Citations

Background and purpose The use of computed tomography angiography (CTA) as the sole vascular imaging study for preoperative planning for clipping of aneurysms is well described in the literature. CTA is widely available, provides quick acquisition, has low morbidity, and low cost. In this study, we describe the accuracy of CTA in determining the blood supply dominance in comparison to standard digital subtraction angiography. Materials and methods Sixty-six patients, with both CTAs and angiograms, were reviewed by two independent neuroradiologists. The posterior cerebral artery was determined to have dominant supply from the posterior communicating artery if it was of similar size to the P2 segment and the P1 segment was smaller by approximately 50%. If the posterior communicating artery and P1 segment were the same size, it was considered to have a dual supply. If P1 and P2 segments were the same caliber and the posterior communicating artery was smaller by 50%, it was deemed to have posterior circulation dominance. Results Based on the findings of our reviewers, CTA had a sensitivity and specificity of 69% and 96%, respectively, in predicting the presence of a fetal PCA. The positive predictive value was found to be 82% while a negative predictive value was estimated as 93%. A small-caliber P1 segment and large-caliber posterior communicating artery led to inaccurate interpretations of the CTAs. Conclusion This study shows that one cannot accurately predict blood supply dominance of the posterior cerebral artery. Knowledge of the blood flow dominance is essential when clipping a posterior communicating artery aneurysm to avoid compromise in posterior circulation.

Abstract The aim of this study was to estimate the effect of exposure to secondhand tobacco smoke on the incidence of lung adenocarcinoma in situ/minimally invasive adenocarcinoma (AIS/MIA). Data from seven case–control studies participating in the International Lung Cancer Consortium (ILCCO) were pooled, resulting in 625 cases of AIS/MIA and 7,403 controls, of whom 170 cases and 3,035 controls were never smokers. Unconditional logistic regression was used to estimate adjusted ORs (ORadj) and 95% confidence intervals (CI), controlling for age, sex, race, smoking status (ever/never), and pack-years of smoking. Study center was included in the models as a random-effects intercept term. Ever versus never exposure to secondhand tobacco smoke was positively associated with AIS/MIA incidence in all subjects (ORadj = 1.48; 95% CI, 1.14–1.93) and in never smokers (ORadj = 1.45; 95% CI, 1.00–2.12). There was, however, appreciable heterogeneity of ORadj across studies (P = 0.01), and the pooled estimates were largely influenced by one large study (40% of all cases and 30% of all controls). These findings provide weak evidence for an effect of secondhand tobacco smoke exposure on AIS/MIA incidence. Further studies are needed to assess the impact of secondhand tobacco smoke exposure using the newly recommended classification of subtypes of lung adenocarcinoma. Cancer Epidemiol Biomarkers Prev; 24(12); 1902–6. ©2015 AACR.

AbstractThe schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3‐deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X‐receptor (LXR) activation. The effects of 3dSB on ATP‐binding cassette transporter 1 levels and other LXR targets are similar to that of 25‐hydroxycholesterol, an LXR agonist. Unlike 25‐hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.

Abstract The role of the transcription factor GLI1 in pancreatic tumor initiation promoting the progression of preneoplastic lesions into tumors is well established. However, its function at later stages of pancreatic carcinogenesis remains poorly understood. To address this issue, we crossed the GLI1 knockout animal (GKO) with cre-dependent pancreatic activation of oncogenic KRAS concomitant with loss of the tumor suppressor TP53 (KPC). Interestingly, in this model, GLI1 played a tumor protective function, where survival of GKO/KPC mice was reduced compared to KPC littermates. Both cohorts developed pancreatic cancer without significant histopathological differences in survival studies. However, analysis of mice using ultrasound-based imaging at earlier time-points showed increased tumor burden in GKO/KPC mice. These animals have larger tumors, decreased body weight, increased lactate dehydrogenase production, and leukopenia. Expression studies identified FAS and FAS ligand as potential mediators of this phenomenon. The FAS /FASL axis, an apoptotic inducer, plays a role in the progression of pancreatic cancer, where its expression is usually lost or significantly reduced in advanced stages of the disease. Chromatin immunoprecipitation assays identified FAS and FASL as direct targets of GLI1 where GKO/KPC mice showed lower levels of this ligand compared to KPC animals. Furthermore, GLI1 overexpression and knockdown studies demonstrate a key regulatory role for GLI1 in both FAS and FASL expression. Finally, decreased levels of apoptosis were detected in the tumor tissue in the absence of GLI1 by TUNEL staining. Together, these findings define a novel pathway regulated by GLI1 controlling pancreatic tumor progression and provide a new theoretical framework to help the design and analysis of trials targeting GLI1-related pathways. Citation Format: Lisa D. Mills, Lizhi Zhang, Ronald J. Marler, Phyllis A. Svingen, Maite Fernandez-Barena, Maneesh Dave, William Bamlet, Robert McWilliams, William A. Faubion, Martin E. Fernandez-Zapico. Loss of GLI1 accelerates pancreatic cancer progression in the KPC mouse model. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A76.