INSPIRE: A phase III study of the BLP25 liposome vaccine (L-BLP25) in Asian patients with unresectable stage III non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Previous research suggests the therapeutic cancer vaccine L-BLP25 potentially provides a survival benefit in patients with locally advanced unresectable stage III non-small cell lung carcinoma (NSCLC). These promising findings prompted the phase III study, INSPIRE, in patients of East-Asian ethnicity. East-Asian ethnicity is an independent favourable prognostic factor for survival in NSCLC. The favourable prognosis is most likely due to a higher incidence of EGFR mutations among this patient population.</p> <p>Methods/design</p> <p>The primary objective of the INSPIRE study is to assess the treatment effect of L-BLP25 plus best supportive care (BSC), as compared to placebo plus BSC, on overall survival time in East-Asian patients with unresectable stage III NSCLC and either documented stable disease or an objective response according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria following primary chemoradiotherapy. Those in the L-BLP25 arm will receive a single intravenous infusion of cyclophosphamide (300 mg/m²) 3 days before the first L-BLP25 vaccination, with a corresponding intravenous infusion of saline to be given in the control arm. A primary treatment phase of 8 subcutaneous vaccinations of L-BLP25 930 μg or placebo at weekly intervals will be followed by a maintenance treatment phase of 6-weekly vaccinations continued until disease progression or discontinuation from the study.</p> <p>Discussion</p> <p>The ongoing INSPIRE study is the first large study of a therapeutic cancer vaccine specifically in an East-Asian population. It evaluates the potential of maintenance therapy with L-BLP25 to prolong survival in East-Asian patients with stage III NSCLC where there are limited treatment options currently available.</p> <p>Study number</p> <p>EMR 63325-012</p> <p>Trial Registration</p> <p>Clinicaltrials.gov reference: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01015443">NCT01015443</a></p

Conquering the Outdoors with On-site Mass Spectrometry

In recent years, mass spectrometers with a membrane inlet separating gases from water for final analysis have been used successfully for the on-site quantification of dissolved gases in surface waters. In 'classical' membrane inlet mass spectrometers (MIMS), the membrane directly separates the water from the high-vacuum environment of the mass spectrometer. The gas equilibrium MIMS (GE-MIMS) that is described in this review, however, makes use of an intermediate pressure reduction stage after the membrane inlet. Hence, the gas concentrations after the membrane are at steady state, near solubility equilibrium with the water to be analyzed. This setup has several advantages over classical MIMS, which enable autonomous and continuous in-field operation. The GE-MIMS can be used to acquire noble gas concentration time series (NGTS). Noble gases are useful tracers for physical gas exchange and transport in groundwater and other aqueous systems. Hence NGTS enable the temporal dynamics of physical gas exchange and transport in groundwater and other aqueous systems to be investigated. To determine the O2 turnover that has occurred in groundwater since recharge, both the O2 concentration in situ and the total input of O2 to the groundwater since recharge is needed. Determination of the latter is only possible if the relevant physical exchange and transport mechanisms can be quantified. In particular, gas exchange between soil air and groundwater often significantly affects groundwater O2 concentrations. Determination of O2 turnover in groundwater therefore requires a combined analysis of O2 and noble gas concentrations

Djelovanje miozmina na antioksidativne sustave u jetri štakora

Myosmine [3-(1-pyrrolin-2-yl) pyridine] is an alkaloid structurally similar to nicotine, which is known to induce oxidative stress. In this study we investigated the effects of myosmine on enzymatic and nonenzymatic antioxidative defence in rat liver. Wistar rats received a single i.p. injection of 19 mg kg-1 of myosmine and an oral dose of 190 mg kg-1 by gavage. Nicotine was used as a positive control. Through either route of administration, myosmine altered the hepatic function by decreasing the levels of reduced glutathione, superoxide dismutase, and glutathione peroxidase activities on one hand and by increasing malondialdehyde, catalase, and glutathione reductase activity on the other. Compared to control, both routes caused significant lipid peroxidation in the liver and altered hepatic enzymatic and non-enzymatic antioxidative defences. The pro-oxidant effects of myosmine were comparable with those of nicotine.Miozmin (3-(1-pirolin-2-il)piridin) alkaloid je strukturno sličan nikotinu, za koji se zna da potiče oksidativni stres. Istražili smo djelovanje miozmina na enzimske i neenzimske antioksidativne sustave u jetri štakora. Wistar štakori primili su jednokratno pokusni spoj intraperitonealno u dozi od 19 mg kg-1, odnosno na usta u dozi od 190 mg kg-1. Za pozitivnu kontrolu rabili smo nikotin. Nakon primjene, bez obzira na put, zamijećena je promjena u jetrenoj funkciji u obliku pada razina glutationa, aktivnosti superoksid dismutaze i glutation peroksidaze te rasta razina malondialdehida, aktivnosti katalaze i glutation reduktaze. Ovi nalazi upućuju na to da intraperitonealna i oralna primjena miozmina dovode do značajne lipidne peroksidacije u jetrenome tkivu te promjena u enzimskoj i neenzimskoj zaštiti jetre. Prooksidativno djelovanje miozmina pokazalo se sličnim onomu nikotina