Sunitinib and other targeted therapies for renal cell carcinoma

Targeted therapy has radically altered the way metastatic renal cancer is treated. Six drugs are now licensed in this setting, with several other agents under evaluation. Sunitinib is currently the most widely used in the first line setting with impressive efficacy and an established toxicity profile. However, as further randomised studies report and as newer drugs become available this may change. In this review, we address our current understanding of targeted therapy in renal cancer. We also discuss areas in which our knowledge is incomplete, including the identification of correlative biomarkers and mechanisms of drug resistance. Finally, we will describe the major areas of clinical research that will report over the next few years

Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization

The cytogenetic characteristics of osteosarcoma (OS) remain controversial. The establishment of a new human OS cell line may improve the characterization. We report the establishment of a new human osteosarcoma cell line, UTOS-1, from a typical osteoblastic OS of an 18-year-old man. Cultured UTOS-1 cells are spindle-shaped, and have been maintained in vitro for over 50 passages in more than 2 years. Xenografted UTOS-1 cells exhibit features typical of OS, such as production of osteoid or immature bone matrix, and proliferation potency in vivo. UTOS-1 also exhibit morphological and immunohistochemical characteristics typical of osteoblastic OS. Chromosomal analysis by G-band show 73~85 chromosomes with complicated translocations. Array CGH show frequent gains at locus DAB2 at chromosome 5q13, CCND2 at 12p13, MDM2 at 12q14.3-q15, FLI and TOP3A at 17p11.2-p12 and OCRL1 at Xq25, and show frequent losses at HTR1B at 6q13, D6S268 at 6q16.3-q21, SHGC17327 at 18ptel, and STK6 at 20q13.2-q13.3. The UTOS-1 cell line may prove useful for biologic and molecular pathogenetic investigations of human OS

Exposure–response relationship of AMG 386 in combination with weekly paclitaxel in recurrent ovarian cancer and its implication for dose selection

To characterize exposure-response relationships of AMG 386 in a phase 2 study in advanced ovarian cancer for the facilitation of dose selection in future studies.A population pharmacokinetic model of AMG 386 (N = 141) was developed and applied in an exposure-response analysis using data from patients (N = 160) with recurrent ovarian cancer who received paclitaxel plus AMG 386 (3 or 10 mg/kg once weekly) or placebo. Reduction in the risk of progression or death with increasing exposure (steady-state area under the concentration-versus-time curve [AUC(ss)]) was assessed using Cox regression analyses. Confounding factors were tested in multivariate analysis. Alternative AMG 386 doses were explored with Monte Carlo simulations using population pharmacokinetic and parametric survival models.There was a trend toward increased PFS with increased AUC(ss) (hazard ratio [HR] for each one-unit increment in AUC(ss), 0.97; P = 0.097), suggesting that the maximum effect on prolonging PFS was not achieved at the highest dose tested (10 mg/kg). Among patients with AUC(ss) ≥ 9.6 mg h/mL, PFS was 8.1 months versus 5.7 months for AUC(ss) < 9.6 mg h/mL and 4.6 months for placebo. No relationship between AUC(ss) and grade ≥ 3 adverse events was observed. Simulations predicted that AMG 386 15 mg/kg once weekly would result in an AUC(ss) ≥ 9.6 mg h/mL in > 90% of patients with median PFS of 8.2 months versus 5.0 months for placebo (HR [15 mg/kg vs. placebo], 0.56).Increased exposure to AMG 386 was associated with improved clinical outcomes in recurrent ovarian cancer, supporting the evaluation of a higher dose in future studies

An EP-SAW for measurements of particulate matter in ambient air

In this article we demonstrate the feasibility of combining the two proven technologies of electrostatic precipitators (EP) and surface acoustic wave devices (SAW) for real time applications in particulate monitoring. A plastic cyclone (Higgins-Dewell), used for personal respirable dust sampling, has been modified to include an ionizing source and a Rayleigh SAW device with biased collection plate in place of the usual filter. The flow rate of the air through the cyclone allows size selectivity of particulate matter and we present data showing the effect of the collection plate bias of the collection efficiency

The fundamental physics of directive beaming at microwave and optical frequencies and the role of leaky waves

This review paper summarizes various aspects of directive beaming and explains these aspects in terms of leaky waves. Directive beaming occurs in antenna design where a narrow beam is obtainable by using fairly simple planar structures excited by a single source. These structures include Fabry-Pérot cavity structures as well as metamaterial structures made from artificial low-permittivity media. Directive beaming also occurs in the optical area where it has been observed that highly directive beams can be produced from small apertures in a metal film when an appropriate periodic patterning is placed on the film. One aspect that these phenomena all have in common is that they are due to the excitation of one or more weakly attenuated leaky waves, the radiation from which forms the directive beam. This is established in each case by examining the role of the leaky waves in determining the near-field on the aperture of the structure and the far-field radiation pattern of the structure. © 2011 IEEE

A theoretical design of ultra-wideband multisection Wilkinson power divider using Euler polynomials

When the broadband impedance matching techniques are applied to the Wilkinson power divider, it operates in a larger frequency range and covers many communication bands. In this study, an ultra-wideband (UWB) multisection Wilkinson power divider (WPD) circuit has been designed. Euler method has applied to the circuit that had equal power dividing feature on its two output ways. In the three-section of the WPD, the Euler function has been modeled as a reflection coefficient on the output branches. The Euler polynomials have been used to calculate the characteristic impedance of each section. The isolation resistors have been calculated by odd-even mode analysis according to the line impedances. In the Euler WPD, center frequency was 2.45 GHz and the limits for the return loss and isolation was selected as 15 dB and 20 dB, respectively. The bandwidth was measured as 0.75 to 3.80 GHz. The percent bandwidth of the WPD was calculated as 124.5%. Along the operation band interval, the minimum insertion loss measured lower than 0.75 dB. The design has been compared with a quarter wave (QW) WPD. It has been shown that the Euler method can achieve higher bandwidth, lower return loss and better Isolation than the conventional WPD