Investigation of drugs for the prevention of doxorubicin-induced cardiac events using big data analysis

Aim: Doxorubicin, an anthracycline anti-tumour agent, is an essential chemotherapeutic drug; however, the adverse events associated with doxorubicin usage, including cardiotoxicity, prevent patients from continuing treatment. Here, we used databases to explore existing approved drugs with potential preventative effects against doxorubicin-induced cardiac events and examined their efficacy and mechanisms. Methods: The Gene Expression Omnibus (GEO), Library of Integrated Network-based Cellular Signatures (LINCS), and Food and Drug Administration Adverse Events Reporting System (FAERS) databases were used to extract candidate prophylactic drugs. Mouse models of doxorubicin-induced cardiac events were generated by intraperitoneal administration of 20 mg/kg of doxorubicin on Day 1 and oral administration of prophylactic candidate drugs for 6 consecutive days beginning the day before doxorubicin administration. On Day 6, mouse hearts were extracted and examined for mRNA expression of apoptosis-related genes. Results: GEO analysis showed that doxorubicin administration upregulated 490 genes and downregulated 862 genes, and LINCS data identified sirolimus, verapamil, minoxidil, prednisolone, guanabenz, and mosapride as drugs capable of counteracting these genetic alterations. Examination of the effects of these drugs on cardiac toxicity using FAERS identified sirolimus and mosapride as new prophylactic drug candidates. In model mice, mosapride and sirolimus suppressed the Bax/Bcl-2 mRNA ratio, which is elevated in doxorubicin-induced cardiotoxicity. These drugs also suppressed the expression of inflammatory cytokines Il1b and Il6 and markers associated with myocardial fibrosis, including Lgal3 and Timp1. Conclusion: These findings suggest that doxorubicin-induced cardiac events are suppressed by the administration of mosapride and sirolimus

High Efficiency Mode Converter for Low-Frequency Gyrotron

A high efficiency quasi-optical (QO) mode converter for high-power, low-frequency gyrotron have been designed and tested. For low-frequency gyrotrons, the scales of the mode converter are comparatively small on the wavelength scale, thus causing significant diffraction losses. Over-1 MW power gyrotron with TE 8,3 cavity at 28 GHz have been developed, which has a high efficiency mode converter designed by the use of numerical methods for launcher optimization. This calculation is sufficiently optimized to maximize the fractional Gaussian content of the far field. The total transmission efficiency from the mode converter to output window is 94.7%. For the experimental result of first tube, the output power of more than 1 MW has been obtained with about 40% efficiency and output burn pattern agrees fairly with the calculated profiles, which imply the design appropriateness. Besides, the frequency dependence for diffraction loss is discussed, and these results give the guiding design principle of the mode converter for high-power, low-frequency and long-pulse gyrotrons. © 2010 Springer Science+Business Media, LLC

Progress on performance tests of ITER gyrotrons and design of dual-frequency gyrotrons for ITER staged operation plan

This paper presents the progress of performance tests of ITER gyrotrons developed at QST and the design of dual-frequency (170 GHz and 104 GHz) gyrotrons to enhance various operation scenarios in ITER, such as characteristics studies of H-mode/ELM at low magnetic fields. The major achievements in developing the ITER gyrotrons are as follows: (i) manufacturing of eight ITER gyrotrons and their auxiliary components has been completed. Performance tests at QST have been progressing and four of the eight gyrotrons achieved the required test criteria—1 MW/300 s/50%, 5 kHz modulation with > 0.8 MW. Excitation of LP01 mode having a purity of > 95% was also successfully demonstrated using a 50 mm-diameter waveguide transmission line, satisfying the specification. (ii) The design of dual-frequency gyrotrons capable of 1 MW continuous-wave operation, was successfully completed

Development of the first ITER gyrotron in QST

This paper presents a summary of recent progress pertaining to the manufacturing and inspection of ITER gyrotrons and the operation system in QST. Major achievements are as follows. (i) The final design of the ITER gyrotron was accomplished and manufacturing of two ITER gyrotrons was completed. Then operation test in QST prior the shipment to ITER has started with ITER relevant high voltage power supply configuration. The 1st ITER gyrotron has achieved 1.05 MW operation for 300 s with 51% efficiency. Measured cooling channel waveform of 300 s pulse demonstrated thermally stable condition representing sufficient cooling performance for 1 MW CW operation; (ii) 5 kHz modulation operation was demonstrated up to 200 s at with >0.8 MW at flat top of pulses; (iii) 300 s/1 MW operation was repeated for 20 shots with successful 19 shots which demonstrating >95% of reliability requirement. These results lead to success of ITER EC H&CD system construction and commissioning toward first plasma

Temporal trends in the surgical outcomes of patients with breast cancer

<p>Abstract</p> <p>Background</p> <p>The incidence of breast cancer has been increasing in Japan over the past three decades, and it is the currently the most common malignancy in Japan. This study investigated the temporal trends of the surgical outcomes in patients with breast cancer.</p> <p>Methods</p> <p>We evaluated 543 consecutive patients who underwent breast-cancer resection between 1980 and 2009. The temporal trends in the surgical outcome and clinicopathological features were evaluated separately for the periods covering 1980 to 1989, 1990 to 1999, and 2000 to 2009.</p> <p>Results</p> <p>The number of patients who underwent resection during these three respective periods were 133, 176, and 234, respectively. All patients were women. The percentage of patients at stages 0 or 1 was 63.2%, 58.5%, and 43.6%, respectively, during the three periods. The mean diameter of tumors in each period was 38, 29, and 30 mm, respectively. The percentage of tumors with positive ER expression was 62.5%, 64.3%, and 69.7%, respectively. In terms of surgical procedures, the use of Halsted’s radical mastectomy decreased during each period: from 40.6% of cases to 8.5% and then to 0.4%, while the proportion of breast-conserving therapies increased, from 0% to 12.5%, and finally to 35.9%. The postoperative 10-year survival rates during the three periods were 75.9%, 83.5%, and 84.9%, respectively. The 10-year survival rates of patients with stage II disease during the three periods were 66.2%, 75.7%, and 90.7%, respectively. The prognosis of stage III disease in the three periods also showed a tendency toward improvement, increasing from 37.8% to 64.2%, and finally to 84.5%.</p> <p>Conclusion</p> <p>The survival of patients with stage II and III disease has improved during the past 30 years. Along with the recent advances in drug therapy, the surgical treatment has become less invasive, often because of drug therapy-related modifications.</p