CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model.

Background: DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a 'general vaccine' across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells.

Validation and toxicity of PI3K/Akt pathway inhibition by HIV protease inhibitors in humans.

Purpose: Activation of the phosphatidylinositol 3-kinase/Akt pathway in tumors leads to radiation resistance, and inhibition of this pathway radiosensitizes tumors in laboratory models. Several first-generation human immunodeficiency virus (HIV) protease inhibitors (HPIs) inhibit Akt activation and are radiosensitizers. In order to validate a biomarker of Akt activity in anticipation of clinical trials using HPIs combined with radiotherapy, we sought to determine whether Akt activation was inhibited in leukocytes of HIV+ patients that were already taking these agents.

The HIV protease inhibitor nelfinavir downregulates Akt phosphorylation by inhibiting proteasomal activity and inducing the unfolded protein response.

HIV protease inhibitors (HPIs), which have been used to treat HIV patients since the mid 1990s, have been shown to downregulate the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Because this pathway is frequently activated in human malignancies and associated with resistance to ionizing radiation, we investigated and confirmed that HPIs could radiosensitize cells. However, the mechanism underlying this downregulation was unclear, prompting the investigations in this report.

Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002.

Multiple genetic alterations such as in Ras or EGFR can result in sustained signaling through PI3K. Our previous experiments have shown that resistance to radiation results from PI3K activity in cells in culture. Here we examined whether inhibition of PI3K in vivo would sensitize tumors to radiation.