Although many clinical and molecular markers for predicting outcomes in bladder cancer (BC) have been reported, their application in clinical practice remains unclear. Bladder carcinogenesis has two distinct molecular pathways that direct the development of BC.FGFR3mutations are common in low-grade BC, whileTP53mutation or loss ofRB1is associated with muscle-invasive BC. However, no tissue-based gene markers confirmed by prospective large-scale trials in BC have been used in clinical practice. Micro-RNA analyses of BC tissue revealed that miR-145 and miR-function as tumor suppressors, whereas miR-183 and miR-17-5p function as oncogenic miRNAs. In liquid biopsy, circulating tumor cells (CTC), exosomes, or cell-free RNA is extracted from the peripheral blood samples of cancer patients to analyze cancer prognosis. It was reported that detection of CTC was associated with poor prognostic factors. However, application of liquid biopsy in BC treatment is yet to be explored. Although several cell-free RNAs, such as miR-497 in plasma or miR-214 in urine, could be promising novel circulating biomarkers, they are used only for diagnosing BC as the case that now stands. Here, we discuss the application of novel biomarkers in evaluating and measuring BC outcomes.
The aim of this study is to elucidate the clinical significance of prostate-specific membrane antigen (PSMA) expression in circulating tumor cells (CTCs) from castration-resistant prostate cancer (CRPC) patients. We analyzed a total of 203 CTC samples from 79 CRPC patients to investigate the proportion of positive mRNA expressions at different treatment phases. Among them, we elected to focus on specimens from 56 CRPC patients who progressed on therapy and were subsequently provided a new treatment (treatment-switch cohort). In this cohort, we investigated the association between PSMA expression in CTCs and treatment response. CTCs were detected in 55/79 patients and median serum PSA in CTC-positive patients was 67.0 ng/ml. In the treatment-switch cohort of 56 patients, 20 patients were positive for PSMA in CTCs. PSMA expression was inversely associated with percentage of change in prostate-specific antigen (PSA). The median PSA progression-free survival and overall survival were significantly shorter in the PSMA-positive cohort. Furthermore, PSMA expression was predictive of poorer treatment response, shorter PSA progression-free survival and overall survival. PSMA expression in circulating tumor cells may be a novel poor prognostic marker for CRPC.
24 June 2010 in IEEE Transactions on Dielectrics and Electrical Insulation
We investigated the characteristics of the partial discharge (PD) with twisted enameled wires by optical emission spectroscopy (OES) in atmospheric humid air. The electric field strength in the gap of the twisted enameled wires during the discharges was estimated from intensity ratio of the spectrum bands of nitrogen molecules obtained by the OES. It was found that the electric field strength was increased when increasing the relative humidity, and the increasing rate was different depending on the temperature. The increase of the electric field strength in the gap of the twisted pair could be related to a reduction of PD inception voltage (PDIV) observed in the experiment. The reduction of the PDIV could be determined by not only dielectric properties of enameled wires such as permittivity and surface conductivity but also changes of the discharge phenomena in the humid air. In this study, effects of the increase of the permittivity of the enameled wire due to the moisture absorption into the insulating layer were quantitatively discussed as one of the candidates to explain the reduction of the PDIV in the humid conditions. On the other hand, the discharge current amplitude was decreased with the increase of relative humidity at high temperature. It was considered that the discharge could be quenched by dissociative electron attachment to the large number of water molecules. The observed PD phenomena with respect to the change of the humidity are very important for quality management of low voltage inverter-fed random wound motors.
1 January 2001 in Review of Scientific Instruments
In this article we present an overview of the plasma diagnostics operating or planned for the sustained spheromak physics experiment device now operating at Lawrence Livermore National Laboratory. A set of 46 wall-mounted magnetic probes provide the essential data necessary for magnetic reconstruction of the Taylor relaxed state. Rogowski coils measure currents induced in the flux conserver. A laser interferometer is used to measure electron line density. Spectroscopic measurements include an absolutely-calibrated spectrometer recording extended domain spectrometer for obtaining time-integrated visible ultraviolet spectra and two time-resolved vacuum monochrometers for studying the time evolution of two separate emission lines. Another time-integrated spectrometer records spectra in the visible range. Filtered silicon photodiode bolometers provide total power measurements, and a 16 channel photodiode spatial array gives radial emission profiles. Two-dimensional imaging of the plasma and helicity injector is provided by gated television cameras and associated image-processing software. An array of fiber-coupled photodetectors with H alpha filters view across the midplane and in the injector region to measure neutral hydrogen concentrations. Several novel diagnostics are being fielded including a transient internal probe (TIP) and an ultrashort-pulse reflectometer (USPR) microwave reflectometer. The TIP probe fires a very high velocity optical bullet through the plasma and will provide fairly nonpertabative internal magnetic field and current measurements to compare with an equilibrium code model fitted to wall-mounted probes. The USPR is being designed to study edge density and turbulent fluctuations. A multipoint Thomson scattering system is currently being installed to give radial temperature and density profiles.
1 December 2014 in Molecular and Clinical Oncology
This study was conducted with the aim to investigate the feasibility of intermittent treatment with docetaxel chemotherapy for castration‑resistant prostate cancer (CRPC). A total of 51 men with CRPC received docetaxel at 75 mg̸m2 every 3 weeks combined with oral dexamethasone 1.0‑2.0 mg̸day between 2008 and 2013. The prostate‑specific antigen (PSA) level was monitored every 3 weeks. Chemotherapy was suspended when the serum PSA level decreased to 50% from the baseline. Treatment was resumed when serum PSA increased to >2 ng/ml, with an increase rate of >50% from the nadir. Of the 51 cases, 27 (52.9%) qualified for intermittent treatment; 17 patients received two courses of docetaxel chemotherapy and 10 received three courses. The median off‑treatment interval was 266 days for the first drug holiday, 129.5 days for the second and 146.5 days for the third. The multivariate analysis indicated low baseline PSA (<median, 30.55 ng̸ml; odds ratio = 0.059, P=0.010) and low Gleason score at diagnosis (≤7; odds ratio = 0.016, P=0.040) as significant factors for receiving intermittent therapy. The overall survival was better in intermittent cases (hazard ratio = 2.98 by log‑rank test, P=0.023). During the off‑treatment period, leukopenia, thrombopenia, appetite loss, diarrhea, alopecia, nail changes and fatigue subsided (0.0‑11.1%), whereas sensory and/or motor neuropathy persisted in 12 of the 27 cases (44.4%). Therefore, our intermittent regimen of docetaxel chemotherapy was found to be feasible for CRPC patients, since it may reduce adverse events without compromising the oncological outcome.
New understanding and improved parameters have been achieved on the Helicity Injected Torus with Steady Inductive helicity injection current drive (HIT-SI) experiment. The experiment has a bowtie-shaped spheromak confinement region with two helicity injectors. The inductive injectors are 180° segments of a small, oval cross section toroidal pinch. Spheromaks with currents up to 38 kA and current amplification of 2 have been achieved with only 6 MW of injector power. The Taylor-state model is shown to agree with HIT-SI surface and internal magnetic profile measurements. Helicity balance predicts the peak magnitude of toroidal spheromak current and the threshold for spheromak formation. The model also accurately predicts the division of the applied loop voltage between the injector and spheromak regions. Single injector operation shows that the two injectors have opposing, preferred spheromak current directions. An electron locking relaxation model is consistent with the preferred direction, with ion Doppler data and with bolometric data. Results from higher frequency operation are given. The impact of the new understanding on the future direction of the HIT programme is discussed.