We performed a phase I trial of FANG vaccine, an autologous tumor-based product incorporating a plasmid encoding granulocyte-macrophage colony-stimulating factor (GMCSF) and a novel bifunctional short hairpin RNAi (bi-shRNAi) targeting furin convertase, thereby downregulating endogenous immunosuppressive transforming growth factors (TGF) β1 and β2. Patients with advanced cancer received up to 12 monthly intradermal injections of FANG vaccine (1 × 10(7) or 2.5 × 10(7) cells/ml injection). GMCSF, TGFβ1, TGFβ2, and furin proteins were quantified by enzyme-linked immunosorbent assay (ELISA). Safety and response were monitored. Vaccine manufacturing was successful in 42 of 46 patients of whom 27 received ≥1 vaccine. There were no treatment-related serious adverse events. Most common grade 1, 2 adverse events included local induration (n = 14) and local erythema (n = 11) at injection site. Post-transfection mean product expression GMCSF increased from 7.3 to 1,108 pg/10(6) cells/ml. Mean TGFβ1 and β2 effective target knockdown was 93.5 and 92.5% from baseline, respectively. Positive enzyme-linked immunospot (ELISPOT) response at month 4 was demonstrated in 9 of 18 patients serially assessed and correlated with survival duration from time of treatment (P = 0.025). Neither dose-adverse event nor dose-response relationship was noted. In conclusion, FANG vaccine was safe and elicited an immune response correlating with prolonged survival. Phase II assessment is justified.

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Fenestration of the middle cerebral artery (MCA) is an unusual anomaly. We recognized and photographed MCA fenestration during an operation performed to clip an internal carotid artery aneurysm. The incidence of angiographic demonstration of this anomaly has been reported to be 0.26%. The clinical significance of fenestration of the vertebral and basilar arteries has primarily been the relationship of fenestration with other intracranial vascular anomalies. This is the first report of MCA fenestration associated with an aneurysm.

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✓ Angiography during the operative procedure is desirable, but is often difficult because of the problem of maintaining a needle or cannula in an artery for long periods of time. Cannulation of the superficial temporal artery avoids this technical problem. The artery is easily found, cannulation is simple, and obliteration of the artery is of no consequence. Cerebral angiography then provides a means for prompt evaluation of the surgical procedure at any time during the actual operation.