scholarly journals Application of a New Genotoxicity Test System with Human Hepatocyte Cell Lines to Improve the Risk Assessment in the Drug Development

10.5772/31779 ◽  
2012 ◽  
Author(s):  
Tsuneo Hashizume ◽  
Hiroaki O
Keyword(s):  
Risk Assessment ◽  
Drug Development ◽  
Cell Lines ◽  
Test System ◽  
Human Hepatocyte ◽  
Genotoxicity Test

Application of a Validated QSTR Model for Repurposing COX-2 Inhibitor Coumarin Derivatives as Potential Antitumor Agents

2019 ◽  
Vol 19 (13) ◽  
pp. 1121-1128 ◽  
Author(s):  
Gulcin Tugcu ◽  
Hande Sipahi ◽  
Ahmet Aydin
Keyword(s):  
Antitumor Activity ◽  
Drug Development ◽  
Linear Model ◽  
Cell Lines ◽  
Cyclooxygenase 2 ◽  
Large Set ◽  
Coumarin Derivatives ◽  
Antitumor Compounds ◽  
Cyclooxygenase 2 Inhibitors ◽  
Potential Antitumor

Background: The discovery of novel potent molecules for both cancer prevention and treatment has been continuing over the past decade. In recent years, identification of new, potent, and safe anticancer agents through drug repurposing has been regarded as an expeditious alternative to traditional drug development. The cyclooxygenase-2 is known to be over-expressed in several types of human cancer. For this reason cyclooxygenase-2 inhibition may be useful tool for cancer chemotherapy. Objective: The first aim of the study was to develop a validated linear model to predict antitumor activity. Subsequently, applicability of the model for repurposing these cyclooxygenase-2 inhibitors as antitumor compounds to abridge drug development process. Method: We performed a quantitative structure-toxicity relationship (QSTR) study on a set of coumarin derivatives using a large set of molecular descriptors. A linear model predicting growth inhibition on leukemia CCRF cell lines was developed and consequently validated internally and externally. Accordingly, the model was applied on a set of 143 cyclooxygenase-2 inhibitor coumarin derivatives to explore their antitumor activity. Results: The results indicated that the developed QSAR model would be useful for estimating inhibitory activity of coumarin derivatives on leukemia cell lines. Electronegativity was found to be a prominent property of the molecules in describing antitumor activity. The applicability domain of the developed model highlighted the potential antitumor compounds. Conclusion: The promising results revealed that applied integrated in silico approach for repurposing by combining both the biological activity similarity and the molecular similarity via the computational method could be efficiently used to screen potential antitumor compounds among cyclooxygenase-2 inhibitors.

scholarly journals Bio-engineered palladium nanoparticles: model for risk assessment study of automotive particulate pollution on macrophage cell lines

RSC Advances ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 1850-1861
Author(s):  
Aarzoo ◽  
Saba Naqvi ◽  
Nidhi Bharal Agarwal ◽  
Manoj P. Singh ◽  
M. Samim
Keyword(s):  
Risk Assessment ◽  
Cell Lines ◽  
Palladium Nanoparticles ◽  
Macrophage Cell ◽  
Particulate Pollution ◽  
Assessment Study

The surge in vehicular activity in densely populated areas has led to an increased concentration of airborne palladium nanoparticles (PdNPs) in the environment.

scholarly journals Infection of Nonhuman Primate Cells by Pig Endogenous Retrovirus

2000 ◽  
Vol 74 (16) ◽  
pp. 7687-7690 ◽  
Author(s):  
Juergen H. Blusch ◽  
Clive Patience ◽  
Yasuhiro Takeuchi ◽  
Christian Templin ◽  
Christian Roos ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Cell Lines ◽  
Nonhuman Primate ◽  
Endogenous Retrovirus ◽  
Papio Hamadryas ◽  
Endogenous Retroviruses ◽  
Human Donor ◽  
Baboon Model ◽  
Primate Cell ◽  
Perv Transmission

ABSTRACT The ongoing shortage of human donor organs for transplantation has catalyzed new interest in the application of pig organs (xenotransplantation). One of the biggest concerns about the transplantation of porcine grafts into humans is the transmission of pig endogenous retroviruses (PERV) to the recipients or even to other members of the community. Although nonhuman primate models are excellently suited to mimic clinical xenotransplantation settings, their value for risk assessment of PERV transmission at xenotransplantation is questionable since all of the primate cell lines tested so far have been found to be nonpermissive for PERV infection. Here we demonstrate that human, gorilla, and Papio hamadryas primary skin fibroblasts and also baboon B-cell lines are permissive for PERV infection. This suggests that a reevaluation of the suitability of the baboon model for risk assessment in xenotransplantation is critical at this point.

scholarly journals Establishment of Human Hepatocyte Cell Lines and Induction of Their Differentiation to Develop a Bioartificial Liver

2003 ◽  
Vol 28 (2) ◽  
pp. 175-180
Author(s):  
Naoya KOBAYASHI ◽  
Teru OKITSU ◽  
Toshinori TOTSUGAWA ◽  
Masanobu MARUYAMA ◽  
Nobuyuki HAYASHI ◽  
...  
Keyword(s):  
Cell Lines ◽  
Bioartificial Liver ◽  
Human Hepatocyte
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