A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer

PURPOSE: We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. PATIENTS AND METHODS: We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. RESULTS: Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. CONCLUSIONS: This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.     

Influence of geosynthetic reinforcement on the load-settlement characteristics of two-layer subgrade

The possibility of realistic prediction of two-layer subgrade load-settlement characteristics is discussed. The case of improvement of the soft subgrade properties using the geosynthetic reinforcement placed at the boundary between two different subgrade layers is analysed. In the first part of the paper, a short review of the main conclusions from experimental results dealing with the influence of geosynthetic reinforcement on the load-settlement characteristics of subgrade is presented. Then, the results of using the selected analytical membrane-action model to describe the reinforcement action in soil are discussed. The model is verified on the basis of data obtained from previously published laboratory tests. Particular attention is devoted to influencing some basic initial parameters on the accuracy of obtained results. Important problems which need intensive investigations are identified.     

Transport of reactants during scale formation on copper in SO2+O2 atmosphere at 973 and 1073 K

The reaction between copper and a mixture of SO₂+O₂ was studied at 973 and 1073 K. The experimental methods included optical microscopy, X-ray diffraction, scanning electron microscopy (SEM), energy-dispersive X-ray analysis, and radiotracer. It is concluded that the inward transport of oxidants through the scale as well as oxygen and sulfur dioxide liberation in the reactions taking place at phase boundaries suggest that secondary processes occur inside the oxide-sulphate layer. Therefore, Cu₂O and CuOCuSO₄ appear inside this layer. In the metal-consumption zone, a Cu₂O layer forms, which contains small amounts of a sulfide phase near the metal-scale interface.     

Preparation of lead (Pb) X-ray fluorescence reference materials for the EPA Pb monitoring program and the IMPROVE network using an aerosol deposition method

X-ray fluorescence (XRF) is a commonly used analytical method to quantify lead (Pb), a toxic element, in atmospheric aerosol. The commercially available reference materials used for calibrating XRF do not mimic the concentrations and filter materials of particulate matter (PM) monitoring networks. In this study, we described an aerosol deposition method to generate Pb reference materials (RMs) over a range of concentrations to serve several purposes for the US Environmental Protection Agency (EPA) and Interagency Monitoring of PROtected Visual Environments (IMPROVE) monitoring networks including laboratory auditing, federal equivalency method evaluation, and calibration and quality control of XRF instruments. The RMs were generated using a laboratory-built aerosol chamber equipped with a federal reference sampler at concentration levels ranging from 0.0125 to 0.70 μg/m³. XRF analysis at UC Davis was demonstrated to be equivalent to a US and EU reference method, inductively coupled plasma—mass spectrometry (ICP-MS), for measuring Pb on RMs following a methodology described in the United States and international standards. The Pb concentrations on subsets of the RMs were verified by three other XRF laboratories with different analyzers and/or quantification methods and were shown to be equivalent to the UC Davis XRF analysis. The generated RMs were demonstrated to have short and long-term stability, satisfying an additional requirement of reference materials.

Copyright © 2016 American Association for Aerosol Research     

Detection of Starch Transformation Under γ-Irradiation by Small-angle X-Ray Scattering

The small angle X-ray scattering (SAXS) was used to examine structural changes of starches after γ-irradiation with 10, 20, 30 kGy doses. The diminution of intensity of small-angle reflexion relating to 100 A spacing indicates destruction of long-range ordering in granules after γ-irradiation. It was observed as well in the case of irradiation of dry pure starches as a starch contained in potatoes. The method suggests possibility of quick identification of irradiated foodstuffs.     

The influence of post-mortem ageing and roasting on the microstructure, texture and collagen solubility of bovine semitendinosus muscle

Bovine semitendinosus (ST) muscles aged for 5 and 12 days at 4?°C were roasted at 170?°C to internal temperatures of 50, 60, 70, 80 and 90?°C. Microstructural changes in meat were evaluated using a scanning electron microscope (SEM). Texture profile analysis (TPA) and measurements of the shear force values of samples were conducted using a texture analyser. The cooking losses and quantity of total and soluble collagen were also estimated. The structure of intramuscular connective tissue and myofibrillar structure of meat after 5 days of ageing was very regular. In 12-day-aged samples fibrous and myofibrillar structures were less distinct, damages of endomysium tubes appeared and fibres of perimysium were swelled. Ageing of ST muscle for 12 days caused a two-fold increase in the quantity of soluble collagen and a two-fold decrease in the value of TPA parameters-hardness and chewiness, as compared to 5-day-aged samples. The decrease in fibre diameter and sarcomere length during roasting started at 60?°C in 5-day-aged meat and at 50?°C in 12-day-aged samples. The shear force values measured after roasting were lower for 12-day-aged meat than for 5-day-aged samples. The quantity of soluble collagen in roasted meat increased at an internal temperature of 80?°C. At a higher temperature of meat this variable depended on the degree of meat ageing. The cooking losses during roasting of meat were about 3% lower for 12-day-aged than for 5-day-aged samples. In the examined range of internal temperature of meat the cooking losses and the sarcomere length were negatively correlated.     

Stability of bioactive polyphenols from honey during different extraction methods

The LC–MS/MS technique was applied to the stability study of several flavonoids and phenolic acids in honey samples during the ultrasonic extraction (USE) and microwave-assisted extraction (MAE). Phenolic compounds from the standard mixture were stable under ultrasounds action with the mean recovery of (90.4% ± 7.1%), but during microwave-assisted extraction the benzoic acid derivatives and aglycones of flavonoids showed lower recovery (70–80%). In honey matrix, the phenolic acids and the glycosides exhibited the high stability for MAE and USE treatments. However, the recoveries of tested aglycones were below 10%. In the presence of an artificial sugar matrix, flavonols were almost completely degraded after successive treatment under MAE and USE conditions. The obtained results indicated that standard addition method for flavonoids quantification in honey samples should not be recommended. Application of the USE conditions provided higher and/or similar extraction yields for phenolic acids than usually applied shaking with solvent. It also allowed shortening the time required for the whole sample preparation procedure. Phenolic acids and glycosides such as quercetrin, rutin and hesperidin appeared to be stable under such conditions.     

The Reaction of Malononitrile with Enamines of some cyclic β-Keto acid anilides and amidines

The reaction of enamines 1 derivatives of cyclohexanon- or cycloheptanon-2-carboxylic acid anilides with malononitrile gave in the first step 2-phenylcarbamoyl-cycloalkylideno-malononitriles 3 , which in turn were converted into 1-oxo-2-phenyl-3-amino-4-cyano-cycloalkenoisoquinolines 4 . Enamines containing an adjacent diphenylamidino group 6 reacted with malononitrile giving 1-phenylimino-2-phenyl-3-amino-4-cyano-cycloalkenoisoquinolines 7 . The alkaline hydrolysis of 7 yielded 1-phenylamino-3-oxo-4-cyano-cycloalkenoisoquinoline 8 .