging of our society. Although it is understood that gastric mucosal injury is most-frequent side-effect of NSAID, there are actually a variety of mechanisms that NSAID has, some which are due to the depressed production of prostaglandin (PG). The main action of PG in the gastric mucosa is the regulation of gastric mucosa protecting mechanism and if PG is insufficient, the gastric mucosa is weakened. As endogenous PG decreases, there is a decrease in mucus production accompanied by a decrease in bicarbonate secretion, problems with, an increase of stomach motility, tissue restoration suppression and so on. As a result, it is considered that the defense mechanisms decrease and gastric mucosal injury occurs.

Subcutaneous administration of botulinum toxin A reduces formalin-induced pain.

Botulinum toxin type A (BoNT-A) produced by the bacterium Clostridium botulinum is a potent inhibitor of acetylcholine release in the neuromuscular junction and has been used to treat many disorders related to excessive muscle contraction. However, BoNT-A has recently been used in pain therapy to treat myofascial pain, low back pain and various types of headaches, including migraine. The purpose of this study is to investigate the antinociceptive effect of BoNT-A and its underlying mechanism in the rat formalin inflammatory pain model. BoNT-A (3.5, 7, 15 and 30 U/kg) or vehicle was administered to the plantar surface of the right hindpaw of male Sprague-Dawley rats. BoNT-A dose-dependently (P<0.05) inhibited formalin-induced nociceptive behavior during phase 2 but not during phase 1 when administered 5 h to 12 days before formalin challenge. The onset of the antinociceptive effect started at 5 h after pre-treatment and this effect lasted for at least 12 days. BoNT-A (7 U/kg) also reduced edema. Consistent with the lack of effect in the formalin phase 1, BoNT-A, at 15 U/kg, had no effect on acute thermal nociception; no local muscle weakness was observed at this dose. Pre-treatment of rats with BoNT-A (3.5, 7 or 15 U/kg) all significantly reduced formalin-evoked glutamate (Glu) release. These results demonstrate that local peripheral injection of BoNT-A significantly reduces formalin-induced nociceptive behaviors with the absence of obvious muscle weakness. Such an antinociceptive effect of BoNT-A is associated with the inhibition of formalin-induced release of Glu (and/or neuropeptides) from primary afferent terminals.

Peristalsis gap sign at cine magnetic resonance imaging for diagnosing strangulated small bowel obstruction: feasibility study.

PURPOSE: The aim of this study was to determine the feasibility of cine magnetic resonance imaging (MRI) for diagnosing strangulated small bowel obstruction (SBO). MATERIALS AND METHODS: This study included 38 patients with clinically confirmed SBO who had undergone cine MRI. Cine MRI scans were evaluated regarding the presence of the "peristalsis gap sign" (referring to an akinetic or severely hypokinetic closed loop), indicating strangulation. Computed tomography (CT) was performed in 34 of 38 patients with (n = 25) or without (n = 9) contrast enhancement. CT images were evaluated using a combination of criteria (presence of hyperattenuation, poor contrast enhancement, mesenteric edema, wall thickening, massive ascites) indicating strangulation. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cine MRI and CT for the diagnosis of strangulation were calculated and compared using surgical findings and the clinical course as the reference standard. RESULTS: Sensitivity, specificity, PPV, and NPV of cine MRI were 100%, 92.9%, 83.3%, and 100%, respectively; and those of CT (of which 26.5% was performed without contrast enhancement) were 66.7%, 92.0%, 75.0%, and 88.5%, respectively. There was no significant difference in diagnostic accuracy between the two methods (P = 0.375). CONCLUSION: Cine MRI is a feasible and promising technique for diagnosing strangulation.

Resection area of 15 mm as dividing line for choosing strip biopsy or endoscopic submucosal dissection for mucosal gastric neoplasm.

BACKGROUND: Endoscopic mucosal resection (EMR) is effective treatment for mucosal gastric neoplasm. Endoscopic submucosal dissection (ESD), a novel EMR method, has been reported to enable en bloc resection more frequently than conventional EMR methods such as strip biopsy (SB). However, ESD requires more time than SB. A small lesion can be resected en bloc and effectively treated with SB. GOAL: To evaluate using a 15 mm resection area as the dividing line between SB and ESD prospectively. STUDY: SB was applied for resection area less than 15 mm (SB group) and ESD for 15 mm or larger resection (ESD group). We compared characteristics of lesions and outcomes of EMR between the 2 groups. RESULTS: Ninety lesions were prospectively assigned to SB group (36 lesions) and ESD group (54 lesions). The average neoplasm size was 9.0+/-3.9 mm in the SB group and 19.1+/-11.3 mm in the ESD group (P<0.01). The average resection time was 11.7+/-5.8 minutes in the SB group and 128.9+/-102.8 minutes in the ESD group (P<0.01). The complete resection rate was 91.6% in the SB group and 83.3% in the ESD group (P=0.25). The complication rate was not significantly different between SB group and ESD group (11.1% vs. 16.7%, P=0.12). During follow-up (median 23+/-5 mo), 1 patient in each group, who had piecemeal resection at original EMR had recurrent neoplasm. CONCLUSIONS: Gastric mucosal neoplasms which require only small (<15 mm) resection can be treated with SB, as effectively as with ESD.

Short-term and long-term benefits of endoscopic hemoclip application for Dieulafoy's lesion in the upper GI tract.

BACKGROUND: Dieulafoy's lesion is an important cause of GI bleeding. The results of hemoclip application as the first treatment of choice for Dieulafoy's lesions have not been reported. This study prospectively examined the short- and long-term outcomes of hemoclip application for Dieulafoy's lesions. METHODS: The study was conducted over a 7-year period beginning in January 1995 during which hemoclip application was used as the first-choice hemostatic treatment for Dieulafoy's lesions. Clinical data, endoscopic findings, and outcome of treatment were evaluated. Long-term outcome for patients was also investigated. RESULTS: A Dieulafoy's lesion was diagnosed in 34 patients (27 men, 7 women; mean age, 54 years, range 21-81 years) after a mean of 1.2 endoscopies; 79.4% of the patients had active bleeding. Initial hemostasis was attained by hemoclip placement in 94.1%. The rate of recurrent bleeding was 9.3%. No patient required additional treatment such as surgery. The 30-day mortality rate was 2.9% (1 death, unrelated). For the remaining 33 patients, median follow-up was 53.8 months (range 19 to 90 months). Another Dieulafoy's lesion developed in one patient during follow-up, but in a different location compared with the index lesion. CONCLUSIONS: Endoscopic hemoclip application for Dieulafoy's lesions was effective and safe with short- and long-term benefits.