Assessment of metabolism-dependent drug efficacy and toxicity on a multilayer organs-on-a-chip

2016 ◽  
Vol 8 (10) ◽  
pp. 1022-1029 ◽  
Author(s):  
Zhongyu Li ◽  
Yaqiong Guo ◽  
Yue Yu ◽  
Cong Xu ◽  
Hui Xu ◽  
...  
Keyword(s):  
Drug Efficacy ◽  
Liver Cells ◽  
Target Cells ◽  
Multiple Target

This work presents a new and multifunctional organs-on-a-chip device that allows for the characterization of the multi-step metabolism processes of pro-drug CAP in liver cells and its resultant efficacy in multiple target cells simultaneously and quantitatively.

Arginine synthesis by hepatomas in vitro. II. Isolation and characterization of Morris hepatoma variants unable to convert ornithine to arginine, and modulation of urea-cycle enzymes by dexamethasone and cyclic-AMP

1984 ◽  
Vol 68 (1) ◽  
pp. 305-319
Author(s):  
S.J. Goss
Keyword(s):  
Cyclic Amp ◽  
Liver Cells ◽  
Isolation And Characterization ◽  
Rat Liver Cells ◽  
Morris Hepatoma ◽  
Ornithine Transcarbamoylase ◽  
Cellular Incorporation

‘77orn’, a derivative of the Morris rat hepatoma 7777, stably expresses high levels of ornithine transcarbamoylase (OTC) and carbamoylphosphate synthetase I (CPS-I), and is able to grow indefinitely in ornithine-medium (medium with ornithine in place of arginine). Variants that have lost this ability are isolated from 77orn by a ‘suicide’ selective technique dependent on the cellular incorporation of [3H]ornithine. These variants, which have reduced levels of CPS-I, or of both CPS-I and OTC, are shown to have developed multiple hormonal requirements; their enzyme deficiencies can be reversed by use of an appropriately supplemented medium. In particular, CPS-I is inducible by dexamethasone and dibutyryl-cyclic-AMP in combination. Cholera toxin can be used instead of cyclic-AMP, but then butyrate is additionally required if the induction is to be maintained in the long term. The use of these agents in excess can depress OTC. Several other hepatomas, and alos explanted foetal rat liver cells, have similar requirements for CPS-I expression. It is argued that multiple hormonal requirements for CPS-I production are normal in liver cells in vitro, and that hormone-independent hepatomas should be regarded as abnormal. The implications of this for the somatic cell genetic investigation of differentiation are briefly discussed.

Characterization of the ERK1/2 phosphorylation profile in human and fish liver cells upon exposure to chemicals of environmental concern

2021 ◽  
pp. 103749
Author(s):  
Bojana Stanic ◽  
Jelena Petrovic ◽  
Branka Basica ◽  
Sonja Kaisarevic ◽  
Kristin Schirmer ◽  
...  
Keyword(s):  
Environmental Concern ◽  
Liver Cells ◽  
Fish Liver

scholarly journals Avian sarcoma leukosis virus receptor-envelope system for simultaneous dissection of multiple neural circuits in mammalian brain

2015 ◽  
Vol 112 (22) ◽  
pp. E2947-E2956 ◽  
Author(s):  
Makoto Matsuyama ◽  
Yohei Ohashi ◽  
Tadashi Tsubota ◽  
Masae Yaguchi ◽  
Shigeki Kato ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Cross Reactivity ◽  
Vector System ◽  
Target Cells ◽  
Specific Gene ◽  
Multiple Target ◽  
Neuronal Systems ◽  
Avian Sarcoma

Pathway-specific gene delivery is requisite for understanding complex neuronal systems in which neurons that project to different target regions are locally intermingled. However, conventional genetic tools cannot achieve simultaneous, independent gene delivery into multiple target cells with high efficiency and low cross-reactivity. In this study, we systematically screened all receptor–envelope pairs resulting from the combination of four avian sarcoma leukosis virus (ASLV) envelopes (EnvA, EnvB, EnvC, and EnvE) and five engineered avian-derived receptors (TVA950, TVBS3, TVC, TVBT, and DR-46TVB) in vitro. Four of the 20 pairs exhibited both high infection rates (TVA–EnvA, 99.6%; TVBS3–EnvB, 97.7%; TVC–EnvC, 98.2%; and DR-46TVB–EnvE, 98.8%) and low cross-reactivity (<2.5%). Next, we tested these four receptor–envelope pairs in vivo in a pathway-specific gene-transfer method. Neurons projecting into a limited somatosensory area were labeled with each receptor by retrograde gene transfer. Three of the four pairs exhibited selective transduction into thalamocortical neurons expressing the paired receptor (>98%), with no observed cross-reaction. Finally, by expressing three receptor types in a single animal, we achieved pathway-specific, differential fluorescent labeling of three thalamic neuronal populations, each projecting into different somatosensory areas. Thus, we identified three orthogonal pairs from the list of ASLV subgroups and established a new vector system that provides a simultaneous, independent, and highly specific genetic tool for transferring genes into multiple target cells in vivo. Our approach is broadly applicable to pathway-specific labeling and functional analysis of diverse neuronal systems.

scholarly journals Cell surface phenotyping of megakaryoblasts

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 957-960 ◽  
Author(s):  
T Koike ◽  
S Aoki ◽  
S Maruyama ◽  
M Narita ◽  
T Ishizuka ◽  
...  
Keyword(s):  
Cell Surface ◽  
Acute Leukemia ◽  
Peroxidase Activity ◽  
Down’S Syndrome ◽  
Phenotypic Characterization ◽  
Target Cells ◽  
Monocytic Cells ◽  
Transient Abnormal Myelopoiesis ◽  
Hla Dr

Abstract Surface phenotypic characterization of megakaryoblasts, identified by platelet peroxidase activity, was investigated in four patients who showed increased proliferation of megakaryoblasts: one patient with typical features of acute leukemia, one presenting with acute myelofibrosis, and two with Down's syndrome in whom blasts disappeared spontaneously (transient abnormal myelopoiesis, TAM). MY10 and/or MY9 antigens were expressed on the surface of some megakaryoblasts, but MY7, and MY4, antigens specific to granulocytic or monocytic cells, were not. Some megakaryoblasts were positive for only anti-HLA-DR antibodies. It was speculated that, during the differentiation of the megakaryocytic lineage, MY9 antigen appears transiently on the surface of megakaryoblasts that have lost HLA-DR antigens and have gained the glycoprotein IIb/IIIa antigen. This study also demonstrated that the proliferating blasts in some patients with TAM were mainly megakaryoblasts and suggested that the target cells in TAM are CFU-GEMM.

Nanocrystal formulations of a poorly soluble drug. 1. In vitro characterization of stability, stabilizer adsorption and uptake in liver cells

2017 ◽  
Vol 518 (1-2) ◽  
pp. 29-40 ◽  
Author(s):  
Kalle Sigfridsson ◽  
Urban Skantze ◽  
Pia Skantze ◽  
Svante Johansson ◽  
Iain Grant ◽  
...  
Keyword(s):  
Liver Cells ◽  
In Vitro Characterization ◽  
Poorly Soluble ◽  
Poorly Soluble Drug
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