Imatinib-mediated inactivation of Akt regulates ABCG2 function in head and neck squamous cell carcinoma.

Objective: To investigate whether the mechanism for the reversal of ABCG2 (also known as ABCP, MXR, and BCRP)-mediated drug resistance by imatinib mesylate (Gleevec, STI571; Novartis Pharmaceuticals Corp, East Hanover, New Jersey) is caused by the downregulation of Akt kinase. The adenosine triphosphatase-binding cassette protein ABCG2 has been suggested to be involved in the resistance against various anticancer drugs. Recent studies show that imatinib reverses ABCG2-mediated drug resistance to topotecan hydrochloride and SN-38.

Gefitinib (Iressa) potentiates the effect of ionizing radiation in thyroid cancer cell lines.

Objectives/hypothesis: To determine whether inactivation of epidermal growth factor receptor (EGFR) kinase activity will sensitize thyroid cancer cell lines to ionizing radiation-induced death.

Study Design: Established human thyroid cancer cells lines were studied.

Methods: Colony formation assay was used to determine the effect of Gefitinib, a small molecule inhibitor of EGFR, on anaplastic (ARO) and follicular (WRO) thyroid cancer cell lines.

Gefitinib inhibition of drug resistance to doxorubicin by inactivating ABCG2 in thyroid cancer cell lines.

Objective: To investigate the regulation of the breast cancer resistance protein ABCG2/BRCP1 drug transporter by epidermal growth factor receptor (EGFR) kinase activity, and to determine whether gefitinib, an EGFR small molecule inhibitor, will modulate the effects of doxorubicin hydrochloride by inhibiting its extrusion from thyroid cancer cells.

Design: Extrusion assays using flow cytometry analysis were used to determine the ability of thyroid cancer cells to extrude the chemotherapy drug, doxorubicin, via the ABCG2 drug transporter in the presence or absence of gefitinib. Immunofluorescence was employed to determine the cellular expression of ABCG2.

EGFR regulates the side population in head and neck squamous cell carcinoma.

Objective: To identify the presence of side population (SP) cells in established head and neck squamous carcinoma cell (HNSCC) lines and to determine the role of EGFR in the regulation of the side population of these cells.

Methods: SP cells were identified using flow cytometry analysis by the ability of these cells to extrude the Hoechst 33342 dye via the drug transporter BCRP1/ABCG2. Effect of EGFR on the side population was determined also by difference in Hoechst extrusion and by immunofluorescence.

Parathyroid hormone-related protein expression is correlated with clinical course in patients with glial tumors.

Background: Parathyroid hormone-related protein (PTHrP) expression modulates cell survival in a number of human solid tumors. Although PTHrP is expressed in normal developing and neoplastic central nervous system tissue, clinical data indicating the importance of this protein with respect to local control and/or survival in patients with glial tumors are scarce.

Methods: Using a standard immunoperoxidase technique, the authors examined PTHrP expression in a population of 51 patients with Daumas-Duport Grade II-IV astrocytomas over a 15-year period.

Correlation of FDG-PET interpretation with survival in a cohort of glioma patients.

Adult supratentorial gliomas continue to be one of the most challenging diagnostic and therapeutic problems for the neuro-oncologist. Despite a variety of therapeutic approaches, local control and survival rates remain disappointingly low, largely due to a relative inability to localize diffusely infiltrating glial tumor cells. FDG PET provides a relatively noninvasive method for studying glucose metabolism in normal and pathologic brain tissues.