Characterization of three new serous epithelial ovarian cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Cell lines constitute a powerful model to study cancer, and here we describe three new epithelial ovarian cancer (EOC) cell lines derived from poorly differentiated serous solid tumors (TOV-1946, and TOV-2223G), as well as the matched ascites for one case (OV-1946).</p> <p>Methods</p> <p>In addition to growth parameters, the cell lines were characterized for anchorage independent growth, migration and invasion potential, ability to form spheroids and xenografts in SCID mice.</p> <p>Results</p> <p>While all cell lines were capable of anchorage independent growth, only the TOV-1946 and OV-1946 cell lines were able to form spheroid and produce tumors. Profiling of keratins, p53 and Her2 protein expression was assessed by immunohistochemistry and western blot analyses. Somatic <it>TP53 </it>mutations were found in all cell lines, with TOV-1946 and OV-1946 harboring the same mutation, and none harbored the commonly observed somatic mutations in <it>BRAF</it>, <it>KRAS </it>or germline BRCA1/2 mutations found to recur in the French Canadian population. Conventional cytogenetics and spectral karyotype (SKY) analyses revealed complex karyotypes often observed in ovarian disease.</p> <p>Conclusion</p> <p>This is the first report of the establishment of matched EOC cell lines derived from both solid tumor and ascites of the same patient.</p

The 20S proteasome core, active within apoptotic exosome-like vesicles, induces autoantibody production and accelerates rejection

Autoantibodies to components of apoptotic cells, such as anti-perlecan antibodies, contribute to rejection in organ transplant recipients. However, mechanisms of immunization to apoptotic components remain largely uncharacterized. We used large-scale proteomics, with validation by electron microscopy and biochemical methods, to compare the protein profiles of apoptotic bodies and apoptotic exosome-like vesicles, smaller extracellular vesicles released by endothelial cells downstream of caspase-3 activation. We identified apoptotic exosome-like vesicles as a central trigger for production of anti-perlecan antibodies and acceleration of rejection. Unlike apoptotic bodies, apoptotic exosome-like vesicles triggered the production of anti-perlecan antibodies in naïve mice and enhanced anti-perlecan antibody production and allograft inflammation in mice transplanted with an MHC (major histocompatibility complex)–incompatible aortic graft. The 20S proteasome core was active within apoptotic exosome-like vesicles and controlled their immunogenic activity. Finally, we showed that proteasome activity in circulating exosome-like vesicles increased after vascular injury in mice. These findings open new avenues for predicting and controlling maladaptive humoral responses to apoptotic cell components that enhance the risk of rejection after transplantation

Ligelizumab for Chronic Spontaneous Urticaria

Background: In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose–response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists. Methods: In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose–response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial. Results: A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose–response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged. Conclusions: A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332. opens in new tab.

The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA(2)LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria

The international EAACI/GA(2)LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria

Publisher Copyright: © 2021 GA²LEN. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA(2)LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.Peer reviewe

A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity.

BACKGROUND: In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. MAIN BODY: We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. CONCLUSION: In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system

Specimen Collections from Abraham Gesner’s Geological Survey of New Brunswick (1838 to 1842)

Abraham Gesner (1797–1864), the first government-appointed geologist in a British colony, developed a collection of rocks, minerals and fossils organized for scientific study that was more than simply a collector’s curiosity cabinet. While his public museum was meant to show a variety of specimens representing the geological sciences, his New Brunswick collection was built largely for reference and documentation to support the geological survey of the Province that he conducted from 1838 to 1842. The collection of Gesner’s specimens at the New Brunswick Museum can be matched to the localities that he visited and described in his five reports, published from 1839 to 1843. Gesner’s collection of New Brunswick specimens likely represents the second oldest government geological survey collection in the British Empire.RÉSUMÉAbraham Gesner (1797–1864), premier géologue nommé par un gouvernement dans une colonie britannique, a constitué une collection de roches, de minéraux et de fossiles cataloguée aux fins d’études scientifiques : bien plus qu’une simple chambre des merveilles. Ouvert au public, son musée avait pour but d’exposer une variété de spécimens représentatifs des sciences géologiques. Quant à sa collection de spécimens du Nouveau Brunswick, elle a principalement été amassée aux fins de référence et de documentation pour appuyer l’étude géologique de la province qu’il avait menée de 1838 à 1842. La collection de Gesner exposée au musée du Nouveau Brunswick contient des spécimens recueillis dans les localités qu’il a visitées et décrites dans cinq rapports parus entre 1839 et 1843. La collection de spécimens du Nouveau Brunswick de Gesner occupe vraisemblablement le deuxième rang des plus anciennes collections de l’Empire britannique amassées à la suite d’une étude géologique commandée par un gouvernement.[Traduit par la redaction