Radiation-induced Notch signaling in breast cancer stem cells.

Purpose: To explore patterns of Notch receptor and ligand expression in response to radiation that could be crucial in defining optimal dosing schemes for γ-secretase inhibitors if combined with radiation.

Methods And Materials: Using MCF-7 and T47D breast cancer cell lines, we used real-time reverse transcription-polymerase chain reaction to study the Notch pathway in response to radiation.

Results: We show that Notch receptor and ligand expression during the first 48 hours after irradiation followed a complex radiation dose-dependent pattern and was most pronounced in mammospheres, enriched for breast cancer stem cells.

Ionizing radiation activates the Nrf2 antioxidant response.

The transcription factor NF-E2-related factor 2 (Nrf2) binds the antioxidant DNA response element (ARE) to activate important cellular cytoprotective defense systems. Recently several types of cancers have been shown to overexpress Nrf2, but its role in the cellular response to radiation therapy has yet to be fully determined. In this study, we report that single doses of ionizing radiation from 2 to 8 Gy activate ARE-dependent transcription in breast cancer cells in a dose-dependent manner, but only after a delay of five days.

Differential Effects of the Proteasome Inhibitor NPI-0052 against Glioma Cells.

Proteasome inhibitors are emerging as a new class of cancer therapeutics, and bortezomib has shown promise in the treatment of multiple myeloma and mantle cell lymphoma. However, bortezomib has failed to have an effect in preclinical models of glioma. NPI-0052 is a new generation of proteasome inhibitors with increased potency and strong inhibition of all three catalytic activities of the 26S proteasome.

Effects of recombinant erythropoietin on breast cancer-initiating cells.

Background: Cancer anemia causes fatigue and correlates with poor treatment outcome. Erythropoietin has been introduced in an attempt to correct these defects. However, five recent clinical trials reported a negative impact of erythropoietin on survival and/or tumor control, indicating that experimental evaluation of a possible direct effect of erythropoietin on cancer cells is required.

The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation.

Background: If cancer arises and is maintained by a small population of cancer-initiating cells within every tumor, understanding how these cells react to cancer treatment will facilitate improvement of cancer treatment in the future. Cancer-initiating cells can now be prospectively isolated from breast cancer cell lines and tumor samples and propagated as mammospheres in vitro under serum-free conditions.

Methods: CD24(-/low)/CD44+ cancer-initiating cells were isolated from MCF-7 and MDA-MB-231 breast cancer monolayer cultures and propagated as mammospheres.