Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This important conference focused on the latest developments in therapeutic antibodies, particularly for their design, production and formulation for cancer therapy. Engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials, highlighted by the recent FDA approvals of Zevalin (ibritumomab tiuxetan, IDEC Pharmaceuticals) for cancer radioimmunotherapy and Humira (adalimumab, Abbott Laboratories) for rheumatoid arthritis [1,2]. An impressive array of international speakers was assembled in Banff by the organisers L Weiner (Fox Chase Cancer Center, USA) and P Carter (Amgen and Seattle Genetics). The meeting highlighted emerging new technologies, both for the discovery of novel cancer biomarkers and for innovative immunotherapeutic designs. The latest successes were also presented for antibodies directed to the conventional cancer targets, including CD20, carcinoembryonic antigen (CEA), erbB-family proteins and vascular endothelial growth factor (VEGF). Importantly, recent structural details emerged that will direct future designs of these cancer-targeting molecules, ranging from antibody-dependent cellular-cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) enhancement to improved cytotoxic payloads using radionuclides, toxins, enzymes, drugs and viral delivery. The conference also highlighted the latest in vitro antibody libraries for the selection of high-affinity reagents against refractory cancer targets, and included the design of small domain modules for highly-efficient in vivo targeting to large, high avidity complexes for enhanced cytotoxicity. The major challenges in this rapidly growing area include the need to initiate and sustain innate and adaptive immune responses for the generation of efficient, long-term tumour therapy. This conference was sponsored by Amgen and accredited by the Accreditation Council for Continuing Medical Education (ACCME).
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PMID:Keystone symposia: antibody-based therapeutics for cancer. 1266 51

Accumulating evidence suggests that in the vertebrate embryo, acquisition of arterial and venous identity is established early by genetic mechanisms, including those regulated by vascular endothelial growth factor (VEGF) and Notch signaling. However, although the COUP-TFII nuclear receptor has recently been shown to regulate vein identity, very little is known about the molecular mechanisms of transcriptional regulation in arterial specification. Here, we show that mouse embryos compound mutant for Foxc1 and Foxc2, two closely related Fox transcription factors, exhibit arteriovenous malformations and lack of induction of arterial markers whereas venous markers such as COUP-TFII are normally expressed, suggesting that mutant endothelial cells fail to acquire an arterial fate. Notably, consistent with this observation, overexpression of Foxc genes in vitro induces expression of arterial markers such as Notch1 and its ligand Delta-like 4 (Dll4), and Foxc1 and Foxc2 directly activate the Dll4 promoter via a Foxc-binding site. Moreover, compound Foxc mutants show a defect in sprouting of lymphatic endothelial cells from veins in early lymphatic development, due to reduced expression of VEGF-C. Taken together, our results demonstrate that Foxc transcription factors are novel regulators of arterial cell specification upstream of Notch signaling and lymphatic sprouting during embryonic development.
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PMID:The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. 1667 47

The Forkhead/Fox transcription factor Foxc2 is a critical regulator of vascular development. However, the role of Foxc2 in pathological angiogenesis in cancer remains unknown. Here we show that FoxC2 is highly expressed in human breast and colonic tumors and in the tumor endothelium in human and mouse melanomas. Using the B16 melanoma tumor model, we investigated the function of Foxc2 in tumor angiogenesis. After subcutaneous injection of B16 melanoma cells, primary tumor growth as well as neovascularization was markedly reduced in mice lacking one copy of the Foxc2 gene (Foxc2+/-). Consistently, expression levels of several angiogenic factors, including vascular endothelial growth factor (Vegf), matrix metallopeptidase 2 (Mmp2), and platelet-derived growth factor-B (Pdgfb), were significantly decreased in B16 tumors grown in Foxc2+/- mice, and tumor blood vessels formed in Foxc2+/- mice showed reduced coverage of mural cells and endothelial cell apoptosis. In addition, the tumor tissue in Foxc2+/- mice had an accumulation of necrotic cells. Taken together, these findings demonstrate that haplodeficiency of Foxc2 results in impaired formation of tumor blood vessels as well as reduced tumor growth and thereby provide evidence that Foxc2 is critical for tumor development and angiogenesis.
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PMID:The Foxc2 transcription factor regulates tumor angiogenesis. 2006 Aug 10