BackgroundElevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer.MethodsEligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed.ResultsEight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3–9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0–10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF.ConclusionsBEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease.Trial registrationClinicalTrials.gov identifying number NCT01281696.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1290-1) contains supplementary material, which is available to authorized users.
A small-displacement sensing system based on multiple total internal reflections in heterodyne interferometry is proposed. In this paper, a small displacement can be obtained only by measuring the variation in phase difference between s- and p-polarization states for the total internal reflection effect. In order to improve the sensitivity, we increase the number of total internal reflections by using a parallelogram prism. The theoretical resolution of the method is better than 0.417 nm. The method has some merits, e.g., high resolution, high sensitivity, and real-time measurement. Also, its feasibility is demonstrated.
It was found by our previous work [1] that for Ca--SiAlON composition (Ca x Si 12-3x Al 3x O n N 16-x ) about 70% of Ca ++ in nominal composition entered into -SiAlON structure with the remainder in grain boundary. By half Ca ++ replaced by Mg ++ in multi-cation Ca,Mg--SiAlON compositions, the results indicated that the cell dimensions of Ca,Mg--SiAlON phase were obviously smaller than that of Ca--SiAlON with the same compositions. EDAX analysis further revealed that the Ca ++ contents in the grains were much higher than Mg ++ and the average value of Ca ++ contents could be close to the one in nominal composition, implying that more active cation, Ca ++ , could be incorporated into -SiAlON structure in multi-cation -SiAlONs case. Based on the above results, -SiAlON ceramics, in which Ca ++ was partly replaced by La +++ has been designed. The lattice parameters of the -SiAlONs, in which 30%Ca ++ were replaced by La +++ as additives, were close to the ones of single-cation Ca--SiAlON under the same compositions, indicating that most of Ca ++ were incorporated in -SiAlON because almost no La +++ was detected by EDS analysis of -SiAlON grains. The advantage of using additives Ca ++ combined with La +++ to form -SiAlON was expected because of high refractory of glassy grain boundary containing lanthanum. Consequently,The flexural strength of one composition of Ca ++ /La +++ doped -SiAlON ceramics at 1250°C reached as high as 555MPa was obtained, whose value was 20% higher than that at room temperature.
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