RING-finger protein 6 enhances c-Myc-mediated Warburg effect by promoting MAD1 degradation to facilitate pancreatic cancer metastasis

xlomafota13 shared this article with you from Inoreader RING-finger protein 6 enhances c-Myc-mediated Warburg effect by promoting MAD1 degradation to facilitate pancreatic cancer metastasis Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):2025-2043. eCollection 2021. ABSTRACT Aerobic glycolysis (the Warburg effect) promotes tumor metastasis; hence, drugs targeting its regulators are being developed. c-Myc, a critical transcription factor that regulates the Warburg effect, is involved in the tumorigenesis of many cancers, including pancreatic cancer (PC). However, the upstream regulating mechanisms of c-Myc in PC are unclear. Herein, we reported that E3 ubiquitin ligase RING-finger protein 6 (RNF6) was upregulated in PC tissues, and an elevated RNF6 level was closely associated with metastasis and poor prognosis in patients with PC. In functional experiments, RNF6 over-expression accelerated the metastatic ability of PC cells, whereas RNF6 knockdown impaired PC cell motility and invasiveness along with metastasis in an orthotopic mouse model. Furthermore, we found that RNF6 promoted PC cell metastasis by enhancing c-Myc-mediated aerobic glycolysis. Mechanistically, RNF6 increased the expression level of c-Myc by catalyzing the ubiquitination of Max-dimerization protein-1 (MAD1), a cellular antagonist of c-Myc. Lastly, RNF6 promoted the degradation of MAD1 via the ubiquitin-proteasome pathway, and this reduction in the MAD1 levels enabled c-Myc to promote the Warburg effect in PC. Our results demonstrate that RNF6 may be a novel biomarker in PC carcinogenesis, thereby indicating that targeting the RNF6/MAD1/c-Myc axis is a potential strategy for PC therapy. PMID:34094667 | PMC:PMC8167688 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anti-ovarian cancer potential of phytocompound and extract from South African medicinal plants and their role in the development of chemotherapeutic agents

xlomafota13 shared this article with you from Inoreader Anti-ovarian cancer potential of phytocompound and extract from South African medicinal plants and their role in the development of chemotherapeutic agents Via American Journal of Cancer Research Am J Cancer Res. 2021 May 15;11(5):1828-1844. eCollection 2021. ABSTRACT Ovarian cancer (OC) accounts for the highest tumor-related mortality among the gynecologic malignancies. Most of the OC patients diagnosed with advanced-stage (III and IV) this situation creates panic and provokes an emergency to discover a new therapeutic strategy. Plants that possess medicinal properties are gaining attention as they are enriched with various chemical compounds that are potential to treat various diseases. It is a prolonged process to provide innovative and significant leads against a range of pharmacological targets for a human disease management system. Though challenges and difficulties are faced in the development of a new drug, the emergence of combinatorial chemistry is providing a new ray of hope and also, the executed effort in discovering the drug, and a chemical compound has been remarkably successful. This review discussed the role of medicinal plants that are native of South Africa in treating the Ovarian Cancer and in drug discovery. PMID:34094656 | PMC:PMC8167668 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Intracranial Hypotensive Crisis From an Insidious Spinal Cerebrospinal Fluid-Venous Fistula: A Case Report

xlomafota13 shared this article with you from Inoreader Intracranial Hypotensive Crisis From an Insidious Spinal Cerebrospinal Fluid-Venous Fistula: A Case Report Via leak of cerebrospinal fluid Oper Neurosurg (Hagerstown). 2021 Jun 7:opab154. doi: 10.1093/ons/opab154. Online ahead of print. ABSTRACT BACKGROUND AND IMPORTANCE: Progressive episodic spells of altered levels of consciousness, often advancing to include paroxysmal autonomic instability, may be indicative of a diencephalic dysfunction underlying spontaneous intracranial hypotension (SIH). A rare, and often indolent, etiology may be spinal cerebrospinal fluid (CSF) leak-an elusive diagnosis, especially in cases of CSF-venous fistula (CVF) that are often missed on routine computed tomography (CT) myelography and magnetic resonance imaging (MRI). CLINICAL PRESENTATION: We report an unusual case of a 50-yr-old woman who presented with rapidly progressive cyclical, self-resolving episodes of altered mentation and decreased arousal later in the day. Scrutiny of serial brain MRIs led to a diagnosis of SIH, with severe downward diencephalic and brain stem displacement-resul ting in cerebral aqueduct occlusion with obstructive hydrocephalus. Initial clinical improvement occurred with CSF diversion, but the patient quickly deteriorated-developing diencephalic spells, including extensor posturing and severely depressed levels of consciousness. Clinical improvement was seen with stopping CSF diversion and Trendelenburg-positioning. After intensive spinal imaging, dynamic CT myelography identified a left T10 nerve root diverticula and CSF-venous fistula. Surgical obliteration resulted in rapid, profound neurological improvement, and ultimately full neurological recovery by 1 yr. CONCLUSION: In our patient, worsening episodes of confusion, postural headaches, and autonomic instability developed due to SIH, which induced profound downward displacement and compression of the diencephalon and brain stem, and accompanied by subsequent obstructive hydrocephalus. Diagnostic persistence identified the CVF, which had caused the complex multifold pathophysiolog y and clinical presentation. If suspicion remains high for CVF, persistent spinal imaging, particularly with dynamic myelography, may be crucial. PMID:34097739 | DOI:10.1093/ons/opab154 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Adjuvant therapy for high‐risk cutaneous squamous cell carcinoma: A 10‐year review

xlomafota13 shared this article with you from Inoreader Adjuvant therapy for high‐risk cutaneous squamous cell carcinoma: A 10‐year review Via Head & Neck Abstract Standard of care for high-risk cutaneous squamous cell carcinoma (cSCC) is surgical excision of the primary lesion with clear margins when possible, and additional resection of positive margins when feasible. Even with negative margins, certain high-risk factors warrant consideration of adjuvant therapy. However, which patients might benefit from adjuvant therapy is unclear, and supporting evidence is conflicting and limited to mostly small retrospective cohorts. Here, we review literature from the last decade regarding adjuvant radiation therapy and systemic therapy in high-risk cSCC, including recent and current trials and the role of immune checkpoint inhibitors. We demonstrate evidence gaps in adjuvant therapy for high-risk cSCC and the need for prognostic tools, such as gene expression profiling, to guide patient selection. More large-cohort clinical studies are needed for collecting high-quality, evidence-based data for determining which patients with high-risk cSCC may bene fit from adjuvant therapy and which therapy is most appropriate for patient management. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Compact Valveless Pressure Control Source for Soft Rehabilitation Glove

xlomafota13 shared this article with you from Inoreader A Compact Valveless Pressure Control Source for Soft Rehabilitation Glove Via The International Journal of Medical Robotics and Computer Assisted Surgery Abstract: Background Soft pneumatic robots have shown great promises in hand rehabilitation systems as alternatives to conventional rigid systems. However, their application is limited to clinical rehabilitation programs due to their dependency on large-sized compressors as air suppliers. This disadvantage triggered the search for compact portable pneumatic sources. Method A compact valveless pneumatic source to control the bending angle of a soft actuator is proposed in this paper. The source incorporates two series of serially connected commercially available microcompressors to provide additional pressure and flowrate in two directions. In the proposed design, an inner-loop controller, controls the output characteristics of the source while an outer-loop controller handles the trajectory tracking of the angular position. Results Experimental results show that the source is capable of providing up to 160kPa of output. The controller is able to track up to 2rad/sec sinusoidal trajectory with a maximum 0.066rad root-mean-square error. Conclusion Experimental measurements showed satisfactory results in the maximum ratings and tracking errors whilst relatively low average power was consumed by eliminating control valves. This article is protected by copyright. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Emergency presentations of head and neck cancer: our experience in the wake of the Covid‐19 pandemic

xlomafota13 shared this article with you from Inoreader Emergency presentations of head and neck cancer: our experience in the wake of the Covid‐19 pandemic Via Clinical Otolaryngology Abstract The COVID-19 pandemic imposed dramatic changes on delivery of medical services, leading to significant reductions in urgent referrals for suspected cancer. A resultant surge in patients presenting with advanced disease, potentially in an emergency context, has been anticipated but, until now, no real-world data have been disseminated. Herein, we report a dramatic surge in new and newly recurrent HNCs presenting with advanced disease in an emergency context in the period immediately following the COVID-19-induced UK national lockdown. To minimise adverse outcomes HNC services should prepare for a fluctuant but ongoing increase in such presentations, with expansion and streamlining of secondary healthcare capacity, together with accurate public health messaging tailored towards patients and primary care. These data are likely to have lasting significance and will help inform practice and healthcare policy during and following any future COVID-19 outbreaks. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Bezold's abscess complicating acute otomastoiditis: transmastoid approach for surgical drainage with an exoscope (with video)

xlomafota13 shared this article with you from Inoreader Bezold's abscess complicating acute otomastoiditis: transmastoid approach for surgical drainage with an exoscope (with video) Via European Annals of Otorhinolaryngology, Head and Neck Diseases Publication date: Available online 8 June 2021 Source: European Annals of Otorhinolaryngology, Head and Neck Diseases Author(s): Pedro Correia-Rodrigues, João Levy, Leonel Luís View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.