CONTRIBUTION OF ORGAN-BASED TUBE CURRENT MODULATION TO THE REDUCTION OF LENS EXPOSURE DOSE IN HEAD 4D CT IMAGING: A PHANTOM STUDY.

The purpose of this study was to evaluate the effectiveness of organ effect modulation (OEM) in reducing the lens dose in 4D computed tomography (CT) of the head in volume-acquisition (NVA) mode. Six radiophotoluminescent dosemeters were placed on the head of a RANDO phantom. The doses absorbed by the organs and image noise change rate were determined. The lens doses without OEM (i.e. in the OEMoff case) were higher than those with the same target standard deviation and volume-computed tomography dose index (CTDIvol) as in the OEMoff case (p < 0.01). The image noise change rate was 11%. OEM reduced the lens dose during head 4D CT imaging in the NVA mode by 18%. Furthermore, the feasibility of lens dose reduction while ensuring sufficient image quality was confirmed under the condition in which OEM was employed with the same CTDIvol as in the OEMoff case.

Proliferation of poorly differentiated endometrial cancer cells through autocrine activation of FGF receptor and HES1 expression.

Patients with poorly differentiated endometrial cancer show poor prognosis, and effective molecular target-based therapies are needed. Endometrial cancer cells proliferate depending on the activation of HES1 (hairy and enhancer of split-1), which is induced by several pathways, such as the Notch and fibroblast growth factor receptor (FGFR) signaling pathways. In addition, aberrant, ligand-free activation of the FGFR signaling pathway resulting from mutations in FGFR2 was also reported in endometrial cancer. However, a clinical trial showed that there was no difference in the effectiveness of FGFR inhibitors between patients with and without the FGFR2 mutation, suggesting a presence of another signaling pathway for the FGFR activation. Here, we investigated the signaling pathway regulating the expression of HES1 and proliferation of poorly and well-differentiated endometrial cancer cell lines Ishikawa and HEC-50B, respectively. Whereas Ishikawa cells proliferated and expressed HES1 in a Notch signaling-dependent manner, Notch signaling was not involved in HES1 and proliferation of HEC-50B cells. The FGFR inhibitor, NVP-BGJ398, decreased HES1 expression and proliferation of HEC-50B cells; however, HEC50B cells had no mutations in the FGFR2 gene. Instead, HEC-50B cells highly expressed ligands for FGFR2, suggesting that FGFR2 is activated by an autocrine manner, not by ligand-free activation. This autocrine pathway activated Akt downstream of FGFR for cell proliferation. Our findings suggest the usefulness of HES1 as a marker for the proliferation signaling and that FGFR inhibitor may be effective for poorly differentiated endometrial cancers that harbor wild-type FGFR.