Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that recently gained Food and Drug Administration approval for late-line metastatic breast cancer (MBC).
In this single-arm, ...multicentre open-label phase II trial Japanese patients pretreated with an anthracycline and a taxane received 1.4 mg/m2 eribulin mesylate (2- to 5-min i.v. infusion on days 1 and 8 of a 21-day cycle). The primary efficacy end point was overall response rate (ORR) by independent review.
Patients (N = 80) had received a median of three prior chemotherapy regimens (range 1–5). ORR was 21.3% 95% confidence interval (CI) 12.9–31.8; all partial responses (PRs), stable disease (SD) occurred in 30 patients (37.5%) and the clinical benefit rate (complete response + PR + SD ≥6 months) was 27.5% (95% CI 18.1–38.6). Median duration of response was 3.9 months (95% CI 2.8–4.9), progression-free survival was 3.7 months (95% CI 2.0–4.4) and overall survival was 11.1 months (95% CI 7.9–15.8). The most frequent treatment-related grade 3/4 adverse events were neutropenia (95.1%), leukopenia (74.1%) and febrile neutropenia (13.6%). Grade 3 peripheral neuropathy occurred in 3.7% of patients (no grade 4).
Eribulin exhibited efficacy and tolerability in Japanese patients with heavily pretreated MBC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Evaluation of Mg ion as-implanted GaN by photothermal deflection spectroscopy.•Variation of the implanted GaN caused by thermal annealing.•Relationship among deep-level defect, Urbach energy, and ...luminescence in the gap.•Shift of the Femi level for Mg-implanted GaN by the annealing for p-type activation.
Both structure of the valence band maximum (VBM) and deep-level defects for box-profile Mg-ion implanted (4 × 1019 cm−3) GaN samples are characterized by photothermal deflection spectroscopy (PDS). Compared with the results evaluated by positron annihilation spectroscopy, the variations caused by the thermal annealing is discussed with respect to Urbach energy, defect levels in the band gap, and photoluminescence. Forming Urbach tail gradually at the VBM at the 1000 °C annealing, vacancy-type defects clusters without drastic decrease of deep-level defects. Green and yellow luminescence emits slightly as the PDS signal at the deep-level is decreased by the annealing at 1100 °C due to the decrease of non-radiative recombination centers. The Urbach energy is improved by the further annealing so that the luminescence becomes intense due to the energy transfer through the phonon from Urbach region. The shift of Fermi level towards the valence band at the 1300 °C annealing, the sign of p-conduction, is confirmed from the valence band spectra. Compared to the Mg-doped GaN with p-conduction, it is considered that the improvement of Urbach energy is crucial for p-type activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PLA2G6 is the causative gene for infantile neuroaxonal dystrophy, neurodegeneration associated with brain iron accumulation, and Karak syndrome. Based on previous reports, patients with PLA2G6 ...mutations could show axonal dystrophy, dystonia, dementia, and cerebellar signs. Recently, PLA2G6 was also reported as the causative gene for early-onset PARK14-linked dystonia-parkinsonism.
To clarify the role of PLA2G6 mutation in parkinsonism, we conducted mutation analysis in 29 selected patients with very early-onset (≤ 30, mean 21.2 ± 8.4 years, ± SD) parkinsonism. These patients had other clinical features (e.g., mental retardation/dementia 14/29, psychosis 15/29, dystonia 11/29, and hyperreflexia 11/29).
Two novel compound heterozygous PLA2G6 mutations were detected (patient A: p.F72L/p.R635Q; patients B1 and B2: p.Q452X/p.R635Q). All 3 patients had early-onset l-dopa-responsive parkinsonism with dementia and frontotemporal lobar atrophy. Disease progression was relatively rapid. SPECT in patient B1 showed frontotemporal lobar hypoperfusion. MRI in patient A showed iron accumulation in the substantia nigra and striatum.
Although the clinical presentation of PLA2G6-associated neurodegeneration was reported to be homogeneous, our findings suggest patients with PLA2G6 mutation could show heterogeneous phenotype such as dystonia-parkinsonism, dementia, frontotemporal atrophy/hypoperfusion, with or without brain iron accumulation. Based on the clinical heterogeneity, the functional roles of PLA2G6 and the roles of PLA2G6 variants including single heterozygous mutations should be further elucidated in patients with atypical parkinsonism, dementia, or Parkinson disease. PLA2G6 mutations should be considered in patients with early-onset l-dopa-responsive parkinsonism and dementia with frontotemporal lobar atrophy.
We present a 115In NMR study of the quasi-two-dimensional heavy-fermion superconductor CeCoIn5 believed to host a Fulde-Ferrel-Larkin-Ovchinnikov (FFLO) state. In the vicinity of the upper critical ...field and with a magnetic field applied parallel to the ab plane, the NMR spectrum exhibits a dramatic change below T*(H) which well coincides with the position of reported anomalies in specific heat and ultrasound velocity. We argue that our results provide the first microscopic evidence for the occurrence of a spatially modulated superconducting order parameter expected in a FFLO state. The NMR spectrum also implies an anomalous electronic structure of vortex cores.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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