Citations

AbstractBackgroundRadiation exposure to the surgeon is a concern in spinal surgery, especially with the increasing popularity of minimally invasive spinal surgery techniques. Three‐dimensional (3D) image guidance used in conjunction with cone beam computed tomography (cbCT) has a theoretical advantage of decreased radiation exposure to the surgeon and operating room (OR) staff. Radiation scatter to the environment immediately surrounding a CT scanner during acquisition of a CT scan is a known entity. This in vivo study measures the radiation exposure to the surgeon when using cbCT registration in 3D image‐guided spinal surgery.MethodsTwo badge dosimeters were worn by the surgeon (EWN), one on the right waistband of the surgeon's scrubs and the other located over the thyroid area during 25 consecutive spinal surgery cases in which cbCT was used in conjunction with 3D image guidance. No lead protection was worn by the surgeon. The cbCT device was used for registration of the anatomy and to confirm adequate instrumentation placement. The surgeon stood behind a clear lead shield in the same location during every spin of the cbCT device. After the 25th case, the badge dosimeters were sent to the radiology department for analysis.ResultsOverall, 63 cbCT spins were accomplished in 25 patients. A total of 228 screws were placed into spinal levels spanning from C2 to the ileum. No complications resulted from instrumentation placement or the use of image guidance.Analysis of both badge dosimeters revealed 0 millirem (mRem) exposure.ConclusionsOur study demonstrates that no radiation exposure to the surgeon occurs in cbCT‐based, 3D image‐guided spinal surgery procedures. Additionally, radiation scatter does not result in surgeon radiation exposure during patient registration if the surgeon stands behind a lead shield 10 feet from the cbCT device and not in direct line with the opening of the cbCT tube. Copyright © 2011 John Wiley & Sons, Ltd.

Abstract The mammalian target of rapamycin (mTOR) plays crucial roles in proliferative and antiapoptotic signaling in lymphoid malignancies. Rapamycin analogs, which are allosteric mTOR complex 1 (mTORC1) inhibitors, are active in mantle cell lymphoma and other lymphoid neoplasms, but responses are usually partial and short-lived. In the present study we compared the effects of rapamycin with the dual mTORC1/mTORC2 inhibitor OSI-027 in cell lines and clinical samples representing divers lymphoid malignancies. In contrast to rapamycin, OSI-027 markedly diminished proliferation and induced apoptosis in a variety of lymphoid cell lines and clinical samples, including specimens of B-cell acute lymphocytic leukemia (ALL), mantle cell lymphoma, marginal zone lymphoma and Sezary syndrome. Additional analysis demonstrated that OSI-027–induced apoptosis depended on transcriptional activation of the PUMA and BIM genes. Overexpression of Bcl-2, which neutralizes Puma and Bim, or loss of procaspase 9 diminished OSI-027–induced apoptosis in vitro. Moreover, OSI-027 inhibited phosphorylation of mTORC1 and mTORC2 substrates, up-regulated Puma, and induced regressions in Jeko xenografts. Collectively, these results not only identify a pathway that is critical for the cytotoxicity of dual mTORC1/mTORC2 inhibitors, but also suggest that simultaneously targeting mTORC1 and mTORC2 might be an effective anti-lymphoma strategy in vivo.

Abstract Emerging evidence demonstrates that proangiogenic cells (PACs) originate from the BM and are capable of being recruited to sites of ischemic injury where they contribute to neovascularization. We previously determined that among hematopoietic progenitor stem cells, common myeloid progenitors (CMPs) and granulocyte-macrophage progenitor cells (GMPs) differentiate into PACs and possess robust angiogenic activity under ischemic conditions. Herein, we report that a TGF-β1–responsive Krüppel- like factor, KLF10, is strongly expressed in PACs derived from CMPs and GMPs, ∼ 60-fold higher than in progenitors lacking PAC markers. KLF10−/− mice present with marked defects in PAC differentiation, function, TGF-β responsiveness, and impaired blood flow recovery after hindlimb ischemia, an effect rescued by wild-type PACs, but not KLF10−/− PACs. Overexpression studies revealed that KLF10 could rescue PAC formation from TGF-β1+/− CMPs and GMPs. Mechanistically, KLF10 targets the VEGFR2 promoter in PACs which may underlie the observed effects. These findings may be clinically relevant because KLF10 expression was also found to be significantly reduced in PACs from patients with peripheral artery disease. Collectively, these observations identify TGF-β1 signaling and KLF10 as key regulators of functional PACs derived from CMPs and GMPs and may provide a therapeutic target during cardiovascular ischemic states.