42 research outputs found

    Recruited Cells Can Become Transformed and Overtake PDGF-Induced Murine Gliomas In Vivo during Tumor Progression

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    Gliomas are thought to form by clonal expansion from a single cell-of-origin, and progression-associated mutations to occur in its progeny cells. Glioma progression is associated with elevated growth factor signaling and loss of function of tumor suppressors Ink4a, Arf and Pten. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration.We performed lineage tracing in a retrovirally mediated, molecularly and histologically accurate mouse model of hPDGFb-driven gliomagenesis. We were able to distinguish cells in the tumor that were derived from the cell-of-origin from those that were not. Phenotypic, tumorigenic and expression analyses were performed on both populations of these cells. Here we show that during progression of hPDGFb-induced murine gliomas, tumor suppressor loss can expand the recruited cell population not derived from the cell-of-origin within glioma microenvironment to dominate regions of the tumor, with essentially no contribution from the progeny of glioma cell-of-origin. Moreover, the recruited cells can give rise to gliomas upon transplantation and passaging, acquire polysomal expression profiles and genetic aberrations typically present in glioma cells rather than normal progenitors, aid progeny cells in glioma initiation upon transplantation, and become independent of PDGFR signaling.These results indicate that non-cell-of-origin derived cells within glioma environment in the mouse can be corrupted to become bona fide tumor, and deviate from the generally established view of gliomagenesis

    Stand structure and regeneration of Cedrus libani (A. Rich) in Tannourine Cedar Forest Reserve (Lebanon) affected by cedar web-spinning sawfly (Cephalcia tannourinensis, Hymenoptera: Pamphiliidae)

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    The analysis of forest structure is a useful tool to understand stand biodiversity characterizing forest ecosystems, and could help in suggesting appropriate management plans. Cedar forests in Lebanon are remnant patches that survived past human activities but are still threatened by other different anthropogenic and natural disturbances. Among these threats, the cedar web-spinning sawfly (Cephalcia tannourinensis) discovered in Tannourine Cedar Forest Nature Reserve in 1997, which is able to cause the death of trees. The aim of this study is to investigate the impact of this pest on the stand structure and regeneration of Cedrus libani in Tannourine Cedar Forest Nature Reserve located in North Lebanon. The dependence of stand structural attributes (diameter at breast height, total height and basal area) on the presence of infestation by the cedar web-spinning sawfly was identified using the Student’s t-test. The Ripley’s K(d) function was used to analyse the spatial pattern of cedar stands. In addition, the diameter, the vertical structure and the crown projection were characterized using the Weibull function and graphic representations. The results showed that stand structure and regeneration are significantly different between infested and non-infested stands. The cedar of Lebanon remains as the dominant species, with abundant young individuals and a good regeneration status (c = 1.0). The analysis of the spatial pattern showed a positive spatial relationship between mature Lebanese cedar trees as well as between mature and juvenile cedars, with a bigger aggregation in infested plots (6 to 10 meters) than in non-infested quadrates (2 to 7 meters), reflecting the impact of the cedar web-spinning sawfly on the stand structure and regeneration of Cedrus libani stands

    Corticosteroid use in otolaryngology: current considerations during the COVID-19 era

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    Objective To offer pragmatic, evidence-informed advice on administering corticosteroids in otolaryngology during the coronavirus disease 2019 (COVID-19) pandemic, considering therapeutic efficacy, potential adverse effects, susceptibility to COVID-19, and potential effects on efficacy of vaccination against SARS-CoV-2, which causes COVID-19. Data Sources PubMed, Cochrane Library, EMBASE, CINAHL, and guideline databases. Review Methods Guideline search strategies, supplemented by database searches on sudden sensorineural hearing loss (SSNHL), idiopathic facial nerve paralysis (Bell’s palsy), sinonasal polyposis, laryngotracheal disorders, head and neck oncology, and pediatric otolaryngology, prioritizing systematic reviews, randomized controlled trials, and COVID-19–specific findings. Conclusions Systemic corticosteroids (SCSs) reduce long-term morbidity in individuals with SSNHL and Bell’s palsy, reduce acute laryngotracheal edema, and have benefit in perioperative management for some procedures. Topical or locally injected corticosteroids are preferable for most other otolaryngologic indications. SCSs have not shown long-term benefit for sinonasal disorders. SCSs are not a contraindication to vaccination with COVID-19 vaccines approved by the US Food and Drug Administration. The Centers for Disease Control and Prevention noted that these vaccines are safe for immunocompromised patients. Implications for Practice SCS use for SSNHL, Bell’s palsy, laryngotracheal edema, and perioperative care should follow prepandemic standards. Local or topical corticosteroids are preferable for most other otolaryngologic indications. Whether SCSs attenuate response to vaccination against COVID-19 or increase susceptibility to SARS-CoV-2 infection is unknown. Immunosuppression may lower vaccine efficacy, so immunocompromised patients should adhere to recommended infection control practices. COVID-19 vaccination with Pfizer-BioNTech, Moderna, or Johnson & Johnson vaccines is safe for immunocompromised patients

    Prevalence and clinical relevance of Helicobacter pylori cagA and vacA genes in Lebanese patients with gastritis and peptic ulcer disease

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    Background: The prevalence and clinical relevance of H. pylori cagA and vacA virulence genes in the pathogenesis of disease phenotype was assessed by a novel approach for this organism consisting of determination and comparisons of H. pylori gene transcription levels directly in gastric biopsies according to disease phenotype.Methodology: Gastric mucosal biopsies were collected from patients with peptic ulcer disease (PUD), gastritis, and normal mucosa in an academic medical center in Lebanon. H. pylori was detected in these biopsies by rapid urease (CLOâ„¢) test and PCR amplification of the ureA gene. H. pylori virulence genes, their transcription and transcription levels were determined respectively by PCR, RT-PCR and real time RT-PCR. Results: Forty-five percent of patients were H. pylori positive by PCR of the ureA gene, 37.5% of whom had cagA and 59.4% vacA.Conclusions: The cagA and vacA genes were detected more frequently in PUD patients with significantly higher transcription levels than in gastritis and normal mucosa
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