Final safety and efficacy analysis of a phase I/II trial with imatinib and vinorelbine for patients with metastatic breast cancer.

Background: Imatinib is a tyrosine kinase inhibitor of BCR-ABL, ABL, PDGFR-α and -β, KIT, and DDR. In solid tumors, it inhibits proliferation and invasiveness and facilitates higher intratumoral cytotoxic drug concentrations. Vinorelbine has good tolerability and efficacy in metastatic breast cancer (MBC).

Activation of Six1 target genes is required for sensory placode formation.

In vertebrates, cranial placodes form crucial parts of the sensory nervous system in the head. All cranial placodes arise from a common territory, the preplacodal region, and are identified by the expression of Six1/4 and Eya1/2 genes, which control different aspects of sensory development in invertebrates as well as vertebrates. While So and Eya can induce ectopic eyes in Drosophila, the ability of their vertebrate homologues to induce placodes in non-placodal ectoderm has not been explored.

A balance of FGF, BMP and WNT signalling positions the future placode territory in the head.

The sensory nervous system in the vertebrate head arises from two different cell populations: neural crest and placodal cells. By contrast, in the trunk it originates from neural crest only. How do placode precursors become restricted exclusively to the head and how do multipotent ectodermal cells make the decision to become placodes or neural crest? At neural plate stages, future placode cells are confined to a narrow band in the head ectoderm, the pre-placodal region (PPR).

Redox factor 1 (Ref-1) enhances specific DNA binding of p53 by promoting p53 tetramerization.

Sequence-specific DNA binding is a major activity of the tumor suppressor p53 and a prerequisite for the transactivating potential of the protein. p53 interaction with target DNA is tightly regulated by various mechanisms, including binding of different components of the transcription machinery, post-translational modifications, and interactions with other factors that modulate p53 transactivation in a cell context- and promoter-specific manner. The bi-functional redox factor 1 (Ref-1/APE1) has been identified as one of the factors, which can stimulate p53 DNA binding by redox-dependent as well as redox-independent mechanisms.