Neuropilin-2/PlexinA3 Receptors Associate with GluA1 and Mediate Sema3F-Dependent Homeostatic Scaling in Cortical Neurons.

Regulation of AMPA-type glutamate receptor (AMPAR) number at synapses is a major mechanism for controlling synaptic strength during homeostatic scaling in response to global changes in neural activity. We show that the secreted guidance cue semaphorin 3F (Sema3F) and its neuropilin-2 (Npn-2)/plexinA3 (PlexA3) holoreceptor mediate homeostatic plasticity in cortical neurons. Sema3F-Npn-2/PlexA3 signaling is essential for cell surface AMPAR homeostatic downscaling in response to an increase in neuronal activity, Npn-2 associates with AMPARs, and Sema3F regulates this interaction. Therefore, Sema3F-Npn-2/PlexA3 signaling controls both synapse development and synaptic plasticity.

Targeting angiogenesis driven by vascular endothelial growth factors using antibody-based therapies.

PURPOSE: Angiogenesis, one of the hallmarks of cancer, has recently become the target of therapeutic approaches in oncology. Among the complex system of pro- and antiangiogenic factors, the vascular endothelial growth factor system stands out as key mediator of tumor-initiated angiogenesis and as target of antiangiogenesis agents introduced in clinical practice. Although antivascular endothelial growth factor therapies, and in particular, bevacizumab as monoclonal antibody against vascular endothelial growth factor has clearly demonstrated antitumor efficacy, its mechanism of action is not fully understood. DESIGN: This review will discuss the rationale for using antiangiogenesis as anticancer therapy with focus on antibody-based approaches toward the vascular endothelial growth factor-system. Results of clinical trials using bevacizumab will be discussed in detail. RESULTS: Bevacizumab has well-documented efficacy as part of first-line therapy in various malignancies ranging from colorectal to breast and lung cancer. Although it mainly exerts its efficacy in conjunction with conventional cytotoxic chemotherapy, several, apparently vascular endothelial growth factor-dependent malignancies such as renal cell cancer, ovarian cancer, and glioblastoma have shown to be susceptible to single-agent bevacizumab. DISCUSSION: Antiangiogenesis therapy with antibodies, namely bevacizumab as antivascular endothelial growth factor agent, has demonstrated efficacy in various human malignancies. The mechanism of action of antivascular endothelial growth factor therapy in general and bevacizumab in particular, however, is not fully understood. Predictive markers have not yet been identified and questions regarding bevacizumab's usefulness in the adjuvant setting as well as its value as continued therapy beyond progression are still unanswered. It is indisputable, though, that antiangiogenesis has greatly enhanced the therapeutic arsenal of anticancer therapies and has changed oncology forever.