Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer.

Histone methyltransferases (HMTases), as chromatin modifiers, regulate the transcriptomic landscape in normal development as well in diseases such as cancer. Here, we molecularly order two HMTases, EZH2 and MMSET, that have established genetic links to oncogenesis. EZH2, which mediates histone H3K27 trimethylation and is associated with gene silencing, was shown to be coordinately expressed and function upstream of MMSET, which mediates H3K36 dimethylation and is associated with active transcription. We found that the EZH2-MMSET HMTase axis is coordinated by a microRNA network and that the oncogenic functions of EZH2 require MMSET activity. Together, these results suggest that the EZH2-MMSET HMTase axis coordinately functions as a master regulator of transcriptional repression, activation, and oncogenesis and may represent an attractive therapeutic target in cancer.

Retrievable IVC Filters: Comprehensive Review of Device-related Complications and Advanced Retrieval Techniques.

Use of retrievable inferior vena cava filters (RIVCFs) has grown exponentially since their introduction into clinical practice, but many of these devices are not retrieved. Some are not retrieved due to poor clinical follow-up, but other devices remain in situ for extended periods because they present significant technical challenges during retrieval. Because of these and other factors, many of these devices were thus left in place permanently. However, recent data have placed a renewed emphasis on device retrieval due to increased risk of RIVCF-related complications, which are positively correlated with filter dwell time. Development of advanced filter retrieval techniques has had a significant impact on the removal of embedded RIVCFs, permitting retrieval of the majority of devices. The purpose of this article is to present an imaging and data review of the dominant device-related factors that complicate RIVCF retrieval and to describe the relevant advanced retrieval techniques to manage these factors. RIVCF imaging is frequently encountered in daily clinical practice via various imaging modalities. Therefore, diagnostic radiologists can play a vital role in identifying filter-related issues. Familiarity with the context for managing these issues in the interventional suite is essential for improving triage and care of patients with RIVCFs. © RSNA, 2017.

Endoscopic ultrasound-guided embolization of refractory splenic pseudoaneurysm.

Video 1EUS-guided embolization of splenic arterial pseudoaneurysm refractory to previous percutaneous transcatheter arterial embolizations.

Understanding the Basics of Commonly Used Wires in Interventional Radiology.

A wide variety of wires are available for use in interventional radiology, with wires demonstrating differences in construction, diameter, length, coating, shape, and taper. It is crucial to understand the difference in characteristics between these wires to select the most effective and safe wire for the intended purpose when undertaking a procedure. This article reviews the qualities and functions of different types of wires to aid in this decision-making process.

Corrigendum to "Enchondroma protuberans of the hand: A case report" [Radiology Case Reports 15 (2020) 943-946].

[This corrects the article DOI: 10.1016/j.radcr.2020.04.026.].

Enchondroma protuberans of the hand: A case report.

Enchondroma protuberans (EP) is a rare form of enchondroma which demonstrates exophytic growth outside the margins of the bony cortex. A previously healthy 18-year-old male presented with chronic painless palpable mass of the left third finger. Radiograph showed a well-circumscribed expansile lucent lesion in the middle phalanx of the left third finger. The magnetic resonance imaging confirmed an expansile cortical-based lesion extending through the cortex into the soft tissues, which demonstrated high T2 signal with internal foci with low to intermediate signal suggestive of internal chondroid matrix. The patient underwent surgical excision, curettage and bone grafting, and surgical pathology study confirmed the diagnosis of EP. A rare case of EP involving a phalanx of the hand was described in this study. Imaging, particularly magnetic resonance imaging, plays a key role for accurate preprocedural diagnosis.

Emergent Transjugular Intrahepatic Portosystemic Shunt Creation in Acute Variceal Bleeding.

Emergent transjugular intrahepatic portosystemic shunt (TIPS) creation is most commonly employed in the setting of acute variceal hemorrhage. Given a propensity for decompensation, these patients often require a multidisciplinary, multimodal approach involving prompt diagnosis, pharmacologic therapy, and endoscopic intervention. While successful in the majority of cases, failure to medically control initial bleeding can prompt interventional radiology consultation for emergent portal decompression via TIPS creation. This article discusses TIPS creation in emergent, acute variceal hemorrhage, reviewing the natural history of gastroesophageal varices, presentation and diagnosis of acute variceal hemorrhage, pharmacologic therapy, endoscopic approaches, patient selection and risk stratification for TIPS, technical considerations for TIPS creation, adjunctive embolotherapy, and the role of salvage TIPS versus early TIPS in acute variceal hemorrhage.

Emergent Percutaneous Nephrostomy for Pyonephrosis: A Primer for the On-Call Interventional Radiologist.

Pyonephrosis is gross accumulation of pus within an obstructed renal collecting system that, if left untreated, can lead to potentially fatal septic shock. Treatment requires urgent decompression coupled with systemic antibiotics. Percutaneous nephrostomy (PCN) placement, first described in 1976 for the treatment of pyonephrosis, is now widely utilized for emergent decompression in these patients. When performed by an experienced interventional radiologist, PCN is a safe procedure with technical success rates of over 96 to 99%. This article will address the clinical presentation of pyonephrosis, and will discuss the indications, technique, complications, and outcomes of emergent PCN placement. Additionally, the expanded indications for PCN placement in nonemergent scenarios will also be described.

Endovascular Treatment for Variceal Hemorrhage: TIPS, BRTO, and Combined Approaches.

Variceal hemorrhage is a feared complication of portal hypertension, with high rates of morbidity and mortality. Optimal management requires a thoughtful, multidisciplinary approach. In cases of refractory or recurrent esophageal hemorrhage, endovascular approaches such as transjugular intrahepatic portosystemic shunt (TIPS) have a well-defined role. For hemorrhage related to gastric varices, the optimal treatment remains to be established; however, there is increasing adoption of balloon-occluded retrograde transvenous obliteration (BRTO). This article will review the concept, history, patient selection, basic technique, and outcomes for TIPS, BRTO, and combined TIPS + BRTO procedures for variceal hemorrhage.

The Role of Inferior Vena Cava Filters in Cancer Patients.

Cancer induces a hypercoagulable state and renders patients susceptible to venous thromboembolism. While anticoagulation remains the mainstay of treatment, many of these patients require placement of an inferior vena cava (IVC) filter, often due to a contraindication to or failure of anticoagulation. In this article, the available data on IVC filter usage in cancer patients will be reviewed.

Genetic and epigenetic loss of microRNA-31 leads to feed-forward expression of EZH2 in melanoma.

MicroRNAs (miRs) play a key role in cancer etiology by coordinately repressing numerous target genes involved in cell proliferation, migration and invasion. The genomic region in chromosome 9p21 that encompasses miR-31 is frequently deleted in solid cancers including melanoma; however the expression and functional role of miR-31 has not been previously studied in melanoma. Here, we queried the expression status and performed functional characterization of miR-31 in melanoma tissues and cell lines. We found that down-regulation of miR-31 was a common event in melanoma tumors and cell lines and was associated with genomic loss in a subset of samples. Down-regulation of miR-31 gene expression was also a result of epigenetic silencing by DNA methylation, and via EZH2-mediated histone methylation. Ectopic overexpression of miR-31 in various melanoma cell lines inhibited cell migration and invasion. miR-31 targets include oncogenic kinases such as SRC, MET, NIK (MAP3K14) and the melanoma specific oncogene RAB27a. Furthermore, miR-31 overexpression resulted in down-regulation of EZH2 and a de-repression of its target gene rap1GAP; increased expression of EZH2 was associated with melanoma progression and overall patient survival. Taken together, our study supports a tumor suppressor role for miR-31 in melanoma and identifies novel therapeutic targets.

Coordinated regulation of polycomb group complexes through microRNAs in cancer.

Polycomb Repressive Complexes (PRC1 and PRC2)-mediated epigenetic regulation is critical for maintaining cellular homeostasis. Members of Polycomb Group (PcG) proteins including EZH2, a PRC2 component, are upregulated in various cancer types, implicating their role in tumorigenesis. Here, we have identified several microRNAs (miRNAs) that are repressed by EZH2. These miRNAs, in turn, regulate the expression of PRC1 proteins BMI1 and RING2. We found that ectopic overexpression of EZH2-regulated miRNAs attenuated cancer cell growth and invasiveness, and abrogated cancer stem cell properties. Importantly, expression analysis revealed an inverse correlation between miRNA and PRC protein levels in cell culture and prostate cancer tissues. Taken together, our data have uncovered a coordinate regulation of PRC1 and PRC2 activities that is mediated by miRNAs.