202 research outputs found

    Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial

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    Background The efficacy of crizotinib treatment for recurring EML4‐ALK‐positive non‐small cell lung cancer (NSCLC) previously treated with alectinib is unclear. Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib‐refractory, EML4‐ALK‐positive NSCLC. Methods Patients with ALK‐rearranged tumors treated with alectinib immediately before enrolling in the trial received crizotinib monotherapy. The objective response rate was the primary outcome of interest. Results Nine (100%) patients achieved a partial response with alectinib therapy with a median treatment duration of 6.7 months. Crizotinib was administered with a median treatment interval of 50 (range, 20–433) days. The overall response rate was 33.3% (90% confidence interval [CI]: 9.8–65.5 and 95% CI: 7.5–70.1), which did not reach the predefined criteria of 50%. Two (22%) patients who achieved a partial response had brain metastases at baseline. Progression‐free survival (median, 2.2 months) was not affected by the duration of treatment with alectinib. The median survival time was 24.1 months. The most common adverse events were an increased aspartate transaminase/alanine transaminase (AST/ALT) ratio (44%) and appetite loss (33%); one patient developed transient grade 4 AST/ALT elevation, resulting in treatment discontinuation. Other adverse events were consistent with those previously reported; no treatment‐related deaths occurred. Conclusions Although the desired response rate was not achieved, crizotinib monotherapy following treatment with alectinib showed efficacy alongside previously described adverse events

    Curated genome annotation of Oryza sativa ssp. japonica and comparative genome analysis with Arabidopsis thaliana

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    We present here the annotation of the complete genome of rice Oryza sativa L. ssp. japonica cultivar Nipponbare. All functional annotations for proteins and non-protein-coding RNA (npRNA) candidates were manually curated. Functions were identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs (including 58 antisense transcripts) were found. Almost 5000 annotated protein-coding genes were found to be disrupted in insertional mutant lines, which will accelerate future experimental validation of the annotations. The rice loci were determined by using cDNA sequences obtained from rice and other representative cereals. Our conservative estimate based on these loci and an extrapolation suggested that the gene number of rice is ~32,000, which is smaller than previous estimates. We conducted comparative analyses between rice and Arabidopsis thaliana and found that both genomes possessed several lineage-specific genes, which might account for the observed differences between these species, while they had similar sets of predicted functional domains among the protein sequences. A system to control translational efficiency seems to be conserved across large evolutionary distances. Moreover, the evolutionary process of protein-coding genes was examined. Our results suggest that natural selection may have played a role for duplicated genes in both species, so that duplication was suppressed or favored in a manner that depended on the function of a gene

    The Japanese space gravitational wave antenna; DECIGO

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    DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

    DECIGO pathfinder

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    DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

    Visual field defects of optic neuritis in neuromyelitis optica compared with multiple sclerosis

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    <p>Abstract</p> <p>Background</p> <p>Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that predominantly affects the optic nerves and the spinal cord, and is possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Central scotoma is recognized as a characteristic visual field defect pattern of optic neuritis (ON), however, the differing pathogenic mechanisms of NMO and MS may result in different patterns of visual field defects for ON.</p> <p>Methods</p> <p>Medical records of 15 patients with NMO and 20 patients with MS having ON were retrospectively analyzed. A thorough systemic and neurological examination was performed for evaluating ON. The total number of relapses of ON and visual fields was investigated. Visual fields were obtained by Goldmann perimeter with each ON relapse.</p> <p>Results</p> <p>All MS patients experienced central scotoma, with 90% of them showing central scotoma with every ON relapse. However, 53% of NMO patients showed central scotoma with every ON relapse (p = 0.022), and the remaining 47% of patients experienced non-central scotoma (altitudinal, quadrant, three quadrant, hemianopia, and bitemporal hemianopia). Thirteen percent of NMO patients did not experience central scotoma during their disease course. Altitudinal hemianopia was the most frequent non-central scotoma pattern in NMO.</p> <p>Conclusions</p> <p>NMO patients showed higher incidence of non-central scotoma than MS, and altitudinal hemianopia may be characteristic of ON occurring in NMO. As altitudinal hemianopia is highly characteristic of ischemic optic neuropathy, we suggest that an ischemic mechanism mediated by anti-aquaporin-4 antibody may play a role in ON in NMO patients.</p

    The status of DECIGO

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    DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) is the planned Japanese space gravitational wave antenna, aiming to detect gravitational waves from astrophysically and cosmologically significant sources mainly between 0.1 Hz and 10 Hz and thus to open a new window for gravitational wave astronomy and for the universe. DECIGO will consists of three drag-free spacecraft arranged in an equilateral triangle with 1000 km arm lengths whose relative displacements are measured by a differential Fabry-Perot interferometer, and four units of triangular Fabry-Perot interferometers are arranged on heliocentric orbit around the sun. DECIGO is vary ambitious mission, we plan to launch DECIGO in era of 2030s after precursor satellite mission, B-DECIGO. B-DECIGO is essentially smaller version of DECIGO: B-DECIGO consists of three spacecraft arranged in an triangle with 100 km arm lengths orbiting 2000 km above the surface of the earth. It is hoped that the launch date will be late 2020s for the present

    The Japanese space gravitational wave antenna—DECIGO

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    DECIGO and DECIGO pathfinder

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