Serine/threonine kinase AKT is frequently activated in human bile duct cancer and is associated with increased radioresistance

The prognosis for patients with bile duct cancer (BDC) remains poor. Although BDC cells are essentially radioresistant, recent reports have suggested that radiation therapy, in addition to its palliative role in the management of BDC, may improve patient survival. A better understanding of the mechanisms that lead to cellular radioresistance may assist in the development of more effective BDC therapies based on radiotherapy in combination with radiosensitizing agents. The serine/threonine kinase AKT/protein kinase B, a downstream effector of phosphatidylinositol 3'-kinase, is a well-characterized kinase that is known to play a critical role in antiapoptotic signaling pathways. In this investigation, we sought to clarify the role of AKT signaling in the radioresistance in BDC cells. First, to examine whether activated AKT is expressed in BDCs, tumor specimens were obtained from 19 consecutive BDC cases. Immunohistochemical staining using an anti-phosphorylated-AKT antibody showed that phosphorylated (activated) AKT was expressed in cancer cells but not in neighboring normal mucosa in 16 cases (84.2%). Next, to evaluate the role of AKT activation in the regulation of BDC cell radiosensitivity, clonogenic assays were performed using the phosphatidylinositol 3'-kinase inhibitor LY294002 with and without irradiation. LY294002 inhibited AKT activation in BDC cells and, on irradiation, decreased clonogenic survival in a radiation dose-dependent manner. Only a small decrease in cell viability was observed in cells exposed to LY294002. Expression of constitutively active AKT in BDC cells resulted in decreased radiosensitivity, whereas a dominant-negative AKT increased radiosensitivity. Furthermore, constitutively active AKT also inhibited radiation-induced apoptosis. Collectively, these results indicate that activated AKT in BDC cells is associated with radioresistance and suggest that pharmacological or genetic modulation of AKT activity may have important therapeutic implications in BDC patients treated with radiation.     

Detection of hypervascular hepatocellular carcinoma with dynamic magnetic resonance imaging with simultaneously obtained in-phase and opposed-phase echo images

PURPOSE: The technique of double-phase echo chemical shift gradient-echo magnetic resonance (MR) imaging with the fast low-angle shot sequence (double-echo FLASH) provides in-phase and opposed-phase (double-phase) images simultaneously. The purpose of this study was to assess whether the dynamic study with a combination of in-phase and opposed-phase (double-phase) echo images improves the detectability of hypervascular hepatocellular carcinoma (HCC) compared with that with either in-phase or opposed-phase images alone. METHOD: Thirty-seven patients with 107 hypervascular HCCs who underwent the whole-liver double-phase echo dynamic MR imaging were enrolled in the study. Three radiologists blindly read in-phase images alone, opposed-phase images alone, and then double-phase images together. Sensitivity and positive predictive values as well as the areas below the alternative-free response receiver operating characteristic curve (Az values) for each imaging technique were calculated and compared statistically. RESULTS: The mean sensitivity, positive predictive values, and Az values for hypervascular HCCs were 51%, 77%, and 0.52 for in-phase imaging; 55%, 86%, and 0.58 for opposed-phase imaging; and 57%, 84%, and 0.63 for double-phase imaging, respectively. The mean sensitivity for opposed-phase imaging was significantly higher than that for in-phase imaging (P < 0.05), and the mean sensitivity for double-phase imaging was higher than that for in-phase imaging (P < 0.01). The mean Az value for the double-phase imaging was significantly higher than that for in-phase imaging (P < 0.01). CONCLUSION: Dynamic MR imaging with double-phase images was recommended for the detection of hypervascular HCC.     

Computed tomographic image of an inflammatory fibroid polyp of the stomach

Inflammatory fibroid polyp (IFP) is a rare benign lesion of the gastrointestinal tract. We report a case of IFP and its computed tomographic (CT) findings. On CT, the tumor protruded into the stomach and was covered with mucosa that was well enhanced. The inside of the tumor was irregularly enhanced, reflecting the typical histological findings of IFPs. Not only endoscopy and endoscopic ultrasonography (EUS) but also CT findings may be useful to diagnose IFP before polypectomy.     

New constituents of the leaves of Alpinia flabellata

Two new compounds were isolated from the leaves of Alpinia flabellata. The structures of these compounds were determined by a combination of NMR techniques and HREIMS as 4-hydroxy-2-(2,4,5-trimethoxyphenyl)-2E-butenal (1) and rel-labd-12-en-15(16)-olid-7-one-8R-spiro-1'-[2S-(2,4,5-trimethoxyphenyl)-3-cyclohexene] (2).     

Clinical value of serial measurement of serum C-reactive protein level in neutropenic patients

C-reactive protein (CRP) is an acute phase reactant of inflammation. We evaluated the clinical value of serial measurement of CRP in neutropenic patients. CRP was shown to be useful to monitor the response to therapy for febrile episodes in neutropenia. However, we failed to show statistically significant differences in CRP levels between febrile episodes with or without clinically documented infection (p= 0.10) and with or without bacteremia (p = 0.55). Also, we could not predict febrile episodes within three days by the elevation of CRP value. The area under receiver-operating characteristic curve depicting the relationship between CRP levels and forthcoming febrile episodes was only 0.60. In conclusion, serial measurement of CRP was considered to be not useful to predict fever within three days, or to differentiate the types of infection.     

Effect of multislice acquisition on T1 and T2 measurements of articular cartilage at 3T

PURPOSE: The aim of this study was to investigate the effect of magnetization transfer on multislice T1 and T2 measurements of articular cartilage. MATERIALS AND METHODS: A set of phantoms with different concentrations of collagen and contrast agent (Gd-DTPA2-) were used for the in vitro study. A total of 20 healthy knees were used for the in vivo study. T1 and T2 measurements were performed using fast-spin-echo inversion-recovery (FSE-IR) sequence and multi-spin-echo (MSE) sequence, respectively, in both in vitro and in vivo studies. We investigated the difference in T1 and T2 values between that measured by single-slice acquisition and that measured by multislice acquisition. RESULTS: Regarding T1 measurement, a large drop of T1 in all slices and also a large interslice variation in T1 were observed when multislice acquisition was used. Regarding T2 measurement, a substantial drop of T2 in all slices was observed; however, there was no apparent interslice variation when multislice acquisition was used. CONCLUSION: This study demonstrated that the adaptation of multislice acquisition technique for T1 measurement using FSE-IR methodology is difficult and its use for clinical evaluation is problematic. In contrast, multislice acquisition for T2 measurement using MSE was clinically applicable if inaccuracies caused by multislice acquisition were taken into account.