Effects of carbon-ion beams on human pancreatic cancer cell lines that differ in genetic status.

The relative biologic effectiveness (RBE) of carbon-ion beams at 3 different linear energy transfer (LET) values (13, 50, and 80 keV/microm) accelerated by the Heavy Ion Medical Accelerator in Chiba on human pancreatic cancer cell lines differing in genetic status was determined. The RBE values were calculated as D10, the dose (Gy) required to reduce the surviving fraction to 10%, relative to X-rays. We also investigated apoptosis and the relationship between D10 and the cell cycle checkpoint using morphologic examination and flow cytometry analysis, respectively. The RBE values calculated by the D10 values ranged from 1.16 to 1.77 for the 13-keV/microm beam and from 1.83 to 2.46 for the 80-keV/microm beam. A correlation between the D10 values of each cell line and intensity of G2/M arrest was observed. In contrast, LET values did not clearly correlate with induction of apoptosis. These results suggest that carbon-ion beam therapy is a promising modality. Elucidation of the mechanisms of G2/M arrest and apoptosis may provide clues to enhancing the effects of radiation on pancreatic cancer

Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor

We investigated the effects of the farnesyl transferase inhibitor (FTI) manumycin and the MEK inhibitor PD98059 on growth of human pancreatic cancer, with mutant (SUIT2) or wild-type (BxPC-3) K-ras, xenografted into nude mice. Tumor growth was not reduced by either of the agents at a dose of 3 mg/kg without irradiation. Growth of SUIT2 irradiated at 15 Gy or 30 Gy was reduced by manumycin and PD98059: at 15 Gy, tumor volume doubling time (TVDT) increased from 18.6+/-3.8 to 36.3+/-14.2 days with PD98059 (p<0.05); at 30 Gy, TVDT increased from 32.8+/-6.8 to 70.5+/-10.5 days and 70.7+/-1.5 days, respectively. Manumycin tended to reduce growth of BxPC-3, but the difference in TVDT was not statistically significant. PD98059 significantly increased the TVDT of BxPC-3 at 30 Gy from 34.4+/-18 to 62.6+/-9.8 at 30 Gy. The present results suggest that Ras signaling pathways are potential targets for manipulation of radiosensitivity, and that induction of an alternative pathway may enhance radiosensitivity of pancreatic cancer

Bile duct penetrating duodenal wall sign: a novel computed tomography finding of common bile duct stone impaction into duodenal major papilla

Purpose:Impacted common bile duct stones cause severe acute cholangitis. However, the early and accurate diagnosis, especially iso-attenuating stone impaction, is still challenging. Therefore, we proposed and validated the bile duct penetrating duodenal wall sign (BPDS), which shows the common bile duct penetrating the duodenal wall on coronal reformatted computed tomography (CT), as a novel sign of stone impaction.Purpose:Impacted common bile duct stones cause severe acute cholangitis. However, the early and accurate diagnosis, especially iso-attenuating stone impaction, is still challenging. Therefore, we proposed and validated the bile duct penetrating duodenal wall sign (BPDS), which shows the common bile duct penetrating the duodenal wall on coronal reformatted computed tomography (CT), as a novel sign of stone impaction.Results:A total of 40 patients (mean age 70.6 years; 18 female) were enrolled. The BPDS was observed in 15 patients. Stone impaction occurred in 13/40 (32.5%) cases. Overall accuracy, sensitivity, and specificity were 34/40 (85.0%), 11/13 (84.6%), and 23/27 (85.2%), respectively; 14/16 (87.5%), 5/6 (83.3%), and 9/10 (90.0%) for iso-attenuating stones; and 20/24 (83.3%), 6/7 (85.7%), and 14/17 (82.4%) for high-attenuating stones. Interobserver agreement of the BPDS was substantial (κ = 0.68). In addition, the BPDS was significantly correlated with the number of factors in the systemic inflammatory response syndrome (P = 0.03) and total bilirubin (P = 0.04).Conclusion:The BPDS was a unique CT imaging finding to identify common bile duct stone impaction regardless of stone attenuation with high accuracy