A review of the development and implementation of a 4-year medical student integrated ultrasound curriculum is presented. Multiple teaching and assessment modalities are discussed as well as results from testing and student surveys. Lessons learned while establishing the curriculum are summarized. It is concluded that ultrasound is a well received, valuable teaching tool across all 4 years of medical school, and students learn ultrasound well, and they feel their ultrasound experience enhances their medical education.

Objective microRNA-155 (miR155) plays a critical role in immunity and macrophage inflammation. We aim to investigate the role of miR155 in atherogenesis. Approach and Results Quantitative real-time PCR showed that miR155 was expressed in mouse and human atherosclerotic lesions. miR155 expression in macrophages was positively correlated with proinflammatory cytokine expression. Lentivirus-mediated overexpression of miR155 in macrophages enhanced their inflammatory response to LPS through targeting SOCS-1, and impaired cholesterol efflux from acetylated LDL-loaded macrophages, whereas deficiency of miR155 blunted macrophage inflammatory responses, and enhanced cholesterol efflux possibly via enhancing lipid loading-induced macrophage autophagy. We next examined the atherogenesis in apoE−/− and miR155−/−/apoE−/− (DKO) mice fed a western diet. Compared with apoE−/− mice, the DKO mice developed less atherosclerosis lesion in aortic root, with reduced neutral lipid content and macrophages. Flow cytometric analysis showed that there were increased number of regulatory T cells, and reduced numbers of Th17 cells and CD11b+/Ly6Chigh cells in the spleen of DKO mice. Peritoneal macrophages from the DKO mice had significantly reduced pro-inflammatory cytokine expression and secretion both in the absence and presence of LPS stimulation. To determine whether miR155 in leukocytes contributes to atherosclerosis, we performed bone marrow transplantation study. Deficiency of miR155 in bone marrow-derived cells suppressed atherogenesis in apoE−/− mice, demonstrating that hematopoietic cell-derived miR155 plays a critical role. Conclusion miR155 deficiency attenuates atherogenesis in apoE−/− mice by reducing inflammatory responses of macrophages, enhancing macrophage cholesterol efflux and resulting in an anti-atherogenic leukocyte profile. Targeting miR155 may be a promising strategy to halt atherogenesis.

Colorectal cancer risk is increased in shift workers with presumed circadian disruption. Intestinal epithelial cell proliferation is gated throughout each day by the circadian clock. Period 2 (Per2) is a key circadian clock gene. Per2 mutant (Per2m/m) mice show an increase in lymphomas and deregulated expression of cyclin D and c-Myc genes that are key to proliferation control. We asked whether Per2 clock gene inactivation would accelerate intestinal and colonic tumorigenesis. The effects of PER2 on cell proliferation and β-catenin were studied in colon cancer cell lines by its down-regulation following RNA interference. The effects of Per2 inactivation in vivo on β-catenin and on intestinal and colonic polyp formation were studied in mice with Per2 mutation alone and in combination with an Apc mutation using polyp-prone ApcMin/+ mice. Down-regulation of PER2 in colon cell lines (HCT116 and SW480) increases β-catenin, cyclin D, and cell proliferation. Down-regulation of β-catenin along with Per2 blocks the increase in cyclin D and cell proliferation. Per2m/m mice develop colonic polyps and show an increase in small intestinal mucosa β-catenin and cyclin D protein levels compared with wild-type mice. ApcMin/+Per2m/m mice develop twice the number of small intestinal and colonic polyps, with more severe anemia and splenomegaly, compared with ApcMin/+ mice. These data suggest that Per2 gene product suppresses tumorigenesis in the small intestine and colon by down-regulation of β-catenin and β-catenin target genes, and this circadian core clock gene may represent a novel target for colorectal cancer prevention and control.

Lung cancer is the leading cause of cancer-related deaths with current chemotherapies lacking adequate specificity and efficacy. β-Lapachone (β-lap) is a novel anticancer drug that is bioactivated by NAD(P)H:quinone oxidoreductase 1, an enzyme found specifically overexpressed in non-small cell lung cancer (NSCLC). Herein, we report a nanotherapeutic strategy that targets NSCLC tumors in two ways: (a) pharmacodynamically through the use of a bioactivatable agent, β-lap, and (b) pharmacokinetically by using a biocompatible nanocarrier, polymeric micelles, to achieve drug stability, bioavailability, and targeted delivery. β-Lap micelles produced by a film sonication technique were small (∼30 nm), displayed core-shell architecture, and possessed favorable release kinetics. Pharmacokinetic analyses in mice bearing subcutaneous A549 lung tumors showed prolonged blood circulation (t 1/2 , ∼28 h) and increased accumulation in tumors. Antitumor efficacy analyses in mice bearing subcutaneous A549 lung tumors and orthotopic Lewis lung carcinoma models showed significant tumor growth delay and increased survival. In summary, we have established a clinically viable β-lap nanomedicine platform with enhanced safety, pharmacokinetics, and antitumor efficacy for the specific treatment of NSCLC tumors. Cancer Res; 70(10); 3896-904. ©2010 AACR.