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OBJECTIVES: To explore the behaviour-related factors influencing influenza vaccination among elderly people using a framework derived from the Health Belief Model (HBM) and the Theory of Reasoned Action (TRA). STUDY DESIGN: Systematic review. METHODS: Five databases were searched using predetermined strategies in March 2016, and 1927 citations were identified. Articles were selected according to inclusion and exclusion criteria. Key information was extracted from selected studies using a predesigned sheet. Both authors assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) or Critical Appraisal Skills Programme (CASP) checklist. RESULTS: Thirty-six articles were selected. A new framework was proposed that contributes to shared understanding of factors influencing health behaviour. Possible determinants of influenza vaccination among elderly people were knowledge, health promotion factors, all constructs of the HBM, and some concepts of the TRA. Key factors were threat perception, behavioural beliefs, subjective norms, recommendations, past behaviour and perceived barriers. CONCLUSIONS: This is the first systematic review to analyse the factors influencing influenza vaccination behaviour of elderly people using a framework integrating the HBM and the TRA. The framework identified key factors of influenza vaccination and presented the inter-relation of behaviour-related variables. However, further well-designed studies are required to explore the inter-relationships accurately and comprehensively.

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BACKGROUND: Adult patients with undiagnosed atrial septal defect (ASD) may have right heart cavity enlargement and functional tricuspid valve insufficiency. Moderate or more severe tricuspid regurgitation has been associated with a worse prognosis, and more serious complications are typically seen in older patients. This study aimed to evaluate the improvement in functional tricuspid regurgitation and heart geometry after transcatheter ASD closure in older patients. PATIENTS AND METHODS: The data of 111 patients over 60 years of age with moderate or severe tricuspid regurgitation before ASD closure were analyzed. RESULTS: At the 1­month and 6­month follow-up after closure, both tricuspid regurgitation jet area and right atrial volume decreased significantly. Right ventricular volume decreased 1 month after closure, showing a further decrease at the end of the 6­month follow-up. However, 24 patients (21.6%) still had persistent severe tricuspid regurgitation after the procedure. Multivariate analysis revealed that patient age at ASD closure and pulmonary artery systolic pressure determined by echocardiography before closure were predictors of persistent tricuspid regurgitation after closure. CONCLUSION: Transcatheter ASD closure in older patients could significantly decrease tricuspid regurgitation and improve right heart geometry.

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The ecteinascidin family comprises a number of biologically active compounds, containing two to three tetrahydroisoquinoline subunits. Although isolated from marine tunicates, these compounds share a common pentacyclic core with several antimicrobial compounds found in terrestrial bacteria. Among the tetrahydroisoquinoline natural products, ecteinascidin 743 (Et-743) stands out as the most potent antitumor antibiotics that it is recently approved for treatment of a number of soft tissue sarcomas. In this article, we will review the backgrounds, the mechanism of action, the biosynthesis, and the synthetic studies of Et-743. Also, the development of Et-743 as an antitumor drug is discussed.

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INTRODUCTION: Minimally invasive esophagectomy has been increasingly accepted to treat esophageal cancer. In Japan, neoadjuvant chemotherapy followed by surgery has become the standard procedure for advanced esophageal cancer. A randomized control study has shown neoadjuvant chemotherapy's survival benefits, but it is unknown whether minimally invasive esophagectomy after chemotherapy is viable. This study investigated the feasibility of thoracoscopic esophagectomy after neoadjuvant chemotherapy. METHODS: From a database of patients with esophageal cancer, 105 patients who had undergone thoracoscopic esophagectomy with radical lymphadenectomy were analyzed retrospectively. Among them, 51 patients had received neoadjuvant chemotherapy with 5-fluorouracil and cisplatin (NAC group). Their operative outcomes, including operative duration, blood loss, the number of dissected lymph nodes, and postoperative morbidity and mortality, were compared with those of 54 patients who underwent surgery without neoadjuvant chemotherapy (control group). The efficacy of neoadjuvant chemotherapy was also assessed. RESULTS: The operating time in the NAC group was significantly longer than in the control group (543 vs 472 min, P < 0.001), but the blood loss was less (323 vs 528 mL, P < 0.001). Recurrent laryngeal nerve palsy was the most frequently observed complication in both groups (27% vs 32%, P = 0.65). No significant differences were observed in the frequency of postoperative complications. There was no mortality in either group. In the NAC group, 43 patients (84.3%) underwent curative resection, and response of more than two-thirds of the pathological tumor was achieved in 11 patients (21.6%), including complete response in one patient (2.0%). CONCLUSION: Thoracoscopic esophagectomy following neoadjuvant chemotherapy could be safely adopted for patients with advanced esophageal cancer.

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The dismal outcome of gastric cancer patients highlights the need for diagnostic biomarkers and effective therapeutic targets, such as microRNAs. We sought to discover microRNAs involved in gastric cancer, and to elucidate their downstream target mechanisms. Both cultured gastric epithelial cells (HFE145 and NCI-N87) and primary human gastric tissues (31 non-neoplastic stomach (NS) and 25 gastric carcinomas (GC)) were studied. MicroRNA microarrays and quantitative RT-PCR were applied to discover and verify differentially expressed microRNAs. in vitro cell migration and invasion, cell proliferation, cell cycle and apoptosis assays were executed to elucidate biological effects of microRNA-192 and -215. Western blotting and luciferase assays were performed to confirm direct messenger RNA targeting by microRNA-192 and -215. MicroRNA microarray analyses revealed that 25 and 20 microRNAs were upregulated and downregulated in GC vs NS, respectively. Expression levels of both microRNA-192 and -215 were significantly higher in GC than in NS (P<0.05). Luciferase assays suggested that microRNA-215 inhibits activated leukocyte cell adhesion molecule (ALCAM) expression at the posttranscriptional level. In addition, expression levels of ALCAM were significantly lower in GC than in NS. Mimics and inhibitors, respectively, of microRNA-192 or -215 exerted no effect on cell cycle or apoptosis in the immortalized normal gastric cell line HFE145 or the gastric cancer cell line NCI-N87. However, mimics of microRNA-192 or -215 significantly increased growth rates in HFE145 cells, whereas inhibitors of microRNA-192 or -215 caused significant decreases in growth rates in NCI-N87 cells. ALCAM knockdown by an ALCAM-specific siRNA significantly increased cell growth in HFE145 cells. Both transfection of mimics of microRNA-192 or -215 and ALCAM knockdown by an ALCAM-specific siRNA significantly increased the migration of HFE145 cells. In conclusion, in gastric cancer, both microRNA-192 and -215 are overexpressed in vivo and exert cell growth and migration-promoting effects in vitro, thus representing potential microRNAs with a role in cancer in the human stomach.

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The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter hypermethylation was examined by real-time methylation-specific polymerase chain reaction in 259 human esophageal tissues. Hypermethylation of this promoter showed highly discriminative receiver-operator characteristic curve profiles, clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from normal esophagus (NE) (P<0.001). NELL1 normalized methylation values were significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's (D) and EAC than in NE (P<0.0000001). NELL1 hypermethylation frequency was zero in NE but increased early during neoplastic progression, to 41.7% in BE from patients with Barrett's alone, 52.5% in D and 47.8% in EAC. There was a significant correlation between NELL1 hypermethylation and BE segment length. Three (11.5%) of 26 ESCCs exhibited NELL1 hypermethylation. Survival correlated inversely with NELL1 hypermethylation in patients with stages I-II (P=0.0264) but not in stages III-IV (P=0.68) EAC. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2'-deoxycytidine reduced NELL1 methylation and increased NELL1 mRNA expression. NELL1 mRNA levels in EACs with an unmethylated NELL1 promoter were significantly higher than those in EACs with a methylated promoter (P=0.02). Promoter hypermethylation of NELL1 is a common, tissue-specific event in human EAC, occurs early during Barrett's-associated esophageal neoplastic progression, and is a potential biomarker of poor prognosis in early-stage EAC.

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To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

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Standard treatment for malignant pleural mesothelioma (MPM) has not been proved yet. However, it has been recognized that extrapleural pneumonectomy (EPP) is a treatment of choice for epithelial MPM when combined with adjuvant therapies though EPP may frequently cause fetal complications. We report 5 cases of MPM with EPP, including 1 with good prognosis. Sixteen patients with MPM were admitted to our hospital between 1988 and 2003. Five patients underwent EPP, among which 4 were male and 1 female with ages from 46 to 61 years old. Histologically, 3 of them were epithelial and 2 were biphasic. Those with biphasic experienced acute respiratory failure and empyema, and died 81 days and 8 months after the surgery respectively. Among those with epithelial MPM, 2 are alive with no recurrence at 129 and 29 months after the surgery, and the other, followed by postoperative radiotherapy, died at 12 months. More cases with EPP or randomized controlled trials regarding EPP are necessary to evaluate efficacy of EPP for MPM.

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The aim of this paper is to examine whether intraoperative examination of paratracheal nodes can indicate cervical node dissection and whether this approach is valid. From 1988 to 1997, 76 patients with thoracic esophageal squamous cell carcinoma received esophagectomies with and without cervical lymph node (LN) dissection based on the results of intraoperative pathological diagnosis from selective checking of paratracheal LN. We retrospectively examined the outcomes for the patients and the micro metastasis in the dissected lymph node using cytokeratin staining. Three of the seven patients with cervical LN dissection were detected as having cervical LN metastasis by postoperative hematoxylin-eosin or cytokeratin staining. Five (7%) of the 69 patients without cervical LN dissection had cervical LN recurrence after the operation. Four of the seven patients who were diagnosed as having metastasis or micro metastasis in paratracheal LN by postoperative examination had cervical LN recurrence after the operation. In conclusion, the esophagectomy with and without cervical LN dissection for thoracic esophageal squamous cell carcinoma based on the results of intraoperative pathological diagnosis from selective checking of paratracheal LN was not fully acceptable. The reliability of intraoperative pathological diagnosis of selective checking may improve by increasing the number of checked LN and the detection of micro metastasis.

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We studied the validity of the bronchoscopic criteria of the early lung cancer using the surgical specimen excised between 1980 and 1999. Twenty-four cases with squamous cell carcinoma of the lung of clinical stage I were located subsegmental or more proximal bronchi and trachea, and the size less than 20 mm in greatest dimension. We histopathologically investigated the endoscopic features in relation to the width of superficial extent, the depth of cancer invasion, and lymph node metastasis. Tumors of the thickened type lesions less than 20 mm in greatest dimension showed no invasion into the cartilaginous layer and no lymph node metastasis. On the other hand, in the nodular and polypoid types, invasion beyond the cartilaginous layer was observed more or less, and lymph node metastasis was observed in 1 case. These cases would not be suitable for bronchoscopic (photodynamic) therapy. In conclusion, the bronchoscopic criteria of early lung cancer is valid in the thickened type, but not in the nodular type or polypoid type.

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Human esophageal cancer cell lines and human esophageal cancer tissues were profiled on cDNA microarrays. In esophageal cancer cell lines, KYAE and OE-33 (adenocarcinomas) were distinguished from KYSE series (squamous cell carcinomas). Although SK-GT-4 and TE7 were derived from adenocarcinomas, they had a comparatively similar expression profile to the KYSE series. A set of genes whose expression commonly either increased or decreased in cancer cell lines was identified. Genes that were characteristically expressed in KYAE and OE-33 were also identified. The gene expression profiles of cancer tissues (CTs) were remarkably different from those of the cancer cell lines (CCLs). Notable differences between CCLs and CTs were observed in matrix metalloproteinases, plasminogen activator, collagens, paxillin, and thrombospondin 2, etc., whose expression was not increased in CCLs but increased in CTs. Twenty-three genes were extracted to categorize patients according to their prognoses, and clustering analyses, using these genes, were performed successfully.

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A gas chromatographic (GC) method was developed for the determination of sucrose monoesters of fatty acids (mono-SuE) and sucrose acetate isobutyrate (SAIB) in food additive premixes. Mono-SuE and SAIB fractions were prepared by column chromatography with either a C8 or a silica gel solid-phase extraction column. The mono-SuE fraction was acetylated and applied to a wide-bore GC column (0.53 mm x 15 m) by splitless injection for determination. The SAIB fraction was applied to the GC column without derivatization. Gas chromatography/mass spectrometry was used to confirm the identity of GC peaks. The detection limits for mono-SuE and SAIB were 0.005 and 0.01%, respectively. Mono-SuE (C12, C14, C16, C18, and C18:1) and SAIB were found in commercial food additive premixes and some foods.

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A 70-year-old male complaining cough was admitted to our hospital. Bronchoscopic examination revealed a tumor mass which occluded the orifice of the right upper lobe. Chest computed tomographic (CT) scans gave the image of tumor invasion at the carina. The pathological diagnosis of the tumor was squamous cell carcinoma. Operation was accomplished by right posterolateral thoracotomy approach through the fifth rib bed. The carinal resection with right upper lobectomy was followed by a double-barreled anastomosis of the right intermediate trunk and left main-stem bronchus into the carina. The operation was successfully performed and was considered curative. The length of resected airway measured 4.0 cm from tracheal line of resection to the divided the right intermediate trunk. Reinforcement of the anastomosis was not performed in this case. No postoperative complication occurred but mild ischemia of the anastomosis. The patient died of recurrent tumor in a year and 2 months after operation.

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(2-Hydroxyethyl) dimethylsulfoxonium chloride (1), the well-known causative agent of Dogger Bank Itch, has been isolated as a cytotoxic constituent from the marine sponge Theonella aff. mirabilis. The structure of 1 was determined by spectral and X-ray crystallographic analyses.

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Telomeres of Drosophila consist of multiple copies of LINE-like transposable elements. These elements are assigned to two classes, HeT-A and TART. They are attached to terminal deletions at their 3' end, thus compensating for the absence of telomerase in Drosophila cells. The attachment of HeT-A elements to the X-chromosome terminal deletions of the regulatory region of the yellow gene was studied. It was shown that, in the case of degradation of the yellow promoter sequence (chromosome underreplication), the Het-A promoter located at the 3' end of this element can activate transcription of the gene. The minimal size of the 3'-end HeT-A element sequence sufficient for the yellow expression was shown to be 400 bp. Since the yellow mutation is expressed phenotypically and the gene impairment is not lethal, we created a convenient model genetic system based on this effect. Using this system, the frequency of attachments of the HeT-A elements to the chromosome end can be visually recorded. This frequency varied in a wide range (from 0.2 x 10(-4) to 2 x 10(-3)) and was strain-specific.

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In 1997, the latest revision of the International System for Staging Lung Cancer was published. To validate the new pathologic TNM classification for non-small cell lung cancer (NSCLC), we analyzed the survival data of 455 patients who underwent pulmonary resection and pathologic staging at our institution from January 1980 through December 1999. The overall 5-year survival rate was 51.0%. Using the revised new stage classification, the survival rate for each stage was as follows; IA: 74.2%, IB: 66.4%, IIA: 56.0%, IIB: 51.8%, IIIA: 21.0%, IIIB: 16.0%, and IV: 0%. The current TNM classification well reflected the long-term prognostic hierarchy. There were significant differences in survival rates between patients with stage IA and IB, and between patients with stage IIB and IIIA. However, there was no significant difference between patients with stage IIA and IIB. No significant difference in survival was observed among patients with stage IIIA, stage IIIB, and stage IV. Five-year survival rate of 48.3% in the T3N0M0 category was significantly better than that of 21.0% found in the new stage IIIA. The survival of patients with intrapulmonary metastases in the same lobe (pm1) was not significantly better than that found in the stage IV. The TNM staging system accurately reflects the prognosis in NSCLC, but some stage definitions can be discussed.

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Total synthesis of spider toxins HO-416b (1) and Agel-489 (2) was accomplished using the 2-nitrobenzenesulfonamide (Ns) group as both a protecting and activating group. In this strategy, the C-N bonds were constructed by alkylation of sulfonamides with alkyl halides or Mitsunobu reaction with the corresponding alcohol. Beginning with monoprotection of the symmetrical diamine, the construction of the backbone from diamine 3 was efficiently accomplished in 7 steps for 14 and 9 steps for 29. Removal of the Ns group while the substrate was attached to a novel solid support enabled the efficient isolation of this highly polar compound.

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Polyoxygenated six-membered carbocycles were derived from carbohydrates with complete stereocontrol through hydroxy-directed coupling cyclization induced by SmI(2). For example, the cis-1,3-cyclohexanediol 3 is obtained from the D-glucopyranoside derivative 1 in excellent yield. The coupling cyclization is initiated by single-electron transfer from SmI(2) to the formyl group of the delta-hydroxy aldehyde 2 generated in an equilibrium process.