RPL35 promotes neuroblastoma progression via the enhanced aerobic glycolysis

xlomafota13 shared this article with you from Inoreader RPL35 promotes neuroblastoma progression via the enhanced aerobic glycolysis Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5701-5714. eCollection 2021. ABSTRACT Neuroblastoma (NB) is an rare type of tumor that almost affects children age 5 or younger due to its rapid proliferation ability. The overall survival rate of patients with advanced NB is not satisfactory. Ribosomal proteins (RPs) play a critical role in the development and progress of cancer. However, the contribution of RPL35 in NB has not been proven. In this study, we reveal that RPL35 is upregulated in NB tissues and the upregulation of RPL35 promotes proliferation and migration of NB while RPL35 knockdown significantly restrained the proliferation of NB cells. In terms of mechanism, glycolysis was decreased and the mitochondrial respiration was increased with knockdown of RPL35 in NB cells, indicating that RPL35 function as a positive regulator in aerobic glycolysis. Importantly, our data indicated that RPL35 deficiency decreased HIF1α expression both in m RNA and protein levels. Western blot analysis showed that RPL35 knockdown has a negative regulatory effect on the ERK pathway, and RPL35 modulated aerobic glycolysis in part through its regulation of the RPL35/ERK/HIF1α axis. Overall, RPL35 functions as a positive regulator of aerobic glycolysis, and the RPL35/ERK/HIF1α axis could be a potential therapeutic target for the therapy of NB. PMID:34873488 | PMC:PMC8640819 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

From development to cancer - an ever-increasing role of AGR2

xlomafota13 shared this article with you from Inoreader From development to cancer - an ever-increasing role of AGR2 Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5249-5262. eCollection 2021. ABSTRACT Anterior gradient 2, AGR2, is a small, 20 kDa protein that plays a vital role in oxidative protein folding in the endoplasmic reticulum. AGR2 is involved in several signal transduction pathways that are essential for cell survival. It was initially discovered in the African clawed frog, Xenopus laevis, where it plays an important function in embryonic development. Akin to several other developmental genes, it is also frequently deregulated in cancer, where it plays a decisive role in tumor initiation, progression and metastasis. In this review, we have summarized currently known AGR2 functions, its expression and function in embryonic and cancer development, as well as its potential as a candidate tumor biomarker and promising new target for cancer immunotherapy. PMID:34873459 | PMC:PMC8640830 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Low intratumoral genetic neutrophil-to-lymphocyte ratio (NLR) is associated with favorable tumor immune microenvironment and with survival in triple negative breast cancer (TNBC)

xlomafota13 shared this article with you from Inoreader Low intratumoral genetic neutrophil-to-lymphocyte ratio (NLR) is associated with favorable tumor immune microenvironment and with survival in triple negative breast cancer (TNBC) Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5743-5755. eCollection 2021. ABSTRACT Patients with triple negative breast cancer (TNBC) have a poor prognosis. A novel prognostic biomarker may guide management by appropriately selecting patients for particular treatments. Peripheral blood neutrophil-to-lymphocyte ratio (NLR) was reported to associate with cancer progression, thus we hypothesized that intratumor genetic NLR will reflect tumor immune microenvironment (TIME) and breast cancer biology. The intratumoral genetic NLR previously defined as the ratio of CD66b (CEACAM8) and CD8 (CD8A) gene expressions was utilized to analyze total of 2,994 patients from METABRIC, TCGA, GSE21094, GSE22358, GSE25088, GSE32646, and GSE2603 cohorts. Intratumoral genetic NLR did not correlate with cancer stage nor clinical parameters of cancer cell proliferation such as Nottingham histological grade or MKI67 expression levels in neither the METABRIC or TC GA cohorts. Intratumoral genetic NLR-high breast cancer was not associated with pathologic complete response (pCR) after neoadjuvant chemotherapy in 5 independent cohorts with different regimens. Despite these results, intratumoral genetic NLR-high TNBC demonstrated worse disease-free, disease-specific, and overall survival. Intratumoral genetic NLR-low TNBC enriched multiple immune-related gene sets, was associated with higher favorable immune-related scores and with a favorable TIME, whereas no gene sets enriched to NLR-high TNBC. In conclusion, intratumoral genetic NLR-low TNBC was associated with favorable TIME and with better survival. PMID:34873491 | PMC:PMC8640806 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Synergistic radiosensitizing effect of BR101801, a specific DNA-dependent protein kinase inhibitor, in various human solid cancer cells and xenografts

xlomafota13 shared this article with you from Inoreader Synergistic radiosensitizing effect of BR101801, a specific DNA-dependent protein kinase inhibitor, in various human solid cancer cells and xenografts Via American Journal of Cancer Research Am J Cancer Res. 2021 Nov 15;11(11):5440-5451. eCollection 2021. ABSTRACT DNA-dependent protein kinase (DNA-PK), an essential component of the non-homologous end-joining (NHEJ) repair pathway, plays an important role in DNA damage repair (DDR). Therefore, DNA-PK inhibition is a promising approach for overcoming radiotherapy or chemotherapy resistance in cancers. In this study, we demonstrated that BR101801, a potent DNA-PK inhibitor, acted as an effective radiosensitizer in various human solid cancer cells and an in vivo xenograft model. Overall, BR101801 strongly elevated ionizing radiation (IR)-induced genomic instability via induction of cell cycle G2/M arrest, autophagic cell death, and impairment of DDR pathway in human solid cancer cells. Interestingly, BR101801 inhibited not only phosphorylation of DNA-PK catalytic subunit in NHEJ factors but also BRCA2 protein level in homologous recombination (HR) factors. In addition, combination BR101801 and IR suppressed tumor growth compared with IR alone by reducing phosphorylation of DNA-PK in human solid cancer xenografts. Our findings suggested that BR101801 is a selective DNA-PK inhibitor with a synergistic radiosensitizing effect in human solid cancers, providing evidence for clinical applications. PMID:34873471 | PMC:PMC8640799 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Morphometric analysis of the lumbar vertebrae and intervertebral discs in relation to abdominal aorta: CT-based study

xlomafota13 shared this article with you from Inoreader Morphometric analysis of the lumbar vertebrae and intervertebral discs in relation to abdominal aorta: CT-based study Via radiol anat Surg Radiol Anat. 2021 Dec 7. doi: 10.1007/s00276-021-02865-9. Online ahead of print. ABSTRACT PURPOSE: Although lumbar discectomy is the most common procedure in spine surgery, reports about anatomical relations between discs and prevertebral vessels are limited. Aim of this research was to investigate morphometric of the lumbar region and the relations between intervertebral discs (IVDs) and abdominal aorta. METHODS: 557 abdominal computed tomography scans were assess ed. For each spinal column level from Th12/L1 down to L4/L5, we investigated: intervertebral disc's and vertebra's height, width, length, and distance from aorta or common iliac artery (CIA). Those arteries were also measured in two dimensions and classified based on location. RESULTS: 54.58% of patients were male. There was a significant difference in arterial-disc distances (ADDs) between genders at the levels: L1/L2 (1.32 ± 1.97 vs. 0.96 ± 1.78 mm; p = 0.0194), L2/L3 (1.97 ± 2.16 vs. 1.15 ± 2.01 mm; p < 0.0001), L3/L4 (2.54 ± 2.78 vs. 1.71 ± 2.61 mm; p = 0.0012), also for both CIAs (left CIA 3.64 ± 3.63 vs. 2.6 ± 3.06 mm; p = 0.0004 and right CIA: 7.96 ± 5.06 vs. 5.8 ± 4.57 mm; p < 0.001)-those ADDs were higher in men at all levels. The length and width of IVD increased alongside with disc level with the maximum at L4/L5. CONCLUSION: Bifurcations of the aorta in most cases occurred at the L4 level. Collected data suggest that at the highest lumbar leve ls, there is a greater possibility to cause injury of the aorta due to its close anatomical relationship with discs. Females have limited, in comparison to males, ADD at L1/L2, L2/L3, and L3/L4 levels what should be taken into consideration during preoperative planning of surgical intervention. PMID:34874459 | DOI:10.1007/s00276-021-02865-9 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Treatment of Hypophonia in Parkinson's Disease Through Biofeedback in Daily Life Administered with A Portable Voice Accumulator

xlomafota13 shared this article with you from Inoreader Treatment of Hypophonia in Parkinson's Disease Through Biofeedback in Daily Life Administered with A Portable Voice Accumulator Via Journal of Voice The purpose of this study was to assess the outcome following continuous tactile biofeedback of voice sound level administered, with a portable voice accumulator to individuals with Parkinson's disease (PD). View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Exoscopic visualisation with VITOM® 3D in paediatric cochlear implantation: preliminary results

xlomafota13 shared this article with you from Inoreader Exoscopic visualisation with VITOM® 3D in paediatric cochlear implantation: preliminary results Via Clinical Otolaryngology Abstract 3D exoscopy is an emerging visualisation technique designed to improve ergonomics and image quality during surgeries. We present a novel application of the VITOM® 3D exoscope in cochlear implantation (IDEAL Stage 2a prospective case series). The system enabled high-quality visualisation during both posterior tympanotomy and electrode insertion. Both the chief surgeon and the staff members rated the ergonomics of the system highly. 3D exoscopy is a useful alternative to conventional microscopy, but the two techniques remain to be directly compared in larger studies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prediction of Oxygen Desaturation by Using Sound Data From a Noncontact Device: A Proof‐of‐Concept Study

xlomafota13 shared this article with you from Inoreader Prediction of Oxygen Desaturation by Using Sound Data From a Noncontact Device: A Proof‐of‐Concept Study Via The Laryngoscope Objectives/Hypothesis Prediction of the apnea-hypopnea index (AHI) from breathing sounds during sleep could be used to prescreen for obstructive sleep apnea (OSA). In addition, the oxygen desaturation index (ODI) is a known risk factor for developing cardiovascular disease in OSA patients. This study focused on estimation of ODI from a noncontact manner from sleep breathing sounds. Study Design Retrospective study. Methods Patients who visited the sleep center due to snoring or sleep apnea underwent polysomnography in lab overnight. Sound recordings were made during polysomnography using a microphone. After noise reduction, the sound data were segmented into 5 seconds windows and features were extracted. Binary classification and regression analyses were performed to estimate the ODI during sleep (model 1). This was re-tested after inclusion of body mass index (BMI) and age as additional features (model 2: BMI only, model 3: BMI and age). Results We included 116 patients. The mean age and AHI of all patients were 50.4 ± 16.7 years and 23.0 ± 24.0 events/hr. In binary classification, for ODI cutoff values of 5, 15, and 30 events/hr, the areas under the curve were 0.88, 0.93, 0.91, respectively, and accuracies were 85.34, 86.21, and 87.07, respectively. In regression analysis, the correlation coefficient and mean absolute error were 0.80 and 9.60 events/hr, respectively. In models 2 and 3, the correlation coefficient and mean absolute error were 0.82, 9.44 events/hr and 0.81, 9.6 events/hr, respectively. Conclusion Prediction of ODI from sleep sound seems to be feasible. Additional clinical feature such as BMI may increase overall predictability. Level of Evidence IV Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Third molar surgical difficulty scales: systematic review and preoperative assessment form

xlomafota13 shared this article with you from Inoreader Third molar surgical difficulty scales: systematic review and preoperative assessment form Via pubmed: "med oral patol oral... Med Oral Patol Oral Cir Bucal. 2021 Dec 7:24951. doi: 10.4317/medoral.24951. Online ahead of print. ABSTRACT BACKGROUND: The main objective of this systematic review was to collect the pre-existing scales for assessing the difficulty of third molar extraction. The secondary objective was to design a proposal for a preoperative evaluation protocol for the difficulty of third molar extraction. MATERIAL AND METHODS: Two independent researchers conducted an electronic search in Pubmed (MEDLINE), Cochrane, and Scopus databases during March 2021. Included studies evaluated the prediction of the difficulty of surgical removal of impacted upper or lower third molars using new indices/scales or pre-existing scales with or without modifications. Articles referring to coronectomies or assessing pre-surgical difficulty using other tools were excluded. Neither language nor publication date restrictions were applied. RESULTS: Out of 242 articles, 13 prospective cohort studies were finally selected. Seven developed new indices/scales, and 6 assessed the predictive ability of some pre-existing scales. Most of the indices/scales contained radiological variables and few added any patient-related variables. We proposed a preoperative assessment protocol of the difficulty of third molar extraction to facilitate treatment planning and/or considerate referral in cases of high difficulty. This proposal used patient-related, radiological and surgical variables. CONCLUSIONS: Using a preoperative protocol to evaluate the surgical difficulty, including different patient-specific, radiological and surgical variables, could facilitate treatment planning, help clinicians prevent complications and assess the possibility of referral. PMID:34874928 | DOI:10.4317/medoral.24951 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization

xlomafota13 shared this article with you from Inoreader Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization Via Melanoma Research - Published Ahead-of-Print Macrophage inhibitory cytokine-1 (MIC-1) has been reported to be elevated in various human cancers including melanoma; however, the function of MIC-1 in cancer remains unclear. In this study, we attempt to clarify the role of MIC-1 in tumor pathogenesis by employing the orthotopic B16F1 melanoma mouse model in which seru m MIC-1 levels are positively correlated with tumor size. By stably transfecting a MIC-1 expression construct into B16F1 melanoma cells, we increased the expression and secretion levels of MIC-1. This increase in MIC-1 expression significantly enhanced the growth of tumors derived from B16F1 cells in vivo, despite not affecting in vitro cell growth. The elevated MIC-1 expression in B16F1 cells also resulted in lymph node metastasis in B16F1 tumor-bearing mice, significantly increasing mortality. Interestingly, among small melanoma tumors of similar size, tumors derived from the MIC-1-transfected B16F1 cells exhibited enhanced blood vessel formation compared with those of mock transfectant cells. Also, more MIC-1 was found in well-vascularized tumor regions than in poorly vascularized tumor regions. Moreover, conditioned medium (CM) of the MIC-1-transfected melanoma cells enhanced the angiogenic properties of endothelial cells more than CM of mock transfectant cells. Notably, hypoxic culture conditions forced parental B16F1 cells to secrete more endothelial cell-stimulating factors, among which the function of MIC-1 was confirmed by blocking the effects with an anti-MIC-1 antibody. Taken together, these results suggest that the MIC-1 produced by melanoma cells in response to oxygen deprivation promotes tumor vascularization during melanoma development in vivo, leading to enhanced tumor growth and metastasis. * Jaeseob Lee and Young-June Jin contributed equally to the writing of this article. Received 29 March 2021 Accepted 22 September 2021 Correspondence to Hansoo Lee, PhD, Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea, Tel: +82 33 250 8530; e-mail: hslee@kangwon.ac.kr Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical features, molecular characteristics and surgical management of primary penile mucosal melanoma based on the European Association of Urology Penile Cancer Guidelines

xlomafota13 shared this article with you from Inoreader Clinical features, molecular characteristics and surgical management of primary penile mucosal melanoma based on the European Association of Urology Penile Cancer Guidelines Via Melanoma Research - Published Ahead-of-Print Penile mucosal melanoma is an aggressive and rare genital malignancy. The aim of the present study was to review the management and outcomes of a homogenous cohort of patients with histologically confirmed penile mucosal melanoma, at a single specialist centre. A retrospective review of an institutional database ident ified patients with penile mucosal melanoma over a 10-year period. Patient demographics, histopathological characteristics, type of primary surgery, recurrence, presence of metastatic disease and molecular markers were evaluated. The management of the patients was initially based on the European Association of Urology (EAU) penile cancer guidelines which are primarily for squamous cell carcinoma with inputs from a melanoma multidisciplinary team. Twelve patients with penile mucosal melanoma were analysed. Median [interquartile range (IQR)] age was 69.5 (67.25−81) years. The overall median follow-up (IQR) was 69.5 (20−114) months, while median follow-up for cancer-specific survival (CSS) was 11.5 (8−37) months. Location of primary tumour was glans penis (n = 7), urethra (n = 2) and inner prepuce (n = 3). The CSS at 1, 2 and 5 years after primary surgery was 33%, 16.7% and 0%, respectively. The recurrence-free survival at 1, 3 and 5 months after the primary surge ry was 90%, 67% and 56%, respectively. All patients with metastatic disease or with inguinal lymph node invasion at presentation, died within 25 months of the primary diagnosis. Management based on the modified EAU penile cancer guidelines still led to poor outcomes. We present a management diagram based on our experience. Received 6 June 2021 Accepted 18 September 2021 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Asif Muneer, MD, FRCS (Urol), Division of Surgery and Interventional Science, NIHR Biomedical Research Centre, University College London Hospital, University College London, 235 Euston Rd, London NW1 2BU, UK, Tel: +44 0203 447 9280; e-mail: asif.muneer@nhs.net Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.