Haque M.,NorthShore University HealthSystem
Journal of magnetic resonance imaging : JMRI | Year: 2010
To demonstrate feasibility of functional MRI of liver using glucose as a stimulus to monitor metabolic changes using blood oxygenation level dependent (BOLD) contrast. We hypothesized that during hyperglycemia, liver stores the glucose and consequently there is a reduction in oxygen consumption, which can be detected using BOLD MRI. In four mini pigs, measurements were made before and after 54 g of glucose administered intravenously. In six healthy young human subjects, measurements were made before and after oral ingestion of 75 g of glucose. T(2)* weighted images of the liver were obtained on a Siemens 3 Tesla Verio MRI scanner using multiple gradient recalled echo (mGRE) sequence. A statistically significant decrease (P < 0.05) in R2* (1/T(2)*) was observed postglucose both in swine (110.41 ± 14.1 s(-1) to 72.22 ± 5.7 s(-1)) and human (55.84 ±3.8 s(-1) to 50.6 ±0.5 s(-1)), suggesting improved liver oxygenation during hyperglycemia. Our preliminary data presented here demonstrate the feasibility of obtaining functional liver images that illustrate the changes in oxygen consumption. Further studies are necessary to fully validate the technique. J. Magn. Reson. Imaging 2010;32:988-991. © 2010 Wiley-Liss, Inc.
Liu W.,NorthShore University HealthSystem
Asian Journal of Andrology | Year: 2016
Although most prostate cancer (PCa) cases are not life-threatening, approximately 293 000 men worldwide die annually due to PCa. These lethal cases are thought to be caused by coordinated genomic alterations that accumulate over time. Recent genome-wide analyses of DNA from subjects with PCa have revealed most, if not all, genetic changes in both germline and PCa tumor genomes. In this article, I first review the major, somatically acquired genomic characteristics of various subtypes of PCa. I then recap key findings on the relationships between genomic alterations and clinical parameters, such as biochemical recurrence or clinical relapse, metastasis and cancer-specific mortality. Finally, I outline the need for, and challenges with, validation of recent findings in prospective studies for clinical utility. It is clearer now than ever before that the landscape of somatically acquired aberrations in PCa is highlighted by DNA copy number alterations (CNAs) and TMPRSS2-ERG fusion derived from complex rearrangements, numerous single nucleotide variations or mutations, tremendous heterogeneity, and continuously punctuated evolution. Genome-wide CNAs, PTEN loss, MYC gain in primary tumors, and TP53 loss/mutation and AR amplification/mutation in advanced metastatic PCa have consistently been associated with worse cancer prognosis. With this recently gained knowledge, it is now an opportune time to develop DNA-based tests that provide more accurate patient stratification for prediction of clinical outcome, which will ultimately lead to more personalized cancer care than is possible at present.
Shevrin D.,NorthShore University HealthSystem
Asian Journal of Andrology | Year: 2016
In spite of the development of new treatments for late stage prostate cancer, significant challenges persist to match individuals with effective targeted therapies. Genomic classification using high-throughput sequencing technologies has the potential to achieve this goal and make precision medicine a reality in the management of men with castrate-resistant prostate cancer. This chapter reviews some of the most recent studies that have resulted in significant progress in determining the landscape of somatic genomic alterations in this cohort and, more importantly, have provided clinically actionable information that could guide treatment decisions. This chapter reviews the current understanding of common alterations such as alterations of the androgen receptor and PTEN pathway, as well as ETS gene fusions and the growing importance of PARP inhibition. It also reviews recent studies that characterize the evolution to neuroendocrine tumors, which is becoming an increasingly important clinical problem. Finally, this chapter reviews recent innovative studies that characterize the compelling evolutionary history of lethal prostate cancer evidenced by polyclonal seeding and interclonal cooperation between metastasis and the importance of tumor clone dynamics measured serially in response to treatment. The genomic landscape of late stage prostate cancer is becoming better defined, and the prospect for assigning clinically actionable data to inform rationale treatment for individuals with this disease is becoming a reality.
Ji Y.,NorthShore University HealthSystem
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013
The 3 + 3 design is the most common choice among clinicians for phase I dose-escalation oncology trials. In recent reviews, more than 95% of phase I trials have been based on the 3 + 3 design. Given that it is intuitive and its implementation does not require a computer program, clinicians can conduct 3 + 3 dose escalations in practice with virtually no logistic cost, and trial protocols based on the 3 + 3 design pass institutional review board and biostatistics reviews quickly. However, the performance of the 3 + 3 design has rarely been compared with model-based designs in simulation studies with matched sample sizes. In the vast majority of statistical literature, the 3 + 3 design has been shown to be inferior in identifying true maximum-tolerated doses (MTDs), although the sample size required by the 3 + 3 design is often orders-of-magnitude smaller than model-based designs. In this article, through comparative simulation studies with matched sample sizes, we demonstrate that the 3 + 3 design has higher risks of exposing patients to toxic doses above the MTD than the modified toxicity probability interval (mTPI) design, a newly developed adaptive method. In addition, compared with the mTPI design, the 3 + 3 design does not yield higher probabilities in identifying the correct MTD, even when the sample size is matched. Given that the mTPI design is equally transparent, costless to implement with free software, and more flexible in practical situations, we highly encourage its adoption in early dose-escalation studies whenever the 3 + 3 design is also considered. We provide free software to allow direct comparisons of the 3 + 3 design with other model-based designs in simulation studies with matched sample sizes.
Edelman R.R.,NorthShore University HealthSystem
Radiology | Year: 2014
The first reports in Radiology pertaining to magnetic resonance (MR) imaging were published in 1980, 7 years after Paul Lauterbur pioneered the first MR images and 9 years after the first human computed tomographic images were obtained. Historical advances in the research and clinical applications of MR imaging very much parallel the remarkable advances in MR imaging technology. These advances can be roughly classified into hardware (eg, magnets, gradients, radiofrequency [RF] coils, RF transmitter and receiver, MR imaging-compatible biopsy devices) and imaging techniques (eg, pulse sequences, parallel imaging, and so forth). Image quality has been dramatically improved with the introduction of high-field-strength superconducting magnets, digital RF systems, and phased-array coils. Hybrid systems, such as MR/positron emission tomography (PET), combine the superb anatomic and functional imaging capabilities of MR imaging with the unsurpassed capability of PET to demonstrate tissue metabolism. Supported by the improvements in hardware, advances in pulse sequence design and image reconstruction techniques have spurred dramatic improvements in imaging speed and the capability for studying tissue function. In this historical review, the history of MR imaging technology and developing research and clinical applications, as seen through the pages of Radiology, will be considered.