Search results for "Genesis"
showing 10 items of 12136 documents
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity
2021
Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from the endoderm did not disrupt intestinal growth or development but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching, and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a prosurvival cue. ERK was active t…
Mutations in p53 Gene Exons in a Sample from the South of Spain in Oral Cancer
2021
[Background+ Cancer is a genetic disease caused by mutations in DNA and epigenetic alterations that control gene expression. The majority of epidermoid carcinomas develop within the fields of epithelial genetic alterations. The mechanisms underlying tumorigenesis of epidermoid carcinoma are as yet unknown; therefore, precise identification of the risk factors is needed.
Targeting HSP90 with the small molecule inhibitor AUY922 (luminespib) as a treatment strategy against hepatocellular carcinoma
2018
Hepatocellular carcinoma (HCC) is a highly malignant tumor that responds very poorly to existing therapies, most probably due to its extraordinary inter- and intra-tumor molecular heterogeneity. The modest therapeutic response to molecular targeted agents underlines the need for new therapeutic approaches for HCC. In our study, we took advantage of well-characterized human HCC cell lines, differing in transcriptomic subtypes, DNA mutation and amplification alterations, reflecting the heterogeneity of primary HCCs, to provide a preclinical evaluation of the specific heat shock protein 90 (HSP90) inhibitor AUY922 (luminespib). Indeed, HSP90 is highly expressed in different tumor types, but it…
Plausible Role of Estrogens in Pathogenesis, Progression and Therapy of Lung Cancer
2021
Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor gene-p53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlatio…
Molecular mechanisms of MYCN-dependent apoptosis and the MDM2-p53 pathway: an Achille’s heel to be exploited for the therapy of MYCN amplified neurob…
2012
The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mecha- nisms cooperate to its functional inactivation in this tumor. Increased MDM2 levels, due to genetic amplification or constitutive inhibition of p14ARF, significantly contribute to this event highlighting p53 reactivation as an attractive perspective for neuroblastoma treat- ment. In addition to its role in tumorigenesis, MYCN sensitizes untransformed and cancer cells to apoptosis. This is associated to a fine modulation of the MDM2-p53 pathway Indeed MYCN induces p53 and MDM2 transcription, and, by evoking a DNA damage response (DDR), it stabilizes p53 and its proapoptotic kinase Homeodomain Interacting Prote…
Methylprednisolone-induced hepatotoxicity in a 16-year-old girl with multiple sclerosis.
2018
Multiple sclerosis (MS) is a chronic inflammatory disease with demyelination of the central nervous system. High-dosage corticosteroids are the first-line therapy in the acute relapsing of MS. We report a case of severe high-dose methylprednisolone-induced acute hepatitis in a patient with a new diagnosis of MS. A 16-year-old girl was admitted for urticaria, angioedema, nausea and vomiting a month later she had been diagnosed with MS and treated with high-dosage methylprednisolone. Laboratory investigations showed hepatic insufficiency with grossly elevated liver enzymes. A liver biopsy showed focal centrilobular hepatocyte necrosis with interface hepatitis. Methylprednisolone-induced hepat…
Experimental evolution of an RNA virus in cells with innate immunity defects
2015
Experimental evolution studies have shown that RNA viruses respond rapidly to directional selection and thus can adapt efficiently to changes in host cell tropism, antiviral drugs, or other imposed selective pressures. However, the evolution of RNA viruses under relaxed selection has been less extensively explored. Here, we evolved vesicular stomatitis virus in mouse embryonic fibroblasts knocked-out for PKR, a protein with a central role in antiviral innate immunity. Vesicular stomatitis virus adapted to PKR-negative mouse embryonic fibroblasts in a gene-specific manner, since the evolved viruses exhibited little or no fitness improvement in PKR-positive cells. Full-length sequencing revea…
Global Trends in Scientific Research on Pediatric Obesity
2022
(1) Introduction: The aim of this study was to analyze scientific production, collaboration among countries, and research topics focusing on pediatric obesity. (2) Methods: The papers that were included in the study were retrieved from the Web of Science Core Collection from Clarivate Analytics. A bibliometric analysis of several focuses, including journals of publication, subject categories, most frequent author keywords, and journal impact factors, was conducted. Social network analysis was used to recognize collaboration groups between countries and the co-occurrences of author keywords. (3) Results: A total of 12,171 research articles were published in 2036 journals classified under a v…
Total Pain and Illness Acceptance in Pelvic Cancer Patients: Exploring Self-Efficacy and Stress in a Moderated Mediation Model.
2022
Cancer patients experience pain not only in its physical dimension, but also in a broader context that includes psychological, social, and spiritual aspects due to a higher level of anxiety and stress. The present prospective, longitudinal study examined the relationship between total pain and illness acceptance among pelvic cancer patients, taking into consideration the moderated mediation effects of self-efficacy and stress. The study involved a sample of pelvic cancer patients receiving radiotherapy treatment. Assessments were completed at T1 (before radiotherapy), T2 (after 3–4 weeks), and T3 (after radiotherapy) to assess the psychosocial dynamics of illness acceptance (N = 267). The m…
Predictors of long-term outcomes in patients undergoing periodontal maintenance
2017
Abstract Aim This retrospective study aimed to characterize the baseline status of patients following periodontal maintenance, analysing the association between the long‐term outcome of these patients, smoking, bruxism, and the main clinical and radiographic variables. Material and methods A sample of 174 patients with moderate to severe periodontitis was refined into homogeneous subsamples according to smoking and bruxism and the rate of tooth loss due to periodontal disease (TLPD): 0, 1–2, and >2 teeth. The association and the distribution (χ² test) of the variables within the subsamples were analysed. Results Smoking and bruxism were significantly associated with higher TLPD rates. Verti…