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Objective: Rheumatoid arthritis (RA) has been associated with inhaled pollutants in several studies, and it is a disease of chronic inflammation. The association between air pollution and the risk of RA remains unclear. Therefore, we conducted this nationwide, retrospective, sex-stratification study to evaluate this association. Methods: We collected data from the Longitudinal Health Insurance Database (LHID), maintained by the Taiwan Bureau of National Health Insurance, and the Taiwan Air Quality-Monitoring Database (TAQMD), released by the Taiwan Environmental Protection Agency. The TAQMD provides the daily concentrations of particulate matter with the aerodynamic diameter

Background Nasopharyngeal carcinoma (NPC) is a race-specific malignancy. The nasal cavity is the main entry point for air pollutants or poisonous gases into the human body. However, the risk of NPC in populations exposed to air pollution remains unknown. Methods We combined data from the Taiwan Air Quality Monitoring Database (TAQMD) and the Longitudinal Health Insurance Database (LHID) to assess the risk of NPC in a population exposed to air pollution. Results Multivariate analysis revealed positive trends for the association between the risk of NPC and exposure to air pollution. After adjusting for potential covariates, the risk of developing NPC increased with the increase in nitrogen dioxide (NO2) and fine particulate matter (PM2.5) exposure concentrations from 1.39 to 2.28 and 2.01 to 1.97, respectively, compared to the risks at the lowest concentration levels. Conclusions We identified a significant risk of NPC in a population exposed to air pollution. However, this study had several limitations. Moreover, additional experimental and clinical studies on the associations between environmental factors and NPC risk are warranted.

MicroRNAs (miRNAs) are short noncoding RNA molecules involved in the regulation of carcinogenesis. Tumor-derived miRNAs will be released into the circulation, and these miRNAs, also known as circulating miRNAs, have stable properties in plasma and serum. Thus miRNAs have been suggested as a potential biomarker for cancer diagnosis. The aim of this study was to develop a miRNA biochip platform. First, we used three types of reverse transcription (RT) primers; we constructed the miRNA-containing poly(A) tail and used RT primer oligo(dT) to make the complementary DNA (cDNA), and we also designed a linear-form RT primer and a stem-loop RT primer to synthesize cDNA. Second, we selected 11 candidate miRNAs related to colorectal cancer (CRC) from our previous studies and then designed the probes based on the sequence of the candidate miRNAs and constructed a miRNA biochip. miRNAs were extracted from CRC cell line SW620 and were detected by enzymatic biochip assay. According to the results, we found that this miRNA biochip can effectively detect the miRNAs by using a specific stem-loop RT primer to synthesize cDNA. In the future, we will design more oligonucleotides for miRNA detection and also evaluate the consistency between the results of the miRNA biochip and quantitative real-time polymerase chain reaction (PCR).

According to recent studies, the Plantaginaceae, which are traditional Chinese herbal remedies, have potential for use in viral infection treatment and cancer therapy. Linalool and p-coumaric acid are two of the biologically active compounds that can be isolated from the Plantaginaceae. This study mainly focused on investigating the bioactivity of linalool as well as the bioactivity of p-coumaric acid in terms of their cytotoxic effects on cancer cells. Whether the mechanisms of such effects are generated through apoptosis and immunoregulatory activity were also investigated. By using WST-1 analysis, it was shown that linalool and p-coumaric acid have good inhibitory effects against breast, colorectal and liver cancer cells. The IC50 values of linalool for those cancer cell types were 224 μM, 222 μM, and 290 μM, respectively, and the IC50 values of p-coumaric acid were 693 μM, 215 μM and 87 μM, respectively. Cell cycle analysis also confirmed that linalool and p-coumaric acid can lead to apoptosis. By using flow cytometry, it was determined that treatment with linalool rather than p-coumaric acid significantly increased the sub-G1 phase and that there were more cells concentrated in the G1 phase. Furthermore, by using cytokine array analysis, we found that linalool can stimulate IFN-γ, IL-13, IL-2, IL-21, IL-21R, IL-4, IL-6sR and TNF-α secretion. This demonstrated that in addition to the bidirectional regulation capabilities found in linalool, it also induces Th1 cellular immune response in T-47D cells. These results showed that linalool holds great potential for use in cancer therapy, and we believe that it could provide an alternative way to take action against tumors.

Background Several case reports have indicated that tamoxifen induced acute pancreatitis (AP); but no pharmacoepidemiological data support the claim. Therefore, we investigated whether tamoxifen use is correlated with the risk of AP in patients with breast cancer. Methods This population-based cohort study used the Taiwan National Health Insurance Research Database. A cohort of 22 005 patients aged ≥20 years with breast cancer from January 1, 2000 to December 31, 2009 was identified and the date of cancer diagnosis was set as the index date. The end point was developing AP during the follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated to determine the correlation between the risk of AP and tamoxifen use. Because the drug use varied over time, it was measured as a time-dependent covariate in the Cox proportional hazard model. The same approaches were applied in PS-matched cohorts. Results After adjustment for covariates and medication use including fluorouracil and doxorubicin, the risk of AP was not significant between tamoxifen users and tamoxifen nonusers (adjusted HR = 0.94, 95% CI = 0.74–1.19) in the non-matching cohorts. The results revealed no dose–response trend between tamoxifen use and the risk of AP (adjusted HR = 0.98, 95% CI = 0.96–1.00). The comorbidities DM and gallstones were associated with a significantly increased risk of AP. Similar trends were observed in PS-matched cohorts. Conclusions No significant correlation was observed between tamoxifen use and the risk of AP in patients with breast cancer.

Taiwan has been recognized by the World Organization for Animal Health as rabies-free since 1961. Surprisingly, rabies virus (RABV) was identified in a dead Formosan ferret badger in July 2013. Later, more infected ferret badgers were reported from different geographic regions of Taiwan. In order to know its evolutionary history and spatial temporal dynamics of this virus, phylogeny was reconstructed by maximum likelihood and Bayesian methods based on the full-length of glycoprotein (G), matrix protein (M), and nucleoprotein (N) genes. The evolutionary rates and phylogeographic were determined using Beast and SPREAD software. Phylogenetic trees showed a monophyletic group containing all of RABV isolates from Taiwan and it further separated into three sub-groups. The estimated nucleotide substitution rates of G, M, and N genes were between 2.49 × 10(-4)-4.75 × 10(-4) substitutions/site/year, and the mean ratio of dN/dS was significantly low. The time of the most recent common ancestor was estimated around 75, 89, and 170 years, respectively. Phylogeographic analysis suggested the origin of the epidemic could be in Eastern Taiwan, then the Formosan ferret badger moved across the Central Range of Taiwan to western regions and separated into two branches. In this study, we illustrated the evolution history and phylogeographic of RABV in Formosan ferret badgers.

Peptic ulcer is a common gastrointestinal disease and produces mucosa erosion. The current study assessed the ability of burdock essence to repair gastrointestinal mucosa in clinical trials. In the experimental group, two tablets of burdock essence (500 mg/tablet) were administered three times a day after meals and a placebo was administered in controls. Four weeks after drug administration, the subjects in the study underwent an assessment for the efficacy of burdock essence as health supplements before and after administration of the drug. The presence of gastric mucosal lesions was determined in all of the peptic ulcer patients using electronic endoscopy before and after taking burdock essence. A rapid urease test on tissue samples from ulcers was conducted to verify Helicobacter pylori infection. Endoscopy confirmed gastric or duodenal ulcers in 30 patients. In clinical trials of 27 patients, 20 patients took burdock essence; 17 (85%) recovered completely and three (15%) did not. Of the seven patients who took placebos, five (71%) did not completely recover and two (29%) recovered. In the experimental group, the ulcer wounds of the three patients who had taken burdock essence did not completely heal, but wounds were reduced in size by 30%, 75%, and 33%. Moreover, 10 out of 11 patients who originally were positive for H. pylori infections no longer had the pathogen by the end of the trial. These results indicate that burdock essence has an inhibitory effect on H. pylori . This study confirms that two tablets (500 mg/tablet) of burdock essence taken orally three times a day after meals can help abolish H. pylori infection and promote the therapeutic effect of conventional medication on gastric mucosal repair in gastrointestinal ulcer patients.

Epidemiological evidence has suggested that vegetables and fruits may have a role in cancer prevention. The aim of the present study was to examine the anti-proliferative activity of ten related pure compounds from common vegetables and fruits. Studies were conducted on a series of carcinoma cells derived from eight human organs. The results show that linalool possessed the strongest activity against nine carcinoma cells, and that baicalein and luteolin also exhibited a broad spectrum of anti-proliferative activities. Among them, linalool showed the strongest activity against carcinoma of the cervix (IC50: 0.37 microg/ml), stomach (IC50: 14.1 microg/ml), skin (IC50: 14.9 microg/ml), lung (IC50: 21.5 microg/ml) and bone (IC50: 21.7 microg/ml). As for the flavonoids, luteolin exhibited the strongest activity against carcinoma of the stomach (IC50: 7.1 microg/ml), cervix (IC50: 7.7 microg/ml), lung (IC50: 11.7 microg/ml) and bladder (IC50: 19.5 microg/ml), whereas baicalein possessed the strongest anti-proliferative activity against carcinoma of the cervix (IC50: 9.8 microg/ml), stomach (IC50: 16.1 microg/ml) and skin (IC50: 19.5 microg/ml). The present study indicates that linalool possessed the strongest activity against a broad spectrum of carcinoma cells, especially cervical carcinoma cells, suggesting that linalool and flavonoids are partially responsible for the cancer prevention of common vegetables and fruits.

Plantaginaceae, a popular traditional Chinese medicine, has long been used for treating various diseases from common cold to cancer. Linalool is one of the biologically active compounds that can be isolated from Plantaginaceae. Most of the commonly used cytotoxic anticancer drugs have been shown to induce apoptosis in susceptible tumor cells. However, the signaling pathway for apoptosis remains undefined. In this study, the cytotoxic effect of linalool on human cancer cell lines was investigated. Water-soluble tetrazolium salts (WST-1) based colorimetric cellular cytotoxicity assay, was used to test the cytotoxic ability of linalool against U937 and HeLa cells, and flow cytometry (FCM) and genechip analysis were used to investigate the possible mechanism of apoptosis. These results demonstrated that linalool exhibited a good cytotoxic effect on U937 and HeLa cells, with the IC50 value of 2.59 and 11.02 μM, respectively, compared with 5-FU with values of 4.86 and 12.31 μM, respectively. After treating U937 cells with linalool for 6 h, we found an increased sub-G1 peak and a dose-dependent phenomenon, whereby these cells were arrested at the G0/G1 phase. Furthermore, by using genechip analysis, we observed that linalool can promote p53, p21, p27, p16, and p18 gene expression. Therefore, this study verified that linalool can arrest the cell cycle of U937 cells at the G0/G1 phase and can arrest the cell cycle of HeLa cells at the G2/M phase. Its mechanism facilitates the expression of the cyclin-dependent kinases inhibitors (CDKIs) p53, p21, p27, p16, and p18, as well as the non-expression of cyclin-dependent kinases (CDKs) activity.

Peripheral neuropathy and inflammatory reactions of the central nervous system may accompany rheumatoid arthritis (RA). Inflammatory processes play a critical role in epilepsy. Therefore, we conducted this study to determine the risk of epilepsy in patients with RA. The RA cohort comprised patients ages 20 years and older who were newly diagnosed with RA between 2000 and 2011, with data obtained from the Registry of Catastrophic Illnesses Patient Database. Patients without RA were frequency matched with an RA cohort at a 1:1 ratio according to age, sex, and year of RA diagnosis. The overall crude hazard ratio (HR) for epilepsy was 1.27-fold higher in the RA cohort compared with that in the controls. After adjustment for age, sex, comorbidities, and medications, the patients with RA were associated with an increased risk of epilepsy compared with those without RA (adjusted HR [aHR] = 1.52, 95% confidence interval [CI] = 1.12–2.07). Compared with the RA patients with ≤ 560 days of nonsteroidal anti-inflammatory drug (NSAID) use, the RA patients with 1181 to 2145 and >2145 days of NSAID use had a significantly lower risk of epilepsy (aHR = 0.35, 95% CI = 0.24–0.52 and aHR = 0.15, 95% CI = 0.09–0.24, respectively). This study provides compelling evidence of an increased risk of epilepsy in patients with RA. The period of NSAID treatment is negatively associated with the risk of epilepsy in RA patients.

Combination of multiple mRNA markers has been largely investigated for detection of circulating cancer cells. However, current PCR-based methods are relatively expensive and time consuming. The aim of this study was to develop a membrane array-based multimarker assay for detection of circulating cancer cells in nonsmall cell lung cancer (NSCLC) patients. At first, we selected 22 candidate genes by means of suppression subtractive hybridization and Northern blot analysis. The diagnostic value of each candidate gene was then preliminarily evaluated in 50 pairs of blood samples by membrane array method. Accordingly, 17 genes with area under the ROC curve (AUC) ≥ 0.8 were selected as target genes to reconstruct the diagnostic membrane array, which was then used to test peripheral blood samples from 100 NSCLC patients and 147 control subjects. ROC curve analysis demonstrated that the optimal threshold number of overexpressed markers on membrane array for discrimination between NSCLC patients and control subjects was 12. As a result, the diagnostic membrane array could detect circulating cancer cells in 90 (90%) of 100 NSCLC patients and in 14 (9.5%) of 147 control subjects (including 6 of 100 normal persons, 3 of 20 breast cancer patients, 3 of 15 colorectal cancer patients and 2 of 12 gastric cancer patients). Moreover, the detection rate was significantly correlated with NSCLC patients' metastatic status and overall stage (p = 0.028 and 0.014, respectively). These results suggested that our blood-based membrane array assay for molecular detection of circulating lung cancer cells has great potential for clinical applications. © 2006 Wiley-Liss, Inc.

Extensive researches have found that the mutation of p53 tumor suppressor gene is the most frequent event in many human cancers and associated with a poor clinical outcome in lung cancer patients. Because the p53 molecular mutation involved in tumorigenesis of patients with lung cancer in Taiwan remains poorly defined, the aim of this study was to assess the p53 mutation spectrum and possible etiological factors of Taiwan's patients with Non-Small Cell Lung Cancer (NSCLC). Cancer specimens were obtained surgically from 61 patients with pathologically proven NSCLC. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were used to study p53 mutations in exon 4-8. We also performed immunohistochemistry (IHC) to detect p53 protein expression. Our results provided that 34 mutations of p53 gene were found in 27 cases with a mutation rate of 44% (27/61). There were six cases having more than two p53 mutations. Among the 34 mutations, 19 were point mutations (56%, 19/34) consisted of a majority of missense mutations including transversion (13/19, 68%) and transitions (6/19, 32%) with four cases (4/6, 67%) occurring in the CpG sequence. One of the most important finding in our study was the high frequency of frameshift (44%, 15/34) which included 11 insertions and 4 deletions of p53 in NSCLC in Taiwan. Surprisingly, our results disclosed distinct novel mutations at codon 181, 185, 208 (Exon 5-6) of p53. Especially, 4 cases with mutation at codon181 and codon 185 seemed to have more advanced clinical outcome with survival time less than 6 months. In addition, there were two recurring mutations at codon 168 and three at condon193. The different mutation spectrum in our series, including a high frequency of frameshift mutations and distinctly novel hot spots suggested the heterogenous entity of exogenous mutagens in NSCLC in Taiwan.

Somatic mutation of BRCA2 has been thought to be rare in breast cancers, though common allelic deletions in the BRCA2 locus (13q12-q13) imply an important role of somatic mutation in these tumors. Reasons of the reported rare incidence could be related to very few studies focusing on the mutational analysis of BRCA2 in sporadic tumors. The mutational status of the BRCA2 gene in exon11, the largest exon harboring the RAD51 interacting BRC domains which are critical for BRCA2 function, was screened by polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis followed by direct sequencing. Tumor and paired normal tissue sample from 175 patients unselected for family history or age were taken after mastectomy for breast cancer and evaluated. There were 20 mutations of BRCA2 gene in exon 11 in 15 cases (15/175, 8.6%). Most mutations we identified were point mutation (19/20, 95%), except for one nucleotide insertion. Furthermore, among these mutations, missense mutations comprised 80% (16/20) of the BRCA2 mutations. All mutations we found were novel mutation after searched in the BIC database. There were three recurrent mutations at codon 1904; and two recurrent mutations at 1907, 1936, 1937 and 1968, respectively. The mutations were associated with ductal carcinoma in situ (P=0.038) and borderline with low histological grade (P=0.072). Besides, there were three cases possessing multiple mutations in the region we studied and one of them demonstrated aggressive lymph node metastasis. These findings implicated that somatic mutations of BRCA2 genes may play a significant role in the pathogenesis of breast carcinoma in Taiwan. In addition, those events were associated with some early clinicopathological features.

A number of Plantago spp. especially P. major has long been used in the treatment of diseases such as infection, inflammation and cancer. In this study, we evaluated the immunomodulatory activities of five chemical classes of pure compounds obtained from the Plantago genus on human peripheral blood mononuclear cells (PBMC). Studies were conducted on lymphocyte transformation by BrdU immunoassay and secretion of interferon-gamma (IFN-gamma) using an ELISA assay. Results showed that the water-soluble compounds, namely aucubin, chlorogenic acid, ferulic acid, p-coumaric acid and vanillic acid, enhanced the activity of human lymphocyte proliferation and secretion of IFN-gamma. Among the water-insoluble compounds, with the exception of luteolin, both baicalein and baicalin showed an enhancement of the human PBMC. Although oleanolic acid and ursolic acid of the triterpenoids did not significantly affect the proliferation of PBMC, they exhibited a strong stimulation of IFN-gamma secretion. Linalool, a monoterpenoid, showed a similar immunomodulatory activity as the triterpenoids. The present study concludes that the tested compounds, which possess immunostimulating activities, may contribute to the traditional claims of Plantago-based natural products used in treating cancers and infectious diseases.

The aim of the present study was to evaluate the antileukemic activity of six chemical classes of pure compounds present in commonly used medicinal plants in Taiwan – such as the genus Plantago. Studies were conducted on a series of human leukemia and lymphoma cell lines. Results showed that water soluble compounds (aucubin, caffeic acid, chlorogenic acid, ferulic acid, p-coumaric acid and vanillic acid) exhibited a weak antileukemic activity (IC50: 26–56 μg/ml, SI: 2–11). On the other hand, water insoluble compounds such as triterpenoids (oleanolic acid and ursolic acid), monoterpene (linalool) and flavonoid (luteolin) possessed strong activity against human leukemia and lymphoma cell lines. Among them, linalool showed the strongest activity against histiocytic lymphoma cells U937 (IC50: 3.51 μg/ml, SI: 592.6) and Burkitt lymphoma cells P3HR1 (IC50: 4.21 μg/ml, SI: 494.1). Ursolic acid was effective against P3HR1 cells (IC50: 2.5 μg/ml, SI: 262.6) and chronic myelogenous leukemia cells K562 (IC50: 17.79 μg/ml, SI: 36.91), whereas oleanolic acid inhibited the growth of P3HR1 cells (IC50: 26.74 μg/ml, SI: 11.37). Luteolin exhibited effective activity against K562 cells (IC50: 18.96 μg/ml, SI: 5.14) and P3HR1 cells (IC50: 18.99 μg/ml, SI: 5.13). We conclude that terpenes and flavonoid in commonly used medicinal plants possess strong activity against lymphoma and leukemia cells, especially human lymphoma cells, suggesting the potential use of these compounds for treatment of lymphoma.

Plantago major Linn. and P. asiatica Linn. (Plantaginaceae) are commonly used as folk medicine in Taiwan for treating infectious diseases related to the respiratory, urinary and digestive tracts. In this study, we investigated the antiviral, cytotoxic and immunomodulatory activities of hot water extracts of these two species in vitro on a series of viruses, namely herpesviruses (HSV-1 and HSV-2), adenoviruses (ADV-3, ADV-8 and ADV-11), and on various human leukemia, lymphoma and carcinoma cells with XTT, BrdU and IFN-γ kits. Results showed that hot water extract of P. asiatica possessed significant inhibitory activity on the proliferation of lymphoma (U937) and carcinoma (bladder, bone, cervix, kidney, lung and stomach) cells and on viral infection (HSV-2 and ADV-11). P. major and P. asiatica both exhibited dual effects of immunodulatory activity, enhancing lymphocyte proliferation and secretion of interferon-γ at low concentrations (< 50 μg/ml), but inhibiting this effect at high concentration (< 50 μg/ml). The present study concludes that hot water extracts of P. major and P. asiatica possess a broad-spectrum of antileukemia, anticarcinoma and antiviral activities, as well as activities which modulate cell-mediated immunity. Further investigations to elucidate the active component(s) of P. asiatica and P. major and to evaluate their clinical application are warranted.

Plantago major L., a popular traditional Chinese medicine, has long been used for treating various diseases varying from cold to viral hepatitis. The aim of present study was to examine the antiviral activity of aqueous extract and pure compounds of P. major. Studies were conducted on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The antiviral activity of EC50 was defined as the concentration achieved 50% cyto-protection against virus infection and the selectivity index (SI) was determined by the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extract of P. major possessed only a slight anti-herpes virus activity. In contrast, certain pure compounds belonging to the five different classes of chemicals found in extracts of this plant exhibited potent antiviral activity. Among them, caffeic acid exhibited the strongest activity against HSV-1 (EC50 =15.3 g/ml, SI= 671), HSV-2 (EC50 = 87.3 g/ml, SI= 118) and ADV-3 (EC50 =14.2 g/ml, SI=727), whereas chlorogenic acid possessed the strongest anti-ADV-11 (EC50= 13.3 g/ml, SI= 301) activity. The present study concludes that pure compounds of P. major, which possess antiviral activities are mainly derived from the phenolic compounds, especially caffeic acid. Its mode of action against HSV-2 and ADV-3 was found to be at multiplication stages (postinfection of HSV-1: 0–12 h; ADV-3: 0–2 h), and with SI values greater than 400, suggesting the potential use of this compound for treatment of the infection by these two viruses. © 2002 Elsevier Science B.V. All rights reserved.

National welfare programs are importantly affected by models of welfare activity institutionalized at the global level. This article examines the impact of the welfare regime advocated by and within the International Labor Organization (ILO). Countries that have recently ratified ILO conventions related to welfare show increased growth in spending, net of national characteristics. Subanalyses show that the effects of ILO ratification are strong in the industrialized capitalist democracies, particularly where prior welfare spending is low and the working class has a weakly institutionalized role in policymaking. ILO ratification seems disconnected from spending in the less developed countries. Legislative case studies point to similar patterns. These findings suggest that international norms contribute to policy where they offer compelling models that powerful actors can use to legitimate policy innovation.

The present study systematically explores the biological pathways and altered expression of genes speculatively participating in lung carcinogenesis by using oligonucleotide microarray-bioinformatic analysis methods. The results revealed that 1,396 genes were up-regulated and 1,965 were down-regulated in lung adenocarcinoma carcinogenesis. Gene ontology and relevant bioinformatics tools indicated that the functional category to which the most frequently differentially expressed genes were classified, was to the cytokine-cytokine receptor interaction pathway, focal adhesion pathway and the mitogen-activated protein kinase signaling pathway. Furthermore, we constructed a membrane array, consisting of 51 up-regulated genes in lung adenocarcinoma, in order to verify the biological pathways involved in the carcinogenesis of lung cancer. The analysis of 45 lung adenocarcinoma tissue specimens demonstrated that the genes involved in these three biological pathways had high rates of overexpression. Out of the 51 genes, 17 genes were demonstrated to be overexpressed in all 45 lung adenocarcinoma tissues compared to the paired normal lung tissues. These findings could have implications in understanding the process of lung adenocarcinoma carcinogenesis. Moreover, our developed membrane arrays could be a potentially feasible and promising tool in clinical practice for analyzing the molecular mechanisms of lung adenocarcinoma carcinogenesis.

The ability to detect K-ras oncogene may provide additional information for the management of patients with non-small cell lung cancer (NSCLC). In the present study, we detected the K-ras oncogene in 76 patients with NSCLC by two methods: direct sequencing of K-ras in tumor tissues and membrane array detection of the gene overexpression specific for activated K-ras in peripheral blood. The results showed that 28 (36.8%) of the 76 Taiwanese NSCLC patients had K-ras mutations, with a frequency of 36.4% (20/55) in adenocarcinomas and 38.1% (8/21) in squamous cell carcinomas. The K-ras mutations were more frequently found in smokers than in non-smokers (51.4 vs. 24.4%, P=0.015). The incidences of K-ras mutation in the subgroups of non-smokers and squamous cell carcinomas are relatively higher in Taiwan than in other countries. On the other hand, the membrane array method could positively detect circulating activated K-ras in all of the 27 NSCLC patients with K-ras mutations at codons 12, 13 and 61, and in 4 of the 48 patients with wild-type K-ras. Our results suggest that the K-ras oncogene membrane array serves as a sensitive and convenient tool for the detection of K-ras oncogene, and therefore, has a great potential for clinical applications.

Several studies have indicated that air pollution induces systemic as well as tissue-specific inflammation. Chronic inflammatory diseases such as rheumatoid arthritis and chronic obstructive pulmonary disease reduce bone mineral density (BMD), leading to increased release of immune cells from the bone marrow. However, the association between air pollution and osteoporosis remains poorly defined. Therefore, we conducted this population-based retrospective cohort study to evaluate the risk of osteoporosis in Taiwanese residents exposed to air pollution. We combined 2 nationwide databases in this study. The National Health Insurance Research Database of Taiwan was available from 2000 to 2010. Detailed daily data on air pollution were collected by Taiwan Environmental Protection Agency (EPA) from 1998 to 2010. We calculated the yearly average concentrations of air pollutants from the study start to the date of osteoporosis occurrence, or withdrawal from the NHI program, or December 31, 2010. The yearly average concentrations of air pollutants were categorized into quartiles, and the risks of osteoporosis were evaluated among 4 stages of air pollutants. Among Q1, Q2, Q3, and Q4 of pollutants in all subjects, the adjusted hazard ratios (HRs) of osteoporosis in Q2, Q3, and Q4 were compared with Q1. For carbon monoxide (CO), the adjusted HRs were 1.05 (95% confidence interval [CI], 0.97–1.14), 1.78 (95% CI, 1.65–1.92), and 1.84 (95% CI, 1.71–1.98), respectively. For nitrogen dioxide (NO2), the adjusted HRs were 1.35 (95% CI, 1.25–1.45), 1.24 (95% CI, 1.15–1.35), and 1.60 (95% CI, 1.48–1.73), respectively, in all subjects. The findings of the present study show that CO and NO2 exposure is associated with an increased risk of osteoporosis in the Taiwanese population.

Research on molecular mechanisms underlying the carcinogenesis of non-small cell lung cancer (NSCLC) may provide gene targets in critical pathways valuable for improving the efficacy of therapy and survival of patients with NSCLC. However, the molecular markers highly sensitive for the prognosis and treatment evaluation of NSCLC are not yet available. To explore candidates, we conducted an oligonucleotide microarray study with three pairs of NSCLC and normal lung tissue, and determined 8 differentially expressed genes including the Human MutT homologue (hMTH1), Surfactant protein D (SPD), Human hyaluronan binding protein 2 (HABP2), Crystalline-mu (CRYM), Ceruloplasmin (CP), Integrin alpha-11 subunit (ITGA11), Collagen type XI alpha I (COL11A1), and Lung-specific X protein (Lun X). Four lung cancer-related markers MUC-1, hTERT, hnRNP B1, and CK-19 were also incorporated for further analysis. The expression profiles of the twelve genes in seventy pairs of NSCLC tumor and normal lung tissue were then detected quantitatively by using membrane array and quantitative real-time PCR (qRT-PCR). The data of the membrane array and qRT-PCR were compared for consistency and the potential of these mRNA markers in clinical application. The results showed that membrane array and qRT-PCR obtained consistent data for the tested genes in both sensitivity and specificity (correlation coefficient 0.921, p

Objective: Detection of tumor-related mRNA in blood has become a potential cancer diagnostic approach. However, the sensitivity of single-marker assays is not high enough for clinical applications. The present study was aimed to evaluate the efficacy of a multimarker panel for molecular diagnosis of non-small cell lung cancer (NSCLC). Methods: Carcinoembryonic antigen (CEA), cytokeratin 19 (CK-19), c-met and heterogeneous nuclear ribonucleoprotein (hnRNP) B1 mRNAs were quantified by quantitative real-time reverse transcriptase polymerase chain reaction in 34 tumor tissues and 69 peripheral blood samples of NSCLC patients. Results: All four markers displayed high overexpression rates (range 82.3–97.1%) in NSCLC tumors. When used as single markers in blood for NSCLC diagnosis, CEA, CK-19, c-met and hnRNP B1 could only reach sensitivities of 52.2, 50.7, 42 and 17.4%, respectively. However, the sensitivity was enhanced up to 85.5% when CEA, CK-19 and c-met were combined in a 3-marker panel. Moreover, the expression of c-met and hnRNP B1 in blood was significantly correlated with patients’ pathological stages. Conclusions:The combined detection of CEA, CK-19 and c-met mRNAs in blood provided a valuable tool for molecular diagnosis of NSCLC. In addition, our results also suggested that hnRNP B1 was not a valuable diagnostic marker but a potential prognostic marker for NSCLC.

The c-met receptor and its ligand hepatocyte growth factor have been shown to be involved in tumor invasiveness and metastasis. Overexpression of c-met has been demonstrated in lung cancer tissues and cell lines, but the expression of c-met in peripheral blood (circulating c-met) has not been addressed. The molecular monitoring of circulating c-met could be helpful for selecting patients for adjuvant therapy.To investigate the expression of circulating c-met in non-small cell lung cancer (NSCLC) patients and to assess its prognostic implications.We quantified the levels of c-met messenger RNA (mRNA) in paired tumor and normal lung tissues and their peripheral bloods in 45 patients with NSCLC by real-time polymerase chain reaction (PCR). The expression status of c-met protein in tumor tissues was further evaluated by immunohistochemistry.c-Met mRNA was significantly higher by 1.5 to 11 times in 34 of 45 tumor tissues (75.5%) than it was in their normal counterparts by real-time PCR. A comparison of this assay to immunohistochemistry suggested that real-time PCR was more sensitive than immunohistochemistry (27 of 45 tumor tissues, 60.0%) for the detection of c-met (p = 0.016). Of these patients with overexpression of c-met in tumors, 67.6% (23 of 34 patients) expressed higher amounts of circulating c-met by 1.4 to 8 times that of the normal control subjects. In addition, overexpression of circulating c-met was significantly correlated with nodal (N) stage (p = 0.011), but weakly correlated with tumor (T) stage (p = 0.056) and overall stages (p = 0.054) in patients with NSCLC. However, no correlations were found among circulating c-met and other factors such as age, gender, and pathologic types. Moreover, by univariate analysis, circulating c-met overexpression and pathologic stages (including T and N stages) were the most important factors correlated with early recurrence (p0.05). Only the circulating c-met remained as an independent predictor of early recurrence (hazard ratio, 3.94; 95% confidence interval, 1.17 to 13.33; p = 0.027) after Cox regression multivariate analysis.Overexpression of circulating c-met is significantly correlated with the N stage and early recurrence. Moreover, early recurrence is frequently noted in patients with overexpression of circulating c-met, indicating that circulating c-met is an independent negative prognostic indicator in NSCLC.

Current researches have proposed a genetic model for colorectal cancer (CRC), in which the sequential accumulation of mutations in specific cancer-related genes, including adenomatous polyposis coli (APC), K- ras, and p53, drives the transition from normal epithelium through increasing adenomatous dysplasia to colorectal cancer. To identify patients with an increased risk of tumor recurrence or metastasis and evaluate the prognostic values of APC, K- ras, and p53 gene mutations, we investigated the frequency of these three mutated genes in tumors and sera of CRC patients. APC, K- ras, and p53 gene mutations in primary tumor tissues and their paired preoperative serum samples of 118 CRC patients were detected by using polymerase chain reaction– single strand conformation polymorphism (PCR-SSCP) analysis, followed by direct DNA sequencing of the PCR-amplified genomic DNA. Subsequently, serum molecular markers were analyzed for their correlation with patients’ clinicopathologic features and presence of postoperative recurrence/metastasis. We did not observe any significant difference in the association of APC or K- ras or p53 gene mutations in primary tumors with patients’ demographic data (all were P > 0.05). In contrast, both serum APC and p53 molecular markers were closely correlated with lymph node metastasis and TNM stage (both P < 0.05). Moreover, the serum overall molecular markers (at least one of the three markers) were prominently associated with depth of tumor invasion ( P = 0.033), lymph node metastasis ( P < 0.001), and TNM stage ( P < 0.001). In addition, a significantly higher postoperative metastasis/recurrence rate in patients positive for overall molecular markers compared to those negative for these molecular markers were also demonstrated ( P < 0.001). APC and K- ras molecular markers were more frequently observed in patients with locoregional metastasis (both P < 0.05), while p53 molecular marker was usually detected in the cases of peritoneal metastasis ( P = 0.004). Our findings suggest that serum molecular markers are potentially useful in the determination of colorectal cancer patients harboring gene mutations at high risk of metastasis. Serial analysis is warranted in order to assess their long-term prognostic significance and the therapeutic implications.

Early detection of tumor DNA in serum/plasma prior to the development of recurrence or metastases could help improve the outcome of patients with colorectal cancer (CRC) after tumor resection. Recent advances in the detection of tumor DNA in the serum/plasma has opened up numerous new areas for investigation and new possibilities for molecular diagnosis. APC and K- ras mutations are considered to be early-stage developments of CRCs, whereas p53 mutations are thought to be relatively late events in the tumorigenesis of CRCs. The aim of this study was to search for the presence of genetic mutations in the DNA extracted from the serum of CRC patients and healthy subjects. We simultaneously evaluate the significance of APC, K- ras, and p53 gene mutations in cancer tissues and their paired serum samples of 104 CRC patients by polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP) followed by direct sequencing. Additionally, analysis was carried out to detect the serum carcinoembryonic antigen (CEA) levels in CRC patients. Overall, we found at least one of the gene mutations in tumor tissues from 75% (78/104) of the CRC patients. Comparison of the three molecular markers showed that the detection rates in the serum were 30.4%, 34.0%, and 34.2% for APC, K- ras, and p53 genes, respectively. Of these patients, 46.2% (36/78) were identified as having positive serum results, whereas all healthy controls remained negative. The overall positive tumor DNA detection rates in the serum were 0% (0/7) for Dukes' A classification, 22.4% (11/49) for Dukes' B, 48.7% (19/39) for Dukes' C, and 66.7% (6/9) for Dukes' D. The detection rate increased as the tumor stage progressed ( p = 0.012). Concurrently, a significant difference was observed between lymph node metastases and positive serum tumor DNA detection ( p0.001). A significantly higher postoperative metastasis/recurrence rate in patients harboring gene mutations with serum tumor DNA than those without serum tumor DNA was also demonstrated ( p0.001). However, no significant correlation between the postoperative metastasis/recurrence and serum CEA levels was observed ( p = 0.247). These data suggest that the identification of circulating tumor DNA using the molecular detection of APC, K- ras, and p53 gene mutations is a potential tool for early detection of postoperative recurrence/metastases. Moreover, these genes may be potential molecular markers of poor clinical outcome in CRC patients.

This collection of essays by ten of the nation's prominent social scientists and theologians offers serious commentary on our culture's obsession with material goods and examines the uneasy relation of materialism to religion. The contributors assess the ways in which materialism has been understood in recent analyses of American character, how the economy shapes our understandings of ourselves, the ways in which religious thought is being reshaped by economic circumstances, and the nature of consumerism. The complement to Wuthnow's God and Mammon in America, this volume challenges us all to look at materialism in new ways and suggests viable means for reversing our country's prevailing material fixation and its destructive effects on our spiritual lives.

Little information is known about the genetic mechanisms of the pathophysiology of varicose veins (VVs). The purpose of this study was to systematically explore the biological pathways of genes speculatively participating in VVs by microarray bioinformatics analysis methods. The results showed that 32 genes were upregulated and 74 genes were downregulated in VVs. Gene Ontology and relevant bioinformatics tools indicated that the functional categories in which 106 genes (2.8%; 106/3800) of the most frequent alteration belonged to were apoptosis and angiogenesis. The analysis of 20 VV tissue specimens demonstrated that genes involved in angiogenesis and apoptosis pathways had high rates of overexpression. In addition, we discovered that genes involved in the angiogenesis pathways included HSP90, ILK , and TGFB1 , and they played key roles in the development of VVs. This study demonstrated that the angiogenesis and apoptosis pathways may play an important role in the formation of VVs, but their molecular mechanisms need further investigation.

Before proceeding it is necessary to briefly outline the general points of Durkheim's structural theory of social solidarity. These are first stated in Durkheim's early work The Division of Labor in Society (DL). In DL Durkheim explores the causes and consequences of social solidarity. He posits two forms of solidarity that correspond to two different typesof social structure; mechanical solidarity, which integrates society on the basis of similarity and organic solidarity, which integrates society on the basis of interdependence. Durkheim believes that mechanical solidarity is the more primitive or traditional form and arises from the states of consciousness that are common to all members of the same society. Where this common consciousness makes itself felt, it forms relationships linking the individual to society as a whole. The degree to which these links are felt in diverse spheres of activity reflects the degree of social integration and cohesion in society, in its extreme form, confounding the identity of