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Effects of Chemotherapeutic Agents on Expression of Somatostatin Receptors in Pancreatic Tumor Cells

Departments of Nuclear Medicine, Internal Medicine I, and Oncology, University of Vienna, Vienna; Ludwig Boltzmann Institute of Clinical Oncology and Department of Nuclear Medicine, Hospital Lainz, Vienna; and Department of Radiochemistry, Seibersdorf Research Center, Seibersdorf, Austria

View larger version (37K): [in a new window]   FIGURE 1. (A) Relative intensities of chemoluminescence detection of SSTR1–SSTR5 after hybridization with respective cDNA clones for 4 pancreatic cancer cell lines (mean ± SEM; 3 experiments). Intensities obtained for SSTR1 and SSTR2 are not statistically different from SSTR-negative COS7 cells (not shown). (B) Results of binding experiments using DOTA-LAN determined as specific binding (femtomoles per million cells), number of sites per cell (x 104), and Kd (nmol/L) for high- and low-affinity sites (1 and 2), respectively, from 3 experiments (mean ± SD; determinations done in triplicate). Number of binding sites per cell is not statistically significant for BxPC-3, Panc-1, and ASPC-1 cells.

View larger version (48K): [in a new window]   FIGURE 2. (A) Inhibitory effects of respective chemotherapeutic agents on BxPC-3 cells (% inhibition compared with medium controls; n = 3; mean ± SEM) and percentage of subG1 cells in same cultures (n = 3; mean ± SEM). (B) Alterations in cell cycle distributions in BxPC-3 cells in response to chemotherapeutic agents. Percentage of cells in G1/0 phase, G2M phase, and S phase were calculated from histograms of propidium iodide–stained cells (n = 3; mean ± SEM). con = control; gemca = gemcitabine (1 and 2 µg/mL); cisPt = cisplatin (2.5 and 5 µg/mL); cpt = camptothecin (1.5 and 3 µg/mL); mito = mitomycin C (0.1 and 0.2 µg/mL); doxo = doxorubicin (1 and 2 µg/mL).

View larger version (37K): [in a new window]   FIGURE 3. Effects of chemotherapeutic agents on binding of DOTA-LAN and number of binding sites per cell for high- and low-affinity sites (1 and 2), respectively, in BxPC-3 cells (n = 3; mean ± SEM). gemca = gemcitabine (1 and 2 µg/mL); cisPt = cisplatin (2.5 and 5 µg/mL); cpt = camptothecin (1.5 and 3 µg/mL); mito = mitomycin C (0.1 and 0.2 µg/mL); doxo = doxorubicin (1 and 2 µg/mL).

View larger version (36K): [in a new window]   FIGURE 4. Reexpression of SSTR in pancreatic cancer cells after pretreatment with gemcitabine at 1 µg/mL (gemca1) and further incubation for 4 d (reexp; n = 3; mean ± SEM). Low-affinity binding of ASPC-1 cell reexpression exceeds scale used here (636.5 ± 11.5 fmol/106 cells). con = control.