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Galunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor, blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein) and TGF-β-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments included chemokine, cytokine, and T cell subsets alterations. 158 patients were randomized to galunisertib plus lomustine (n = 79), galunisertib (n = 39) and placebo+lomustine (n = 40). In 127 of these patients, tissue was adequate for central pathology review and biomarker work. Isocitrate dehydrogenase (IDH1) negative glioblastoma patients with baseline pSMAD2+ in cytoplasm had median overall survival (OS) 9.5 months vs. 6.9 months for patients with no tumor pSMAD2 expression (p = 0.4574). Eight patients were IDH1 R132H+ and had a median OS of 10.4 months compared to 6.9 months for patients with negative IDH1 R132H (p = 0.5452). IDH1 status was associated with numerically higher plasma macrophage-derived chemokine (MDC/CCL22), higher whole blood FOXP3, and reduced tumor CD3+ T cell counts. Compared to the baseline, treatment with galunisertib monotherapy preserved CD4+ T cell counts, eosinophils, lymphocytes, and the CD4/CD8 ratio. The T-regulatory cell compartment was associated with better OS with MDC/CCL22 as a prominent prognostic marker.
The Earwig Collection (Dermaptera) of the Manchester Museum, UK, with a complete type catalogue
(2015)
This paper presents a description of the worldwide Dermaptera collection of the Manchester Museum, UK. In total, the collection contains over 16,700 specimens and represents 835 species and subspecies (approximately 44% of the Dermaptera world fauna). The composition of the collection is described and a brief account is given of its history and those instrumental in its development, notably W.D. Hincks (1906–1961) and A. Brindle (1915–2001). Correspondence held at the museum relating to their work on Dermaptera is listed and examples relating to Labidura herculeana (Fabricius, 1798) and some of the parasitic earwigs in the collection are explored. Finally, a complete type catalogue of the Manchester Museum’s Dermaptera is presented; it is arranged alphabetically by species name as originally described, with photographs of all holotypes and their corresponding data labels. The collection contains 40 holotypes and 694 secondary types (allotypes, syntypes or paratypes), representing 283 species and subspecies, an estimated 15% of the Dermaptera world fauna.