Characterizing Exoplanets in the Visible and Infrared: A Spectrometer Concept for the EChO Space Mission

Transit-spectroscopy of exoplanets is one of the key observational techniques to characterize the extrasolar planet and its atmosphere. The observational challenges of these measurements require dedicated instrumentation and only the space environment allows an undisturbed access to earth-like atmospheric features such as water or carbon-dioxide. Therefore, several exoplanet-specific space missions are currently being studied. One of them is EChO, the Exoplanet Characterization Observatory, which is part of ESA's Cosmic Vision 2015-2025 program, and which is one of four candidates for the M3 launch slot in 2024. In this paper we present the results of our assessment study of the EChO spectrometer, the only science instrument onboard this spacecraft. The instrument is a multi-channel all-reflective dispersive spectrometer, covering the wavelength range from 400 nm to 16 microns simultaneously with a moderately low spectral resolution. We illustrate how the key technical challenge of the EChO mission - the high photometric stability - influences the choice of spectrometer concept and drives fundamentally the instrument design. First performance evaluations underline the fitness of the elaborated design solution for the needs of the EChO mission.Comment: 20 pages, 8 figures, accepted for publication in the Journal of Astronomical Instrumentatio

A phase II study of capecitabine plus 3-weekly oxaliplatin as first-line therapy for patients with advanced gastric cancer

Capecitabine plus oxaliplatin every 3 weeks (XELOX regimen) has proven efficacy in patients with colorectal carcinoma. We investigated this combination in patients with previously untreated advanced gastric carcinoma. The study population comprised patients with histologically confirmed nonresectable advanced gastric adenocarcinoma. Patients received intravenous oxaliplatin 130 mg m−2 over 2 h on day 1 plus oral capecitabine 1000 mg m−2 twice daily on days 1–14, every 3 weeks. Patients received a maximum of eight cycles. Twenty evaluable patients (17 men, 3 women) with a median age of 64 years (range 38–75) were enrolled. The overall response rate was 65% (95% confidence interval (CI), 44–86%), with complete responses in two patients and partial responses in 11 patients. Median progression-free survival was 7.5 months (95% CI, 3.2–11.7 months); median overall survival was not reached during the study period. There was no grade 4 and little grade 3 toxicity. The most common haematological adverse event was anaemia (65% of patients) and the most common nonhaematological toxicities were vomiting (65%), neuropathy (60%), diarrhoea (30%), and hand–foot syndrome (20%). In conclusion, XELOX is apparently as effective as triplet combinations and is well tolerated as first-line therapy for advanced gastric carcinoma. We are starting a large multi-institutional phase II study of XELOX in this setting

Effective combination chemotherapy with paclitaxel and cisplatin with or without human granulocyte colony-stimulating factor and/or erythropoietin in patients with advanced gastric cancer

A phase II trial was performed to determine the antitumour efficacy and tolerance of combined paclitaxel and cisplatin with or without hematopoetic growth factor support in patients with advanced gastric cancer. Forty-five patients with histologically confirmed metastatic gastric cancer were entered in this trial. Treatment consisted of 2-weekly courses of paclitaxel 160 mg per m2 and cisplatin 60 mg per m2 both given on day 1. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1000–2000 per μl), a 5-day course of human granulocyte colony-stimulating factor 5 μg kg−1 per day was given subcutaneously; in addition, if haemoglobin was <12.0 mg dl−1, erythropoietin 10 000 IU was administered subcutaneously three times per week. The confirmed overall response rate (intent-to-treat) was 44%, including five complete (11%) and 15 partial remissions (33%). Twelve patients had stable disease (27%), 11 (24%) progressed while on chemotherapy, and two patients were not evaluable. The median time to response was 3 months, the median time to progression 7.0 months, and the median survival time was 11.2 months with 12 patients currently alive. Haematologic toxicity was common, though WHO grade 4 neutropenia occurred in only five patients (11%). Apart from total alopecia in 16 patients (36%), severe non-haematologic adverse reactions included grade 3 peripheral neuropathy in six (13%) and anaphylaxis in two patients. In addition, there was one patient each who experienced grade 3 emesis, diarrhea, and infection, respectively. Our data suggest that the combination of paclitaxel and cisplatin with or without G-CSF and/or erythropoietin has promising therapeutic activity in patients with advanced gastric cancer

Deficient activation of CD95 (APO-1/ Fas)-mediated apoptosis: a potential factor of multidrug resistance in human renal cell carcinoma

The pronounced resistance of human renal cell carcinoma (RCC) to anticancer-induced apoptosis has primarily been related to the expression of P-glycoprotein and effective drug detoxification mechanisms. Because the CD95 system has recently been identified as a key mediator of anticancer drug-induced apoptosis, we analysed the contribution of the CD95 system to chemotherapy-induced apoptosis in four newly established RCC cell lines. Here, we demonstrate that all RCC cell lines expressed CD95-receptor and -ligand. Exposure to agonistic anti-CD95 antibodies resulted in induction of apoptosis and significant (P< 0.05) reduction of cell number in three out of four cell lines, indicating that the essential components for CD95-mediated apoptosis were present and functionally intact in the majority of these RCC cell lines. Moreover, treatment of cultures with bleomycin or topotecan, a novel topoisomerase I inhibitor with little substrate affinity for P-glycoprotein, led to induction of apoptosis and significant (P< 0.05) dose-dependent reduction of cell number in all RCC cell lines. Both anticancer drugs also induced upregulation of CD95 ligand expression in all cell lines. Additionally, augmentation of CD95 receptor expression was found in three RCC cell lines, including one p53-mutated cell line, whereas another p53-mutated cell line showed no or only a weak CD95 receptor upregulation after exposure to topotecan or bleomycin, respectively. Despite this upregulation of CD95 receptor and ligand, antagonistic antibodies directed against CD95 receptors or ligands could not inhibit induction of apoptosis by topotecan and bleomycin in any cell line. Thus, although a functionally intact CD95 signalling cascade is present in most RCC cell lines, the anticancer drugs topotecan and bleomycin that induce upregulation of CD95 receptor and ligand fail to effectively activate CD95-mediated apoptosis. This deficient activation of CD95-mediated apoptosis might be an important additional factor for the multidrug resistance phenotype of human RCCs. © 2000 Cancer Research Campaig