Non-traumatic thoracic aortic emergencies: imaging diagnosis and management.

The major component of non-traumatic thoracic aortic emergencies is the acute aortic syndromes. These include acute aortic dissection, intramural haematoma and penetrating atherosclerotic ulcer, grouped together because they are indistinguishable clinically and highly fatal. All three entities involve disruption to the tunica intima and media and may be complicated by rupture, end-organ ischaemia or aneurysmal transformation. Early diagnosis is vital to allow timely and appropriate management. Paired unenhanced and electrocardiogram-gated computed tomography angiography of the chest, extending more distally if required, is recommended for diagnosis. Specific computed tomography features of all three entities are reviewed, with a focus on morphological features associated with complications. Those with type A pathology are usually managed with open surgery because this has a high risk of complication. Patients with uncomplicated type B pathology are usually managed with best medical therapy whereas those with complicated type B pathology are usually offered either surgery or thoracic endovascular aortic repair. The limited evidence regarding the use of thoracic endovascular aortic repair in patients with subacute uncomplicated type B pathology is briefly discussed.

Antitumor efficacy of a monoclonal antibody that inhibits the activity of cancer-associated carbonic anhydrase XII.

Carbonic anhydrase XII (CA XII) is a membrane-tethered cell surface enzyme that is highly expressed on many human tumor cells. Carbonic anhydrase members in this class of exofacial molecules facilitate tumor metabolism by facilitating CO2 venting and intracellular pH regulation. Accordingly, inhibition of exofacial CAs has been proposed as a general therapeutic strategy to target cancer. The recent characterization of 6A10, the first CA XII-specific inhibitory monoclonal antibody, offered an opportunity to evaluate this strategy with regard to CA XII-mediated catalysis. Using functional assays, we showed that 6A10 inhibited exofacial CA activity in CA XII-expressing cancer cells. 6A10 reduced spheroid growth in vitro under culture conditions where CA XII was active (i.e., alkaline pH) and where its catalytic activity was likely rate-limiting (i.e., restricted extracellular HCO3-supply). These in vitro results argued that the antibody exerted its growth-retarding effect by acting on the catalytic process, rather than on antigen binding per se. Notably, when administered in a mouse xenograft model of human cancer, 6A10 exerted a significant delay on tumor outgrowth. These results corroborate the notion that exofacial CA is critical for cancer cell physiology and they establish the immunotherapeutic efficacy of targeting CA XII using an inhibitory antibody.