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.

Modified Transpterygoid Approach to Sphenoid Meningoencephaloceles: A Shorter Run for a Longer Slide

xlomafota13 shared this article with you from Inoreader Modified Transpterygoid Approach to Sphenoid Meningoencephaloceles: A Shorter Run for a Longer Slide Via The Laryngoscope Objectives Cerebrospinal fluid (CSF) leaks and meningoencephaloceles originating in the lateral recess of the sphenoid sinus can be challenging. The traditional transpterygoid approach through the pterygopalatine fossa (PPF) is time consuming and places important structures at risk, which can lead to significant morbidity. We report a multi-institutional experience using a simplified, endoscopic modified transpterygoid approach (MTPA), which spares the PPF contents in the management of lateral sphenoid sinus meningoencephaloceles and CSF leaks. Study Design Multi-Institutional, Retrospective Case Series. Methods Patients with lateral sphenoid recess CSF leaks and meningoencephaloceles between 2014 and 2020 who underwent the MTPA at two academic medical centers were identified. Repair techniques and outcomes were evaluated. Results Thirty-three patients underwent the MTPA for management. Skull base reconstruction was performed using a free mucosal graft (24/33, 72.7%), nasoseptal flap (4/33, 12.1%), bone grafts (3/33, 9.1%), and abdominal fat grafts (2/33, 6.1%). Lumbar drains and perioperative intracranial pressure measurements were routinely employed. Postoperative complications were uncommon and included three patients (9.7%) with temporary V2 anesthesia, one patient (3.2%) with prolonged V2 anesthesia, and one patient (3.2%) with subjective dry eye, all of which resolved at 9 months postoperatively. There were no recurrent CSF leaks resulting in a 100% success rate. Average follow-up was 13 months. Conclusion The MTPA reduces morbidity and greatly simplifies access to the lateral sphenoid sinus for the management of CSF leaks and meningoencephaloceles, without compromising exposure. This technique avoids the need for extensive PPF dissection and should be considered for the management of benign lesions involving the lateral sphenoid sinus. Level of Evidence IV Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Management Strategy of Local Subcutaneous Effusion After Auricle Reconstruction

xlomafota13 shared this article with you from Inoreader Management Strategy of Local Subcutaneous Effusion After Auricle Reconstruction Via ear nose throat Ear Nose Throat J. 2021 Jun 7:1455613211022104. doi: 10.1177/01455613211022104. Online ahead of print. ABSTRACT OBJECTIVES: Microtia is a severe congenital malformation of the external ear, and auricular reconstruction is still a challenge for plastic surgeons because of the complicated procedures and rare conditions. This study aimed to describe the location of subcutaneous effusion after auricular reconstruction and explore the clinical efficacy of the indwelling needle pu ncture drainage method in the treatment of local subcutaneous effusion. METHODS: From January 2017 to December 2019, 1240 patients (1296 affected sides) who underwent auricular reconstruction using autogenous cartilage framework in the Plastic Surgery Hospital of Chinese Academy of Medical Science and Peking Union Medical College were selected. The local subcutaneous effusion occurred within 5 days after the drainage tube was removed, and the indwelling needle was used for puncture and drainage in the postoperative treatment. RESULTS: A total of 55 patients had subcutaneous effusion after the operation, including 24 cases with Nagata's method and 31 cases with the expanded single-flap method. One patient showed no obvious reduction after puncture and drainage by indwelling needle and improved after the secondary operation. Two patients had slight cartilage absorption. The remaining patients had good results. CONCLUSIONS: The method of the indwelling needle for punc ture and drainage is easy to operate. The problem of local subcutaneous effusion after auricular reconstruction can be solved and good efficacy can be obtained. PMID:34098768 | DOI:10.1177/01455613211022104 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Diagnostic Yield of Excisional Biopsy in Cervical Lymphadenopathy: A Retrospective Analysis of 158 Biopsies in Adults

xlomafota13 shared this article with you from Inoreader The Diagnostic Yield of Excisional Biopsy in Cervical Lymphadenopathy: A Retrospective Analysis of 158 Biopsies in Adults Via ear nose throat Ear Nose Throat J. 2021 Jun 7:1455613211023009. doi: 10.1177/01455613211023009. Online ahead of print. ABSTRACT OBJECTIVES: Cervical lymph nodes are the most common site of peripheral lymphadenopathy. The underlying etiologies are usually benign and self-limiting but may include malignancies or other severe life-threatening diseases. The aim of the current study was to investigate the various underlying pathologies of cervical lymphadenopathy as assessed by the diagnostic yi eld of excisional lymph node biopsies of the neck in a tertiary adult practice. The evaluation was performed in light of previous literature and regional epidemiological patterns. METHODS: Retrospective analysis of hospital charts of 158 adult patients who underwent an excisional biopsy for suspected cervical lymphadenopathy at a tertiary referral head and neck service between January 2017 and December 2019. RESULTS: The most common underlying pathology was unspecific and/or reactive lymphadenitis in 44.5% of specimens, followed by malignant disease in 38.6% of cases. An age above 40 years was significantly correlated with an increased likelihood of malignant disease. Lower jugular and posterior triangle lymph nodes showed higher malignancy rates than other groups (100% and 66.7%, respectively). The overall surgical complication rate was 2.5%. CONCLUSIONS: The results of the current study serve as an indicator of the variety of etiologies causing cervical lymphaden opathy. In particular, given the increasing incidence of malignant diseases in recent decades, the findings should alert physicians to the importance of lymph node biopsy for excluding malignancy in persistent cervical lymphadenopathy especially in older adults. The findings emphasize the value of excisional lymph node biopsy of the neck as a useful diagnostic tool in adult patients with peripheral lymphadenopathy. PMID:34098767 | DOI:10.1177/01455613211023009 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Study on Surgical Implications and Variations of Suprameatal Spine and Other Landmarks on the Lateral Surface of Temporal Bone

xlomafota13 shared this article with you from Inoreader A Study on Surgical Implications and Variations of Suprameatal Spine and Other Landmarks on the Lateral Surface of Temporal Bone Via Otolaryngology Indian Abstract Mastoidectomy forms the main surgical procedure for eradication of disease in chronic otitis media. Such a surgery which contemplates a complete exenteration of all the tympano-mastoid cavities is rightly considered as a difficult one mainly because a large number of vitally important structures are crowded together in the small field of operation and there is always a risk of damaging them. It is therefore, extremely important that the otologist who would undertake this surgery be thorough with the details of the surgical relations of this region. Out of the various structures seen on the lateral surface of temporal bone one very important structure is the suprameatal spine. It is shown to have great variations in shape and size and has been a mystery to researchers due to the implications it is known to have on mastoid region anatomy. In this study we have evaluated the various types of suprameatal spine, prevalence of each type and the effect of each to other landmarks encountered during surgery and also the effect of mastoid pneumatisation on the same. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.