Hormone therapies for advanced prostate cancer target the androgen receptor (AR) ligand-binding domain (LBD), but these ultimately fail and the disease progresses to lethal castration-resistant prostate cancer (CRPC). The mechanisms that drive CRPC are incompletely understood, but may involve constitutively active AR splice variants that lack the LBD. The AR N-terminal domain (NTD) is essential for AR activity, but targeting this domain with small-molecule inhibitors is complicated by its intrinsic disorder. Here we investigated EPI-001, a small-molecule antagonist of AR NTD that inhibits protein-protein interactions necessary for AR transcriptional activity. We found that EPI analogs covalently bound the NTD to block transcriptional activity of AR and its splice variants and reduced the growth of CRPC xenografts. These findings suggest that the development of small-molecule inhibitors that bind covalently to intrinsically disordered proteins is a promising strategy for development of specific and effective anticancer agents.

Purpose:To prospectively evaluate the short-and midterm effectiveness of transforaminal epidural steroid injection (TFESI) for lumbosacral radiculopathy with respect to injection level. Materials and Methods:Institutional review board approval and written informed consent were obtained. From March 2005 to February 2006, 239 consecutive patients (106 male, 133 female; mean age, 49.8 years; range, 13-82 years) who were scheduled to undergo lumbar TFESI were enrolled. The patients were randomly assigned to either the ganglionic (TFESI at the location of the exiting nerve root) or preganglionic group (TFESI at the supraadjacent intervertebral disk level). Follow-up was conducted within 1 month (short term) and more than 6 months (midterm) after injections. Short-and midterm outcomes were measured by using a visual analog scale and a four-grade scale. Univariate analysis (by using the Fisher exact and 2 tests) and multiple logistic regression analysis were performed to evaluate the relationship between possible outcome predictors (ganglionic or preganglionic injection levels, cause of radiculopathy, duration of symptoms, age group, and sex) and the therapeutic effect. Results:Univariate analysis showed that the preganglionic group had a better treatment effect (99 of 112, 88.4%) than did the ganglionic group (90 of 127, 70.9%) at short-term follow-up (P ϭ .001). Multiple logistic regression analysis showed that the only significant outcome predictor at short-term follow-up was injection level (odds ratio ϭ 2.232, P ϭ .037). No significant difference was identified regarding TFESI approach or cause of radiculopathy at midterm follow-up. Conclusion:TFESI for lumbosacral radiculopathy with a preganglionic approach is more effective than TFESI with a ganglionic approach at short-term follow-up. RSNA, 2007

Little is known about the ultrasonographic (US) features of ductal carcinoma in situ (DCIS) of the breast because this entity usually manifests as pure mammographic calcifications and is rarely evaluated with US. US findings were recorded in 70 patients with DCIS and then analyzed and correlated with mammographic and histologic findings. A microlobulated mass with mild hypoechogenicity, ductal extension, and normal acoustic transmission was the most common US finding in DCIS. Spiculated margins, marked hypoechogenicity, a thick echogenic rim, and posterior acoustic shadowing at US often suggested the presence of invasion. US performed with a 10-13-MHz transducer and optimal technique can be used as a complement to mammography in detecting and evaluating DCIS of the breast, as it demonstrates breast lesions associated with malignant microcalcifications in most cases. The main benefit of identifying a US abnormality in women with mammographically detected DCIS is to allow the use of US to guide interventional procedures (eg, needle biopsy, needle localization). US may also be helpful in detecting DCIS without calcifications and in evaluating disease extent in women with dense breasts. Nevertheless, further research is needed to delineate the role of US in the evaluation of patients with DCIS.

The diagnoses of entrapment and compressive neuropathies have been based on the findings from clinical examinations and electrophysiologic tests, such as electromyography and nerve conduction studies. The use of magnetic resonance (MR) imaging for the diagnosis of entrapment or compressive neuropathies is increasing because MR imaging is particularly useful for discerning potential causes and for identifying associated muscle denervation. However, it is sometimes difficult to localize nerve entrapment or demonstrate nerve compression lesions with MR imaging. Nevertheless, even in these cases, MR imaging may show denervation-associated changes in specific muscles innervated by the affected nerves. The analysis of denervated muscle distributions by using MR imaging, with a knowledge of nerve innervation patterns, would be helpful for determining the nerves involved and the levels of nerve entrapment or compression. In this context, the mapping of skeletal muscle denervation with MR imaging has a supplementary or even a primary role in the diagnosis of entrapment and compressive neuropathies.

Obesity and older age are associated with development of NASH. Type 2 NASH is the most common form and associated with a greater severity of obesity and advanced fibrosis.