Esophageal Glomus Tumors: Rare Neoplasms with Aggressive Clinical Behavior

AlexandrosSfakianakis shared this article with you from Inoreader Esophageal Glomus Tumors: Rare Neoplasms with Aggressive Clinical Behavior via Histopathology Aims Glomus tumors are neoplasms with perivascular smooth muscle differentiation, which rarely occur in the esophagus and may behave aggressively in this site based upon prior case reports. This study describes the clinicopathologic features of 3 esophageal glomus tumors diagnosed at 2 large academic institutions between 1984 and 2022. Methods and Results Three cases of esophageal glomus tumors were identified. Patients included 2 females and 1 male, with an age range of 19-65 years. All 3 tumors behaved in a malignant fashion, with metastases to various sites (lymph nodes, lung, pericardium, pleura, diaphragm, scalp). One patient developed an aorto-esophageal fistula, resulting in a fatal hemorrhage. Tumors ranged in size from 4.5 to 8.1 cm. Histologically, all tumors had a multinodular, perivascular growth pattern. The neoplasms showed varying degrees of cytologic atypia and spindling, elevated mitotic activity (2-12 mitotic figures per 10 high-power fields), and necrosis was seen in in 2 cases. All tumors expressed smooth muscle actin by immunohistochemistry, and harbored NOTCH gene alterations (MIR143::NOTCH2 fusion in 2 cases; NOTCH3 rearrangement and NOTCH1 point mutation in 1 case). An ATRX splicing mutation in exon 10 was also identified in 1 case. Conclusions Esophageal glomus tumors pose diagnostic challenges given their rarity at this site but can be recognized by their characteristic perivascular growth pattern, round central nuclei, and supportive ancillary studies. Given the propensity for aggressive behavior in this location, we recommend management by a multidisciplinary sarcoma team for optimal outcome. View on Web

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Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers

AlexandrosSfakianakis shared this article with you from Inoreader Investigation of Shared Genetic Risk Factors Between Parkinson's Disease and Cancers via Movement Disorders Abstract Background Epidemiological studies that examined the association between Parkinson's disease (PD) and cancers led to inconsistent results, but they face a number of methodological difficulties. Objective We used results from genome-wide association studies (GWASs) to study the genetic correlation between PD and different cancers to identify common genetic risk factors. Methods We used individual data for participants of European ancestry from the Courage-PD (Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in Parkinson's Disease; PD, N = 16,519) and EPITHYR (differentiated thyroid cancer, N = 3527) consortia and summary statistics of GWASs from iPDGC (International Parkinson Disease Genomics Consortium; PD, N = 482,730), Melanoma Meta-Analysis Consortium (MMAC), Breast Cancer Association Consortium (breast cancer), the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (prostate cancer), International Lung Cancer Consortium (lung cancer), and Ovarian Cancer Association Consortium (ovarian cancer) (N comprised between 36,017 and 228,951 for cancer GWASs). We estimated the genetic correlation between PD and cancers using linkage disequilibrium score regression. We studied the association between PD and polymorphisms associated with cancers, and vice versa, using cross-phenotypes polygenic risk score (PRS) analyses. Results We confirmed a previously reported positive genetic correlation of PD with melanoma (Gcorr = 0.16 [0.04; 0.28]) and reported an additional significant positive correlation of PD with prostate cancer (Gcorr = 0.11 [0.03; 0.19]). There was a significant inverse association between the PRS for ovarian cancer and PD (odds ratio [OR] = 0.89 [0.84; 0.94]). Conversely, the PRS of PD was positively associated with breast cancer (OR = 1.08 [1.06; 1.10]) and inversely associated with ovarian cancer (OR = 0.95 [0.91; 0.99]). The association between PD and ovarian cancer was mostly driven by rs183211 located in an intron of the NSF gene (17q21.31). Conclusions We show evidence in favor of a contribution of pleiotropic genes to the association between PD and specific cancers. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. View on Web

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Exposure to Particulate Matter and Respirable Crystalline Silica in Tunnel Construction Workers Using Tunnel Boring Machines

AlexandrosSfakianakis shared this article with you from Inoreader Exposure to Particulate Matter and Respirable Crystalline Silica in Tunnel Construction Workers Using Tunnel Boring Machines via Annals of Work Exposures and Health Advance Access Abstract Objectives This study aimed to assess the exposure to a selection of aerosols and gases in the work environment for workers performing tunnel construction using tunnel boring machines (TBMs), to identify determinants of exposure based on the information available and to calculate robust estimates of exposure using a statistical model. The focus was particulate matter (PM) and respirable crystalline silica (RCS). In addition, concentrations of nitrogen dioxide (NO2), elemental carbon (EC), and oil mist were assessed. Methods Personal sampling was conducted from February 2017 to February 2019. PM in the thoracic and the respirable aerosol fractions was collected, and RCS was determined in the respirable aerosol fraction. Context information was collected on questionnaires. Because the workers could participate in the sampling more than once and multiple measurements were performed on the same date a mixed model was use d in the analysis. Concentrations of PM and RCS are presented as estimated and measured geometric means (GMest and GMmea) and estimated arithmetic mean (AMest) in addition to the median. Measured concentrations of NO2, EC, and oil mist are presented as geometric means. Results A total of 290 and 289 personal samples of PM in the thoracic and respirable aerosol fractions were available for analysis, respectively. Work title/work location, type of work (production, maintenance, or a combination of the two), and date of sampling were identified as determinants of exposure. Workers in the front of the TBMs had the highest exposure to PM and RCS. The GMest of RCS exposure varied from 35 to 413 μg m–3 depending on the work title. The geometric standard deviations for measured RCS concentrations by work title ranged from 1.6 to 3.5. A total of 16 samples of NO2 and EC and 12 samples of oil mist were co llected. Maximum values of NO2 and EC were 54 µg m–3 and 23 µg m–3, respectively. The maximum measured value of oil mist was 0.08 mg m–3. Conclusions All TBM workers were exposed to PM and RCS. Exposure to RCS may be substantial, and workers in front of the TBM were exposed to the highest concentrations of both PM and RCS. A day-to-day variation was found, probably caused by differences in drilling activities. Preventive measures are warranted to keep the exposure to PM and consequently the exposure to RCS as low as possible to protect the health of workers in tunnel construction. View on Web

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TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models

AlexandrosSfakianakis shared this article with you from Inoreader TRIM21 inhibits irradiation-induced mitochondrial DNA release and impairs antitumour immunity in nasopharyngeal carcinoma tumour models via Nature Communications - current - nature.com science feeds Nature Communications, Published online: 16 February 2023; doi:10.1038/s41467-023-36523-y The molecular mechanisms determining the response to radiotherapy remain incompletely understood. Here, the authors demonstrate that the E3 ubiquitin ligase and intracellular Fc receptor, TRIM21, impairs CD8+ T cell responses in nasopharyngeal carcinoma tumour models following ionizing radiation. View on Web

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Trends in the global antibiotics market

AlexandrosSfakianakis shared this article with you from Inoreader Trends in the global antibiotics market via Nature Reviews Drug Discovery - Issue - nature.com science feeds Nature Reviews Drug Discovery, Published online: 15 February 2023; doi:10.1038/d41573-023-00029-5 Trends in the global antibiotics market View on Web

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Structural Analysis of MALAT1 long non-coding RNA in cells and in evolution [Article]

AlexandrosSfakianakis shared this article with you from Inoreader Structural Analysis of MALAT1 long non-coding RNA in cells and in evolution [Article] via RNA In Advance Although not canonically polyadenylated, the long non-coding RNA MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is stabilized by a highly conserved 76 nucleotide triple helix structure on its 3' end. The entire MALAT1 transcript is over 8,000 nucleotides long in humans. The strongest structural conservation signal in MALAT1 (as measured by co-variation of base-pairs) is in the triple helix structure. Primary sequence analysis of co-variation alone does not reveal the degree of structural conservation of the entire full-length transcript, however. Furthermore, RNA structure is often context dependent; RNA binding proteins that are differentially expressed in different cell types may alter structure. We investigate here the in cell and cell free structures of the full-length human and green monkey (Chlorocebus sabaeus) MALAT1 transcripts in multiple tissue-derived cell lines using SHAPE chemical probing. Our data reveal levels of uniform str uctural conservation in different cell lines, in cells and cell free, and even between species, despite significant differences in primary sequence. The uniformity of the structural conservation across the entire transcript suggests that, despite seeing co-variation signals only in the triple helix junction of the lncRNA, the rest of the transcript's structure is remarkably conserved at least in primates and across multiple cell types and conditions. View on Web

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