Category: Hot Topics in Research

Prostate cancer discovery may make it easier to kill cancer cells

PJ Grier Hot Topics in Research, Oncology, Prostate, Uncategorized

Checkpoint Kinase 2 Negatively Regulates Androgen Sensitivity and Prostate Cancer Cell Growth Abstract: Prostate cancer is the second leading cause of cancer death in American men, and curing metastatic disease remains a significant challenge. Nearly all patients with disseminated prostate cancer initially respond to androgen deprivation therapy (ADT), but virtually all patients will relapse and develop incurable castrationresistant prostate cancer (CRPC). A high-throughput RNAi screen to identify signaling pathways regulating prostate cancer cell growth led to our discovery that checkpoint kinase 2 (CHK2) knockdown dramatically increased prostate cancer growth and hypersensitized cells to low androgen levels. Mechanistic investigations revealed that…

Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis

PJ Grier Cardiology, Hot Topics in Research, Uncategorized

Non-lethal Inhibition of Gut Abstract: Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol (DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production from physiologic polymicrobial cultures (e.g., intestinal contents, human feces) and reduce TMAO levels in mice fed a high-choline or L-carnitine diet. DMB…

Practical experiences with eribulin in patients with metastatic breast cancer

PJ Grier Breast, Hot Topics in Research, Oncology

Practical experiences with eribulin in patients with metastatic breast cancer Background There is currently no standard therapy for women with metastatic or locally recurrent breast cancer. The microtubule polymerization inhibitor eribulin, approved in March 2011, is the first monochemotherapy with a proven survival benefit and tolerable toxicity in this patient group. Patients and methods Using a retrospective analysis of 27 mostly heavily pretreated patients in two large German breast cancer centers, the efficacy and tolerability of eribulin in daily practice were compared with the results of the pivotal EMBRACE and 301 studies. Results Despite the patients being older and having…

Management of Pulmonary Nodules by Community Pulmonologists

PJ Grier Hot Topics in Research, Lung, Oncology

Management of Pulmonary Nodules by Community Pulmonologists BACKGROUND: Pulmonary nodules (PNs) are a common reason for referral to pulmonologists. Th e majority of data for the evaluation and management of PNs is derived from studies performed in academic medical centers. Little is known about the prevalence and diagnosis of PNs, the use of diagnostic testing, or the management of PNs by community pulmonologists. METHODS: Th is multicenter observational record review evaluated 377 patients aged 40 to 89 years referred to 18 geographically diverse community pulmonary practices for intermediate PNs (8-20 mm). Study measures included the prevalence of malignancy, procedure/test use,…

Effects of aging on circadian patterns of gene expression in the human prefrontal cortex

PJ Grier Brain, Dementia, Hot Topics in Research, Memory Impairment, Neurology

Effects of aging on circadian patterns of gene expression in the human prefrontal cortex With aging, significant changes in circadian rhythms occur, including a shift in phase toward a “morning” chronotype and a loss of rhythmicity in circulating hormones. However, the effects of aging on molecular rhythms in the human brain have remained elusive. Here, we used a previously described time-of-death analysis to identify transcripts throughout the genome that have a significant circadian rhythm in expression in the human prefrontal cortex [Brodmann’s area 11 (BA11) and BA47]. Expression levels were determined by microarray analysis in 146 individuals. Rhythmicity in expression…

Findings from Structural MR Imaging in Military Traumatic Brain Injury

PJ Grier Brain, Hot Topics in Research, Neurosurgery, Radiology

Findings from Structural MR Imaging in Military Traumatic Brain Injury Purpose To describe the initial neuroradiology findings in a cohort of military service members with primarily chronic mild traumatic brain injury (TBI) from blast by using an integrated magnetic resonance (MR) imaging protocol. Materials and Methods This study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI…

MRI compatible remote catheter navigation system with 3 degrees of freedom

PJ Grier Hot Topics in Research, Radiology

Magnetic resonance imaging compatible remote catheter navigation system with 3 degrees of freedom   To facilitate MRI-guided catheterization procedures, we present an MRI-compatible remote catheter navigation system that allows remote navigation of steerable catheters with 3 degrees of freedom. Methods The system consists of a user interface (master), a robot (slave), and an ultrasonic motor control servomechanism. The interventionalist applies conventional motions (axial, radial and plunger manipulations) on an input catheter in the master unit; this user input is measured and used by the servomechanism to control a compact catheter manipulating robot, such that it replicates the interventionalist’s input motion…