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MCL1 is essential for the survival of stem and progenitor cells of multiple lineages, and is unique among pro-survival BCL2 family members in that it is rapidly turned over through the action of ubiquitin ligases. B- and mantle-cell lymphomas, chronic myeloid leukaemia, and multiple myeloma, however, express abnormally high levels of MCL1, contributing to(More)
Microtubules have pivotal roles in fundamental cellular processes and are targets of antitubulin chemotherapeutics. Microtubule-targeted agents such as Taxol and vincristine are prescribed widely for various malignancies, including ovarian and breast adenocarcinomas, non-small-cell lung cancer, leukaemias and lymphomas. These agents arrest cells in mitosis(More)
Inhibitors against the p110δ isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumours. Here we report that p110δ inactivation in mice protects against a broad range of(More)
Innate immunity is the first line of defense against infection, protecting the host during the development of adaptive immunity and critically affecting the nature of the adaptive response. We show that, in contrast to tumor necrosis factor alpha (TNF-alpha), the related protein TWEAK attenuates the transition from innate to adaptive mechanisms. TWEAK-/-(More)
Inhibitors against the p110δ isoform of PI3K have shown remarkable therapeutic efficacy in some human leukaemias 1,2. Since p110δ is primarily expressed in leukocytes 3 , drugs against p110δ have not been considered for the treatment of solid tumours 4. We report here that p110δ inactivation in Users may view, print, copy, and download text and data-mine(More)
Pharmacological inhibition of the MAPK pathway with MEK or BRAF antagonists has proved successful in inducing regression of melanoma tumors bearing the targeted activating mutations. Moreover, antibodies targeting T-cell immune checkpoint inhibitors CTLA-4 or PD-L1/PD-1 have demonstrated the capacity to generate durable responses in patients with multiple(More)
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