Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

Primary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities

Siglecg Limits the Size of B1a B Cell Lineage by Down-Regulating NFκB Activation

BACKGROUND: B1 B cells are believed to be a unique lineage with a distinct developmental pathway, function and activation requirement. How this lineage is genetically determined remained largely obscure. METHODS AND PRINCIPAL FINDINGS: Using the Siglecg-deficient mice with a knockin of green-fluorescent protein encoding sequence, we show here that, although the Siglecg gene is broadly expressed at high levels in all stages and/or lineages of B cells tested and at lower levels in other lineages, its deletion selectively expanded the B1a B cell lineages, including the frequency of the B1 cell progenitor in the bone marrow and the number of B1a cells in the peritoneal cavity, by postnatal expansion. The expansion of B1a B cells in the peritoneal correlated with enhanced activation of NFkappaB and was ablated by an IKK inhibitor. CONCLUSION AND SIGNIFICANCE: Our data revealed a critical role for Siglec G-NFkappaB pathway in regulating B1a B cell lineage. These data lead to a novel model of B1a lineage development that explains a large array of genetic data in this field

Knetex – Development of a textile-integrated sensor system for feedback-supported rehabilitation after surgery of the anterior cruciate ligament

Patients often report an effect after surgery of the anterior cruciate ligament which is called "giving way". This manifest itself by a drop of the knee or a felt instability. This phenomenon is difficult to measure and validate because it usually does not occur regularly and is not reproducible under laboratory conditions. The Knetex project takes up this point by trying to actively support the rehabilitation process with a bandage that can be worn in everyday life and is constructed as a smart textile using sensors and actuators. For this purpose, on the one hand it is attempted to actively record the phenomenon of the "giving way" by measuring knee angles etc. and by active user feedback. At the same time, the patient is specifically advised by means of actuators to correct incorrect posture or movement in order to make the rehabilitation process more effective and prevent further damage. Two 9-axis IMUs (inertial measurement units) form the basis of the system. These are used together with a textile strain sensor to calculate the knee angles. This paper gives an overview of the planned system, the initial experiments to measure the knee angles and the first results of the actuator study