Improvement in the clinical outcome of lung cancer is likely to be achieved by identification of the molecular events that underlie its pathogenesis. Here we show that a small inversion within chromosome 2p results in the formation of a fusion gene comprising portions of the echinoderm microtubule-associated protein-like 4 (EML4) gene and the anaplastic lymphoma kinase (ALK) gene in non-small-cell lung cancer (NSCLC) cells. Mouse 3T3 fibroblasts forced to express this human fusion tyrosine kinase generated transformed foci in culture and subcutaneous tumours in nude mice. The EML4-ALK fusion transcript was detected in 6.7% (5 out of 75) of NSCLC patients examined; these individuals were distinct from those harbouring mutations in the epidermal growth factor receptor gene. Our data demonstrate that a subset of NSCLC patients may express a transforming fusion kinase that is a promising candidate for a therapeutic target as well as for a diagnostic molecular marker in NSCLC.

The status of IPF in the Japanese population was clarified for the first time through our study. Our results showed that in men, the incidence of death caused by acute exacerbation was higher and that caused by cardiovascular disease was lower in Japan than in Western countries. These results may suggest ethnic differences in IPF.

These results suggest that initial evaluation of serum KL-6 level can predict survival in patients with IPF.

Zoonotic transmission of hepatitis E virus (HEV) from captured wild deer or boars to humans has been suggested. Antibody to HEV was detected in 9% of 35 wild boars and 2% of 117 wild deer tested, and a presumably indigenous HEV of genotype 3 was isolated from a boar in Japan.Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important human pathogen (4,18,21). The genome of HEV is approximately 7.2 kb in size and contains three open reading frames (ORF1, ORF2, and ORF3) (18). Although only one serotype has been recognized, extensive genomic diversity has been noted among HEV isolates, and HEV sequences have tentatively been classified into four genotypes (genotypes 1 to 4) (20). Transmission of HEV occurs primarily by the fecal-oral route through contaminated water supplies in developing countries (18). In addition, increasing evidence has indicated that hepatitis E is a zoonosis (4, 8, 10-13, 15, 16, 21, 24, 29). It has recently been suggested that zoonotic foodborne transmission of HEV from domestic pigs, wild boars, or wild deer to humans plays an important role in the occurrence of cryptic hepatitis E in Japan, where people have distinctive habits of ingesting raw fish (sushi or sashimi) and, less frequently, uncooked or undercooked meat (including the liver and colon or intestine of animals) (9,23,24,29). The first animal strain of HEV to be isolated and characterized was a swine HEV from a pig in the United States in 1997 (10). Since then, many swine HEV isolates, which exhibit extensive genetic heterogeneity, have been identified worldwide and shown to be genetically closely related to strains of human HEV (1,3,5,6,16,17,(25)(26)(27)30). In previous studies, a high prevalence of the swine immunoglobulin G (IgG) class of antibody to HEV (anti-HEV) was found among 2-to 6-month-old Japanese pigs (58% or 1,448 of 2,500) (22), and a pair of Japanese swine and human HEV isolates of genotype 4 with 99% identity over the entire genome were identified (15). In addition, a certain proportion of packaged raw pig livers for sale in stores as food (1.9% or 7 of 363) were contaminated with HEV, which had high nucleotide sequence identity, up to 100%, with the HEV isolates recovered from Japanese patients with hepatitis E who had ingested undercooked pig liver before disease onset (29). As for HEV from wild boars, although Chandler et al. (1)

A randomised, double-blind, phase II, dose escalation trial was conducted to assess the safety, tolerability and pharmacokinetics of the tyrosine kinase inhibitor nintedanib, alone and when added to ongoing pirfenidone therapy, in Japanese patients with idiopathic pulmonary fibrosis.50 Japanese patients were randomised to receive nintedanib or placebo in one of three cohorts (nintedanib 50 mg twice daily or 100 mg twice daily for 14 days, or 150 mg twice daily for 28 days). Patients receiving pirfenidone at inclusion were stratified to every nintedanib dose group and placebo.Adverse events were reported in nine out of 17 patients receiving nintedanib alone and 10 out of 21 patients receiving nintedanib added to pirfenidone. All adverse events were mild or moderate in intensity. Gastrointestinal disorders were the most common adverse event. Maximum plasma concentration and area under the curve at steady state for nintedanib and its metabolites tended to be lower when nintedanib was added to pirfenidone. Nintedanib had no effect on the pharmacokinetics of pirfenidone.In conclusion, further study is needed to evaluate the safety and tolerability profile of nintedanib when added to pirfenidone in patients with idiopathic pulmonary fibrosis. There was a trend toward lower exposure of nintedanib when it was added to pirfenidone. @ERSpublications Nintedanib had acceptable safety and tolerability in Japanese patients with IPF