Total FDG lesion number on PET/CT predicts survival of esophageal carcinoma patients with recurrence following curative surgery.

BACKGROUND: Total lesion number is a prognostic determinant in recurrent esophageal cancer, but this requires multiple tests. Here, we investigated the prognostic value of total FDG lesion number obtained from a single PET/CT study. METHODS: Subjects were 153 esophageal squamous cell carcinoma patients with loco-regional or distant recurrence following curative surgery. FDG PET/CT performed within 30 days was inspected for abnormal FDG uptake lesions using a SUVmax of 3.0 as threshold for significance. Prognostic associations were assessed by Cox proportional hazards regression and Kaplan-Meier analysis. RESULTS: PET/CT showed significant local FDG lesions in 49.0%, regional lesions in 78.4%, and distant lesions in 44.4% of patients. Among 73 patients with loco-regional recurrence, 54 had 0-3 and 19 had ≥4 FDG lesions. Among 80 patients with distant recurrence, 31 had 0-3 and 49 had ≥4 FDG lesions. During a median follow-up of 11.8 months, 99 deaths occurred. Univariate variables associated with poor survival included ≥4 FDG lesions and no treatment for loco-regional recurrence and no treatment for distant recurrence. Kaplan Meier analysis showed worse survival for ≥4 than 0-3 FDG lesions in patients with loco-regional recurrence (15.6 vs. 32.1 months; P=0.009), but not in those with distant recurrence. Significant independent predictors of poor survival were ≥4 FDG lesions and no treatment for loco-regional recurrence and no treatment for distant recurrence. CONCLUSIONS: Total FDG lesion number assessed by PET/CT is a significant independent prognostic factor in esophageal cancer patients with loco-regional recurrence following curative surgery.

Inhibition of STAT3 phosphorylation by sulforaphane reduces adhesion molecule expression in vascular endothelial cell.

Intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) play key roles in the initiation of vascular inflammation. In this study, we explored whether sulforaphane, a dietary phytochemical, can inhibit the expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVEC) stimulated with lipopolysaccharide (LPS), and the mechanisms involved. Sulforaphane prevented the LPS-mediated increase in ICAM-1 and VCAM-1 expression, (P < 0.01) in HUVEC. Sulforaphane also prevented the LPS-mediated increase in the phosphorylation of signal transducer and activator of transcription 3 (STAT3) (P < 0.01). Stattic, a STAT3 inhibitor, reduced the LPS-induced expression of ICAM-1 and VCAM-1, and STAT3 phosphorylation (P < 0.01). STAT3 small interfering RNA treatment reduced the LPS-induced expression of ICAM-1, VCAM-1, and STAT3 (P < 0.01). Sulforaphane reduced LPS-mediated THP-1 monocyte adhesion to HUVEC (P < 0.01). In C57BL/6 mice, injection of LPS increased aortic ICAM-1 and VCAM-1 expression, and this effect was prevented by sulforaphane. These data provide insight into the mechanism through which sulforaphane partly reduces the expression of ICAM-1 and VCAM-1 on the vascular wall by inhibiting STAT3 phosphorylation.

Incidental 99mTc MDP uptake in the intestines and intravenous CT contrast.

AIM: We evaluated the association between intestinal visualization on bone scintigraphy and IV CT contrast in patients with breast cancer. PATIENTS, METHODS: 452 patients with breast cancer underwent a 99mTc methylene diphosphonate (MDP) bone scan for surveillance of bone metastasis. Presence, site and intensity of intestinal uptake were visually assessed. For patients with intestinal visualization, medical records were reviewed to identify the alleged potential causes. When IV CT contrast was administrated on the same day as bone scan, the time between IV CT contrast injection, 99mTc MDP administration and bone scan was assessed. RESULTS: Intestinal 99mTc MDP uptake was observed in 44 of the 452 patients (9.7%). Bone scans showed no thyroid or gastric uptake that suggested free pertechnetate. There were no patients with documented causes of intestinal uptake except for one patient with vesicoenteric fistula. Of the 452 patients, 149 (33.0%) underwent IV contrast-enhanced CT on the same day as bone scan. Forty of the 44 patients (90.9%) with intestinal uptake on bone scan underwent IV contrast-enhanced CT on the same day, whereas 109 of 408 (26.7%) patients without intestinal uptake on bone scintigraphy underwent IV contrast-enhanced CT on the same day (p < 0.001). The patients who underwent IV contrast injection between Tc-99m MDP administration and acquisition of bone scans had significantly more frequent intestinal uptake than patients who underwent IV contrast injection either before 99mTc MDP administration or after bone scanning (42.4% vs. 1.8%, p < 0.001). CONCLUSIONS: IV CT contrast injection administered on the same day as bone scintigraphy is significantly associated with 99mTc MDP uptake in the intestines among patients with breast cancer.

Lipopolysaccharide-induced expression of TRAIL promotes dendritic cell differentiation.

Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is a death-inducing cytokine whose physiological function is not well understood. Here, we show that TRAIL has a role in programming human dendritic cell (DC) differentiation. TRAIL expression was strongly induced in DCs upon stimulation with lipopolysaccharide (LPS) or Polyinosine-polycytidylic acid (poly(I:C)) stimulation. Blockade of TRAIL with neutralizing antibody partially inhibited LPS-induced up-regulation of co-stimulatory molecules and the expression of inflammatory cytokines including interleukin-12 (IL-12) p70. In addition, neutralization of TRAIL in LPS-treated DCs inhibited the DC-driven differentiation of T cells into interferon-gamma (IFN-gamma) -producing effectors. The effects of TRAIL neutralization in poly(I:C)-treated DCs were similar, except that IL-12 production and the differentiation of effector T cells into IFN-gamma producers were not inhibited. Strikingly, TRAIL stimulation alone was sufficient to induce morphological changes resembling DC maturation, up-regulation of co-stimulatory molecules, and enhancement of DC-driven allogeneic T-cell proliferation. However, TRAIL alone did not induce inflammatory cytokine production. We further show that the effects of TRAIL on DC maturation were not the result of the induction of apoptosis, but may involve p38 activation. Hence, our data demonstrate that TRAIL co-operates with other cytokines to facilitate DC functional maturation in response to Toll-like receptor activation.

Gene structure and differential modulation of multiple rockbream (Oplegnathus fasciatus) hepcidin isoforms resulting from different biological stimulations.

Hepcidin, an antimicrobial and iron-regulating peptide, is a key molecule of the innate immune system of bony fish. In this study, four isoforms of hepcidin genes were characterized from a marine Perciform fish, rockbream (Oplegnathus fasciatus), and the transcriptional modulations of these isoforms in response to different biological stimulations were also examined. All rockbream hepcidin isoform genes exhibited a tripartite structure and their promoter regions displayed typical binding motifs for the transcription factors including C/EBP, HNF, AP, NF-kbeta, GATA, USF and/or STAT. Hepcidin transcripts in juvenile or fingerling tissues were dramatically induced during experimental challenges with various bacterial species, iron overload and rockbream iridovirus infection. The transcription ofhepcidins was regulated in an isoform- and tissue-specific fashion. In addition, we identified for the first time that partially processed hepcidin transcripts were significantly elevated during bacterial infection and iron overload. Results from this study provide a good basis to better understand the isoform-specific role of hepcidin in the fish innate immune system.

Three-dimensional finite-element analysis of maxillary protraction with and without rapid palatal expansion.

The aims of this study were to determine the reaction of the craniofacial bones on the protraction force transferred to the maxillary body, and whether or not the midpalatal suture had opened during skeletal Class III treatment. A computerized tomograph was obtained from a dry skull with a normal occlusion to construct a three-dimensional finite-element model (3D.FEM) of the craniofacial bones and the maxillary teeth to simulate actual bone reactions. A protraction force of 500 g was applied at the first premolar region, directed 20 degrees inferior to the occlusal plane. The displacement and the stress distribution of the craniofacial bones and sutures were then calculated using the ANSYS 5.3 program dividing the analysis into two simulations, based on whether or not the midpalatal suture was opened. The results showed that there was less compressive stress and greater tensile stress in the circumaxillary suture areas when the midpalatal suture was opened. The amount of displacement and deformation when the midpalatal suture was opened also demonstrated a decrease in upward-forward rotation of the maxilla and zygomatic arch and greater amounts of displacement in the frontal, vertical, and lateral directions compared with no opening of the midpalatal suture. Analysis of these results showed that maxillary protraction produce similar changes to normal downward and forward growth of the maxilla and was achieved with accompanying opening of the midpalatal suture.

Altered expression of Skp2, c-Myc and p27 proteins but not mRNA after H. pylori eradication in chronic gastritis.

Helicobacter pylori infection is associated with increased gastric epithelial cell turnover and non-cardia gastric cancer. Cell cycle progression is dependent on the proteasomal degradation of p27, a cyclin-dependent kinase inhibitor and gastric tumor suppressor, following ubiquitination mediated by Skp2. c-Myc is a transcriptional repressor of p27 and also a target of Skp2. In vitro, H. pylori decreases p27 protein post-translationally. We aimed to determine how p27 is regulated by H. pylori in vivo. The effect of eradicating H. pylori on gastric epithelial p27, Skp2, and c-Myc proteins and mRNA was investigated in 22 patients with chronic gastritis, by immunohistochemistry and laser capture microdissection. The percentage of gastric antral epithelial cells expressing p27 protein was significantly higher after eradication of H. pylori (mean+/-s.e.m. 37+/-2.4% pre-eradication vs 55+/-2.8% post-eradication; P<0.001), while Skp2 and c-Myc protein-expressing cells were lower (Skp2: 35+/-3.8 vs 23+/-2.6%, P=0.009; c-Myc: 47+/-3.6 vs 30+/-3.8%, P<0.001). mRNA expressions of p27, Skp2, and c-Myc (normalized for 18SrRNA) were not changed by H. pylori eradication. H. pylori increases c-Myc and decreases gastric epithelial p27 protein expression in association with increased expression of Skp2, the regulator of p27's ubiquitin ligase complex. H. pylori may influence cell cycle progression and carcinogenesis through post-translational effects on specific gene expression.

NDT response of spectral analysis of surface wave method to multi-layer thin high-strength concrete structures.

This study presents the results of the non-destructive testing using spectral analysis of surface waves (SASW) based on high-strength concrete materials. This SASW method was used to evaluate the compressive strength of single-layer high-strength concrete slabs through a correlation with the surface wave velocities. This paper also presents the relationship between the theoretical and experimental compact dispersion curves when the SASW test is applied to multi-layer thin high-strength concrete slab systems with a finite thickness. The test results show that the surface wave velocity profile obtained from the theoretical dispersion curve has lower values than the profile obtained from the experimental compact dispersion curve under the condition of a finite thickness due to different boundary conditions and reflections from the boundaries. Based on the measured response, an experimental study was conducted to examine if the dispersive characteristics of Rayleigh wave exist in the multi-layer high-strength concrete slab systems. This study can be utilized in examining structural elements of high-strength concrete structures and can also be applied in the integrity analysis of high-strength concrete structures with a finite thickness.

A novel chemokine, Leukotactin-1, induces chemotaxis, pro-atherogenic cytokines, and tissue factor expression in atherosclerosis.

Chemokines such as monocyte chemoattractant protein (MCP) -1 and interleukin (IL)-8 are known to be involved in various processes in atherosclerosis such as plaque formation, plaque rupture, and thrombus formation. We investigated whether a new chemokine, Leukotactin (LKN)-1, is involved in atherosclerosis. We tested the expression of LKN-1 by immunohistochemical methods in carotid atherosclerotic plaque specimen. Induction of pro-inflammatory cytokines, transmigration, and tissue factor (TF) expression were tested in THP-1 cells and human peripheral blood monocytes treated with recombinant human LKN-1. Immunohistochemical analyses revealed that expression of LKN-1 occurs in regions of plaques rich in foam cells. In a Boyden chamber assay, THP-1 cells treated with 0.01--10 nM of LKN-1 transmigrated through gelatin coated filters in a dose dependent manner. LKN-1 also induced the transient expression of TNF-alpha, IL-8, and MCP-1 within 15 min of the treatment of the THP-1 cells. When peripheral blood monocytes were treated with LKN-1, expression levels of TF and TF-mediated procoagulating activity were induced in a time- and dose-dependent manner. These results raise the possibility that LKN-1 is another chemokine that is involved in the atherogenesis. LKN-1 may chemoattract immune cells into the plaque, induce pro-inflammatory cytokines, and produce thrombi by inducing TF expression.