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Intraoperative Management of an Incidentally Identified Ectopic Ureter Inserting Into the Prostate of a Patient Undergoing Radical Prostatectomy for Prostate Cancer: A Case Report. - Medicine
Congenital variations in urinary tract anatomy present unique surgical challenges when they present without prior knowledge. Ectopic ureters occur as a rare anatomic variation of the urinary tract and are often associated with duplicated renal collecting systems. While the condition is uncommon, even more atypical is its discovery and subsequent diagnosis during surgical intervention for treatment of localized prostate cancer.We describe the intraoperative management of a unique case of bilateral ectopic ureters, with a right-sided ureter inserting into the prostate of a 54-year-old male undergoing robotic-assisted radical prostatectomy. While unknown at the time of surgery, this right-sided ureter was associated with a nonfunctioning right upper renal moiety of a duplex renal collecting system. This aberration was discovered intraoperatively and confirmed with imaging, and a robotic-assisted radical prostatectomy with right distal ureterectomy was performed.
The landscape of long noncoding RNAs in the human transcriptome. - Nature genetics
Long noncoding RNAs (lncRNAs) are emerging as important regulators of tissue physiology and disease processes including cancer. To delineate genome-wide lncRNA expression, we curated 7,256 RNA sequencing (RNA-seq) libraries from tumors, normal tissues and cell lines comprising over 43 Tb of sequence from 25 independent studies. We applied ab initio assembly methodology to this data set, yielding a consensus human transcriptome of 91,013 expressed genes. Over 68% (58,648) of genes were classified as lncRNAs, of which 79% were previously unannotated. About 1% (597) of the lncRNAs harbored ultraconserved elements, and 7% (3,900) overlapped disease-associated SNPs. To prioritize lineage-specific, disease-associated lncRNA expression, we employed non-parametric differential expression testing and nominated 7,942 lineage- or cancer-associated lncRNA genes. The lncRNA landscape characterized here may shed light on normal biology and cancer pathogenesis and may be valuable for future biomarker development.
Analysis of geminivirus AL2 and L2 proteins reveals a novel AL2 silencing suppressor activity. - Journal of virology
Both posttranscriptional and transcriptional gene silencing (PTGS and TGS, respectively) participate in defense against the DNA-containing geminiviruses. As a countermeasure, members of the genus Begomovirus (e.g., Cabbage leaf curl virus) encode an AL2 protein that is both a transcriptional activator and a silencing suppressor. The related L2 protein of Beet curly top virus (genus Curtovirus) lacks transcription activation activity. Previous studies showed that both AL2 and L2 suppress silencing by a mechanism that correlates with adenosine kinase (ADK) inhibition, while AL2 in addition activates transcription of cellular genes that negatively regulate silencing pathways. The goal of this study was to clarify the general means by which these viral proteins inhibit various aspects of silencing. We confirmed that AL2 inhibits systemic silencing spread by a mechanism that requires transcription activation activity. Surprisingly, we also found that reversal of PTGS and TGS by ADK inactivation depended on whether experiments were conducted in vegetative or reproductive Nicotiana benthamiana plants (i.e., before or after the vegetative-to-reproductive transition). While AL2 was able to reverse silencing in both vegetative and reproductive plants, L2 and ADK inhibition were effective only in vegetative plants. This suggests that silencing maintenance mechanisms can change during development or in response to stress. Remarkably, we also observed that AL2 lacking its transcription activation domain could reverse TGS in reproductive plants, revealing a third, previously unsuspected AL2 suppression mechanism that depends on neither ADK inactivation nor transcription activation.RNA silencing in plants is a multivalent antiviral defense, and viruses respond by elaborating multiple and sometimes multifunctional proteins that inhibit various aspects of silencing. The studies described here add an additional layer of complexity to this interplay. By examining geminivirus AL2 and L2 suppressor activities, we show that L2 is unable to suppress silencing in Nicotiana benthamiana plants that have undergone the vegetative-to-reproductive transition. As L2 was previously shown to be effective in mature Arabidopsis plants, these results illustrate that silencing mechanisms can change during development or in response to stress in ways that may be species specific. The AL2 and L2 proteins are known to share a suppression mechanism that correlates with the ability of both proteins to inhibit ADK, while AL2 in addition can inhibit silencing by transcriptionally activating cellular genes. Here, we also provide evidence for a third AL2 suppression mechanism that depends on neither transcription activation nor ADK inactivation. In addition to revealing the remarkable versatility of AL2, this work highlights the utility of viral suppressors as probes for the analysis of silencing pathways.Copyright Â© 2015, American Society for Microbiology. All Rights Reserved.
Unilateral ossified ligamentum flavum in the high cervical spine causing myelopathy. - Indian journal of orthopaedics
High cervical ossified ligamentum flavum (OLF) is rare and may cause progressive quadriparesis and respiratory failure. Our two patients had unilateral OLF between C1 and C4 levels. MR showed a unilateral, triangular bony excrescence with low signal and a central, intermediate or high signal on all pulse sequences due to bone marrow within. There was Type I thecal compression (partial deficit of contrast media ring). The first patient had a linear and nodular OLF with calcification within tectorial membrane, C2-3 fusion and unilateral C2-facetal hypertrophy; and the second patient, a lateral, linear OLF with loss of lordosis and C3-6 spondylotic changes. A decompressive laminectomy using "posterior floating and enbloc resection" brought significant relief in myelopathy. Histopathology showed mature bony trabeculae, bone marrow and ligament tissue. The coexisting mobile cervical vertebral segment above and congenitally fused or spondylotic rigid segment below the level of LF may have led to abnormal strain patterns within resulting in its unilateral ossification. In dealing with cervical OLF, carefully preserving facets during laminectomy or laminoplasty helps in maintaining normal cervical spinal curvature.
Long noncoding RNAs in cancer: from function to translation. - Trends in cancer
While our understanding of the molecular mechanisms underlying cancer has significantly improved, most of our knowledge focuses on protein-coding genes that make up a fraction of the genome. Recent studies have uncovered thousands of long noncoding RNAs (lncRNAs) that populate the cancer genome. A subset of these molecules shows striking cancer- and lineage-specific expression patterns, suggesting they may be potential drivers of cancer biology and have utility as clinical biomarkers. Here, we discuss emerging modalities of lncRNA biology and their interplay with cancer-associated concepts, including epigenetic regulation, DNA damage and cell cycle control, microRNA silencing, signal transduction pathways, and hormone-driven disease. Additionally, we highlight the translational impact of lncRNAs, tools for their mechanistic investigation, and directions for future lncRNA research.
The lncRNA landscape of breast cancer reveals a role for DSCAM-AS1 in breast cancer progression. - Nature communications
Molecular classification of cancers into subtypes has resulted in an advance in our understanding of tumour biology and treatment response across multiple tumour types. However, to date, cancer profiling has largely focused on protein-coding genes, which comprise <1% of the genome. Here we leverage a compendium of 58,648 long noncoding RNAs (lncRNAs) to subtype 947 breast cancer samples. We show that lncRNA-based profiling categorizes breast tumours by their known molecular subtypes in breast cancer. We identify a cohort of breast cancer-associated and oestrogen-regulated lncRNAs, and investigate the role of the top prioritized oestrogen receptor (ER)-regulated lncRNA, DSCAM-AS1. We demonstrate that DSCAM-AS1 mediates tumour progression and tamoxifen resistance and identify hnRNPL as an interacting protein involved in the mechanism of DSCAM-AS1 action. By highlighting the role of DSCAM-AS1 in breast cancer biology and treatment resistance, this study provides insight into the potential clinical implications of lncRNAs in breast cancer.
Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy. - Urologic oncology
Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP.A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score â‰¥7, (2) primary Gleason pattern â‰¥4, (3) Gleason score â‰¥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern â‰¥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction.Of the 5 definitions assessed, 1 (primary Gleason pattern â‰¥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP.Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern â‰¥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa.Copyright Â© 2016 Elsevier Inc. All rights reserved.
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