Interferon-alpha modulates the chemosensitivity of CD133-expressing pancreatic cancer cells to gemcitabine.

Pancreatic cancer is a lethal disease as current chemotherapies with gemcitabine (GEM) are still insufficient. Accumulating evidence suggests that cancer stem cells (CSC) are responsible for chemoresistance and that CD133 is one of the CSC markers in pancreatic cancer. Interferon-alpha (IFN-α), a cytokine with pleiotropic effects, has direct cytotoxic and cytostatic effects on tumor cells. The aim of the present study was to investigate whether IFN-α can modulate the chemosensitivity of a human pancreatic cancer cell line, Capan-1, to GEM. Cell cycles were evaluated for response to GEM with and without IFN-α by BrdU assay. GEM inhibited Capan-1 cell growth in a dose-dependent manner. GEM (IC(50); 100 ng/mL) treatment reduced the number of both CD133(+) and CD133(-) cells in the S phase, induced apoptosis of CD133(-) cells more than that of CD133(+) cells and increased accumulation of CD133(+) cells into the G0/G1 phase. These results infer that CD133(+) cells take shelter into the G0/G1 phase from GEM treatment. IFN-α modulated CD133(+) cells from the G0/G1 phase to the S phase. Consequently, apoptosis was accelerated in both CD133(+) and CD133(-) cells after IFN-α combined with GEM treatment. Furthermore, GEM combined with IFN-α treatment showed a significant tumor suppressive effect in the in vivo study. Importantly, CD133(+) cells showed CSC-like properties, such as generation of spheres, highly invasive ability and high tumorigenesis. These results suggest that IFN-α, as a modulator, could contribute to the treatment of CD133(+) cancer cells and be effective in combined chemotherapies with GEM for pancreatic cancer stem-like cells.

Unfolding of polonium distribution in depth of irradiated lead-bismuth eutectic from alpha-particle pulse-height distribution.

The alpha-particle pulse-height distribution measured from irradiated LBE is determined from the polonium distribution in it. The unfolding of vertical polonium distribution in irradiated LBE ingot is performed with the unfolding code UFOQ. The code uses quadratic programming to consider the constraint that polonium distribution does not have negative values. The response function defined as normalized alpha-particle pulse-height distributions caused by alpha-particles emitted from polonium in surface region, which is divided vertically to thin layers, of LBE ingot is calculated by Monte Carlo method. The polonium distribution around surface of irradiated LBE ingot is obtained clearly with the response function calculated for the surface region divided narrowly. Also, the polonium distribution in deeper layer of the surface region is obtained consistently with the response function calculated for the surface region divided widely.

A new irradiation method with a neutron filter for silicon neutron transmutation doping at the Japan research reactor no. 3 (JRR-3).

We studied a new silicon irradiation holder with a neutron filter designed to make the vertical neutron flux profile uniform. Since an irradiation holder has to be made of a low activation material, we applied aluminum blended with B4C as the holder material. Irradiation methods to achieve uniform flux with a filter are discussed using Monte-Carlo calculation code MVP. Validation of the use of the MVP code for the holder's analyses is also discussed via characteristic experiments.

Establishment of a highly migratory subclone reveals that CD133 contributes to migration and invasion through epithelial-mesenchymal transition in pancreatic cancer.

Pancreatic cancer is a lethal disease because of invasion and early metastasis. Although CD133, a marker of cancer stem cells (CSCs) in a variety of solid tumors, has been studied in recent decades, its function remains obscure. Recent reports suggest that epithelial-mesenchymal transition (EMT) may be related to the properties of CSCs. In this study, we investigated whether CSC markers are associated with EMT. For Capan1M9, a highly migratory cell subclone established from human pancreatic cancer cell line Capan-1, CD133 expression, migration, and invasion were greater than for the parent cells. In Capan1M9 cells, the EMT-related transcription factors Slug and Snail were up-regulated, and N-cadherin and fibronectin were also substantially increased. In contrast, occludin and desmoplakin were suppressed. Knockdown of endogenous CD133 in the Capan1M9 cells led to Slug suppression and reduction of migration and invasion. Taken together, CD133 has an important role in migration and invasion by facilitating EMT in pancreatic cancer cells.