Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes.

Novel multistage redox tetrathiafulvalenes (TTFs) bearing 6-aryl-1,4-dithiafulvene moieties were synthesized by palladium-catalyzed direct C-H arylation. In the presence of a catalytic amount of Pd(OAc)2, P(t-Bu3)·HBF4, and an excess of Cs2CO3, the C-H arylation of TTF with several aryl bromides bearing 1,3-dithiol-2-ylidenes took place efficiently to produce the corresponding π-conjugated molecules. We also succeeded in the estimation of the oxidation potentials and number of electrons involved in each oxidation step of the obtained compounds by digital simulations.

Enthalpy-driven interactions with sulfated glycosaminoglycans promote cell membrane penetration of arginine peptides.

The first step of cell membrane penetration of arginine peptides is thought to occur via electrostatic interactions between positive charges of arginine residues and negative charges of sulfated glycosaminoglycans (GAGs) on the cell surface. However, the molecular interaction of arginine peptides with GAG still remains unclear. Here, we compared the interactions of several arginine peptides of Tat, R8, and Rev and their analogues with heparin in relation to the cell membrane penetration efficiency. The high-affinity binding of arginine peptides to heparin was shown to be driven by large favorable enthalpy contributions, possibly reflecting multidentate hydrogen bondings of arginine residues with sulfate groups of heparin. Interestingly, the lysine peptides in which all arginine residues are substituted with lysine residues exhibited negligible binding enthalpy despite of their considerable binding to heparin. In CHO-K1 cells, arginine peptides exhibited a great cell-penetrating ability whereas their corresponding lysine peptides did not penetrate into cells. The degree of cell penetration of arginine peptides markedly decreased by the chlorate treatment of cells which prevents the sulfation of GAG chains. Significantly, the cell penetration efficiency of arginine peptides was found to be correlated with the favorable enthalpy of binding to heparin. These results suggest that the enthalpy-driven strong interaction with sulfated GAGs such as heparan sulfate plays a critical role in the efficient cell membrane penetration of arginine peptides.

Kinetic and thermodynamic analyses of spontaneous exchange between high-density lipoprotein-bound and lipid-free apolipoprotein A-I.

It is thought that apolipoprotein A-I (apoA-I) spontaneously exchanges between high-density lipoprotein (HDL)-bound and lipid-free states, which is relevant to the occurrence of preß-HDL particles in plasma. To improve our understanding of the mechanistic basis for this phenomenon, we performed kinetic and thermodynamic analyses for apoA-I exchange between discoidal HDL-bound and lipid-free forms using fluorescence-labeled apoA-I variants. Gel filtration experiments demonstrated that addition of excess lipid-free apoA-I to discoidal HDL particles promotes exchange of apoA-I between HDL-associated and lipid-free pools without alteration of the steady-state HDL particle size. Kinetic analysis of time-dependent changes in NBD fluorescence upon the transition of NBD-labeled apoA-I from HDL-bound to lipid-free state indicates that the exchange kinetics are independent of the collision frequency between HDL-bound and lipid-free apoA-I, in which the lipid binding ability of apoA-I affects the rate of association of lipid-free apoA-I with the HDL particles and not the rate of dissociation of HDL-bound apoA-I. Thus, C-terminal truncations or mutations that reduce the lipid binding affinity of apoA-I strongly impair the transition of lipid-free apoA-I to the HDL-bound state. Thermodynamic analysis of the exchange kinetics demonstrated that the apoA-I exchange process is enthalpically unfavorable but entropically favorable. These results explain the thermodynamic basis of the spontaneous exchange reaction of apoA-I associated with HDL particles. The altered exchangeability of dysfunctional apoA-I would affect HDL particle rearrangement, leading to perturbed HDL metabolism.

Active joint mechanism driven by multiple actuators made of flexible bags: a proposal of dual structural actuator.

An actuator is required to change its speed and force depending on the situation. Using multiple actuators for one driving axis is one of the possible solutions; however, there is an associated problem of output power matching. This study proposes a new active joint mechanism using multiple actuators. Because the actuator is made of a flexible bag, it does not interfere with other actuators when it is depressurized. The proposed joint achieved coordinated motion of multiple actuators. This report also discusses a new actuator which has dual cylindrical structure. The cylinders are composed of flexible bags with different diameters. The joint torque is estimated based on the following factors: empirical formula for the flexible actuator torque, geometric relationship between the joint and the actuator, and the principle of virtual work. The prototype joint mechanism achieves coordinated motion of multiple actuators for one axis. With this motion, small inner actuator contributes high speed motion, whereas large outer actuator generates high torque. The performance of the prototype joint is examined by speed and torque measurements. The joint showed about 30% efficiency at 2.0 Nm load torque under 0.15 MPa air input.

Mechanical analysis of factors affecting clear aligner removability.

It is difficult to control corrective forces in orthodontic treatment with clear aligners. The grip of aligners on teeth is important to ensure accurate corrective forces from aligners. This study aimed to measure the gripping force of aligners under various conditions to clarify factors that influence it. We created aligners with different attachment morphologies and placement sites and different margin lengths. We developed a device to measure the mechanics involved in the removal of these aligners. The gripping force was evaluated at five different aligner removal sites on the teeth. We found that the gripping force of the aligner was the weakest on the lingual side of the first molar and strongest on the labial side of the central incisors and that the attachment morphology and placement sites affected the gripping force of aligners.

Improvement in Cycle Life of Organic Lithium-Ion Batteries by In-Cell Polymerization of Tetrathiafulvalene-Based Electrode Materials.

Redox-active organic molecules are promising candidates for next-generation electrode materials. Nevertheless, finding low-molecular-weight organic materials with a long cycle life remains a crucial challenge. Herein, we demonstrate the application of tetrathiafulvalene and its vinyl analogue bearing triphenylamines as long-cycle-life electrodes for lithium-ion batteries (LIBs). These molecules were successfully synthesized using palladium-catalyzed C-H arylation. Electrochemical analysis revealed that a polymer formed on the electrode. LIBs comprising these molecules exhibited noteworthy charge-discharge properties with a long cycle life (the capacity after 100 cycles was greater than 90% of the discharge capacity in the third cycle) and a high utilization ratio (approximately 100%). "In-cell" polymerization during the first charge process is considered to contribute to the effect. This study indicates new avenues for the creation of organic materials for rechargeable batteries.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents--special references to bacteria isolated between April 2009 and March 2010].

Bacteria isolated from surgical infections during the period from April 2009 to March 2010 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 671 strains including 16 strains of Candida spp. were isolated from 174 (79.1%) of 220 patients with surgical infections. Four hundred and eleven strains were isolated from primary infections, and 244 strains were isolated from surgical site infection. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from surgical site infection aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus spp. in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from surgical site infection. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae, Enterobacter cloacae and Pseudomonas aeruginosa, in this order, and from surgical site infection, E. coli was most predominantly isolated, followed by P. aeruginosa and E. cloacae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Streptococcus constellatus and Finegoldia magna, and from surgical site infection, E. lenta was most predominantly isolated. Among anaerobic Gram-negative bacteria, the isolation rate of Bilophila wadsworthia was the highest from primary infections, followed by Bacteroides fragilis, Bacteroides ovatus and Bacteroides thetaiotaomicron, and from surgical site infection, B. fragilis was most predominantly isolated, followed by B. ovatus, B. wadsworthia and B. thetaiotaomicron, in this order. In this series, we noticed no vancomycin-resistant Gram-positive cocci, nor multidrug-resistant P. aeruginosa. We should carefully follow up B. wadsworthia which was resistant to various antibiotics, and also Bacteroides spp. which was resistant to many beta-lactam antibiotics.

Development of a new evaluation method for orthodontic forces generated in individual patients.

Numerous experimental studies have examined how much orthodontic force is needed to move teeth more smoothly; however, no reports have examined this clinically in individual, living subjects. We aimed to develop a method for quantifying the force exerted on individual teeth by an orthodontic wire to measure how loads placed on crowded teeth change dynamically over time. Accordingly, we fabricated a series of dental casts of patients undergoing orthodontic treatment (using optical impressions and a three-dimensional printer), fitted these models with nickel-titanium wire, and subjected them to bending load tests. During leveling, nickel-titanium wire is generally considered to exert a weak force due to its low elastic modulus, with a weak orthodontic force applied over a long period of time due to its superelasticity; however, we found that the actual energy exerted by nickel-titanium wire is also largely affected by other factors (e.g., amount of crowding).

Quantitative analysis of cisplatin sensitivity of human esophageal squamous cancer cell lines using in-air micro-PIXE.

Cisplatin is a key chemotherapeutic agent for the treatment of esophageal cancer. We examined the intracellular localization of cisplatin in esophageal cancer cell lines and determined their sensitivity to cisplatin using in-air micro-PIXE (particle induced X-ray emission). Two human esophageal squamous cell carcinoma (ESCC) cell lines, TE-2 and TE-13, were examined for their response to cisplatin using MTT assay, flow cytometry, and DNA fragmentation assays. Real-time reverse transcription-polymerase chain reaction was also used to evaluate the mRNA expression of multidrug resistance protein 2 (MRP2) in both cell lines. Platinum localizations of intracellular and intranuclear were measured using in-air micro-PIXE. TE-2 cells were more sensitive to cisplatin than TE-13 cells (IC(50): 37.5 mum and 56.3 mum, respectively). Flow cytometry analysis confirmed that more TE-2 than TE-13 cells were in the sub-G1 phase. DNA fragmentation assay was analyzed to confirm the MTT assay and flow cytometry results. The expression of MRP2 mRNA in TE-13 cells was stronger than in TE-2 cells. In-air micro-PIXE showed that TE-2 cells had higher intracellular cisplatin concentrations than TE-13 cells and the ratio of intranuclear to intracellular cisplatin in individual cells was not significantly different. We observed the intracellular and intranuclear localization of cisplatin using in-air micro-PIXE. The results of this study suggest that in-air micro-PIXE could be a useful quantitative method for evaluating the cisplatin sensitivity of individual cells. Finally, we speculate that MRP2 in the cell membrane may play an important role in regulating the cisplatin sensitivity of ESCC cells.

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents --special references to bacteria isolated between April 2008 and March 2009].

Bacteria isolated from infections in abdominal surgery during the period from April 2008 to March 2009 were investigated in a multicenter study in Japan, and the following results were obtained. In this series, 712 strains including 18 strains of Candida spp. were isolated from 173 (80.5%) of 215 patients with surgical infections. Three hundred and sixty-six strains were isolated from primary infections, and 346 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-negative bacteria were predominant, followed by aerobic Gram-negative bacteria, while from postoperative infections aerobic Gram-positive bacteria were predominant, followed by anaerobic Gram-negative bacteria. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was highest, followed by Streptococcus spp., and Staphylococcus spp. in this order, from primary infections, while Enterococcus spp. was highest, followed by Staphylococcus spp. from postoperative infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa, in this order, and from postoperative infections, P aeruginosa was most predominantly isolated, followed by E. coli, Enterobacter cloacae, and K. pneumoniae. Among anaerobic Gram-positive bacteria, the isolation rate of Eggerthella lenta was the highest from primary infections, followed by Parvimonas micra, Streptococcus constellatus and Gemella morbillorum, and from postoperative infections, E. lenta was most predominantly isolated. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis was the highest from primary infections, followed by Bacteroides thetaiotaomicron, Bacteroides ovatus and Bilophila wadsworthia, and from postoperative infections, B. fragilis was most predominantly isolated, followed by B. thetaiotaomicron, B. wadsworthia and B. ovatus, in this order. In this series, we noticed no vancomycin-resistant methicillin-resistant S. aureus, and Enterococcus spp., nor multidrug-resistant P aeruginosa. We should carefully follow up B. wadsworthia which was resistant to various antibiotics, and also Bacteroides spp. which was resistant to many beta-lactam antibiotics.

Verification of mechanical load generated by functional orthodontic appliances.

Functional appliances are widely used for promoting mandibular growth by utilizing a construction bite position. We aimed to measure the mechanical load generated by movement of functional appliances and determine the factors influencing this load. Thirteen patients aged 8-12 years were selected for the study, and the load was measured using a previously developed measurement device. To investigate the factors affecting the load, the temporomandibular joint morphology and muscles related to the mandible were examined using cone-beam computed tomography. The standard regression coefficients of the factors affecting the load per millimeter of movement distance were 0.64 and 0.66 for (a) the inclination of the articular eminence and (b) the angle between occlusal plane and posterior temporalis, respectively. Measurement of the occlusal plane to the posterior temporalis and the inclination of the articular eminence were significantly different (p < 0.05). The angle of inclination of the articular eminence emerged as a strong influencing factor. Similarly, the influence of measurements from the occlusal plane to the posterior temporalis was considerable since the posterior temporalis muscle is the most active when the mandible is extended forward. We also found a possible relationship between the occlusal force and load at the construction bite position. To our knowledge, this is the first study to determine the actual load associated with the angle of the temporalis muscle to the occlusal plane, inclination angle of the articular eminence, angle between the occlusal plane and the Frankfort plane, and the angle between the geniohyoid muscle and the occlusal plane. Therefore, mechanical considerations need to be more accurate to facilitate safe orthodontic treatment.

Expression of lysyl oxidase is correlated with lymph node metastasis and poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Lysyl oxidase (LOX), an extracellular matrix-remodeling enzyme, has been reported to regulate tumor metastasis. We investigated the clinical significance of LOX expression in esophageal squamous cell carcinoma (ESCC). METHODS: We examined LOX expression in ESCC cell lines by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. We also examined LOX expression by real-time RT-PCR in 39 surgically resected ESCC and by immunohistochemistry in 122 surgically resected ESCC. RESULTS: LOX messenger RNA (mRNA) was expressed at a high level in TTn (originating from an ESCC metastatic lesion); at a moderate level in TE-2 and TE-15; and at a low level in TE-1, TE-8, and TE-13. In Western blotting, all cell lines expressed the catalytically inactive 50-kDa LOX at approximately the same levels, but catalytically active 32-kDa LOX was overexpressed only in TTn. LOX mRNA levels in ESCC tissues were significantly higher than those observed in normal esophageal tissues (P < 0.001) and had no significant correlation with tumor-node-metastasis (TNM) factors. High LOX protein expression had a significant correlation with presence of lymph node metastasis (P = 0.009) and number of lymph node metastases (P = 0.047). Overall and cancer-specific survival rates of patients with ESCC with high LOX expression were significantly lower than those of patients with ESCC with low LOX expression (P = 0.024 and P = 0.012). Univariate and multivariate analyses revealed that high LOX protein expression was an independent prognostic factor for ESCC. CONCLUSIONS: Our findings suggest that LOX can serve as a predictive marker of lymph node metastasis and prognosis in ESCC.

Correlation between connexin 26 expression and poor prognosis of esophageal squamous cell carcinoma.

BACKGROUND: Failure of gap junction formation affects the development of various types of cancer. We aimed to clarify the clinicopathologic outcome and prognostic significance of connexin (Cx) 26 in human esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemical staining for Cx26 was performed on surgical specimens obtained from 123 patients with ESCC. RESULTS: There was no positive staining for Cx26-specific expression in normal esophageal squamous cells. Primary ESCC with Cx26-positive expression was detected in the cytoplasm of cancer cell nests in 60 cases. Cx26 expression was correlated with N (lymph node metastasis, P = 0.014) and the number of metastatic lymph nodes (P = 0.047). The 5-year survival rates of ESCC patients with Cx26-positive expression were significantly lower than those with Cx26-negative expression (positive, 39.7%; negative, 65.7%; P = 0.007). By multivariate analysis, tumor-node-metastasis (TNM) clinical classification (T, P < 0.001; N, P = 0.002; M, P = 0.046) and Cx26 (P = 0.024) were independent prognosis predictors of ESCC. CONCLUSIONS: These results suggest that abnormal expression of Cx26 participates in the progress of ESCC.

Immunohistochemical analysis of phosphorylated epidermal growth factor receptor might provide a surrogate marker of EGFR mutation.

PURPOSE: Overexpression of EGFR is found in several malignancies including lung cancers. Recently, EGFR mutation has been shown to correlate with responsiveness to tyrosine kinase inhibitors (TKI). Although antibodies against phophorylated EGFR have been used in vitro, phosphorylated EGFR has yet not been examined well in resected non-small cell lung cancers (NSCLCs). EXPERIMENTAL DESIGN: We studied the immunohistochemistry of anti-EGFR and phosphorylated EGFR in 97 resected NSCLCs, examined the relationship with EGFR mutation, and performed quantitative RT-PCR of the EGFR gene in the TaqMan assay. RESULT: EGFR mutation was seen in 27% of 97 NSCLCs and 37% of 70 adenocarcinomas. EGFR was stained in 60% of 97 NSCLCs. Phosphorylation of tyrosine 845 (pY845) and 1068 (pY1068) was positive in 49% and 48%, respectively. The observed correlation with EGFR mutation and pY845 or pY1068 was statistically significant (P=0.0001 for pY845, P<0.0001 for pY1068, chi square test), although phospho-EGFR status was not associated with a particular mutation type. pY1068-positive tumors also correlated with female, light smoker, and adenocarcinoma histology, but not with mRNA expression. Moreover, patients with pY1068-positive tumors showed prolonged survival (P=0.0093, log-rank test). CONCLUSION: It is possible that immunohistochemistry of phosphorylated EGFR can substitute for EGFR mutation analysis. Further investigation is necessary to determine whether phospho-EGFR immunohistochemistry predicts response to TKIs and survival benefit.

[Revision of the informed consent form for patients based on investigation of adverse events of mFOLFOX6 regimen].

We retrospectively investigated the frequency and severity of adverse events in 124 patients with colorectal cancer who were treated by mFOLFOX6 regimen from August, 2005 to December, 2006. The incidences of grade 3/4 adverse events were; leucopenia 16%, neutropenia 40%, anemia 11%, thrombocytopenia 7%, febrile neutropenia 7%, nausea 3%, vomiting 2%, anorexia 2%, diarrhea 4%, fatigue 7%, and alopecia 0%. The incidences of all grades and grade 3/4 hypersensitivity reaction were 35% and 4%, and the median number of course when it firstly appeared was 6(range, 1-21). The incidences of all grade and grade 3 peripheral sensory neuropathy were 74% and 6%, and the median number of course when it firstly appeared 11(range, 6-16). The incidences of adverse events in this cohort were similar or lower than those reported in Western countries. Our investigation shows that mFOLFOX6 regimen is tolerable in clinical practice in Japan. The informed consent form was revised based on these results. The incidences of adverse events were renewed to provide useful information and improve self-care ability. The symptoms and the time to appearance of the hypersensitivity reaction and peripheral sensory neuropathy were added. We think it is important to provide the information based on the clinical practice.

Effect of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve to gastrointestinal function: an experimental study in conscious dogs.

OBJECTIVE: To evaluate the effects of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve on gastrointestinal function. SUMMARY BACKGROUND DATA: The operative procedure of distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve is now in the spotlight in Japan with the goal of finding a function-preserving surgical technique. However, there has been no analysis of the effect of this type of surgery on gastrointestinal function. In this article, we describe the results of a fundamental experiment on distal subtotal gastrectomy with preservation of the celiac branch of the vagus nerve. METHODS: Twenty conscious dogs were divided into 2 groups, each subdivided into 2 groups of 5: a normal intact dog group (NG) divided into 2 groups, with preservation (PNG) and resection (RNG; these dogs were truncally vagotomized including transaction of the celiac branch) of the celiac branch, and a gastrectomy dog group (GG) divided into 2 groups, with preservation (PGG) and resection (RGG) of the celiac branch. The motility of the dogs was recorded using strain gauge force transducers. The effects of the preservation of the celiac branch of the vagus nerve on gastrointestinal motility, gastric emptying, and pancreatic insulin release were evaluated. RESULTS: The motility index of gastrointestinal motility with preservation of the celiac branch was higher than the motility index with resection of the celiac branch in fasted and fed of NG and GG. In gastric emptying, significant differences were found between the PNG and RNG but not between the PGG and RGG. In the fasted state for 80 minutes of the PNG and PGG, the serum insulin concentration reached a peak during the early phase III at 20 minutes in the gastric body and the antrum. CONCLUSIONS: This study has shown that it is effective to preserve the celiac branch of the vagus nerve for gastroduodenal motility, gastric emptying, and pancreatic insulin release after a gastrectomy.

The additional value of integrated PET/CT over PET in initial lymph node staging of esophageal cancer.

The purpose of the present study was to assess the contribution of simultaneous functional/anatomical imaging using integrated 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT), compared with PET alone for the evaluation of initial lymph node staging in esophageal cancer. We studied 167 consecutive patients with thoracic esophageal squamous cell carcinoma (SCC) who had radical esophagectomy performed between January 1999 and April 2007. For individual nodal group evaluation, PET/CT showed 46.0% sensitivity (p<0.05 vs. PET), 99.4% specificity, 95.1% accuracy (p<0.05 vs. PET), 87.0% positive and 95.5% negative predictive values. PET showed 32.9% sensitivity, 98.9% specificity, 93.1% accuracy, 74.7% positive predictive value and 93.9% negative predictive value. Thus, the sensitivity and accuracy of PET/CT were significantly higher than those of PET. Comparisons between CT, PET and PET/CT in detecting lymph node metastasis by each region showed that PET/CT had a higher sensitivity in lower thoracic regions than PET and CT (p<0.05 vs. CT and PET). Lymph node staging (N0 vs. N1) was not significantly different, but staging per lymph nodal group was significantly better with PET/CT. Integrated PET/CT imaging with co-registration of anatomic and functional imaging data is useful in the initial lymph node staging of patients with operable esophageal cancer compared with PET alone.

Preoperative serum vascular endothelial growth factor-C (VEGF-C) levels predict recurrence in patients with esophageal cancer.

BACKGROUND: Circulating vascular endothelial growth factor-C (VEGF-C) levels were measured in patients with esophageal cancer to assess the value of VEGF-C as a biomarker for predicting tumor recurrence. PATIENTS AND METHODS: Preoperative serum samples were acquired from 80 patients and healthy volunteers who served as normal controls. VEGF-C levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The preoperative serum VEGF-C level in patients with esophageal cancer was significantly higher than in healthy volunteers. Furthermore, patients with recurrence had significantly higher preoperative serum VEGF-C levels than patients without recurrence, and a high preoperative serum VEGF-C level was found to be an independent risk factor for recurrence, in addition to lymph node metastasis. CONCLUSION: Preoperative VEGF-C levels may reflect malignancy, such as lymph node metastasis, and predict recurrence in patients with esophageal cancer. Therefore, the preoperative VEGF-C level may be a useful biomarker for choice of multimodality therapy.

Clinical applications of 18F-fluorodeoxyglucose positron emission tomography in gastrointestinal stromal tumor of the esophagus.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms affecting the gastrointestinal tract. Esophageal GISTs are very rare, but recognition of esophageal GISTs has been increasing recently. We report a patient with an esophageal GIST that showed increased uptake on 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). In this case, preoperative diagnosis was assumed to be esophageal cancer, but postoperative histopathological and immunohistochemical examination showed it to be a malignant GIST. We also found an activating mutation of kit in this patient; the mutation type was an in-frame deletion of a portion of the juxtamembrane domain (exon11). FDG-PET is useful not only for evaluating the bioactivity but also the malignant potential of esophageal GISTs.

Prognostic significance of EpCAM expression in human esophageal cancer.

EpCAM is a 40-kDa epithelial transmembrane glycoprotein that has a well-known role in Ca2+ -independent homophilic cell-cell adhesion. Recently, correlations between EpCAM expression and clinicopathological features have been investigated in various cancers. We examined EpCAM expression in surgical specimens from esophageal cancer patients (n = 138), using real-time RT-PCR, immunohistochemistry and ELISA. The mean expression level of EpCAM mRNA in tumor tissues was significantly higher than that in corresponding normal tissues (P < 0.0001). Immunohistochemically, positive staining for EpCAM was found in 135 (97.8%) of the 138 primary tumor specimens. EpCAM expression was correlated with tumor depth (P = 0.0005), stage (P = 0.0037), blood-vessel invasion (P = 0.0397) and infiltrative growth pattern (P = 0.0015). The survival rates of patients with tumors with high EpCAM expression was significantly higher than those for patients with tumors with low EpCAM expression (P = 0.0213). Furthermore, the serum EpCAM levels of patients with esophageal cancer were significantly higher than those of normal volunteers (P = 0.0221). The survival rates of patients with a high EpCAM level in the peripheral vein were also significantly higher than those for patients with a low serum EpCAM level (P = 0.0291). The serum EpCAM level in the peripheral vein was independently associated with prognosis (P = 0.0074; hazard ratio 7.40). Tumor-specific EpCAM expression and release into the circulation may serve as effective immunotherapy in esophageal cancer patients.