Experimental study of non-inductive current in Heliotron J

It is important to control non-inductive current for generation and steady-state operation of highperformance plasmas in toroidal fusion devices. Helical devices allow dynamic control of non-inductivecurrent through a wide variety of magnetic configurations. The reversal of non-inductive current consisting of bootstrap current and electron cyclotron driven current in electron cyclotron heating plasmas has been observed in a specific configuration at low density in Heliotron J device. By analyzing thenon-inductive current for normal and reversed magnetic fields, we present experimental evidence for the reversal of bootstrap current. Our experiments and calculations suggest that the reversal is caused bya positive radial electric field of about 10 kV/m. Moreover, we show that the typical electron cyclotron current drive efficiency in Heliotron J plasma is about 1.0 × 1017 AW?1m?2, which is comparable to other helical devices. We have found that the value is about 10 times lower than that of tokamak devices. This might be due to an enhanced Ohkawa effect by trapped particles

Anticancer drug clustering in lung cancer based on gene expression profiles and sensitivity database

BACKGROUND: The effect of current therapies in improving the survival of lung cancer patients remains far from satisfactory. It is consequently desirable to find more appropriate therapeutic opportunities based on informed insights. A molecular pharmacological analysis was undertaken to design an improved chemotherapeutic strategy for advanced lung cancer. METHODS: We related the cytotoxic activity of each of commonly used anti-cancer agents (docetaxel, paclitaxel, gemcitabine, vinorelbine, 5-FU, SN38, cisplatin (CDDP), and carboplatin (CBDCA)) to corresponding expression pattern in each of the cell lines using a modified NCI program. RESULTS: We performed gene expression analysis in lung cancer cell lines using cDNA filter and high-density oligonucleotide arrays. We also examined the sensitivity of these cell lines to these drugs via MTT assay. To obtain our reproducible gene-drug sensitivity correlation data, we separately analyzed two sets of lung cancer cell lines, namely 10 and 19. In our gene-drug correlation analyses, gemcitabine consistently belonged to an isolated cluster in a reproducible fashion. On the other hand, docetaxel, paclitaxel, 5-FU, SN-38, CBDCA and CDDP were gathered together into one large cluster. CONCLUSION: These results suggest that chemotherapy regimens including gemcitabine should be evaluated in second-line chemotherapy in cases where the first-line chemotherapy did not include this drug. Gene expression-drug sensitivity correlations, as provided by the NCI program, may yield improved therapeutic options for treatment of specific tumor types

Gefitinib (IRESSA) sensitive lung cancer cell lines show phosphorylation of Akt without ligand stimulation

BACKGROUND: Phase III trials evaluating the efficacy of gefitinib (IRESSA) in non-small cell lung cancer (NSCLC) lend support to the need for improved patient selection in terms of gefitinib use. Mutation of the epidermal growth factor receptor (EGFR) gene is reported to be associated with clinical responsiveness to gefitinib. However, gefitinib-sensitive and prolonged stable-disease-defined tumors without EGFR gene mutation have also been reported. METHODS: To identify other key factors involved in gefitinib sensitivity, we analyzed the protein expression of molecules within the EGFR family, PI3K-Akt and Ras/MEK/Erk pathways and examined the sensitivity to gefitinib using the MTT cell proliferation assay in 23 lung cancer cell lines. RESULTS: We identified one highly sensitive cell line (PC9), eight cell lines displaying intermediate-sensitivity, and 14 resistant cell lines. Only PC9 and PC14 (intermediate-sensitivity) displayed an EGFR gene mutation including amplification. Eight out of the nine cell lines showing sensitivity had Akt phosphorylation without ligand stimulation, while only three out of the 14 resistant lines displayed this characteristic (P = 0.0059). Furthermore, the ratio of phosphor-Akt/total Akt in sensitive cells was higher than that observed in resistant cells (P = 0.0016). Akt phosphorylation was partially inhibited by gefitinib in all sensitive cell lines. CONCLUSION: These results suggest that Akt phosphorylation without ligand stimulation may play a key signaling role in gefitinib sensitivity, especially intermediate-sensitivity. In addition, expression analyses of the EGFR family, EGFR gene mutation, and FISH (fluorescence in situ hybridization) analyses showed that the phosphorylated state of EGFR and Akt might be a useful clinical marker of Akt activation without ligand stimulation, in addition to EGFR gene mutation and amplification, particularly in adenocarcinomas

Pharmacokinetic study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy (KHBO1101)

Background: Biliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy cannot tolerate the standard gemcitabine regimen (1, 000 mg/m2 on days 1, 8, and 15 every 4 weeks) due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy determined that the recommended dose is 1, 000 mg/m2 on days 1 and 15 every 4 weeks. Here, we evaluate the pharmacokinetics and pharmacodynamics of gemcitabine in these subjects. Methods: We evaluated BTC patients scheduled to undergo surgical resection with major hepatectomy followed by gemcitabine therapy. A pharmacokinetic evaluation of gemcitabine and its main metabolite, 2′, 2′-difluorodeoxyuridine (dFdU), was conducted at the initial administration of gemcitabine, which was given by intravenous infusion over 30 min at a dose of 800-1, 000 mg/m2. Physical examination and adverse events were monitored for 12 weeks. Results: Thirteen patients were enrolled from August 2011 to January 2013, with 12 ultimately completing the pharmacokinetic study. Eight patients had hilar cholangiocarcinoma, three had intrahepatic cholangiocarcinoma, and one had superficial spreading type cholangiocarcinoma. The median interval from surgery to first administration of gemcitabine was 65.5 days (range, 43-83 days). We observed the following toxicities: neutropenia (n = 11, 91.7%), leukopenia (n = 10, 83.3%), thrombocytopenia (n = 6, 50.0%), and infection (n = 5, 41.7%). Grade 3 or 4 neutropenia was observed in 25% (n = 3) of patients. There were differences in clearance of gemcitabine and dFdU between our subjects and the subjects who had not undergone hepatectomy. Conclusion: Major hepatectomy did not affect the pharmacokinetics of gemcitabine or dFdU. Trial Registration: UMIN-CTR in (JPRN) UMIN000005109

Spatial Distribution Analyses of Axially Long Plasmas under a Multi-Cusp Magnetic Field Using a Kinetic Particle Simulation Code KEIO-MARC

To realize the development of a long plasma source with a uniform electron density distribution in the axial direction, the spatial distribution of plasma under a multi-cusp magnetic field was analyzed using a KEIO-MARC code. Considering a cylindrical plasma source with an axial length of 3000 mm and a cross-sectional diameter of 100 mm, in which the filament electrode was the electron source, the electron density distribution was calculated using the residual magnetic flux density, Bres, and the number of permanent magnets installed at different locations surrounding the device, Nmag, as design parameters. The results show that both Bres and Nmag improved the uniformity of the electron density distribution in the axial direction. The maximum axial electron density decreased with increasing Nmag and increased with increasing Bres. These trends can be explained by considering the nature of the multi-cusp field, where particles are mainly confined to the field-free region (FFR) near the center of the plasma column, and the loss of particles due to radial particle transport. The use of multiple filaments at intervals shorter than the plasma decay length dramatically improved axial uniformity. To further improve axial uniformity, the filament length and FFR must be properly set so that electrons are emitted inside the FFR

How Wild-Type TP53 Is Inactivated in Undifferentiated-Type Gastric Carcinomas: Analyses of Intratumoral Heterogeneity in Deletion and Mutation of TP53

Objective: In undifferentiated-type gastric carcinoma (UGC), inactivation of TP53 is infrequent at early stages and comparable to tubular adenocarcinomas (TUBs) at advanced stages. To clarify how TP53 inactivation relates to histogenesis of UGCs, we examined p53 alterations in multiple samples of individual UGCs. Methods: We used 27 UGCs including 12 mixed types with minor tubular component (TC) and 16 with a layered structure (LS), a histological remnant of incipient signet ring cell carcinoma (SIG). We examined p53 expression immunohistochemically and analyzed loss of heterozygosity (LOH) with four microsatellite markers within 17p13.1 in multiple microdissected samples. DNA sequence of mutation hot spots in TP53 was determined in representative samples of each tumor. Results: In the mixed-type UGCs, 5 and 1 of the 8 tumors without LS showed global and regional loss of wild-type TP53, respectively, through mutation and LOH, and one fourth of the tumors with LS showed the regional loss. In the tumors with the mutation, the mutation pattern was identical between TC and poorly differentiated major component. Conclusion: The inactivation of wild-type TP53 is an earlier event before dedifferentiation of TUB to mixed-type UGC, but is less frequent and a later event in a subset of mixed-type UGC deriving from SIG

Tensile Deformation of Ultrafine-Grained Fe-Mn-Al-Ni-C Alloy Studied by In Situ Synchrotron Radiation X-ray Diffraction

Intermetallic compounds are usually considered as deleterious phase in alloy designing and processing since their brittleness leads to poor ductility and premature failure during deformation of the alloys. However, several studies recently found that some alloys containing large amounts of NiAl-type intermetallic particles exhibited not only high strength but also good tensile ductility. To clarify the role of the intermetallic particles in the excellent tensile properties of such alloys, the tensile deformation behavior of an ultrafine-grained Fe-Mn-Al-Ni-C alloy containing austenite matrix and B2 intermetallic particles was investigated by using in situ synchrotron radiation X-ray diffraction in the present study. The elastic stress partitioning behavior of two constituent phases during tensile deformation were quantitively measured, and it was suggested that B2 particles played an important role in the high strength and large tensile ductility of the material