Eosinophils in glioblastoma biology

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Glacially striated, soft sediment surfaces on late Paleozoic tillite at São Luiz do Purunã, PR

Striae and furrows found on the upper surfaces of three stratigraphically superposed decimetric beds of late Paleozoic lodgement tillite of the Itararé Subgroup in the northern Paraná Basin were engraved by ploughing of clasts and possibly also ice protuberances at the base of the glacier, on unconsolidated to partially consolidated sediment. Associated features indicate that the rheology of the bed varied from stiff during lodgement to soft and deformable during ploughing. Poor drainage of meltwater at the glacier-bed interface may have contributed to lower the strength of sediment to deformation. The deformed interval was probably generated during a single glacial phase or advance of a glacier grounding in a marine or lacustrine water body. Changes in the dynamics of the glacier involving slow and fast flow were correlated respectively with alternation of deposition and erosion. The proposed model is analogous to that of lodgement till complexes from the Pleistocene of the northern hemisphere. Retreat of the glacier was probably fast, followed by settling of muds on top of the upper striated and furrowed surface, and progradation of deltaic sands during post-glacial time.<br>Estrias e sulcos encontrados sobre três camadas decimétricas, estratigraficamente superpostas, de tilito de alojamento neopaleozóico do Subgrupo Itararé, na porção norte da Bacia do Paraná, foram formados por aração de clastos e, possivelmente, por protuberâncias de gelo, na base da geleira. Feições associadas indicam que a reologia do sedimento variou de rígido, durante o alojamento, a inconsolidado e deformável durante a aração. A baixa drenagem da água de degelo na interface geleira-substrato pode ter contribuído para reduzir a resistência do sedimento à deformação. A sucessão acima foi gerada provavelmente durante uma única fase glacial ou avanço de geleira sobre corpo de água marinho ou lacustre. Mudanças na dinâmica da geleira envolvendo fluxos lento e rápido corresponderam, respectivamente, a alternâncias entre deposição e erosão. O modelo proposto é análogo ao de complexos de till de alojamento do Pleistoceno do hemisfério do norte. O recuo da geleira foi provavelmente rápido, seguido pela deposição de lama acima da superfície estriada e sulcada superior, e progradação de ciclos de arenitos deltáicos durante a época pós-glacial

Multiphase Phanerozoic Subsidence and Uplift History Recorded in the Congo Basin: A Complex Successor Basin

International audienceThe Congo Basin of central Africa is a large iconic Phanerozoic sedimentary basin whose origin and tectonic evolution are poorly understood, mostly because of a lack of modern stratigraphic data, reflecting a long hiatus in field investigations during the past five decades. It is usually assumed that the Congo Basin experienced a long and continuous history of slow subsidence since the late Precambrian (e.g. 2–4 m/Ma), linked to steady-state mantle processes. Here, we used revised sedimentological and stratigraphic data of the four historic deep boreholes drilled in the center of the basin to calculate a new first-order model for its subsidence and uplift history. Because the sedimentary sequences of this basin are largely terrestrial, we apply a new backstripping method especially designed for continental domain. The results reveal two main episodes of subsidence: initially rapid subsidence during the Carboniferous-Triassic (10–20 m/Ma), and then slower subsidence during the Jurassic-Cretaceous (5–10 m/Ma), punctuated by several uplifts at 160–180 Ma (e.g. ‘Karoo’), 120–140 Ma (e.g. ‘Paraná-Etendeka’), and again in the Cenozoic, ca. 30–50 Ma (e.g. ‘Ethiopian’). This complex, multiphase subsidence and uplift history of the Congo Basin can be linked to evolving far-field geodynamic processes that first led the formation of Pangea (large-scale compression) during the late Paleozoic, and then to its break-up associated with successive outpourings of Large Igneous Provinces (or hotspot plumes) and the opening of the Indian and South Atlantic Oceans around Africa

New regioanal correlations between the Congo, Paranà and Cape-Karoo basins of Southwest gondwana

International audienc

Emerging roles of extracellular vesicles in the adaptive response of tumour cells to microenvironmental stress

Cells are constantly subjected to various types of endogenous and exogenous stressful stimuli, which can cause serious and even permanent damage. The ability of a cell to sense and adapt to environmental alterations is thus vital to maintain tissue homeostasis during development and adult life. Here, we review some of the major phenotypic characteristics of the hostile tumour microenvironment and the emerging roles of extracellular vesicles in these events