A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer

The aim of this study was to evaluate the efficacy and tolerability of gefitinib (‘IRESSA') in Japanese patients with previously untreated stage IV non-small-cell lung cancer (NSCLC). This was a multi-institutional phase II study. Thirty-four patients with previously untreated stage IV NSCLC were enrolled between May 2003 and September 2004. Gefitinib was administered orally 250 mg once a day and was continued until there was either disease progression or severe toxicity. Objective tumour response rate was 26.5% (95% confidence interval, 11.7–41.3%). Adverse events were generally mild (National Cancer Institute-Common Toxicity Criteria grade 1 or 2) and consisted mainly of skin rash, fatigue and liver dysfunction. No pulmonary toxicity was observed. The global health status revealed that there was no change in quality of life during the study. This study found that single-agent gefitinib is active and well tolerated in chemonaive Japanese patients with advanced NSCLC

The Escherichia coli SOS Gene dinF Protects against Oxidative Stress and Bile Salts

DNA is constantly damaged by physical and chemical factors, including reactive oxygen species (ROS), such as superoxide radical (O2−), hydrogen peroxide (H2O2) and hydroxyl radical (•OH). Specific mechanisms to protect and repair DNA lesions produced by ROS have been developed in living beings. In Escherichia coli the SOS system, an inducible response activated to rescue cells from severe DNA damage, is a network that regulates the expression of more than 40 genes in response to this damage, many of them playing important roles in DNA damage tolerance mechanisms. Although the function of most of these genes has been elucidated, the activity of some others, such as dinF, remains unknown. The DinF deduced polypeptide sequence shows a high homology with membrane proteins of the multidrug and toxic compound extrusion (MATE) family. We describe here that expression of dinF protects against bile salts, probably by decreasing the effects of ROS, which is consistent with the observed decrease in H2O2-killing and protein carbonylation. These results, together with its ability to decrease the level of intracellular ROS, suggests that DinF can detoxify, either direct or indirectly, oxidizing molecules that can damage DNA and proteins from both the bacterial metabolism and the environment. Although the exact mechanism of DinF activity remains to be identified, we describe for the first time a role for dinF

Proposed High Speed Pellet Injection System "HIPEL" for Large Helical Device

From the results of the simulation study including pellet ablation and 1-D transport code, it is found that a high speed pellet injector with pellet velocity of more than 3 km/s is necessary for the penetration of the pellet with diameter of 3 mm into the core region under the expected plasma condition of Large Helical Device (LHD) of heliotron/stellarator type with superconducting coils at NIFS in Japan. Therefore, a two stage pellet injector was constructed and tested successfully in order to obtain the pellet velocity range of 3 km/s. Based upon the above results, a high speed flexible multiple-pellet injection system "HIPEL" for LHD is proposed. HIPEL consists of independent (1) 10 two-stage gun barrels and (2) 10 single-stage gun barrels. It has multi purposes such as refueling and flexible density profile control, diagnostics and the other functions

Serological and Virological Evidence of Crimean-Congo Haemorrhagic Fever Virus Circulation in the Human Population of Borno State, Northeastern Nigeria

BACKGROUND:Despite several studies on the seroprevalence of antibodies against Crimean-Congo Haemorrhagic Fever virus (CCHFV) from humans and cattle in Nigeria, detailed investigation looking at IgG and IgM have not been reported. Additionally, there have been no confirmed cases of human CCHFV infection reported from Nigeria. PRINCIPAL FINDINGS:Samples from sera (n = 1189) collected from four Local Government Areas in Borno State (Askira/Uba, Damboa, Jere and Maiduguri) were assessed for the presence of IgG and IgM antibodies. The positivity rates for IgG and IgM were 10.6% and 3.5%, respectively. Additionally, sera from undiagnosed febrile patients (n = 380) were assessed by RT-PCR assay for the presence of CCHFV RNA. One positive sample was characterised by further by next generation sequencing (NGS) resulting in complete S, M and L segment sequences. CONCLUSIONS:This article provides evidence for the continued exposure of the human population of Nigeria to CCHFV. The genomic analysis provides the first published evidence of a human case of CCHFV in Nigeria and its phylogenetic context