Nanosecond Random Telegraph Noise in In-Plane Magnetic Tunnel Junctions.

We study the timescale of random telegraph noise (RTN) of nanomagnets in stochastic magnetic tunnel junctions (MTJs). From analytical and numerical calculations based on the Landau-Lifshitz-Gilbert and the Fokker-Planck equations, we reveal mechanisms governing the relaxation time of perpendicular easy-axis MTJs (p-MTJs) and in-plane easy-axis MTJs (i-MTJs), showing that i-MTJs can be made to have faster RTN. Superparamagnetic i-MTJs with small in-plane anisotropy and sizable perpendicular effective anisotropy show relaxation times down to 8 ns at negligible bias current, which is more than 5 orders of magnitude shorter than that of typical stochastic p-MTJs and about 100 times faster than the shortest time of i-MTJs reported so far. The findings give a new insight and foundation in developing stochastic MTJs for high-performance probabilistic computers.

Sphingosine 1-phosphate attenuates peroxide-induced apoptosis in HaCaT cells cultured in vitro.

BACKGROUND: Sphingosine 1-phosphate (S1P) is a sphingolipid mediator that elicits a wide array of physiological responses in various types of mammalian cells. Among the numerous biological activities elicited by S1P is protection from apoptotic cell death, which seems to take place through the cell-surface S1P receptor and the downstream phosphoinositide 3'-OH kinase (PI3-K)/Akt pathway. It is unclear whether and how S1P protects human keratinocytes from hydrogen peroxide (H2 O2 )-induced apoptosis. AIM: We investigated the effects of S1P on apoptotic cell death in HaCaT cells, spontaneously immortalized human keratinocytes. METHODS: HaCaT cells were treated with hydrogen peroxide (H2 O2 ) 1-2 mmol/L as an inducer of apoptosis. Cellular apoptosis was assessed with terminal dUTP nick-end labelling (TUNEL), WST-8 and immunoblot assays. RESULTS: In WST-8 and TUNEL assays, S1P pretreatment (1 µmol/L for 30 min) attenuated H2 O2 -induced cell death. Promotion of the cleavage of caspase-3 by H2 O2 was markedly attenuated when cells had been preincubated with S1P. S1P markedly potentiated phosphorylation (activation) of Akt in the presence of H2 O2 . Wortmannin, a selective inhibitor of the PI3-K/Akt pathway, significantly suppressed S1P-induced attenuation of caspase-3 cleavage promoted by H2 O2 . CONCLUSIONS: S1P, a sphingolipid mediator, attenuates H2 O2 -induced apoptosis of HaCaT cells, by promoting phosphorylation of the Akt pathway.

Synergistic effects of antibiotics and an N-acyl homoserine lactone analog on Porphyromonas gingivalis biofilms.

AIMS: To investigate the effects of the combined application of an N-acyl homoserine lactone (HSL) analog and antibiotics on biofilms of Porphyromonas gingivalis, a major pathogen of periodontal disease. METHODS AND RESULTS: Antibiotics used were cefuroxime, ofloxacin and minocycline. A flow-cell model was used for biofilm formation. Samples were divided into four groups: control, analog-treated, antibiotic-treated and combined application groups. Biofilm cell survival was determined using adenosine triphosphate (ATP) bioluminescence and confocal laser microscopy (CLSM). In the combined application group, the ATP count in biofilm cells was significantly decreased compared with the antibiotic-treated group (Games-Howell test, P < 0·05). A combination of cefuroxime and the analog was most effective against the P. gingivalis biofilm. CLSM observations revealed that the proportion of dead cells was highest in the combined application group. CONCLUSIONS: The combined application of the N-acyl HSL analog and antibiotics was effective at reducing the viability of P. gingivalis cells in biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: The combined application of the N-acyl HSL analog and antibiotics may be successful for eradicating infections involving bacterial biofilms, such as periodontitis.

Effects of N-acyl homoserine lactone analogues on Porphyromonas gingivalis biofilm formation.

BACKGROUND AND OBJECTIVE: The gram-negative anaerobic rod Porphyromonas gingivalis in oral biofilms is a primary etiological agent of periodontal disease. Biofilm formation of various gram-negative bacteria is regulated by a quorum-sensing circuit that relies on N-acyl homoserine lactones (HSLs). Some synthetic N-acyl HSL analogues act as quorum-sensing inhibitors and suppress biofilm formation in Pseudomonas aeruginosa. Development of chemical control agents against oral biofilms is necessary, because until now, biofilms have been removed only by mechanical debridement. The present study investigated the effect of N-acyl HSL analogues on P. gingivalis biofilm formation, with the aim of developing new drugs that inhibit oral biofilm formation. MATERIAL AND METHODS: A flow-cell model was used for P. gingivalis biofilm formation. Seventeen synthetic N-acyl HSL analogues were quantitatively assessed by spectrophotometry. The effects of three antagonistic compounds against P. gingivalis biofilm formation were further examined by confocal laser scanning microscopy, and investigated for primary attachment using spectrophotometry and phase contrast microscopy. RESULTS: Ten out of 17 analogues affected P. gingivalis biofilm formation. Three out of 10 analogues significantly decreased biofilm-forming cells (p < 0.05), and these biofilm structures were less well formed three-dimensionally. There were no quantitative or qualitative differences in cell attachment between the control and the three analogue-treated groups. CONCLUSION: Three synthetic N-acyl HSL analogues inhibited biofilm formation in P. gingivalis. We suggest that these analogues influence the development stage of P. gingivalis biofilm formation.

Expression and sequence analysis of candidates for the 1p36.31 tumor suppressor gene deleted in neuroblastomas.

Neuroblastomas are characterized by 1p deletions, suggesting that a tumor suppressor gene (TSG) resides in this region. We have mapped the smallest region of deletion (SRD) to a 2 Mb region of 1p36.31 using microsatellite and single nucleotide polymorphisms. We have identified 23 genes in this region, and we have analysed these genes for mutations and RNA expression patterns to identify candidate TSGs. We sequenced the coding exons of these genes in 30 neuroblastoma cell lines. Although rare mutations were found in 10 of the 23 genes, none showed a pattern of genetic change consistent with homozygous inactivation. We examined the expression of these 23 genes in 20 neuroblastoma cell lines, and most showed readily detectable expression, and no correlation with 1p deletion. However, 7 genes showed uniformly low expression in the lines, and 2 genes (CHD5, RNF207) had virtually absent expression, consistent with the expected pattern for a TSG. Our mutation and expression analysis in neuroblastoma cell lines, combined with expression analysis in normal tissues, putative function and prior implication in neuroblastoma pathogenesis, suggests that the most promising TSG deleted from the 1p36 SRD is CHD5, but TNFRSF25, CAMTA1 and AJAP1 are also viable candidates.

Statins induce S1P1 receptors and enhance endothelial nitric oxide production in response to high-density lipoproteins.

BACKGROUND AND PURPOSE: Sphingosine 1-phosphate (S1P) is a serum-borne naturally occurring sphingolipid, specifically enriched in high-density lipoprotein (HDL) fractions. S1P binds to G-protein-coupled S1P1 receptors to activate endothelial NO synthase (eNOS) in vascular endothelial cells. We explored whether and how statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, modulate expression of S1P1 receptors and endothelial responses for subsequent stimulation with S1P or with HDL. EXPERIMENTAL APPROACH: Protein expression and phosphorylation and mRNA expression in cultured bovine aortic endothelial cells (BAEC) were determined using immunoblots and reverse transcription PCR analyses, respectively. NO synthesis was assessed as nitrite production. KEY RESULTS: Stimulation of BAEC with pitavastatin or atorvastatin led to significant increases in S1P1-receptors, at levels of protein and mRNA, in a dose-dependent manner. When BAEC were treated with pitavastatin prior to stimulation with S1P or with normal human HDL, phosphorylation and activation of eNOS evoked by S1P or by HDL was enhanced. These effects of statins were counteracted by L-mevalonate and were mimicked by an inhibitor of geranylgeranyl transferase I, suggesting that inhibition of HMG-CoA reductase activity and subsequent decreases in protein geranylgeranylation may contribute to these actions of statins. Specific knock down of S1P1 receptors by small interfering RNA led to attenuation of eNOS responses to HDL. CONCLUSIONS AND IMPLICATIONS: Statins induce S1P1 receptors and potentiate responses of endothelial cells to HDL-associated sphingolipids, identifying a novel aspect of the pleiotropic actions of statins through which they may exert NO-dependent vascular protective effects.

Effects of n-3 polyunsaturated fatty acids on indomethacin-induced changes in eicosanoid production and blood flow in the gastric mucosa of rats.

We investigated the effects of n-3 polyunsaturated fatty acids (PUFAs) on non-steroidal anti-inflammatory drug (NSAID)-induced changes in microcirculation and eicosanoid production in the gastrointestinal mucosa. We measured gastric mucosal blood flow using laser Doppler flowmetry, assessed the fatty acid composition in the mucosal phospholipids, and quantified the production of prostaglandin E2 (PGE2), leukotriene B4, and leukotriene C4 (LTB4 and C4) from the mucosa with the stimulation of calcium ionophore 20 min after an injection of indomethacin or vehicle in rats fed a diet containing different compositions of alpha-linolenic acid. Four weeks after the initiation of the test diet the arachidonic acid level in gastric mucosal phospholipids was significantly lower in the perilla group than in the other three groups. Conversely, alpha-linolenic acid and eicosapentaenoic acid (EPA) were significantly higher in the perilla group than in the other three groups. The percent of gastric mucosal blood flow in the three groups administered indomethacin were significantly lower than that in the control group injected with vehicle alone. The percent of gastric mucosal blood flow in the perilla group was significantly higher than that in the corn group. LTB4 and LTC4 production from the gastric mucosa in the soybean and corn groups were significantly higher than those in the control group, and the LTC4 production in the perilla group was significantly lower than that in the corn group. There were no significant differences in PGE2 production among the four groups. Our results suggest that alpha-linolenic acid affectively suppressed the indomethacin-induced decreases in gastric mucosal blood flow by increasing EPA and decreasing the levels of arachidonic acid and LTC4 in the gastric mucosa.

Sphingosine 1-phosphate and isoform-specific activation of phosphoinositide 3-kinase beta. Evidence for divergence and convergence of receptor-regulated endothelial nitric-oxide synthase signaling pathways.

Sphingosine 1-phosphate (S1P) is a platelet-derived sphingolipid that elicits diverse biological responses, including angiogenesis, via the activation of G protein-coupled EDG receptors. S1P activates the endothelial isoform of nitric-oxide synthase (eNOS), associated with eNOS phosphorylation at Ser-1179, a site phosphorylated by protein kinase Akt. We explored the proximal signaling pathways that mediate Akt activation and eNOS regulation by S1P/EDG receptors. Akt is regulated by the lipid kinase phosphoinositide 3-kinase (PI3-K). We found that bovine aortic endothelial cells (BAEC) express both alpha and beta isoforms of PI3-K, while lacking the gamma isoform. S1P treatment led to the rapid and isoform-specific activation of PI3-Kbeta in BAEC. PI3-Kbeta can be regulated by G protein betagamma subunits (Gbetagamma). The overexpression of a peptide inhibitor of Gbetagamma attenuated S1P-induced eNOS enzyme activation, as well as S1P-induced phosphorylation of eNOS and Akt. In contrast, bradykinin, a classical eNOS agonist, neither activated any PI3-K isoform nor induced eNOS phosphorylation at Ser-1179, despite activating eNOS in BAEC. Vascular endothelial growth factor activated both PI3-Kalpha and PI3-Kbeta via tyrosine kinase pathways and promoted eNOS phosphorylation that was unaffected by Gbetagamma inhibition. These findings indicate that PI3-Kbeta (regulated by Gbetagamma) may represent a novel molecular locus for eNOS activation by EDG receptors in vascular endothelial cells. These studies also indicate that different eNOS agonists activate distinct signaling pathways that diverge proximally following receptor activation but converge distally to activate eNOS.

Conformational analysis of tandospirone in aqueous solution: lead evolution of potent dopamine D4 receptor ligands.

The significant contribution of folded conformation (2) of the anxiolytic tandospirone (1) in aqueous solution was verified by dynamic 1H NMR. A structurally rigid mimic of 2 was designed and synthesized to evaluate the implication of 2 towards neuroleptic receptor binding. The designed structures provided a new rigid scaffold for dopamine D4 ligands.

Palliative gastrectomy for advanced gastric cancer.

BACKGROUND/AIMS: Although palliative gastrectomy for advanced gastric cancer may be favorable in selected patients presenting with bleeding and obstruction, little has been reported about the clinical significance of palliative gastrectomy, including prognosis. METHODOLOGY: A retrospective comparison between 84 patients with palliative gastrectomy (PG group) and 100 patients with unresectable operation (UO group) for advanced gastric cancer was carried out. RESULTS: The incidence of serosal invasion, peritoneal dissemination, hepatic and lymph node metastases, and undifferentiated tissue type in the UO group were significantly higher than in the PG group. Median survival after operation in the PG group (20.6 months) was significantly longer than in the UO group (5.7 months). Also, in stage IVb patients, median survival time in the PG group (10.2 months) was significantly longer than in the UO group (5.0 months). However, median survival in the patients with synchronous liver metastasis between PG (8.4 months) and UO (4.6 months) groups was not significantly different. Survival rates after operation of 6 months, 1 year and 2 years in all patients between the palliative gastrectomy group versus UO group were 83.6% versus 38.3% (P < 0.01), 63.0% versus 9.3% (P < 0.01) and 35.2% versus 0% (P < 0.01), respectively. CONCLUSIONS: Palliative gastrectomy compared to unresectable operation may be effective for improvement of prognosis even if stage IVb patients with peritoneal dissemination and/or distant lymph node metastasis. However, it may be unfavorable on survival of patients with synchronous liver metastasis.

Sphingosine 1-phosphate and activation of endothelial nitric-oxide synthase. differential regulation of Akt and MAP kinase pathways by EDG and bradykinin receptors in vascular endothelial cells.

Sphingosine 1-phosphate (S1P) is a platelet-derived sphingolipid that elicits numerous biological responses in endothelial cells mediated by a family of G protein-coupled EDG receptors. Stimulation of EDG receptors by S1P has been shown to activate the endothelial isoform of nitric-oxide synthase (eNOS) in heterologous expression systems (Igarashi, J., and Michel, T. (2000) J. Biol. Chem. 275, 32363-32370). However, the signaling pathways that modulate eNOS regulation by S1P/EDG in vascular endothelial cells remain less well understood. We now report that S1P treatment of bovine aortic endothelial cells (BAEC) acutely increases eNOS enzyme activity; the EC(50) for S1P activation of eNOS is approximately 10 nm. The magnitude of eNOS activation by S1P in BAEC is equivalent to that elicited by the agonist bradykinin. S1P treatment activates Akt, a protein kinase implicated in phosphorylation of eNOS. S1P treatment of BAEC leads to eNOS phosphorylation at Ser(1179), a residue phosphorylated by Akt; an eNOS mutant in which this Akt phosphorylation site is inactivated shows attenuated S1P-induced eNOS activation. S1P-induced activation both of Akt and of eNOS is inhibited by pertussis toxin, by the phosphoinositide 3-kinase inhibitor wortmannin, and by the intracellular calcium chelator BAPTA (1,2-bis(aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). By contrast to S1P, activation of G protein-coupled bradykinin B2 receptors neither activates kinase Akt nor promotes Ser(1179) eNOS phosphorylation despite robustly activating eNOS enzyme activity. Understanding the differential regulation of protein kinase pathways by S1P and bradykinin may lead to the identification of new points for eNOS regulation in vascular endothelial cells.

Effects of n-3 polyunsaturated fatty acids and vitamin E on colonic mucosal leukotriene generation, lipid peroxidation, and microcirculation in rats with experimental colitis.

AIMS: We investigated the effect of n-3 polyunsaturated fatty acids (PUFAs) on mucosal levels of leukotrienes (LTs) and lipid peroxide (LPO), and on mucosal microcirculation, in rats with experimental colitis induced by dextran sulfate sodium (DSS). METHODS: We fed Wistar rats a perilla oil-enriched diet containing alpha-linolenic acid (63.2% of total fatty acids) with various doses of vitamin E for 4 weeks, with 4% DSS added to the drinking water during the last week. Control rats were fed a diet produced from soybean oil containing alpha-linolenic acid (5.1% of total fatty acids). Colonic mucosal blood flow was measured with a laser Doppler flowmeter. RESULTS: The mucosal level of arachidonic acid was significantly lower and that of eicosapentaenoic acid was significantly higher in the experimental group. The mucosal level of LPO in the experimental group fed a trace or ordinary dose of vitamin E was significantly higher than that of the controls. The production of LTB(4) and LTC(4) from the colonic mucosa in the experimental group was significantly lower than that in controls. However, only the experimental group fed a vitamin E dose 4-fold higher than that given to the controls showed a significant increase in mucosal blood flow. CONCLUSION: These results suggest that n-3 PUFAs increase mucosal blood flow by inhibiting LT production when there is sufficient vitamin E to inhibit lipid peroxidation in rats with experimental colitis.

A case of chronic expanding hematoma in the tensor fascia lata.

We describe a patient in whom a chronic expanding hematoma was pathologically confirmed by examination of the resected specimen. It developed gradually in the left lateral thigh, which had been bruised 8 months before, but had produced no mass-related symptoms initially. Computed tomography (CT) showed the mass to be homogeneous with capsule formation, whereas ultrasonography showed it to resemble a multilocular cyst. The lesion was treated by complete excision of a perifascial mass. Grossly, a well-circumscribed, fusiform mass with a soft cystic center and a fibrous pseudocapsule was observed. Histologically, the mass was composed of necrotic debris, fibrin and blood clots. This was surrounded by a rim of hyalinized fibrous tissue with a chronic inflammatory infiltrate and granulation tissue with sprouting new capillaries. CT was unable to discriminate the chronic expanding hematoma from other soft tissue masses, ultrasonography being needed to reveal its characteristics in this case.

A primitive myoglobin from Tetrahymena pyriformis: its heme environment, autoxidizability, and genomic DNA structure.

A myoglobin-like protein isolated from Tetrahymena pyriformis is composed of 121 amino acid residues. This is much smaller than sperm whale myoglobin by 32 residues, suggesting a distinct origin from the common globin gene. We have therefore examined this unique protein for its structural, spectral and stability properties. As a result, the rate of autoxidation of Tetrahymena oxymyoglobin (MbO(2)) was found to be almost comparable to that of sperm whale MbO(2) over a wide range of pH 4-12 in 0.1 M buffer at 25 degrees C. Moreover, both pH profiles exhibited the remarkable proton-assisted process, which can be performed in sperm whale myoglobin by the distal (E7) histidine as its catalytic residue. These kinetic observations are also in full accord with spectral examinations for the presence of a distal histidine in ciliated protozoa myoglobin. At the same time, we have isolated the globin genes both from T. pyriformis and Tetrahymena thermophila, and found that there is no intron in their genomic structures. This is in sharp contrast to previous reports on the homologous globin genes from Paramecium caudatum and Chlamydomonas eugametos. Rather, the Tetrahymena genes seemed to be related to the cyanobacterial globin gene from Nostoc commune. These contracted or truncated globins thus have a marked diversity in the cDNA, protein, and genomic structures.

Co-occurrence of mucoepidermoid carcinoma and squamous cell carcinoma of the esophagus: report of a case.

A case of co-occurrence of a mucoepidermoid carcinoma (MEC) and a squamous cell carcinoma (SCC) in the esophagus is described. The present patient was a 61-year-old man who underwent a curative esophagectomy with a regional lymph node dissection for a MEC in the lower esophagus and a SCC near the esophagogastric junction. The two lesions were endoscopically and histologically divided by a normal esophageal mucosa. The MEC of the esophagus consisted of SCC cells and signet-ring cells, and a mucin product and carcinoembryonic antigen, which were found at high levels in the blood serum before surgery, were detected histochemically in the signet-ring cells. The follow-up survey of the patients with esophageal MEC previously reported in Japan showed that most of the patients died of either local recurrence or widespread metastasis after treatment; the overall 5-year survival rate was 24.4% in the total 25 cases, and 27.7% in the 22 resected cases. However, 6 patients who died of therapeutic complications were included among these patients; furthermore, the 5-year survival rate after surgery was 29.2% in the patients treated over the last decade (1989-1998). We expect that the clinical outcome of patients treated for esophageal MEC will therefore improve in the future.

Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae. eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction.

Plasmalemmal caveolae are membrane microdomains that are specifically enriched in sphingolipids and contain a wide array of signaling proteins, including the endothelial isoform of nitric-oxide synthase (eNOS). EDG-1 is a G protein-coupled receptor for sphingosine 1-phosphate (S1P) that is expressed in endothelial cells and has been implicated in diverse vascular signal transduction pathways. We analyzed the subcellular distribution of EDG-1 in COS-7 cells transiently transfected with cDNA constructs encoding epitope-tagged EDG-1. Subcellular fractionation of cell lysates resolved by ultracentrifugation in discontinuous sucrose gradients revealed that approximately 55% of the EDG-1 protein was recovered in fractions enriched in caveolin-1, a resident protein of caveolae. Co-immunoprecipitation experiments showed that EDG-1 could be specifically precipitated by antibodies directed against caveolin-1 and vice versa. The targeting of EDG-1 to caveolae-enriched fractions was markedly increased (from 51 +/- 11% to 93 +/- 14%) by treatment of transfected cells with S1P (5 microm, 60 min). In co-transfection experiments expressing EDG-1 and eNOS cDNAs in COS-7 cells, we found that S1P treatment significantly and specifically increased nitric-oxide synthase activity, with an EC(50) of 30 nm S1P. Overexpression of transfected caveolin-1 cDNA together with EDG-1 and eNOS markedly diminished S1P-mediated eNOS activation; caveolin overexpression also attenuated agonist-induced phosphorylation of EDG-1 receptor by >90%. These results suggest that the interaction of the EDG-1 receptor with caveolin may serve to inhibit signaling through the S1P pathway, even as the targeting of EDG-1 to caveolae facilitates the interactions of this receptor with ligands and effectors that are also targeted to caveolae. The agonist-modulated targeting of EDG-1 to caveolae and its dynamic inhibitory interactions with caveolin identify new points for regulation of sphingolipid-dependent signaling in the vascular wall.

Allelic loss of the region of chromosome 1p35-pter is associated with progression of human gastric carcinoma.

In order to identify the region on distal chromosome 1p that is thought to include one or more tumor suppressor genes for gastric carcinoma, 39 gastric carcinomas were examined for allelic loss using 11 polymorphic microsatellite markers and 1 marker of single strand conformation polymorphism. Loss of heterozygosity (LOH) was found in 18 (46%) of 39 informative patients. The regions with high frequency of loss of heterozygosity were the loci at D1S548 (6 / 17; 35.3%) and D1S2843 (7 / 20; 35%), and we found three commonly deleted regions on chromosome 1p35-pter. The frequency of allelic loss in the region of chromosome 1p35-pter was significantly associated with advanced-stage gastric carcinoma, but not with early-stage tumor or with the histology. These results suggest that allelic loss at chromosome 1p35-pter may play a role in the progression of gastric carcinoma.

Circadian rhythm of serotonin levels in planarians.

In the freshwater planarian Dugesia japonica, which belongs to the most primitive metazoan phylum, serotonin (5-hydroxytryptamine) was detectable by both immunohistochemistry and high-performance liquid chromatography (HPLC) with fluorometric detection. Immunohistochemical studies showed that serotonin was localized primarily in the cephalic ganglion (brain), in the main nerve cords extending posteriorly from the brain and in the commissure axons connecting the main nerve cords. HPLC with fluorometric detection analysis revealed that the serotonin levels of planarians maintained under a 12:12h light:dark cycle showed significant diurnal variations with a trough in the middle of the dark phase. In constant darkness, the serotonin levels fluctuated with a circadian rhythm. These results demonstrate the existence of a circadian timekeeping mechanism in the planarian.

Histochemical study of angiogenesis in basaloid squamous carcinoma of the esophagus.

Angiogenesis of esophageal basaloid squamous carcinoma (BSC) was studied immunohistochemically and compared with that of squamous cell carcinoma (SCC). In tissues taken from six patients with esophageal BSC and 35 with esophageal SCC, angiogenesis was evaluated by measuring microvessel density (MVD), defined as the microvessel count determined using factor VIII-related antigen immunostaining, and by measuring immunoreactivity of vascular endothelial growth factor (VEGF) and thymidine phosphorylase (dThdPase). Three of the six patients with BSC had distant metastases. There was no difference of MVD between BSC and SCC (22.0 +/- 4.6 vs. 27.6 +/- 9.4). VEGF expression tended to be more frequently observed in BSC than in SCC (100% vs. 60.0%; p = 0.066). Strong expression of VEGF was detected in three BSC with distant metastases; however, there was no difference in the rate of strong VEGF expression between BSC and SCC. The MVD in the cases of BSC with strong VEGF expression, i.e. in the cases with distant metastases, was higher than that in the cases of BSC with weak VEGF expression (p=0.049). There was no difference in dThdPase expression of the cancer cells between BSC and SCC (50.0% vs. 54.3%), whereas the infiltrating stromal cells of all the BSC expressed dThdPase. Strong dThdPase expression in the cancer cells or in the infiltrating stromal cells was observed in two and three BSC, respectively. However, there were no differences in the rate of cancer cells or stromal cells with strong dThdPase expression between BSC and SCC. In one BSC with high MVD and distant metastases, VEGF and dThdPase were both strongly expressed. The vascularity of esophageal BSC was not different from that of SCC. VEGF may participate in angiogenesis of esophageal BSC and may influence the rate of metastasis in esophageal BSC patients. dThdPase may play a partial rule in angiogenesis and metastasis in some cases of BSC.