40 research outputs found

    First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07)

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    Background: Oral temozolomide has shown similar efficacy to dacarbazine in phase III trials with median progression-free survival (PFS) of 2.1 months. Bevacizumab has an inhibitory effect on the proliferation of melanoma and sprouting endothelial cells. We evaluated the addition of bevacizumab to temozolomide to improve efficacy in stage IV melanoma. Patients and methods: Previously untreated metastatic melanoma patients with Eastern Cooperative Oncology Group performance status of two or more were treated with temozolomide 150 mg/m2 days 1-7 orally and bevacizumab 10 mg/kg body weight i.v. day 1 every 2 weeks until disease progression or unacceptable toxicity. The primary end point was disease stabilisation rate [complete response (CR), partial response (PR) or stable disease (SD)] at week 12 (DSR12); secondary end points were best overall response, PFS, overall survival (OS) and adverse events. Results: Sixty-two patients (median age 59 years) enrolled at nine Swiss centres. DSR12 was 52% (PR: 10 patients and SD: 22 patients). Confirmed overall response rate was 16.1% (CR: 1 patient and PR: 9 patients). Median PFS and OS were 4.2 and 9.6 months. OS (12.0 versus 9.2 months; P = 0.014) was higher in BRAF V600E wild-type patients. Conclusions: The primary end point was surpassed showing promising activity of this bevacizumab/temozolomide combination with a favourable toxicity profile. Response and OS were significantly higher in BRAF wild-type patient

    Entwicklungsszenarien einer alpinen Aue bei einem natürlichen Geschiebedefizit : die Triftaue im Oberhasli

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    In der zweiten Hälfte des 20. Jahrhunderts hat sich im Zuge des Gletscherrückzugs eine alpine Aue im Triftgebiet gebildet. Zu Beginn prägten dynamische Geschiebeumlagerungsprozesse die Flusslandschaft am Triftwasser und führten zu einer typischen Sukzession einer alpinen Aue. Mit dem weiteren Rückzug des Triftgletschers hat sich Anfang dieses Jahrhunderts der natürliche Triftsee gebildet, der einen Geschiebeeintrag in die darunterliegende Triftaue praktisch vollständig unterbindet. Damit wird die Geschiebedynamik im Triftwasser auf ein absolutes Minimum reduziert. Daher ist es dem Gewässer so gut wie nicht mehr möglich, seinen Verlauf im Zuge von Hochwasserereignissen zu verändern und neue morphologische Strukturen zu bilden. Aufgrund der topografischen Verhältnisse (breiter Kessel) können die natürlicherweise auftretenden Hochwasserereignisse nicht mehr genug Kraft entwickeln, um grossflächige Vegetationsbestände zu entwurzeln. Damit verbunden ist eine rasche Ausbreitung an Grünerlenbeständen, die mittelfristig die heutige Triftaue fast vollständig besiedeln werden. Im Rahmen des Triftprojekts (Vergrösserung des Triftsees mit neuem Kraftwerk auf Höhe der bestehenden Triftfassung) wurden u.a. detaillierte Studien zum Ist-Zustand sowie zur Entwicklung der Triftaue mit und ohne Projekt durchgeführt. Basierend auf diesen Untersuchungen wurden für die Realisierung des Projekts neben dem Restwasserregime zusätzlich auch Hochwasserdotierungen festgelegt

    First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07).

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    BACKGROUND: Oral temozolomide has shown similar efficacy to dacarbazine in phase III trials with median progression-free survival (PFS) of 2.1 months. Bevacizumab has an inhibitory effect on the proliferation of melanoma and sprouting endothelial cells. We evaluated the addition of bevacizumab to temozolomide to improve efficacy in stage IV melanoma. PATIENTS AND METHODS: Previously untreated metastatic melanoma patients with Eastern Cooperative Oncology Group performance status of two or more were treated with temozolomide 150 mg/m(2) days 1-7 orally and bevacizumab 10 mg/kg body weight i.v. day 1 every 2 weeks until disease progression or unacceptable toxicity. The primary end point was disease stabilisation rate [complete response (CR), partial response (PR) or stable disease (SD)] at week 12 (DSR12); secondary end points were best overall response, PFS, overall survival (OS) and adverse events. RESULTS: Sixty-two patients (median age 59 years) enrolled at nine Swiss centres. DSR12 was 52% (PR: 10 patients and SD: 22 patients). Confirmed overall response rate was 16.1% (CR: 1 patient and PR: 9 patients). Median PFS and OS were 4.2 and 9.6 months. OS (12.0 versus 9.2 months; P = 0.014) was higher in BRAF V600E wild-type patients. CONCLUSIONS: The primary end point was surpassed showing promising activity of this bevacizumab/temozolomide combination with a favourable toxicity profile. Response and OS were significantly higher in BRAF wild-type patients

    A Rice Plastidial Nucleotide Sugar Epimerase Is Involved in Galactolipid Biosynthesis and Improves Photosynthetic Efficiency

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    Photosynthesis is the final determinator for crop yield. To gain insight into genes controlling photosynthetic capacity, we selected from our large T-DNA mutant population a rice stunted growth mutant with decreased carbon assimilate and yield production named photoassimilate defective1 (phd1). Molecular and biochemical analyses revealed that PHD1 encodes a novel chloroplast-localized UDP-glucose epimerase (UGE), which is conserved in the plant kingdom. The chloroplast localization of PHD1 was confirmed by immunoblots, immunocytochemistry, and UGE activity in isolated chloroplasts, which was approximately 50% lower in the phd1-1 mutant than in the wild type. In addition, the amounts of UDP-glucose and UDP-galactose substrates in chloroplasts were significantly higher and lower, respectively, indicating that PHD1 was responsible for a major part of UGE activity in plastids. The relative amount of monogalactosyldiacylglycerol (MGDG), a major chloroplast membrane galactolipid, was decreased in the mutant, while the digalactosyldiacylglycerol (DGDG) amount was not significantly altered, suggesting that PHD1 participates mainly in UDP-galactose supply for MGDG biosynthesis in chloroplasts. The phd1 mutant showed decreased chlorophyll content, photosynthetic activity, and altered chloroplast ultrastructure, suggesting that a correct amount of galactoglycerolipids and the ratio of glycolipids versus phospholipids are necessary for proper chloroplast function. Downregulated expression of starch biosynthesis genes and upregulated expression of sucrose cleavage genes might be a result of reduced photosynthetic activity and account for the decreased starch and sucrose levels seen in phd1 leaves. PHD1 overexpression increased photosynthetic efficiency, biomass, and grain production, suggesting that PHD1 plays an important role in supplying sufficient galactolipids to thylakoid membranes for proper chloroplast biogenesis and photosynthetic activity. These findings will be useful for improving crop yields and for bioenergy crop engineering

    World Congress Integrative Medicine & Health 2017: Part one

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    Contamination of ROSETTA measured by ROSINA-DFMS

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