A chemical biology screen identifies glucocorticoids that regulate c-maf expression by increasing its proteasomal degradation through up-regulation of ubiquitin

The oncogene c-maf is frequently overexpressed in multiple myeloma cell lines and patient samples and contributes to increased cellular proliferation in part by inducing cyclin D2 expression. To identify regulators of c-maf, we developed a chemical screen in NIH3T3 cells stably overexpressing c-maf and the cyclin D2 promoter driving luciferase. From a screen of 2400 off-patent drugs and chemicals, we identified glucocorticoids as c-maf-dependent inhibitors of cyclin D2 transactivation. In multiple myeloma cell lines, glucocorticoids reduced levels of c-maf protein without influencing corresponding mRNA levels. Subsequent studies demonstrated that glucocorticoids increased ubiquitination-dependent degradation of c-maf and up-regulated ubiquitin C mRNA. Moreover, ectopic expression of ubiquitin C recapitulated the effects of glucocorticoids, demonstrating regulation of c-maf protein through the abundance of the ubiquitin substrate. Thus, using a chemical biology approach, we identified a novel mechanism of action of glucocorticoids and a novel mechanism by which levels of c-maf protein are regulated by the abundance of the ubiquitin substrate.     

Using an Ultrasound Elasticity Microscope to Map Three-Dimensional Strain in a Porcine Cornea

An ultrasound elasticity microscope was used to map 3-D strain volume in an ex vivo porcine cornea to illustrate its ability to measure the mechanical properties of this tissue. Mechanical properties of the cornea play an important role in its function and, therefore, also in ophthalmic diseases such as kerataconus and corneal ectasia. The ultrasound elasticity microscope combines a tightly focused high-frequency transducer with confocal scanning to produce high-quality speckle over the entire volume of tissue. This system and the analysis were able to generate volume maps of compressional strain in all three directions for porcine corneal tissue, more information than any previous study has reported. Strain volume maps indicated features of the cornea and mechanical behavior as expected. These results constitute a step toward better understanding of corneal mechanics and better treatment of corneal diseases.     

The use of group sessions for the emotional support of families of terminal patients

Abstract

To meet the need for emotional support for family members of terminal patients, a weekly group session was established on a cancer unit. The group has allowed family members to share their fears, concerns, and doubts as well as receive support from other individuals experiencing similar traumatic situations. The development and goals of this group are discussed.     

The role of radiologic imaging and biopsy in renal tumor ablation

Purpose  

The rate of unintentionally discovered renal masses has been increasing along with a parallel increased incidence of renal cell carcinoma both in men and women. Ablation therapy has emerged as an alternative for the treatment of these small renal tumors. Several techniques have been developed for renal tumor ablation with cryoablation (CA) and radiofrequency ablation (RFA) being among the most widely used and studied. The purpose of this article is to review the role of imaging and renal mass biopsy in renal tumor ablation with focus on CA and RFA.     

Outcomes after concurrent inguinal hernia repair and robotic-assisted radical prostatectomy

Inguinal hernias occur more frequently following radical prostatectomy. Simultaneous inguinal hernia repair during open and laparoscopic radical prostatectomy for prostate cancer has been described previously. The emergence of robotic-assisted radical prostatectomy (RALP) has necessitated the evaluation of concomitant herniorrhaphy in this new setting. We report the outcomes of this operation in our series of patients. Retrospective review was performed on 700 patients with localised prostate cancer who underwent RALP performed by a single surgeon from 2004 to 2009. Details of cases where concurrent inguinal hernia repair was performed were recorded and compared with the remainder of the cohort. Hernia repair was performed using a monofilament knitted polypropylene cone mesh plug and fascial defect closure with Hem-o-Lok clips. A total of 38 inguinal herniorraphies were performed in 37 patients as a simultaneous procedure during transperitoneal RALP. The hernia repair on average added 5–10 min to the total procedure time. One patient underwent a bilateral repair. Across this group, mean age was 62.9 years, average body mass index was 27.1, and median follow-up was 29 months. There were no complications at the time of mesh placement. There were no cases complicated by wound infection, fluid collection, or chronic pain. Recurrence of an inguinal hernia occurred in one patient due to migration of the mesh. We conclude that concomitant inguinal hernia repair during RALP is safe, feasible, and effective. The herniorrhaphy can be performed quickly, adds little to the overall procedure time and avoids a further operative procedure for the patient.     

Longitudinal Shapes of the Tibia and Femur are Unrelated and Variable

In general practice, short films of the knee are used to assess component position and define the entry point for intramedullary femoral alignment in TKAs; however, whether it is justified to use the short film commonly used in research settings and everyday practice as a substitute for the whole leg view is controversial and needs clarification. In 138 long leg CT scanograms we measured the angle formed by the anatomic axis of the proximal fourth of the tibia and the mechanical axis of the tibia, the angle formed by the anatomic axis of the distal fourth of the femur and the mechanical axis of the femur, the “bow” of the tibia (as reflected by the offset of the anatomic axis from the center of the talus), and the “bow” of the femur (as reflected by the offset of the anatomic axis from the center of the femoral head). Because the angle formed by these axes and the bow of the tibia and femur have wide variability in females and males, a short film of the knee should not be used in place of the whole leg view when accurate assessment of component position and limb alignment is essential. A previous study of normal limbs found that only 2% of subjects have a neutral hip-knee-ankle axis, which can be explained by the wide variability of the bow in the tibia and femur and the lack of correlation between the bow of the tibia and femur in a given limb as shown in the current study.     

Evaluation of the Rebound Hernia Repair Device for Laparoscopic Hernia Repair

Background:

The characteristics of the ideal type of mesh are still being debated. Mesh shrinkage and fixation have been associated with complications. Avoiding shrinkage and fixation would improve hernia recurrence rates and complications. To our knowledge, this is the first study of a device with a self-expanding frame for laparoscopic hernia repair.

Methods:

Six Rebound Hernia Repair Devices were placed laparoscopically in pigs. This device is a condensed polypropylene, super-thin, lightweight, macro-porous mesh with a self-expanding Nitinol frame. The devices were assessed for adhesions, shrinkage, and histological examination. Laboratory and radiologic evaluations were also performed.

Results:

The handling properties of the devices facilitated their laparoscopic placement. They were easily identified with simple x-rays. The mesh was firmly integrated within the surrounding tissue. One device was associated with 3 small adhesions. The other 5 HRDs had no adhesions. We noted no shrinkage or folding. All devices preserved their original size and shape.

Conclusions:

At this evaluation stage, we found that the Rebound Hernia Repair Device may serve for laparoscopic hernia repair and has favorable handling properties. It prevents folding and shrinkage of the mesh. It may eliminate the need for fixation, thus preventing chronic pain. The Nitinol frame also allowed radiologic evaluation for gross movement. Further studies will be needed to evaluate its clinical application.