Retinoblastoma tumor cell proliferation is negatively associated with an immune gene expression signature and increased immune cells.

This study focuses on gene expression differences between early retinal states that ultimately lead to normal development, late onset retinoblastoma, or rapid bilateral retinoblastoma tumors. The late-onset and early-onset retinoblastoma tumor cells are remarkably similar to normally proliferating retinal progenitor cells, but they fail to properly express differentiation markers associated with normal development. Further, early-onset retinoblastoma tumor cells express a robust immune gene expression signature followed by accumulation of dendritic, monocyte, macrophage, and T-lymphocyte cells in the retinoblastoma tumors. This characteristic was not shared by either normal retinae or late-onset retinoblastomas. Comparison of our data with other human and mouse retinoblastoma tumor gene expression significantly confirmed, that the immune signature is present in tumors from each species. Strikingly, we observed that the immune signature in both mouse and human tumors was most highly evident in those with the lowest proliferative capacity. We directly assessed this relationship in human retinoblastoma tumors by co-analyzing proliferation and immune cell recruitment by immunohistochemistry, uncovering a significant inverse relationship between increased immune-cell infiltration in tumors and reduced tumor cell proliferation. Directly inhibiting proliferation with a PI3K/mTOR inhibitor significantly increased the number of CD45+ immune cells in the retina. This work establishes an in vivo model for the rapid recruitment of immune cells to tumorigenic neural tissue.

Undergraduate, Nonmedical Students can Pass the FLS Manual Skills Exam With Minimal Practice.

OBJECTIVES: The primary objective of this study is to investigate whether undergraduate, nonmedical students could pass the FLS Manual Skills Exam with minimal practice. The secondary objective is to examine ACGME case log data from graduating chief residents over the past 18 years to examine how laparoscopic experience has evolved over that time period. DESIGN: Undergraduate, nonmedical students received training and unlimited practice time before being tested on each task of the FLS Manual Skills Exam. Each task was timed and scored using the MISTELS system. ACGME case log data from graduating chief residents over the past 18 years was obtained. SETTING: The setting is SimPortal, the simulation center associated with the University of Minnesota Medical School. PARTICIPANTS: The participants are 25 undergraduate, nonmedical students from the University of Minnesota. Participants were recruited on campus. RESULTS: Twenty-three out of 25 (92%) undergraduate, nonmedical students successfully completed one attempt for each task of the FLS Manual Skills Exam and 21 out of 25 (84%) completed both attempts. The average total practice time was 39 minutes. Over the past 18 years, the average number of laparoscopic cases completed by a graduating chief increased from 142 to 275 cases (93% increase). Additionally, the average number of cases of the top 5 most common laparoscopic operations increased from 25% to over 400%. CONCLUSIONS: Undergraduate, nonmedical students can pass the FLS Manual Skills Exam with minimal practice. Additionally, general surgery residents and medical students continue to gain more laparoscopic experience throughout medical training as laparoscopic surgery is utilized for more operations. The FLS Manual Skills Exam should be re-examined to determine its utility as a high-stakes exam.