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Epithelial-to-mesenchymal transition (EMT), in which epithelial cells loose their polarity and become motile mesenchymal cells, is a determinant of melanoma metastasis. We compared gene expression signatures of mesenchymal-like melanoma cells with those of epithelial-like melanoma cells, and identified Thrombospondin 1 (THBS1) as highly up-regulated in the mesenchymal phenotype. This study investigated whether THBS1, a major physiological activator of transforming growth factor (TGF)-beta, is involved in melanoma EMT-like process. We sought to examine expression patterns in distinct melanoma phenotypes including invasive, de-differentiated, label-retaining and drug resistant populations that are putatively associated with an EMT-like process. Here we show that THBS1 expression and secretion was elevated in melanoma cells exhibiting invasive, drug resistant, label retaining and mesenchymal phenotypes and correlated with reduced expression of genes involved in pigmentation. Elevated THBS1 levels were detected in Vemurafenib resistant melanoma cells and inhibition of THBS1 led to significantly reduced chemoresistance in melanoma cells. Notably, siRNA-mediated silencing of THBS1 and neutralizing antibody to THBS1 reduced invasion in mesenchymal-like melanoma cells, while ectopic THBS1 expression in epithelial-like melanoma cells enhanced invasion. Furthermore, the loss of THBS1 inhibited in vivo motility of melanoma cells within the embryonic chicken neural tube. In addition, we found aberrant THBS1 protein expression in metastatic melanoma tumor biopsies. These results implicate a role for THBS1 in EMT, and hence THBS1 may serve as a novel target for strategies aimed at the treatment of melanoma invasion and drug resistance.

This study examines the process of dyadic coping among couples who are managing stress related to a partner's breast cancer diagnosis and identifies cultural factors that affect how couples cope together. Utilizing a qualitative method based on relational psychologies, the "Listening Guide," the authors analyzed the narratives of 28 couples who where coping with early-stage breast cancer and lived in Hong Kong-China, India, and the United States. Analysis revealed four cultural factors influencing the process of coping with breast cancer. These factors included (1) family boundaries, (2) gender roles, (3) personal control, and (4) interdependence. Some couples were able to transcend prevailing cultural norms to re-establish balance in their lives and adapt to the cancer. Implications for using couple-based interventions with cancer patients in differing cultural contexts are discussed.

Background: Intratumoral heterogeneity is a major obstacle for the treatment of cancer, as the presence of even minor populations that are insensitive to therapy can lead to disease relapse. Increased clonal diversity has been correlated with a poor prognosis for cancer patients, and we therefore examined genetic, transcriptional, and functional diversity in metastatic melanoma., Methods: Amplicon sequencing and SNP microarrays were used to profile somatic mutations and DNA copy number changes in multiple regions from metastatic lesions. Clonal genetic and transcriptional heterogeneity was also assessed in single cell clones from early passage cell lines, which were then subjected to clonogenicity and drug sensitivity assays., Results: MAPK pathway and tumor suppressor mutations were identified in all regions of the melanoma metastases analyzed. In contrast, we identified copy number abnormalities present in only some regions in addition to homogeneously present changes, suggesting ongoing genetic evolution following metastatic spread. Copy number heterogeneity from a tumor was represented in matched cell line clones, which also varied in their clonogenicity and drug sensitivity. Minor clones were identified based on dissimilarity to the parental cell line, and these clones were the most clonogenic and least sensitive to drugs. Finally, treatment of a polyclonal cell line with paclitaxel to enrich for drug-resistant cells resulted in the adoption of a gene expression profile with features of one of the minor clones, supporting the idea that these populations can mediate disease relapse., Conclusion: Our results support the hypothesis that minor clones might have major consequences for patient outcomes in melanoma.

Background: A few reports suggested that low levels of Wnt signaling might drive cell reprogramming, but these studies could not establish a clear relationship between Wnt signaling and self-renewal networks. There are ongoing debates as to whether and how the Wnt/β-catenin signaling is involved in the control of pluripotency gene networks. Additionally, whether physiological β-catenin signaling generates stem-like cells through interactions with other pathways is as yet unclear. The nasopharyngeal carcinoma HONE1 cells have low expression of β-catenin and wild-type expression of p53, which provided a possibility to study regulatory mechanism of stemness networks induced by physiological levels of Wnt signaling in these cells., Results: Introduction of increased β-catenin signaling, haploid expression of β-catenin under control by its natural regulators in transferred chromosome 3, resulted in activation of Wnt/β-catenin networks and dedifferentiation in HONE1 hybrid cell lines, but not in esophageal carcinoma SLMT1 hybrid cells that had high levels of endogenous β-catenin expression. HONE1 hybrid cells displayed stem cell-like properties, including enhancement of CD24(+) and CD44(+) populations and generation of spheres that were not observed in parental HONE1 cells. Signaling cascades were detected in HONE1 hybrid cells, including activation of p53- and RB1-mediated tumor suppressor pathways, up-regulation of Nanog-, Oct4-, Sox2-, and Klf4-mediated pluripotency networks, and altered E-cadherin expression in both in vitro and in vivo assays. qPCR array analyses further revealed interactions of physiological Wnt/β-catenin signaling with other pathways such as epithelial-mesenchymal transition, TGF-β, Activin, BMPR, FGFR2, and LIFR- and IL6ST-mediated cell self-renewal networks. Using β-catenin shRNA inhibitory assays, a dominant role for β-catenin in these cellular network activities was observed. The expression of cell surface markers such as CD9, CD24, CD44, CD90, and CD133 in generated spheres was progressively up-regulated compared to HONE1 hybrid cells. Thirty-four up-regulated components of the Wnt pathway were identified in these spheres., Conclusions: Wnt/β-catenin signaling regulates self-renewal networks and plays a central role in the control of pluripotency genes, tumor suppressive pathways and expression of cancer stem cell markers. This current study provides a novel platform to investigate the interaction of physiological Wnt/β-catenin signaling with stemness transition networks.

Background & Aims: We performed a genome-wide association study (GWAS) of hepatitis C virus (HCV)-induced liver cirrhosis (LC) to identify predictive biomarkers for the risk of LC in patients with chronic hepatitis C (CHC)., Methods: A total of 682 HCV-induced LC cases and 1045 CHC patients of Japanese origin were genotyped by Illumina Human Hap 610-Quad bead Chip., Results: Eight SNPs which showed possible associations (p<1.0 × 10(-5)) at the GWAS stage were further genotyped using 936 LC cases and 3809 CHC patients. We found that two SNPs within the major histocompatibility complex (MHC) region on chromosome 6p21, rs910049 and rs3135363, were significantly associated with the progression from CHC to LC (pcombined=9.15 × 10(-11) and 1.45 × 10(-10), odds ratio (OR)=1.46 and 1.37, respectively). We also found that HLA-DQA1(*)0601 and HLA-DRB1(*)0405 were associated with the progression from CHC to LC (p=4.53 × 10(-4) and 1.54 × 10(-4) with OR=2.80 and 1.45, respectively). Multiple logistic regression analysis revealed that rs3135363, rs910049, and HLA-DQA1(*)0601 were independently associated with the risk of HCV-induced LC. In addition, individuals with four or more risk alleles for these three loci have a 2.83-fold higher risk for LC than those with no risk allele, indicating the cumulative effects of these variations., Conclusions: Our findings elucidated the crucial roles of multiple genetic variations within the MHC region as prognostic/predictive biomarkers for CHC patients., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Hepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC) in Japan. We previously identified the association of SNP rs2596542 in the 5' flanking region of the MHC class I polypeptide-related sequence A (MICA) gene with the risk of HCV-induced HCC. In the current study, we performed detailed functional analysis of 12 candidate SNPs in the promoter region and found that a SNP rs2596538 located at 2.8 kb upstream of the MICA gene affected the binding of a nuclear protein(s) to the genomic segment including this SNP. By electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay, we identified that transcription factor Specificity Protein 1 (SP1) can bind to the protective G allele, but not to the risk A allele. In addition, reporter construct containing the G allele was found to exhibit higher transcriptional activity than that containing the A allele. Moreover, SNP rs2596538 showed stronger association with HCV-induced HCC (P = 1.82 × 10(-5) and OR = 1.34) than the previously identified SNP rs2596542. We also found significantly higher serum level of soluble MICA (sMICA) in HCV-induced HCC patients carrying the G allele than those carrying the A allele (P = 0.00616). In summary, we have identified a functional SNP that is associated with the expression of MICA and the risk for HCV-induced HCC.

Background: Primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) significantly reduces mortality and morbidity, particularly when door-to-balloon (D2B) time is < 90 min. We sought to minimize preventable delays by instituting an on-site cardiology team-based approach in the emergency department (ED)., Methods: The on-site group comprised 146 consecutive patients with STEMI undergoing primary PCI after implementation of the on-site strategy. This new patient care model was compared with the conventional care administered before instituting the on-site cardiology team-based strategy in ED, which included 90 patients (interim group) receiving primary PCI at a catheterization room in the same building as the ED, and 147 patients (pre-on-site group) undergoing primary PCI at a catheterization room two blocks away from the ED., Results: Median D2B time decreased from 107 min in the pre-on-site group to 72 min in the interim group, and to 47 min in the on-site group, respectively (p < 0.001). The percentage of D2B times < 90 min increased from 34% to 78% and 96%, respectively among the three groups (p < 0.001). Hospitalization costs were significantly reduced in the on-site and interim vs. pre-on-site groups ($5944, $5999, and $6581, respectively; p = 0.008). In-hospital mortality did not differ significantly among the three groups (4.8%, 2.2%, and 6.1%, respectively; p = 0.387)., Conclusions: Institution of an on-site cardiology team-based approach in the ED significantly reduces D2B time in STEMI patients eligible for primary PCI., (© 2011 Blackwell Publishing Ltd.)

Objective. Patients with schizophrenia residing at institutions often suffer from negative symptoms, motor, and functional impairments more severe than their noninstitutionalized counterparts. Tai-chi emphasizes body relaxation, alertness, and movement coordination with benefits to balance, focus, and stress relief. This pilot study explored the efficacy of Tai-chi on movement coordination, negative symptoms, and functioning disabilities towards schizophrenia. Methods. A randomized waitlist control design was adopted, where participants were randomized to receive either the 6-week Tai-chi program and standard residential care or only the latter. 30 Chinese patients with schizophrenia were recruited from a rehabilitation residency. All were assessed on movement coordination, negative symptoms, and functional disabilities at baseline, following intervention and 6 weeks after intervention. Results. Tai-chi buffered from deteriorations in movement coordination and interpersonal functioning, the latter with sustained effectiveness 6 weeks after the class was ended. Controls showed marked deteriorations in those areas. The Tai-chi group also experienced fewer disruptions to life activities at the 6-week maintenance. There was no significant improvement in negative symptoms after Tai-chi. Conclusions. This study demonstrated encouraging benefits of Tai-chi in preventing deteriorations in movement coordination and interpersonal functioning for residential patients with schizophrenia. The ease of implementation facilitates promotion at institutional psychiatric services.

MHC class I polypeptide-related chain A (MICA) molecule is induced in response to viral infection and various types of stress. We recently reported that a single nucleotide polymorphism (SNP) rs2596542 located in the MICA promoter region was significantly associated with the risk for hepatitis C virus (HCV)-induced hepatocellular carcinoma (HCC) and also with serum levels of soluble MICA (sMICA). In this study, we focused on the possible involvement of MICA in liver carcinogenesis related to hepatitis B virus (HBV) infection and examined correlation between the MICA polymorphism and the serum sMICA levels in HBV-induced HCC patients. The genetic association analysis revealed a nominal association with an SNP rs2596542; a G allele was considered to increase the risk of HBV-induced HCC (P = 0.029 with odds ratio of 1.19). We also found a significant elevation of sMICA in HBV-induced HCC cases. Moreover, a G allele of SNP rs2596542 was significantly associated with increased sMICA levels (P = 0.009). Interestingly, HCC patients with the high serum level of sMICA (>5 pg/ml) exhibited poorer prognosis than those with the low serum level of sMICA (≤5 pg/ml) (P = 0.008). Thus, our results highlight the importance of MICA genetic variations and the significance of sMICA as a predictive biomarker for HBV-induced HCC.

Cerebral oximetry is a noninvasive bedside monitor for cerebral oxygen saturation (rSO(2)). A patient with a thoracic aneurysm underwent combined surgical and endovascular repair. A sudden decrease in right rSO(2) led to the finding of acute innominate artery dissection. Immediate repair was instituted. Sudden asymmetry of rSO(2) may be a warning sign of underlying pathology., (Copyright © 2011 Elsevier Inc. All rights reserved.)

THY1 was previously identified as a candidate tumor suppressor gene (TSG) associated with lymph node metastases in nasopharyngeal carcinoma (NPC) through functional studies. It was identified by oligonucleotide microarray analysis as an interesting differentially expressed gene. However, direct functional evidence is still lacking for THY1 being a TSG in NPC, as in vivo tumorigenicity assays have not been previously reported in our last study of THY1. In this study, a tetracycline-inducible expression vector, pETE-Bsd, was used to obtain stable transfectants of THY1. The stringent in vivo tumorigenicity assay results show that the activation of THY1 suppresses tumor formation of HONE1 cells in nude mice, and the tumor formation ability was restored in the presence of doxycycline (a tetracycline analog), when the gene is shut off. Functional inactivation of this gene is observed in all the tumors derived from the tumorigenic transfectant. The tumor suppressive effect could be repressed by knockdown of THY1 expression in nontumorigenic microcell hybrids. Further studies indicate that expression of THY1 inhibits HONE1 cell growth in vitro by arresting cells in G(0)/G(1) phase. It greatly reduces the ability for anchorage-independent growth. The invasiveness of HONE1 cells was also inhibited by the expression of THY1. These findings suggest that THY1 is a TSG in NPC, which is involved in invasion and shows an association with tumor metastasis. Taken together, THY1 clearly plays an important functional role in tumor suppression in NPC.

ADAMTS metalloprotease family member ADAMTS9 maps to 3p14.2 and shows significant associations with the aerodigestive tract cancers esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). However, the functional impact of ADAMTS9 on cancer development has not been explored. In this study, we evaluated the hypothesized antiangiogenic and tumor-suppressive functions of ADAMTS9 in ESCC and NPC, in stringent tumorigenicity and Matrigel plug angiogenesis assays. ADAMTS9 activation suppressed tumor formation in nude mice. Conversely, knockdown of ADAMTS9 resulted in clones reverting to the tumorigenic phenotype of parental cells. In vivo angiogenesis assays revealed a reduction in microvessel numbers in gel plugs injected with tumor-suppressive cell transfectants. Similarly, conditioned medium from cell transfectants dramatically reduced the tube-forming capacity of human umbilical vein endothelial cells. These activities were associated with a reduction in expression levels of the proangiogenic factors MMP9 and VEGFA, which were consistently reduced in ADAMTS9 transfectants derived from both cancers. Taken together, our results indicate that ADAMTS9 contributes an important function in the tumor microenvironment that acts to inhibit angiogenesis and tumor growth in both ESCC and NPC., (Copyright 2010 AACR.)

Relapsing polychondritis (RP) is a rare disease that is characterized by recurrent inflammation and destruction of cartilage and connective tissues. RP can have significant airway pathology that may require procedures to maintain airway patency and thus may have serious implications for anesthesiologists. Anesthesiologists must be prepared to deal with the possible complications that may occur during airway manipulation in patients with RP. Here, we present a case of life-threatening bilateral tension pneumothorax and tension pneumoperitoneum that developed after a tracheal tear during Montgomery T-tube insertion in a patient with tracheal stenosis due to RP. Correct diagnosis was delayed due to a misdiagnosis of airway obstruction. As a result, we emphasize that bilateral tension pneumothorax should be considered during refractory cardiac arrest in patients with increased airway pressure. A high index of suspicion and adequate management are mandatory for patients to survive these life-threatening complications.

A simple selective method for determination of ascorbic acid using polymerized direct blue 71 (DB71) is described. Anodic polymerization of the azo dye DB71 on glassy carbon (GC) electrode in 0.1M H(2)SO(4) acidic medium was found to yield thin and stable polymeric films. The poly(DB71) films were electroactive in wide pH range (1-13). A pair of symmetrical redox peaks at a formal redox potential, E('0)=-0.02V vs. Ag/AgCl (pH 7.0) was observed with a Nernstian slope -0.058V, is attributed to a 1:1 proton+electron involving polymer redox reactions at the modified electrode. Scanning electron microscope (SEM), atomic force microscope (AFM) and electrochemical impedance spectroscopy (EIS) measurements were used for surface studies of polymer modified electrode. Poly(DB71) modified GC electrode showed excellent electrocatalytic activity towards ascorbic acid in neutral buffer solution. Using amperometric method, linear range (1x10(-6)-2x10(-3)M), dynamic range (1x10(-6)-0.01M) and detection limit (1x10(-6)M, S/N=3) were estimated for measurement of ascorbic acid in pH 7.0 buffer solution. Major interferences such as dopamine and uric acid are tested at this modified electrode and found that selective detection of ascorbic acid can be achieved. This new method successfully applied for determination of ascorbic acid in commercial tablets with satisfactory results.

We report electrochemical preparation and characterization of a new biosensor made of nanostructured titanium dioxide (nano-TiO2) particles and deoxyribonucleic acid (DNA). Thionin (TN) redox mediator was electrochemically deposited onto DNA/nano-TiO2 modified glassy carbon electrode (GCE). The X-ray diffraction analysis, atomic force microscope (AFM) and scanning electron microscope (SEM) were used for surface analysis of TN/DNA/nano-TiO2 film. In neutral buffer solution, TN/DNA/nano-TiO2/GCE biosensor exhibited excellent electrocatalytic activity towards the reduction of hydrogen peroxide (H2O2) and oxygen (O2). The biosensor shows excellent analytical performance for amperometric determination of H2O2, at reduced overpotential (-0.2V). The detection limit and liner calibration range were found to be 0.05 mM (S/N=3) and 0.05-22.3 mM, respectively. In addition, determination of H2O2 in real samples was carried out using the new biosensor with satisfactory results. The TN/DNA/nano-TiO2/GCE showed stable and reproducible analytical performance towards the reduction of H2O2. This biosensor can be used as an amperometric biosensor for the determination of H2O2 in real samples.

Here, we report the electrochemical synthesis of TiO(2) nanoparticles (NPs) using the potentiostat method. Synthesized particles have been characterized by using x-ray diffraction (XRD) studies, atomic force microscopy (AFM) and scanning electron microscopy (SEM). The results revealed that the TiO(2) film produced was mainly composed of rutile and that the particles are of a size in the range of 100 ± 50 nm. TiO(2) NPs were used for the modification of a screen printed carbon electrode (SPE). The resulting TiO(2) film coated SPE was used to immobilize flavin adenine dinucleotide (FAD). The flavin enzyme firmly attached onto the metal oxide surface and this modified electrode showed promising electrocatalytic activities towards the reduction of hydrogen peroxide (H(2)O(2)) in physiological conditions. The electrochemistry of FAD confined in the oxide film was investigated. The immobilized FAD displayed a pair of redox peaks with a formal potential of -0.42 V in pH 7.0 oxygen-free phosphate buffers at a scan rate of 50 mV s(-1). The FAD in the nanostructured TiO(2) film retained its bioactivity and exhibited excellent electrocatalytic response to the reduction of H(2)O(2), based on which a mediated biosensor for H(2)O(2) was achieved. The linear range for the determination of H(2)O(2) was from 0.15 × 10(-6) to 3.0 × 10(-3) M with the detection limit of 0.1 × 10(-6) M at a signal-to-noise ratio of 3. The stability and repeatability of the biosensor is also discussed.

Loss of chromosome 13q regions in esophageal squamous cell carcinoma (ESCC) is a frequent event. Monochromosome transfer approaches provide direct functional evidence for tumor suppression by chromosome 13 in SLMT-1, an ESCC cell line, and identify critical regions at 13q12.3, 13q14.11, and 13q14.3. Differential gene expression profiles of three tumor-suppressing microcell hybrids (MCH) and their tumorigenic parental SLMT-1 cell line were revealed by competitive hybridization using 19k cDNA oligonucleotide microarrays. Nine candidate 13q14 tumor-suppressor genes (TSG), including RB1, showed down-regulation in SLMT-1, compared with NE1, an immortalized normal esophageal epithelial cell line; their average gene expression was restored in MCHs compared with SLMT-1. Reverse transcription-PCR validated gene expression levels in MCHs and a panel of ESCC cell lines. Results suggest that the tumor-suppressing effect is not attributed to RB1, but instead likely involves thrombospondin type I domain-containing 1 (THSD1), a novel candidate TSG mapping to 13q14. Quantitative reverse transcription-PCR detected down-regulation of THSD1 expression in 100% of ESCC and other cancer cell lines. Mechanisms for THSD1 silencing in ESCC involved loss of heterozygosity and promoter hypermethylation, as analyzed by methylation-specific PCR and clonal bisulfite sequencing. Transfection of wild-type THSD1 into SLMT-1 resulted in significant reduction of colony-forming ability, hence providing functional evidence for its growth-suppressive activity. These findings suggest that THSD1 is a good candidate TSG.

Background: Although patient-controlled epidural analgesia (PCEA) can effectively relieve postoperative pain in orthopedic patients, some adverse effects are still troublesome. We conducted this study to survey the possible risk factors related to vomiting induced by PCEA., Methods: This retrospective study was conducted to review orthopedic patients receiving postoperative PCEA. The agent for PCEA was bupivacaine prepared as a 0.1% solution with added fentanyl (1 microg/mL). Patients' characteristics including demographic data and types of surgical procedures were collected. All patients were dichotomized into vomiting and non-vomiting groups and subgroup comparisons were also performed. Stepwise logistic regression analyses were conducted to determine significant factors associated with vomiting in these patients., Results: There were 320 patients (111 men, 209 women) included in the analysis. No significant differences in demographic data were noted between the groups except in sex distribution. Factors related to surgery, anesthesia and PCEA were similar between groups (p > 0.05 in all). The incidence of vomiting for orthopedic patients receiving PCEA was about 9.7% (12.4% for female, 4.5% for male). After stepwise model selection, we found female sex was the only risk factor of vomiting. The odds ratio of vomiting for female gender was 3 (95% confidence interval, 1.1-8.1). General anesthesia was not associated with vomiting in these patients., Conclusion: Our study demonstrated the risk factor associated with vomiting for orthopedic patients receiving PCEA was female sex. Other demographic variables and factors related to surgery or anesthesia did not have an influence on vomiting.

Reduced expression or loss of tumor suppressor genes play a key role in many cancers. In this study, we investigated the role of RASSF1A in the pathogenesis of esophageal squamous cell carcinoma (ESCC) and nasopharyngeal carcinoma (NPC). We detected the down-regulated expression of both RASSF1A transcripts and protein in tumor tissues using RT-PCR and tissue microarray immunohistochemical staining analyses. Down-regulated expression of RASSF1A showed a significant association with WHO grade, tumor status, and lymph node metastasis, showing its possible utility as a biomarker for clinical specimens.

A gene critical to esophageal cancer has been identified. Functional studies using microcell-mediated chromosome transfer of intact and truncated donor chromosomes 3 into an esophageal cancer cell line and nude mouse tumorigenicity assays were used to identify a 1.61 Mb tumor suppressive critical region (CR) mapping to chromosome 3p14.2. This CR is bounded by D3S1600 and D3S1285 microsatellite markers. One candidate tumor suppressor gene, ADAMTS9, maps to this CR. Further studies showed normal expression levels of this gene in tumor-suppressed microcell hybrids, levels that were much higher than observed in the recipient cells. Complete loss or downregulation of ADAMTS9 gene expression was found in 15 out of 16 esophageal carcinoma cell lines. Promoter hypermethylation was detected in the cell lines that do not express this gene. Re-expression of ADAMTS9 was observed after demethylation drug treatment, confirming that hypermethylation is involved in gene downregulation. Downregulation of ADAMTS9 was also found in 43.5 and 47.6% of primary esophageal tumor tissues from Hong Kong and from the high-risk region of Henan, respectively. Thus, this study identifies and provides functional evidence for a CR associated with tumor suppression on 3p14.2 and provides the first evidence that ADAMTS9, mapping to this region, may contribute to esophageal cancer development.

The expression of six chromosome 3p21.3 candidate tumor suppressor genes (BLU, FUS2, HYAL2, NPRL2, RASSF1A, and SEMA3B) in esophageal squamous cell carcinoma (ESCC) has been investigated. Reduced expression of BLU was detected in some ESCC cell lines and tumor tissues and the difference was quantitated by real-time quantitative polymerase chain reaction. Methylation specific-PCR revealed the down-regulation of BLU by epigenetic inactivation. However, exogenous expression of BLU did not functionally suppress tumorigenicity in nude mice. These results suggest that over-expression of BLU alone is not sufficient to inhibit tumorigenicity. Further studies on BLU interacting proteins are required to elucidate the possible role of BLU in the development of ESCC.

Despite the abundant evidence of high allelic loss of chromosome arm 14q in human cancers, tumor-suppressor genes mapped to this chromosome have yet to be identified. To narrow the search for candidate genes, we performed monochromosome transfer of chromosome 14 into an esophageal carcinoma cell line, SLMT-1 S1. Statistically significant suppression of the tumorigenic potential of microcell hybrids containing the transferred chromosome 14 provided functional evidence that tumor-suppressive regions of chromosome 14 are essential for esophageal cancer. Tumor segregants emerging in nude mice during the tumorigenicity assay were analyzed by detailed PCR-microsatellite typing to identify critical nonrandomly eliminated regions (CRs). A 680-kb CR mapped to 14q32.13 and an approximately 2.2-Mb CR mapped to 14q32.33 were delineated. Dual-color BAC FISH analysis of microcell hybrids and tumor segregants verified the selective loss of the 14q32.13 region. In contrast, similar transfers of an intact chromosome 11 into SLMT-1 S1 did not significantly suppress tumor formation. These functional complementation studies showing the correlation of tumorigenic potential with critical regions of chromosome 14 validated the importance of the 14q32 region in tumor suppression in esophageal cancer. The present study also paved the path for further identification of novel tumor-suppressor genes that are relevant to the molecular pathogenesis of esophageal cancer., ((c) 2005 Wiley-Liss, Inc.)

The key genes involved in the development of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Previous studies indicate extensive genomic alterations occur on chromosome 9 in ESCC. Using a monochromosome transfer approach, this study provides functional evidence and narrows down the critical region (CR) responsible for chromosome 9 tumor suppressing activity to a 2.4 Mb region mapping to 9q33-q34 between markers D9S1798 and D9S61. Interestingly, a high prevalence of allelic loss in this CR is also observed in primary ESCC tumors by microsatellite typing. Allelic loss is found in 30/34 (88%) tumors and the loss of heterozygosity (LOH) frequency ranges from 67 to 86%. Absent to low expression of a 9q32 candidate tumor suppressor gene (TSG), DEC1 (deleted in esophageal cancer 1), is detected in four Asian ESCC cell lines. Stably expressing DEC1 transfectants provide functional evidence for inhibition of tumor growth in nude mice and DEC1 expression is decreased in tumor segregants arising after long-term selection in vivo. There is 74% LOH in the DEC1 region of ESCC primary tumors. This study provides the first functional evidence for the presence of critical tumor suppressive regions on 9q33-q34. DEC1 is a candidate TSG that may be involved in ESCC development.

Slow/no-reflow phenomenon is a serious problem complicating primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) and is associated with a poor prognosis. From January 2002 to November 2002, 11 of the 70 consecutive patients with ST elevation AMI who were subjected to primary PCI using balloon angioplasty and/or stenting developed slow/no-reflow phenomenon (TIMI 1 flow in 2, TIMI 2 in 8, and TIMI 2.5 in 1). They were 10 men and 1 woman, aged 64 +/- 11 years (range, 46-81). The culprit vessels were six in the left anterior descending coronary artery, three in the right coronary artery, one in the left circumflex coronary artery, and one in saphenous vein graft. Multiple bolus doses (100 microg) of nitroprusside were injected into the index artery through the guiding catheter using a 3 ml syringe until the TIMI flow grade improved by at least one grade or the systolic pressure decline below 80 mm Hg (one patient). The total drug dose varied from 100 to 700 microg. Following the drug treatment, angiographic TIMI flow grade improved by at least one grade in 9 (82%) of the 11 patients (P = 0.007). The TIMI frame counts significantly decreased from 36 +/- 17 frame counts to 16 +/- 11 frame counts (P = 0.012). All patients were discharged without major adverse cardiovascular events. Intracoronary bolus injection of nitroprusside using a 3 ml syringe appears to be a feasible, safe, and effective technique for the management of slow/no-reflow phenomenon complicating primary PCI., ((c) 2004 Wiley-Liss, Inc.)

In many cancers, including nasopharyngeal carcinoma (NPC), extensive and multiple regions of allelic loss occur on chromosome 14. However, to date no functionally conclusive tumor suppressor genes have yet been identified on this chromosome. Through use of the monochromosome transfer technique, this study provides functional evidence for the importance of two discrete regions of chromosome 14. A newly established A9 mouse donor cell line containing an intact copy of chromosome 14 was used for transfer of this intact chromosome into the NPC HONE1 cell line. Twelve independently established microcell hybrids demonstrated uniform loss of specific chromosome 14 loci from both endogenous and exogenous alleles. By microsatellite typing and fluorescence in situ hybridization with BAC probes, the two critical regions were localized to 14q11.2-13.1 and 14q32.1. Selective elimination of these regions during hybrid selection was strongly associated with both hybrid survival and tumor growth in vivo. This functional evidence now narrows down the candidate areas for further studies and suggests that at least two hitherto unidentified growth-related genes localized on two critical regions of chromosome arm 14q play an important role in tumorigenesis., (Copyright 2003 Wiley-Liss, Inc.)

We report 7 symptomatic patients with stenotic double-orifice mitral valve of incomplete bridge type. In each patient, the fibrous bridge tissue between the valve leaflets was successfully split using an Inoue balloon valvuloplasty technique with stepwise dilations applied only to the posteromedial orifice.

We present the short- and intermediate-term results of transcatheter closure of patent ductus arteriosus with Gianturco coils in adolescents and adults. During a 5-year period, 55 patients (44 females, 11 males) with ages ranging from 14 to 72 years (median, 23) underwent attempted transcatheter closure of patent ductus with the Gianturco coils. The diameter of the narrowest segment of the ductus ranged from 0.8 to 7.6 mm (3.9 +/- 1.3 mm). The 55 patients were divided into three groups. Group I consisted of nine patients with a ductal diameter < or = 3 mm, group II consisted of 27 patients with a ductal diameter > 3 mm but < or = 4 mm, and group III consisted of 19 patients with a ductal diameter > 4 mm. Four- to five-loop Gianturco coils were used, which were deployed via retrograde aortic route. Multiple-coil technique was generally applied in group II patients. Balloon occlusion technique in combination with multiple-coil technique was generally used in group III patients. Deployment of coil was successful in 51 patients (93%) but failed in 4. The success rate of coil deployment in group I, II, and III were 100% (9/9), 96% (26/27), and 84% (16/19), respectively. A mean of 1.9 +/- 0.7 coils was deployed per patient. Of the four patients with unsuccessful coil deployment, three underwent surgery and one received implantation with Amplatzer duct occluder. Distal embolization of 21 coils occurred in 10 patients (3 in group II and 7 in group III), from whom 20 coils were retrieved with a gooseneck snare and 1 coil was removed during surgery. The mean diameter of ductus in the 10 patients with distal embolization was significantly larger than that in those without (5.2 +/- 1.4 vs. 3.7 +/- 1.1 mm; P < 0.01). Among the 51 patients with successful coil deployment, immediate complete closure was achieved in 20 (39%), while trivial to mild leak was present in 31 (61%). No significant complications were encountered. After a follow-up period ranging from 5 to 42 months, four patients had a small residual shunt and three underwent a second intervention with complete occlusion. None had left pulmonary artery stenosis documented with Doppler echocardiography. Transcatheter closure of ductus with the Gianturco coils is safe and feasible in the majority of adolescents and adults. Taking high embolization rate in patients with a ductus diameter > 4 mm into consideration, controlled-release coils, Buttoned device, or Amplatzer duct occluder can be a better choice., (Copyright 2002 Wiley-Liss, Inc.)

Background: Therapeutic approaches to reduce the neointimal formation caused by balloon injury have been focused mainly on experimental models of restenosis in the rat carotid artery. However, restenosis in rat carotid artery may not replicate the coronary arterial responses to injury in larger animals and humans., Methods: In this study, we used pig coronary arteries as an animal model to evaluate the preventive effects of a virus-mediated dominant negative mutant RasN17 on balloon injury-induced restenosis. The viral particles were delivered to the balloon-injured coronary arteries via a dispatch catheter to keep the virus in a confined arterial segment for 10 min to reach optimal transfection. Six weeks after balloon injury, the pigs were sacrificed and the left anterior descending arteries were isolated for histological analysis., Results: Neointima formation was prominent in the group receiving balloon injury as compared with the uninjured controls. A remodeling process with migration of collagen was also found in the injured coronary arteries. The application of AdRasN17 led to a 56% decrease in neointima formation and a 75% increase in lumen size, as compared with the balloon-injured vessels treated with AdLacZ control., Conclusions: These results suggest that AdRasN17 is an effective therapeutic gene in preventing balloon injury-induced neointimal formation in pig coronary arteries., (Copyright 2001 Academic Press.)

A 23 year-old Taiwanese male presented with complete membranous obstruction of the inferior vena cava at its suprahepatic portion. After 3 angioplasty procedures using Inoue-balloon catheters, a Wall stent was deployed for restenosis 4 years after the first procedure. Venography at 6 months showed no significant restenosis. At 20 months transfemoral venography confirmed patency of the vena cava.

Objective: To study the safety and feasibility of intracardiac imaging using a novel 8F 10-MHz non-over-the-wire ultrasound catheter system., Subjects and Method: Intracardiac imaging using a transfemoral venous approach was performed in 33 adults, 14 men and 19 women, aged 25 to 66 years (mean, 46 years). Six were normal subjects, 12 had congenital heart diseases (5 atrial septal defects, 3 ventricular septal defects, 1 tetralogy of Fallot, 2 patent ductus arteriosus, and 1 Ebstein anomaly), 14 had valvular heart diseases (12 mitral stenoses and 2 calcific aortic stenoses), and 1 had acute pulmonary embolism., Results: Ultrasound images were obtained, without any complications, from the right side of the heart in all subjects. The atria and ventricles could be recognized by anatomic relationships to the cardiac chambers and the valves by their characteristic motion during each cardiac cycle. The vessels were verified by their connections to the cardiac chamber and by contrast echocardiography if indicated., Conclusion: Intracardiac imaging using the 8F 10-MHz non-over-the-wire ultrasound catheter system via a transfemoral venous approach is feasible and safe. Intracardiac echocardiography is potentially useful for assessing a variety of cardiac anomalies and in guiding and monitoring certain intervention procedures.

Background: There have been no single-center studies that have systematically addressed the acute outcome of Inoue balloon mitral commissurotomy (BMC) performed in a large series of patients. Accordingly, this study sought to examine the impact of operator experience and continuing technical modifications on the success and complication rates of BMC., Methods: BMC was performed in 799 patients: 469 patients with pliable mitral valves (group 1) and 330 patients with calcified valves and/or severe subvalvular disease (group 2). Acute complications were examined and compared between groups before and after modifications in BMC techniques. Major modifications included the use of a height-derived balloon sizing method for the selection of an appropriate balloon catheter, a cautionary stepwise dilation technique, and avoidance of traction on the interatrial septum during balloon inflations., Results: Technical failures were encountered in 4 (0.5%) patients in our early experience. One patient sustained cardiac perforation and tamponade and was the only case requiring emergency surgery. There were no deaths. Systemic embolic events were observed in 11 (1.4%), all among the first 353 patients before the routine use of pre-BMC transesophageal echocardiography. Severe postprocedure angiographic (>/=3+) mitral regurgitation occurred in 4% of patients, 2% in group 1 versus 9% in group 2 (P =.0001). With increased operator experience and technical modifications, this complication was significantly reduced from 5% (7 of 150 patients) to 0% in the last 316 patients in group 1 (P =.0001) and from 11% (26 of 228 patients) to 3% (3 of 101 patients) in group 2 (P =.031). The incidence of significant interatrial shunting (pulmonary-to-systemic flow ratio >/=1.3) was also significantly reduced from 12% to 6% (P =.0034)., Conclusion: Incremental operator experience and ongoing technical refinements in BMC techniques have resulted in a 100% technical success rate and a significant diminution in complications in patients with a wide spectrum of stenotic mitral valve morphologic features.

We report on a rare case of anomalous origin of left coronary artery from the noncoronary sinus of Valsalva. Intraaortic intravascular ultrasound study identified the origin of the left coronary artery and facilitated subsequent selective coronary angiography of the artery.

Radial artery punctures for diagnostic coronary angiography or coronary balloon angioplasty were performed in 211 patients with a success rate of 98% (207 patients). In the four failed transradial accesses, the procedure was accomplished via the transfemoral route. Major local vascular complications included one arteriovenous fistula, one pseudo-aneurysm, and one ischemic contracture of the right hand. Reduced radial pulses were noted in 25 (12%) patients at follow-up without ischemic manifestations. Transradial diagnostic coronary angiography was successfully completed in 184 (98%) of 187 patients. The technical success for balloon angioplasty was obtained in 73 (97%) of 75 patients. Clinical success was observed in 68 (91%) patients; balloon angioplasty resulted in one nonfatal myocardial infarction and four late deaths (3 cardiac and 1 stroke). We believe that transradial catheterization for diagnostic coronary angiography and balloon angioplasty in our relatively small built Chinese population is a safe and practical alternative approach.

Unroofed coronary sinus, a rare congenital anomaly first described by Raghib and colleagues1 in 1965, is a result of an embryologic error involving imperfect or complete failure of development of the left atriovenous fold, which is manifested as a focal (fenestration or partial unroofing of the coronary sinus) or complete absence of the coronary sinus septum. Before the era of echocardiography, precise diagnosis of this anomaly was possible only during surgical procedure or at autopsy. Since the advent of the echocardiography, several studies have reported the usefulness of two-dimensional transthoracic and transesophageal echocardiography in the diagnosis of unroofed coronary sinus. We describe the intracardiac echocardiographic delineation of partially unroofed coronary sinus and persistent left superior vena cava in a patient with atrioventricular nodal reentrant tachycardia. Incidental finding of the dilated coronary sinus during radio frequency ablation of the tachycardia led to the diagnosis of this unusual anomaly.

An acute aortic dissection involved the retroesophageal aortic diverticulum (RAD) and descending thoracic aorta in a patient with right aortic arch. The RAD, which was separated into false and true lumens by an intimal flap-the classic diagnostic sign of aortic dissection-was overlooked on transesophageal echocardiography and computed tomography but was clearly depicted on magnetic resonance imaging (MRI). It was found that MRI can delineate the anatomy of a congenital arch anomaly complicated by great vessels disease.

Transesophageal echocardiography was performed in 7 patients with effusive-constrictive pericarditis to analyze atrial septal motion(ASM). In 3 patients, the ASM was found to be normal with atrial septum (AS) moving toward the right atrium from ventricular mid-systole to early-diastole and toward the left atrium from mid-diastole to early-systole. Respiration had little effect on the ASM. In 2 patients, a brisk inversion of ASM toward the left atrium at ventricular early-to-mid systole was noted during inspiration. In the other 2 patients, a sustained ASM toward the left atrium during ventricular systole was found. In 4 of these 7 patients, hemodynamic studies were performed simultaneously with the transesophageal echocardiography. The ASM reflected the pressure gradient between the left atrium (as measured by pulmonary arterial wedge pressure) and the right atrium. The augmented ASM toward the left atrium occurred as left atrial pressure decreased markedly during inspiration. In conclusion, the ASM in patients with effusive-constrictive pericarditis showed 3 patterns: normal, sustained systolic motion toward the left atrium and a brisk systolic displacement toward the left atrium during inspiration. The ASM reflects changes in the interatrial pressure gradient.

Coronary neovascularization and fistula formation arising from the left circumflex artery demonstrated by coronary angiography is a specific sign for the presence of left atrial appendage thrombus in patients with mitral stenosis. However, the fistula drainage site in the left atrium in relation to the thrombus cannot be ascertained by the angiographic method. We performed transesophageal echocardiography simultaneously with coronary angiography in five patients with severe mitral stenosis and left atrial appendage thrombus. The angiography showed coronary neovascularization and fistula arising from the left circumflex artery in three patients. In these three patients, the transesophageal echocardiography confirmed the presence of a coronary fistula by identifying contrast exuding from the surface of the thrombus. Thus we have shown for the first time the usefulness of contrast transesophageal echocardiography in imaging the exact drainage site of coronary artery fistula from left atrial appendage thrombus.