TRAIL therapy in non-small cell lung cancer cells: sensitization to death receptor-mediated apoptosis by proteasome inhibitor bortezomib.

Activation of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor pathway is a promising therapeutic strategy to selectively eradicate cancer cells, including non-small cell lung cancer (NSCLC) cells. Recombinant human (rh) TRAIL/Apo-2L, a TRAIL-encoding adenovirus, and monoclonal antibodies directed against TRAIL receptors R1 and R2 were used to study cytotoxicity of TRAIL therapy in NSCLC cells. NSCLC cells showed differential sensitivity to TRAIL therapy, regardless of the agent used.

A real-time RT-PCR assay for the quantitative determination of adenoviral gene expression in tumor cells.

Oncolytic adenoviruses are exploited as possible anticancer agents in clinical trails. To monitor adenoviral gene expression, a real-time RT-PCR method with a LightCycler was developed that allows the rapid and easy quantification of a number of early and late adenoviral genes in infected tumor cells. Primers were designed that can amplify the spliced forms of the genes encoding E1A13S, DNA polymerase (Pol), pre-terminal protein (pTP), adenoviral death protein (ADP), Hexon (Hex) and Penton (Pent) genes.

Replication-dependent transgene expression from a conditionally replicating adenovirus via alternative splicing to a heterologous splice-acceptor site.

Background: Oncolytic viruses are promising anticancer agents because they selectively kill cancer cells and multiply within a tumor. Their oncolytic potency might be improved by expressing a therapeutic gene from the virus genome. In this regard, proper kinetics and level of transgene expression are important.

Conditionally replicating adenoviruses kill tumor cells via a basic apoptotic machinery-independent mechanism that resembles necrosis-like programmed cell death.

Conditionally replicating adenoviruses (CRAds) represent a promising class of novel anticancer agents that are used for virotherapy. The E1ADelta24 mutation-based viruses, Ad5-Delta24 [CRAd(E3-); E3 region deleted] and infectivity-enhanced Ad5-Delta24RGD [CRAd(E3+)] have been shown to potently eradicate tumor cells. The presence of the E3 region in the latter virus is known to improve cell killing that can be attributed to the presence of the oncolysis-enhancing Ad death protein.

Bioavailability and pharmacokinetics of the cardioprotecting flavonoid 7-monohydroxyethylrutoside in mice.

Purpose: The pharmacokinetics and bioavailability of monoHER, a promising protector against doxorubicin-induced cardiotoxicity, were determined after different routes of administration.

Methods: Mice were treated with 500 mg.kg(-1) monoHER intraperitoneally (i.

The cardioprotector monoHER does not interfere with the pharmacokinetics or the metabolism of the cardiotoxic agent doxorubicin in mice.

Purpose: Monohydroxyethylrutoside (monoHER) has proved to be a good protector against doxorubicin-induced cardiotoxicity without interfering with the antitumor effect of doxorubicin. The aim of the present study was to determine whether there is a pharmacokinetic interaction between monoHER and doxorubicin which may be involved in monoHER cardioprotection.

Methods: Mice were treated with monoHER (500 mg x kg(-1) i.