STAT3 regulates 5‐Fu resistance in human colorectal cancer cells by promoting Mcl‐1‐dependent cytoprotective autophagy

AlexandrosSfakianakis shared this article with you from Inoreader STAT3 regulates 5‐Fu resistance in human colorectal cancer cells by promoting Mcl‐1‐dependent cytoprotective autophagy via Cancer Science Abstract Chemoresistance to 5-Fluorouracil (5-Fu)-based chemotherapy is one of the primary reasons for the failure of colorectal cancer (CRC) management. STAT3 can mediate tumor drug resistance through a variety of diverse mechanisms. Nonetheless, the underlying mechanisms of STAT3-induced 5-Fu resistance in CRC are still poorly understood. Here, we aimed to investigate the potential mechanism(s) of STAT3-induced 5-Fu resistance in CRC. Quantitative RT-PCR and Western blot were used to test the expression of STAT3 and Mcl-1 in chemosensitive and chemoresistant CRC tissues and cell lines. After overexpression or knockdown of STAT3 or Mcl-1, and/or treated with or without 5-Fu or chloroquine (CQ), we tested cell viability, inhibitory concentration 50% (IC50) value of 5-FU, cell apoptosis, proliferation, migration, and autophagy. STAT3 and Mcl-1 were significantly upregulated in the chemoresistant CRC tissues and cell lines, and STAT3 positively regulated Mcl-1. Functional studies demonstrated that STAT3 promoted 5-Fu resistance in CRC. Mechanistically, STAT3 triggered autophagy via Mcl-1 to induce cancer chemoresistance. Our results show that STAT3 regulates 5-Fu resistance in CRC by promoting Mcl-1-dependent cytoprotective autophagy. Our results provide a novel role of STAT3 and may offer a new approach for managing CRC 5-Fu resistance. View on Web

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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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Non-polar ether-based electrolyte solutions for stable high-voltage non-aqueous lithium metal batteries

AlexandrosSfakianakis shared this article with you from Inoreader Non-polar ether-based electrolyte solutions for stable high-voltage non-aqueous lithium metal batteries via Nature Communications - current - nature.com science feeds Nature Communications, Published online: 16 February 2023; doi:10.1038/s41467-023-36647-1 Ether solvents have poor anodic stabilities in lithium metal batteries. Here, the authors propose a non-aqueous electrolyte solution with a non-polar and non-fluorinated ether solvent. The electrolyte enables stable cycling of high-voltage Li metal batteries in pouch cell configuration. View on Web

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Visualizing orthogonal RNAs simultaneously in live mammalian cells by fluorescence lifetime imaging microscopy (FLIM)

AlexandrosSfakianakis shared this article with you from Inoreader Visualizing orthogonal RNAs simultaneously in live mammalian cells by fluorescence lifetime imaging microscopy (FLIM) via Nature Communications - current - nature.com science feeds Nature Communications, Published online: 16 February 2023; doi:10.1038/s41467-023-36531-y No multi-color RNA fluorescent tags are currently available for use in live cells. Here, the authors show that fluorescence lifetime imaging microscopy is advantageous for multiplexed RNA visualization while achieving robust cellular contrast. 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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Management of epistaxis associated with oral antithrombotic drugs in Emergency Department and impact on prescription thereafter

AlexandrosSfakianakis shared this article with you from Inoreader Management of epistaxis associated with oral antithrombotic drugs in Emergency Department and impact on prescription thereafter via Clinical Otolaryngology ABSTRACT OBJECTIVES To describe management, and to assess factors associated with antithrombotic prescription thereafter in patients who had epistaxis referred to emergency department. DESIGN Prospective cohort study. From emergency departments, clinical, biological and hospital data were collected. The clinical database was linked to the French Health Insurance Database where we retrieved antithrombotic drug deliveries in a 3-month period before and after referral. SETTING Multicentric population-based cohort study within five well-defined areas. PARTICIPANTS We considered 306 patients referred for epistaxis with a stable oral antithrombotic regimen before referral. MAIN OUTCOME MEASURES We considered management, hospital outcome and case fatality. Antithrombotic prescription in a 3-month follow-up period was categorized into 3 classes: no change, class change, or discontinuation. During follow-up, hospitalization for epistaxis or ischemic events were searched. RESULTS Among 306 adult individuals (mean age: 76 years), 166 took oral anticoagulant and 140 an antiplatelet drug. Blood transfusion was needed in 13.7% of patients and anterior packing alone in 61%. Half of the patients were hospitalized; 301 were discharged alive. Considering antithrombotic prescription thereafter we observed no change in 219 patients (72.8%), class changes in 47 patients (15.6%) and discontinuation in 35 patients (11.6%). We identified four independent predictors for antithrombotic prescription: hospitalization (vs. returning home, P = 0.05), age (P = 0.03), hemoglobin level (P = 0.03) and oral anticoagulant (vs. antiplatelet agent, P <.001). During the three months following discharge, 2 thrombotic and 15 bleeding events were identified. CONCLUSIONS Epistaxis referred to emergency department had an impact on subsequent antithrombotic prescription. This article is protected by copyright. All rights reserved. View on Web

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Photoacoustic (532 nm & 1064 nm) & ultrasonic co‐scanning microscopy for in vivo imaging on small animals—a productized strategy

AlexandrosSfakianakis shared this article with you from Inoreader Photoacoustic (532 nm & 1064 nm) & ultrasonic co‐scanning microscopy for in vivo imaging on small animals—a productized strategy via Journal of Biophotonics Abstract Photoacoustic microscopy provides a new dimension of observation in microscopic life science. However, due to the high complexity of building a photoacoustic microscopy system, for many life science practitioners, it usually takes several years to build a stable photoacoustic microscopy system. For the above situation, in this paper, a productized strategy of photoacoustic (532 nm & 1064 nm) & ultrasonic co-scanning microscopy for in vivo imaging on small animals is presented. 532 nm laser is applied to image blood vessels and pigments in label-free manner. 1064 nm laser is applied to image pigments and some novel probes developed for NIR-II windows. Ultrasound is applied to assist photoacoustic imaging to accurately locate its imaging site in tissues. All three-dimensional results are obtained with one single scan. The strategy presented here will help life science practitioners to build a stable photoacoustic microscopy platform. View on Web

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Progression patterns and site‐specific responses in advanced gastric cancer patients treated with nivolumab

AlexandrosSfakianakis shared this article with you from Inoreader Progression patterns and site‐specific responses in advanced gastric cancer patients treated with nivolumab via Cancer Medicine In advanced gastric cancer treated with nivolumab, patients with mixed progression had a longer progression-free survival than those with systemic progression. Lung and liver metastases had a poorer response to nivolumab than lymph node metastases. Abstract Background While the efficacy of immune checkpoint inhibitors (ICIs) reportedly varies among metastatic sites and progression patterns (classified as systemic progression [SP] or mixed progression [MP]), the clinical efficacy of ICIs against gastric cancer remains unclear. The response to nivolumab depending on metastatic site and clinical outcomes according to progression pattern in patients with advanced gastric cancer was investigated retrospectively. Methods Seventy-four advanced gastric cancer patients with measurable lesions who received nivolumab monotherapy between 2015 and 2020 were enrolled. Progression-free survival (PFS), overall survival, response at each metastatic site, and clinical outcomes according to progression pattern were analyzed retrospectively. SP and MP were defined as progression in more than half of the lesions and progression in half or fewer of the lesions, respectively, in cases evaluated as progressive disease. Results Thirty-five (47%) and 27 (36%) patients had SP and MP, respectively, and 12 (16%) patients experienced no progression. The progression rates of target lesions in the lung (44%) and liver (57%) were significantly higher than that in the lymph nodes (18%) (lung vs. lymph node, p < 0.001; liver vs. lymph node, p = 0.03). Patients with MP had superior PFS to those with SP (median, 2.6 vs. 1.5 months; HR, 0.42; 95% CI, 0.23–0.76; p = 0.004). In MP group, patients with treatment beyond progression (TBP) with nivolumab had a trend of longer post-progression survival than those without TBP (median, 8.0 vs. 4.0 months; HR, 0.55; 95% CI, 0.23–1.29; p = 0.161). Conclusion Patients with MP had a longer PFS than those with SP. Lung and liver metastases had a poorer response to an ICI than lymph node metastases. View on Web

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