Predictive value of the MGMT promoter methylation status in metastatic melanoma patients receiving first-line temozolomide plus bevacizumab in the trial SAKK 50/07

The O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status is a predictive parameter for the response of malignant gliomas to alkylating agents such as temozolomide. First clinical trials with temozolomide plus bevacizumab therapy in metastatic melanoma patients are ongoing, although the predictive value of the MGMT promoter methylation status in this setting remains unclear. We assessed MGMT promoter methylation in formalin-fixed, primary tumor tissue of metastatic melanoma patients treated with first-line temozolomide and bevacizumab from the trial SAKK 50/07 by methylation-specific polymerase chain reaction. In addition, the MGMT expression levels were also analyzed by MGMT immunohistochemistry. Eleven of 42 primary melanomas (26%) revealed a methylated MGMT promoter. Promoter methylation was significantly associated with response rates CR + PR versus SD + PD according to RECIST (response evaluation criteria in solid tumors) (p<0.05) with a trend to prolonged median progression-free survival (8.1 versus 3.4 months, p>0.05). Immunohistochemically different protein expression patterns with heterogeneous and homogeneous nuclear MGMT expression were identified. Negative MGMT expression levels were associated with overall disease stabilization CR+PR+SD versus PD (p=0.05). There was only a poor correlation between MGMT methylation and lack of MGMT expression. A significant proportion of melanomas have a methylated MGMT promoter. The MGMT promoter methylation status may be a promising predictive marker for temozolomide therapy in metastatic melanoma patients. Larger sample sizes may help to validate significant differences in survival type endpoints.

Azacytidine for acute myeloid leukemia in elderly or frail patients: A phase II trial (SAKK 30/07)

Abstract This phase II trial treated elderly or frail AML patients with single agent subcutaneous azacytidine at 100 mg/m(2), on 5 of 28 days for up to 6 cycles. Treatment was stopped for lack of response, or continued to progression in responders. Primary endpoint was response within 6 months. A response rate >34% was considered a positive trial outcome. From 9/2008-4/2010, 45 patients from 10 centres (median age 74 (55-86) years) were accrued. Patients received 4 (1-21) cycles. Best response was CR/CRi in 8 (18%; 95% CI: 8%-32%.), 0 (0%) PR, 7 (16%) hematologic improvement, 17 (38%) stable disease. Three nonresponding patients stopped treatment after 6 cycles, 31 patients had stopped early and 11 patients continued treatment for 8-21 cycles. Adverse events (grade >III) were infections (13), febrile neutropenia (14), thrombocytopenia (7), dyspnea (6), bleeding (5) and anemia (4 patients). Median overall survival was 6 months. Peripheral blood blast counts, grouped at 30% had a borderline significant association with response (p = 0.07). This modified azacytidine schedule is feasible for elderly or frail AML patients in an outpatient setting with moderate, mainly hematologic, toxicity and response in a proportion of patients, although the primary objective was not reached.

Efficacy of cetuximab in metastatic castration-resistant prostate cancer might depend on EGFR and PTEN expression: results from a phase II trial (SAKK 08/07)

The EGF receptor (EGFR) is overexpressed in the majority of metastatic castration-resistant prostate cancers (mCRPC) and might represent a valid therapeutic target. The combination of docetaxel and cetuximab, the monoclonal antibody against EGFR, has not been tested in patients with prostate cancer.

Dynamic Languages and Applications. Report on the Workshop Dyla 07 at ECOOP 2007

Following last two years’ workshop on dynamic languages at the ECOOP conference, the Dyla 2007 workshop was a successful and popular event. As its name implies, the workshop’s focus was on dynamic languages and their applications. Topics and discussions at the workshop included macro expansion mechanisms, extension of the method lookup algorithm, language interpretation, reflexivity and languages for mobile ad hoc networks. The main goal of this workshop was to bring together different dynamic language communities and favouring cross communities interaction. Dyla 2007 was organised as a full day meeting, partly devoted to presentation of submitted position papers and partly devoted to tool demonstration. All accepted papers can be downloaded from the workshop’s web site. In this report, we provide an overview of the presentations and a summary of discussions.

Verbreitung der Direktsaat in der Schweiz

Direktsaat ist eine wirksame Erosionsschutzmassnahme, die diverse ökologische und ökonomische Vorteile aufweist. Sie gewann in der Schweiz in den letzten Jahren zunehmend an Bedeutung: Seit Mitte der 1980er hat die direkt gesäte Fläche von wenigen Hektaren auf rund 12'000 ha im Jahre 2006 zugenommen. Gemessen am gesamten Ackerland ist diese Fläche aber nach wie vor gering (3 %). Regional kann die Direktsaat jedoch beachtliche Anteile aufweisen. Die in diesem Artikel vorgestellten Karten geben einen nationalen Überblick über die räumliche Verbreitung der direkt gesäten Fläche im Jahr 2006. Als Datengrundlage diente eine im Winter 2006 / 07 durchgeführte Befragung von Landwirten und Lohnunternehmern. Die Karten zeigen sehr heterogene Muster, machen aber auch verschiedene Schwerpunktregionen sichtbar. Die Interpretation dieser Muster veranschaulicht, dass die Verbreitung der Direktsaat an eine Vielzahl von Faktoren gebunden ist und nicht nur anhand naturräumlicher Gegebenheiten erklärt werden kann. Kantonale Förderprogramme spielen dabei eine ebenso wichtige Rolle wie das persönliche Engagement der beteiligten Experten und Lohnunternehmer, bestehende landwirtschaftliche Netzwerke sowie die Lebenswelten der Landwirte.

Research Partnerships for Addressing Global Challenges: Opening Speech

Humankind today is challenged by numerous threats brought about by global change. Climate has been and is being modified by human activities, which calls for mitigation and adaptation measures at an unprecedented scale. Natural resources have been degraded by human development by means of land cover and land use changes, for which protective and restoration measures have to be taken by land users and governments in most countries of the North and South. Low levels of economic development and insufficient policies in most developing countries have led to widespread poverty, which affects nearly half of the world’s population and directly threatens almost one billion people. Finally, uncontrolled economic growth has increased disparities between and within populations and has led to widespread environmental problems in many nations. Generating and sharing knowledge is a key to addressing such global challenges. Knowledge can be used to develop the best solutions and to avoid or repair threats. Research partnerships have proven to be suitable means to bridge the divides and disparities between knowledge societies and developing countries, thereby reducing gaps. Research partnerships are tools for further capacity development and thereby lead to societal empowerment. Institutional settings allowing for research partnerships are needed both in the North and the South, so that the different networks can work together in a long-term enabling environment.