Results

The oral administration of rebamipide decreased plaque formation in atherosclerotic lesions as well as the markers of metabolic disorder in ApoE-deficient mice with atherosclerosis. Pro-inflammatory cytokines were also suppressed by rebamapide. In addition, the population of Th17 was decreased, whereas Treg was increased in the spleen of rebamipide-treated ApoE deficient mice. Rebamipide also ameliorated the severity of obese arthritis and has the capability to reduce the development of atherosclerosis by controlling the balance between Th17 and Treg cells. Thus, rebamipide could be a therapeutic agent to improve the progression of inflammation in metabolic diseases.

A prospective randomized controlled multicenter phase III trial was conducted to evaluate the effects of neoadjuvant chemotherapy with nimustine (ACNU)-cisplatin (CDDP) when used in conjunction with radiotherapy plus adjuvant temozolomide in patients with newly diagnosed glioblastoma. The study population was randomly assigned into one treatment and one control group. Both groups received radiotherapy followed by six cycles of adjuvant oral temozolomide (150-200 mg/m(2)) for 5 days every 28 days after surgery. Prior to radiotherapy, the treatment group also received two cycles, 6 weeks apart, of neoadjuvant chemotherapy with ACNU (40 mg/m(2)/day) and CDDP (40 mg/m(2)/day) infused continuously for 72 h. The primary end-point was median survival time. The study has closed after interim analysis with a total of 82 patients (48.8% of target number) due to unacceptable high frequency of toxicity profiles in spite of the promising actuarial survival outcome. Median survival time was 28.4 months [90% confidence interval (CI), 21.1 months to not available] in the treatment group and 18.9 months (90% CI, 17.1-27.4 months) in the control group (P = 0.2). The 2-year survival rate and progression-free survival time were 50.9% and 6.6 months (90% CI, 3.5-9.5 months) in the treatment group and 27.8% and 5.1 months (90% CI, 3.8-8.8 months) in the control group. Grade 3 or 4 toxicity was documented in 26 (68.4%) patients in the treatment group, including three neutropenic fever and one death from sepsis, while grade 3 or 4 toxicity occurred in 6 patients (15.8%) in the control group. The high frequency of serious hematological toxicity with ACNU-CDDP neoadjuvant chemotherapy followed by radiotherapy and adjuvant temozolomide limits its usage as primary treatment for glioblastoma. Future studies should aim to identify a subpopulation at reduced risk for ACNU-CDDP toxicity so that the potential of this protocol can be realized.

Optical-frequency synthesizers, which generate frequency-stable light from a single microwave-frequency reference, are revolutionizing ultrafast science and metrology, but their size, power requirement and cost need to be reduced if they are to be more widely used. Integrated-photonics microchips can be used in high-coherence applications, such as data transmission 1, highly optimized physical sensors 2 and harnessing quantum states 3, to lower cost and increase efficiency and portability. Here we describe a method for synthesizing the absolute frequency of a lightwave signal, using integrated photonics to create a phase-coherent microwave-To-optical link. We use a heterogeneously integrated III-V/silicon tunable laser, which is guided by nonlinear frequency combs fabricated on separate silicon chips and pumped by off-chip lasers. The laser frequency output of our optical-frequency synthesizer can be programmed by a microwave clock across 4 terahertz near 1,550 nanometres (the telecommunications C-band) with 1 hertz resolution. Our measurements verify that the output of the synthesizer is exceptionally stable across this region (synthesis error of 7.7 × 10-15 or below). Any application of an optical-frequency source could benefit from the high-precision optical synthesis presented here. Leveraging high-volume semiconductor processing built around advanced materials could allow such low-cost, low-power and compact integrated-photonics devices to be widely used.