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Summary: Axicabtagene ciloleucel (axi‐cel) is an autologous anti‐CD19 chimeric antigen receptor (CAR) T‐cell therapy approved for relapsed or refractory large B‐cell lymphoma (R/R LBCL). To reduce axi‐cel–related toxicity, several exploratory safety management cohorts were added to ZUMA‐1 (NCT02348216), the pivotal phase 1/2 study of axi‐cel in refractory LBCL. Cohort 4 evaluated the rates and severity of cytokine release syndrome (CRS) and neurologic events (NEs) with earlier corticosteroid and tocilizumab use. Primary endpoints were incidence and severity of CRS and NEs. Patients received 2 × 106 anti‐CD19 CAR T cells/kg after conditioning chemotherapy. Forty‐one patients received axi‐cel. Incidences of any‐grade CRS and NEs were 93% and 61%, respectively (grade ≥ 3, 2% and 17%). There was no grade 4 or 5 CRS or NE. Despite earlier dosing, the cumulative cortisone‐equivalent corticosteroid dose in patients requiring corticosteroid therapy was lower than that reported in the pivotal ZUMA‐1 cohorts. With a median follow‐up of 14·8 months, objective and complete response rates were 73% and 51%, respectively, and 51% of treated patients were in ongoing response. Earlier and measured use of corticosteroids and/or tocilizumab has the potential to reduce the incidence of grade ≥ 3 CRS and NEs in patients with R/R LBCL receiving axi‐cel. [ABSTRACT FROM AUTHOR]

The article discusses a study on the role of the protein kinase PKBalpha/Akt1 in bone vascularization and trabecular bone formation. In vivo vascular changes in long bones of PKBalpha-Akt1-deficient and heterozygous wild-type mice were examined using macromolecular dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). The effect of PKBalpha/Akt1 gene dosage on the formation of trabecular bones during endochondral bone growth was investigated through ex vivo µMRI and µcomputed tomography (CT).

Dynamic imaging of gene expression in live animals is among the exciting challenges of molecular imaging. To achieve that, one of the approaches is to use reporter genes that encode for the synthesis of easily detectable products. Such reporter genes can be designed to be expressed under the control of the regulatory elements included in a promoter region of a gene of interest, thus allowing the use of the same reporter gene for the detection of multiple genes. The most commonly used reporter genes include the firefly light-generating enzyme luciferase and the green fluorescent protein detectable by bioluminescence and fluorescence optical imaging, respectively. Over the last years a number of studies demonstrated the ability to use the iron-binding protein ferritin as a reporter gene that allows the detection of gene expression by magnetic resonance imaging (MRI). MRI provides high spatial resolution and soft tissue contrast for deep tissues along with a large arsenal of functional and anatomical contrast mechanisms that can be correlated with gene expression, and can potentially be translated into clinical use Copyright © 2009 John Wiley & Sons, Inc. For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

Blood oxygen level dependent (BOLD) contrast was used to monitor hypoxia induced by cloprostenol, a prostaglandin F2 α (PGF2 α) analog, in the rat embryo-placental unit (EPU). It is shown that administration of cloprostenol (0.025 mg/rat) at mid-gestation (day 16) reduced EPU oxygenation, as detected by BOLD contrast MRI, in correlation with induction of vascular endothelial growth factor (VEGF) gene ( Vegfa) expression in the corresponding placenta ( r = 0.56, p = 0.03). Elevated VEGF mRNA expression in response to cloprostenol treatment was also observed at early gestation (day 9) in the forming placenta ( p = 0.04) and uterus ( p = 0.03). Cloprostenol increased the expression levels of endothelin-1 (ET-1) gene ( Edn1) ( p = 0.03) and its corresponding peptide ( p = 0.02) in the forming placenta, as well as the expression of the endothelin receptor type A (ETA) gene ( Ednra) in both the forming placenta ( p = 0.009) and the uterus ( p = 0.01). The levels of the endothelin receptor type B (ETB) gene ( Ednrb) were not affected in response to cloprostenol, but a significant elevation in the expression level of this receptor was observed in the uterus at mid- and late gestation (day 22) ( p = 0.04 and 0.01 respectively), suggesting a role for ETB in the vasodilatory status of the pregnant uterus. It is suggested that PGF2 α induces uteroplacental vasoconstriction in the rat, and that ET-1 may take part in mediating this effect, probably via activation of ETA receptor. The uteroplacental vasoconstriction induces hypoxia, as manifested by significant changes in BOLD MRI and by upregulation of VEGF. Copyright © 2006 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Uterine receptivity and embryo implantation depend on local induction of angiogenesis and vascular permeability. Poor uterine receptivity has been implicated in implantation failure; however, relatively little is known about the mechanism that underlies endometrial vascular hyperpermeability in implantation sites. Here we show that contrast-enhanced (CE)-MRI and fluorescence microscopy using biotin-BSA-GdDTPA allowed high-resolution detection and quantitative assessment of mouse embryo implantation sites as early as embryonic day 4.5 (E4.5), and subsequent vascular expansion at E5.5. Vessel permeability, but not blood volume, was significantly elevated in E4.5 implantation sites relative to nonimplanted uterus, showing that elevation of vascular permeability is a very early response preceding E4.5. A significantly increased blood volume was detected by MRI and fluorescence microscopy in implantation sites between E4.5 and E5.5. On the other hand, despite the increase in blood volume, implantation sites showed only a small nonsignificant further increase in vascular permeability during these 2 days, demonstrating the rapid dynamics of vascular remodeling during the early days of pregnancy. Functional imaging by MRI, as reported here, allows multiparametric measurement of angiogenesis during normal mouse implantation and would facilitate the application of MRI to evaluate involvement of the vasculature in mouse models of impaired implantation. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The article focuses on the basic principles of intravital microscopy and various applications in Great Britain.. Intravital Microscopy allows one to visualize and capture images in a live animal. Fluorescence intravital video microscopy (FIVM) is the most widely used techniques. FIVM is used to monitor gene expression in the living animal using fluorescent protein tags. FIVM is suitable for many fields of biological research and therefore there are substantial benefits in having a multiuser unit.