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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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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Comparison of treatment strategies for resectable locally advanced primary mucinous adenocarcinoma of the lung

AlexandrosSfakianakis shared this article with you from Inoreader Comparison of treatment strategies for resectable locally advanced primary mucinous adenocarcinoma of the lung via Cancer Medicine Stage III-N2 lung pure mucinous adenocarcinoma (PMA) tended to appear more in lower lobes, with higher differentiation degree, earlier T stage, and more positive lymph nodes(LNs) than other adenocarcinoma. The prognosis of resectable III-N2 PMAs was worse than other adenocarcinoma. Patients with ≤7 positive LNs benefited from PORT and those with >7 positive LNs benefited from chemotherapy. Abstract Background Primary pure mucinous adenocarcinoma (PMA) is a rare type of lung cancer with unique clinical and prognostic features. Previous studies have shown that PMA have more early-stage cancer compared with other adenocarcinoma (ADC) subtypes. The clinicopathological features and optimal treatment strategies of resectable locally advanced mucinous adenocarcinoma lack evidence and require further study. Methods In this study, we collected information from patients with stage III-N2 PMA who underwent radical surgery between 2004 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database. The clinicopathological parameters, treatments, overall survival (OS), and cancer-specific survival (CSS) were evaluated. Results Of 242,699 eligible lung adenocarcinoma patients, 124 with PMA and 3405 with other ADCs of stage III-N2 received radical surgery were identified. Compared with other ADCs, PMA tended to appear more in the lower lobes, with higher degree of differentiation, less early T stage, and more positive lymph nodes numbers. Patients with PMA had significantly worse survival than other ADCs (OS = 45.0 vs. 57.1 months, p = 0.005, CSS = 51.8 vs. 65.5 months, p = 0.017). We explored the benefit population of postoperative radiotherapy (PORT) and found that the population with ≤7 positive lymph nodes could benefit from PORT, and OS was significantly improved (41.2 vs. 69.3 months, p = 0.034). For patients with >7 positive lymph nodes, PORT did not provide a survival benefit, while chemotherapy improved OS (10.9 vs. 23.3 months, p = 0.041). Multivariate analysis showed that race, tumor location, number of positive lymph nodes, and PORT were independent prognostic factors in patients with postoperative III-N2 lung PMA. Conclusion The prognosis of patients with resectable III-N2 primary lung PMA was significantly worse than that of other ADCs, and PORT was an independent prognostic factor. Patients with ≤7 positive lymph nodes could benefit from PORT and those with >7 positive lymph nodes could benefit from chemotherapy. View on Web

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Swallowing Exercise During Head and Neck Cancer Treatment: Results of a Randomized Trial

AlexandrosSfakianakis shared this article with you from Inoreader Swallowing Exercise During Head and Neck Cancer Treatment: Results of a Randomized Trial via Dysphagia AbstractThe diagnosis and treatment of head and neck cancer (HNC) can have substantial impact on swallowing function, nutritional balance, physical function and quality of life (QoL). Early initiated swallowing exercises are hypothesized to improve swallowing function in HNC patients. The aim was to investigate the effects of swallowing exercises and progressive resistance training (PRT) during radiotherapy on swallowing function, physical function and QoL in patients with pharynx-, larynx-, oral cavity cancer or unknown primary compared to usual care. In a multi-centre RCT participants were assigned to (a) twice-weekly PRT and daily swallowing exercises throughout treatment or (b) usual care. Outcomes were measured at end of treatment and 2, 6 and 12  months after. Primary outcome was pe... View on Web

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Clinicopathologic Features and Frozen Diagnostic Pitfalls of Bronchiolar Adenoma/Ciliated Muconodular Papillary Tumors (BA/CMPTs)

AlexandrosSfakianakis shared this article with you from Inoreader Clinicopathologic Features and Frozen Diagnostic Pitfalls of Bronchiolar Adenoma/Ciliated Muconodular Papillary Tumors (BA/CMPTs) via The American Journal of Surgical Pathology - Published Ahead-of-Print To describe the histologic features of bronchiolar adenoma/ciliated muconodular papillary tumors (BA/CMPTs) and analyze the pitfalls in diagnosis from frozen sections. A total of 208 frozen and permanent sections of BA/CMPTs from Shanghai Chest Hospital from July 2018 to July 2021 were retrospectively analyzed. The median age of BA/CMPT patients was 65 years (15 to 79 y), and women accounted for 61.62% (122/198). The median size of BA/C MPTs was 0.6 cm (range 0.2 to 2 cm), of which 88.94% were small (≤1 cm, 185/208). In terms of location, the right lower lobe accounted for 44.23% (92/208), and the left lower lobe accounted for 33.65% (70/208). In 10 patients with 2 independent BA/CMPTs, 5 lesions were located in the left lower lobe and 4 in the right lower lobe. A total of 86.06% of the CT images of BA/CMPT showed solid/subsolid nodules (179/208). Among 208 tumors, 68.75% were distal type (143/208), and 31.25% were proximal type (65/208). The qualitative error rate of frozen sections was 21.33% (32/150), of which the distal type accounted for 75% (24/32); most of them were misdiagnosed as invasive adenocarcinoma during frozen diagnosis. The frozen diagnosis of BA/CMPTs might result in misdiagnosis as invasive adenocarcinoma. A careful search for characteristics of BA/CMPT, such as bilayer epithelial cells with basal cells and a lack of cellular atypia and invasive growth patterns, may be helpful fo r frozen diagnosis. View on Web

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