Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

HAdV-5 infection of cancer cells versus bronchial epithelial cells

ABSTRACT: Measurement of Human adenovirus 5-induced gene expression changes in cancer cells versus bronchial epithelial cells

ORGANISM(S): Homo sapiens

DISEASE(S): normal

SUBMITTER: Frank Holtrup

PROVIDER: E-MEXP-3125 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Replication and virus-induced transcriptome of HAdV-5 in normal host cells versus cancer cells--differences of relevance for adenoviral oncolysis.

Dorer Dominik E DE Holtrup Frank F Fellenberg Kurt K Kaufmann Johanna K JK Engelhardt Sarah S Hoheisel Jörg D JD Nettelbeck Dirk M DM

PloS one 20111130 11

Adenoviruses (Ads), especially HAdV-5, have been genetically equipped with tumor-restricted replication potential to enable applications in oncolytic cancer therapy. Such oncolytic adenoviruses have been well tolerated in cancer patients, but their anti-tumor efficacy needs to be enhanced. In this regard, it should be considered that cancer cells, dependent on their tissue of origin, can differ substantially from the normal host cells to which Ads are adapted by complex virus-host interactions. ...[more]

PMID: 22140489

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Project description:The development of reduced-risk products is aimed at providing adult smokers, who are unable to quit, with alternatives to cigarettes that present less risk of harm and smoking-related disease. The use of flavors in the development of these reduced-risk products fulfils an important role in product acceptance. While most flavors are also used by the food industry and are considered safe when ingested, their impact when inhaled is still debated. To overcome this research gap, we developed a three-step approach combining real-time cellular analysis, phenotypic high-content screening assays and gene expression analysis. As a case study, a list of 28 flavors, commonly used in e-liquid formulation, were selected and dissolved individually or as a mixture in a Base Solution composed of propylene glycol, vegetable glycol, and 0.6% nicotine. Various dilutions of these mixtures were assessed in normal human bronchial epithelial cells. Using a real-time impedance-based assay, a Tox-Score corresponding to the ratio of the Base Solution EC50 over flavored solution EC50 was determined for each tested e-liquid. We complemented the e-liquid evaluation by computing a Phenotypic-Score that recapitulates the exposure effects measured using a battery of high-content screening endpoints. Using a systems toxicology approach, we also identified and quantified perturbed molecular pathways impacted specifically by the Base Solution or by the 28-flavor mixture. To conclude, employing a three-pillar based approaches to investigate the effects of flavored solutions in vitro, we were in a position to identify individual flavors that appeared to have the potential to contribute greatly to the overall mixture effect (citronellol and alpha-pinene). Finally, by assessing modified mixtures we showed that, although cytotoxic effect where found when assessed individually, alpha-pinene was not contributing to the overall mixture cytotoxicity. Most of the cytotoxic effect appeared to mainly derive by the presence of citronellol and remaining flavors were still contributing due to synergistic effects.

Dataset Information

HAdV-5 infection of cancer cells versus bronchial epithelial cells

Publications

Replication and virus-induced transcriptome of HAdV-5 in normal host cells versus cancer cells--differences of relevance for adenoviral oncolysis.

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