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Although widespread metastasis is the major cause of human lung cancer-related deaths, its underlying mechanism remains largely unclear. Our genome-wide comparison of the expression profiles of a highly metastatic lung cancer cell line, NCI-H460-LNM35 (LNM35), and its parental clone, NCI-H460-N15 (N15), resulted in the identification of a cancer metastasis signature composed of 45 genes. Through gene ontology analysis, our study also provided insights into how this 45-gene metastasis signature may contribute to the acquisition of metastatic potential. By applying the signature to datasets of human cancer cases, we could demonstrate significant associations with a subset of cases with poor prognosis not only for the two datasets of cancers of the lung but also for cancers of the breast. Furthermore, we were able to show that enforced expression of the DLX4 homeobox gene, which was identified as a gene with significant downregulation in LNM35 as well as with significant association with favorable prognosis for lung cancer patients, markedly inhibited in vitro motility and invasion as well as in vivo metastasis via both hematogenous and lymphogenous routes. Taken together, these findings indicate that our combined transcriptome analysis is an efficient approach in the search for genes possessing both clinical usefulness in terms of prognostic prediction in human cancer cases and clear functional relevance for studying cancer biology in relation to metastasis.Oncogene (2007) 26, 4600–4608; doi:10.1038/sj.onc.1210242; published online 29 January 2007 [ABSTRACT FROM AUTHOR]

Formation of Fe–Al composite thick layers by using laser surface alloying process with mixture of Al and Fe powders has been investigated to improve the surface hardness and the wear resistance of A5052 commercial Al–Mg alloy substrate. A continuous wave CO2 laser beam with the power of 2200 W was irradiated to the preplaced mixture powder on the substrate at various defocused distance of laser beam (30–150 mm up on the substrate) at the constant traveling speed (100 mm/min) in the argon gas shielding. The thickness of the laser alloyed layer varied from 0.5 to 7.0 mm. The microstructure of the laser alloyed layer changed with increasing Fe content from hypo-eutectic structure to hyper-eutectic structure with needle-like FeAl3, fine needle-like FeAl3 and finally lump-like Fe2Al5 compounds, and their hardnesses were HV100, HV100-300, HV300-500 and HV600-1000, respectively. The alloyed layers with the fine needle-like FeAl3 and Fe2Al5 compound structures showed the high hardness, HV300 and HV800, respectively, even at elevated temperatures up to 673 K. The wear resistance of the laser alloyed layer increased with increasing the hardness. [Copyright &y& Elsevier]

Laser surface remelting of hyper-eutectic Al&z.sbnd;20 and 30 mass%Si cast alloys with CO2 laser beam has been fined to improve the wear resistance of these alloys. A continuous wave CO2 laser beam with the power of 5kW was irradiated on these Al&z.sbnd;Si cast alloy substrates under various defocused distance of laser beam with the argon gas shielding. The microstructure of the laser-remelted layer consisted of fine primary Si particles, primary α-Al matrix phase and fine α-Al&z.sbnd;Si eutectic phase. The size of the primary Si particle decreased from 25 to 3 μm with the defocused distance also decreasing. Fine primary Si particles were distributed uniformly in the matrix of the fully remelted layer. The hardness of the laser remelted layer increased gradually with the decrease of the primary Si particle size, which reached 140 HV at about 5 μm in Al&z.sbnd;30 mass%Si layer. The wear resistance of the remelted layer increased with increasing the hardness and decreasing the size of primary Si particle. The wear resistance of the remelted layer in Al&z.sbnd;30 mass%Si cast alloy was better than that of the Al&z.sbnd;20 mass%Si cast alloy. [Copyright &y& Elsevier]

A Cu–Sn alloy layer containing MoS2 as a solid lubricant was formed on A2014 Al alloy base metal to give a low friction coefficient and high wear resistance by a pulse-current pressure sintering (PCPS) process. This coated layer and the base metal were sintered simultaneously. The hardness of the coated layer increased linearly with increasing density. The friction coefficient was approximately 0.10–0.12, which is comparable to some commercial items. The wear resistance was excellent compared to commercial items and depended on the hardness. [Copyright &y& Elsevier]

We have previously reported that heat-shock protein (hsp) 60-reactive T-cell receptor (TCR)γδ+ T cells appear in the peritoneal cavity during the early stage of infection with Listeria monocytogenes in mice. In this study, we examined the kinetics of TCRγδ+ T cells during listeriosis in F344 ruts by flow cytometry using a V65 monoclonal antibody (mAb) directed to a constant determinant of rat TCRγδ chains. TCRγδ+ T cells significantly increased in the peritoneal cavity on day 6 and then decreased by day 10 after infection, in parallel with the kinetics of hsp 60 expression in the peritoneal macrophages during listeriosis in F344 rats. Most of the early appearing TCRγδ+ T cells were of the CD4- CD8αβ+ CD5+ lymphocyte function-associated antigen (LFA)-1αhigh CD45RC- interleukin-2 receptor (IL-2R) α- phenotype, although a significant fraction of the TCRγδ+ T cells expressed CD8σ only. The increase in TCRγδ+ T cells during listeriosis was prominent in F1 (F344 × Lewis) rats but only marginal in Lewis rats, which was correlated with the expression level of hsp 60 in the peritoneal macrophages. The peritoneal TCRγδ+ T cells in naive F344 rats appeared to proliferate significantly in response to recombinant hsp 60 (rhsp 60) derived from Mycobacterium bovis bacillus Calmette-Guérin (BCG). These results imply that the early appearance of hsp 60-reactive TCRγδ+ T cells during listerial infection can be generalized across species. [ABSTRACT FROM AUTHOR]

The article describes the case of epidermolysis bullosa simplex with mottled pigmentation with noncicatricial alopecia in a 28-year-old Japanese man. Topics discussed include asymptomatic reticulate hyper- and hypopigmentation on the trunk and extremities, anomalous polymorphous keratinocytes with dilated intercellular spaces, and p.P25L mutation in KRT5 in all the affected family members.

Background: The efficacy of programmed death-1 blockade in epidermal growth factor receptor gene (EGFR) mutationpositive non-small-cell lung cancer (NSCLC) patients with different mechanisms of acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) is unknown. We retrospectively evaluated nivolumab efficacy and immune-related factors in such patients according to their status for the T790M resistance mutation of EGFR. Patients and methods: We identified 25 patients with EGFR mutation-positive NSCLC who were treated with nivolumab after disease progression during EGFR-TKI treatment (cohort A). Programmed death-ligand 1 (PD-L1) expression and tumorinfiltrating lymphocyte (TIL) density in tumor specimens obtained after acquisition of EGFR-TKI resistance were determined by immunohistochemistry. Whole-exome sequencing of tumor DNA was carried out to identify gene alterations. The relation of T790M status to PD-L1 expression or TIL density was also examined in an independent cohort of 60 patients (cohort B). Results: In cohort A, median progression-free survival (PFS) was 2.1 and 1.3 months for T790M-negative and T790M-positive patients, respectively (P=0.099; hazard ratio of 0.48 with a 95% confidence interval of 0.20-1.24). Median PFS was 2.1 and 1.3 months for patients with a PD-L1 expression level of⩾1% or<1%, respectively (P=0.084; hazard ratio of 0.37, 95% confidence interval of 0.10-1.21). PFS tended to increase as the PD-L1 expression level increased with cutoff values of⩾10% and⩾50%. The proportion of tumors with a PD-L1 level of⩾10% or⩾50% was higher among T790M-negative patients than among T790M-positive patients of both cohorts A and B. Nivolumab responders had a significantly higher CD8+ TIL density and nonsynonymous mutation burden. Conclusion: T790M-negative patients with EGFR mutation-positive NSCLC are more likely to benefit from nivolumab after EGFR-TKI treatment, possibly as a result of a higher PD-L1 expression level, than are T790M-positive patients. [ABSTRACT FROM AUTHOR]

Background: The clinical implementation of genomic profiling for lung cancer with high-throughput, multiplex tests is warranted to allow prioritization of appropriate therapies for individual patients. We have now applied such testing to detect actionable mutations that may inform treatment recommendations in lung cancer. Patients and methods: We prospectively applied amplicon sequencing panels that cover both mutational hotspots in 22 genes related to lung and colon tumorigenesis as well as 72 major variants of ALK, RET, ROS1, and NTRK1 fusion transcripts. We then determined the proportion of patients who received genotype-directed therapy and their overall survival (OS). Results: Tumor specimens from 110 patients with lung cancer recruited between July 2013 and March 2015 were analyzed. The most common genetic alterations were TP53 mutations in 42 patients, followed by EGFR mutations in 25, STK11 mutations in 12, and KRAS mutations in 10. Potentially actionable mutations were identified in 44 patients including 50% of those with adenocarcinoma and 14% of those with squamous cell carcinoma. The OS of patients with advanced or recurrent cancer who had an actionable mutation and received targeted therapy (median OS not achieved) was significantly longer than that of those with no mutation (18.1 months, P = 0.041) or of those with a mutation not so treated (6.1 months, P = 0.0027). Conclusions: Multiplex genomic testing was performed on formalin-fixed, paraffin-embedded tumor specimens with a success rate of ≥95%. Such testing can assist physicians in matching patients with approved or experimental targeted treatments. Clinical trial registration: The University Medical Hospital Information Network (UMIN) Clinical Trials Registry under the identifier UMIN000014782. [ABSTRACT FROM AUTHOR]

Inherited mutation of hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to Lesch-Nyhan syndrome or HPRT-related gout. On the other hand, PRPS1 mutations cause PRPP synthetase superactivity associated with hyperuricemia and gout, sometimes including neurodevelopmental abnormalities. We have identified two mutations in two Lesch-Nyhan families after our last report. One of them, a new single nucleotide substitution (130G>T) resulting in a missense mutation D44Y was detected in exon 2 of HPRT1. RT-PCR amplification showed not only a cDNA fragment with normal size, but also a small amount of shorter fragment skipping exons 2 and 3. The other missense mutation F74L (222C > A) was detected in a Japanese patient but has been reported previously in European families. In four hyperuricemic patients with mild neurological abnormality, no mutations responsible for partial HPRT deficiency were identified in HPRT1. In these four patients, we also performed molecular analysis of PRPS1, but no mutations in PRPP synthetase were found. [ABSTRACT FROM AUTHOR]