Elevated focal adhesion kinase (FAK) expression occurs in advanced cancers, yet a signaling role for FAK in tumor progression remains undefined. Here, we suppressed FAK activity in 4T1 breast carcinoma cells resulting in reduced FAK Y925 phosphorylation, Grb2 adaptor protein binding to FAK, and signaling to mitogen-activated protein (MAP) kinase (MAPK). Loss of a FAK-Grb2-MAPK linkage did not affect 4T1 cell proliferation or survival in culture, yet FAK inhibition reduced vascular endothelial growth factor (VEGF) expression and resulted in small avascular tumors in mice. This FAK-Grb2-MAPK linkage was essential in promoting angiogenesis as reconstitution experiments using Src-transformed FAK-null fibroblasts revealed that point mutations affecting FAK catalytic activity (R454) or Y925 phosphorylation (F925) disrupted the ability of FAK to promote MAPK- and VEGF-associated tumor growth. Notably, in both FAK-inhibited 4T1 and Src-transformed FAK-null cells, constitutively activated (CA) mitogen-activated protein kinase kinase 1 (MEK1) restored VEGF production and CA-MEK1 or added VEGF rescued tumor growth and angiogenesis. These studies provide the first biological support for Y925 FAK phosphorylation and define a novel role for FAK activity in promoting a MAPK-associated angiogenic switch during tumor progression.

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A new technique extending the incision used for thoracic outlet decompression with a subclavicular approach to the first rib is presented. After the first rib and scalenotomy are removed, the subclavicular incision is continued into the sternum medially and superiorly to the sternal notch. This gives easy access to the innominate-subclavian-axillary vein segment. Eight patients with extensive chronic fibrotic obstruction of the subclavian-innominate vein segment underwent operation with this technique. It allows placement of either long patches of saphenous vein to reestablish normal caliber or replacement, as is our choice, with a small-sized cryopreserved descending thoracic aortic homograft. The operation is carried out in an extrapleural plane preserving the sternoclavicular joint, avoiding the deformity caused by transclavicular techniques. Repair of the sternotomy creates a stable incision. Follow-up to 14 months shows patency of the venous channel with no complications. This surgical approach is recommended to solve the problem of satisfactory exposure of the subclavian-innominate venous channel after decompression of the thoracic outlet.

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A case is presented in which an intraluminal aortic graft prosthesis (ILAP) was implanted in the ascending position for acute dissection. Although the patient had a perfectly competent aortic valve at the time of the implant, he developed severe aortic insufficiency, angina, and arrhythmia within 7 months. The symptoms disappeared after the prosthetic device was removed and replaced by a composite graft. The use of ILAP in the ascending aortic position in cases with dilated aortic root is not recommended since it seems to cause further dilatation and weakening, leading to aortic valve insufficiency.

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