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BACKGROUND & AIMS: Smoking has been implicated in many malignant diseases, but its association with colorectal cancer (CRC) is controversial. We quantitatively evaluated the relation between smoking and incidence of CRC in a meta-analysis of cohort studies. METHODS: Full publications of prospective cohort studies were identified in MEDLINE and EMBASE from 1950 to 2008. Subjects were classified as current smokers, former smokers, or never smokers. The quantity of smoking was assessed by number of cigarettes per day, years of smoking, and pack-years. The reported relative risks of CRC were pooled by random-effects model. Sensitivity analysis was conducted, and publication bias was evaluated. RESULTS: A total of 1,463,796 subjects were recruited in 28 prospective cohorts from America, Europe, and Asia, with median follow-up of 13 years (range, 4-30 years). Current smokers showed a modestly higher risk of CRC (relative risk [RR], 1.20; 95% confidence interval [CI], 1.10-1.30) than never smokers. The risk of CRC among male smokers (RR, 1.38; 95% CI, 1.22-1.56) was more significant than among female smokers (RR, 1.06; 95% CI, 0.95-1.19). Rectal cancer...
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BACKGROUND & AIMS: Smoking has been implicated in many malignant diseases, but its association with colorectal cancer (CRC) is controversial. We quantitatively evaluated the relation between smoking and incidence of CRC in a meta-analysis of cohort studies. METHODS: Full publications of prospective cohort studies were identified in MEDLINE and EMBASE from 1950 to 2008. Subjects were classified as current smokers, former smokers, or never smokers. The quantity of smoking was assessed by number of cigarettes per day, years of smoking, and pack-years. The reported relative risks of CRC were pooled by random-effects model. Sensitivity analysis was conducted, and publication bias was evaluated. RESULTS: A total of 1,463,796 subjects were recruited in 28 prospective cohorts from America, Europe, and Asia, with median follow-up of 13 years (range, 4-30 years). Current smokers showed a modestly higher risk of CRC (relative risk [RR], 1.20; 95% confidence interval [CI], 1.10-1.30) than never smokers. The risk of CRC among male smokers (RR, 1.38; 95% CI, 1.22-1.56) was more significant than among female smokers (RR, 1.06; 95% CI, 0.95-1.19). Rectal cancer was more closely related to smoking (RR, 1.36; 95% CI, 1.15-1.61) than colonic cancer. Former smokers still carried a higher CRC risk than never smokers. The increased risk of CRC was related to cigarettes per day, longer years of smoking, or larger pack-years. CONCLUSIONS: Smoking was associated with a significantly increased risk of CRC. The associated risk was higher for men and for rectal cancers. The association of tobacco consumption and CRC risk appeared to be dose-related.
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ProteinChip surface-enhanced laser desorption/ionization technology and magnetic beads-based ClinProt system are commonly used for semi-quantitative profiling of plasma proteome in biomarker discovery. Unfortunately, the proteins/...
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ProteinChip surface-enhanced laser desorption/ionization technology and magnetic beads-based ClinProt system are commonly used for semi-quantitative profiling of plasma proteome in biomarker discovery. Unfortunately, the proteins/peptides detected by MS are non-recoverable. To obtain the protein identity of a MS peak, additional time-consuming and material-consuming purification steps have to be done. In this study, we developed a magnetic beads-based proteomic fingerprinting method that allowed semi-quantitative proteomic profiling and micropreparative purification of the profiled proteins in parallel. The use of different chromatographic magnetic beads allowed us to obtain different proteomic profiles, which were comparable to those obtained by the ProteinChip surface-enhanced laser desorption/ionization technology. Our assays were semi-quantitative. The normalized peak intensity was proportional to concentration measured by immunoassay. Both intra-assay and inter-assay coefficients of variation of the normalized peak intensities were in the range of 4-30%. Our method only required 2 microL of serum or plasma for generating enough proteins for semi-quantitative profiling by MALDI-TOF-MS as well as for gel electrophoresis and subsequent protein identification. The protein peaks and corresponding gel spots could be easily matched by comparing their intensities and masses. Because of its high efficiency and reproducibility, our method has great potentials in clinical research, especially in biomarker discovery.
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The human cathelicidin LL-37, a pleiotropic host defense peptide, is down-regulated in gastric adenocarcinomas. We therefore investigated whether this peptide suppresses gastric cancer growth. LL-37 lowered gastric cancer cell pro...
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The human cathelicidin LL-37, a pleiotropic host defense peptide, is down-regulated in gastric adenocarcinomas. We therefore investigated whether this peptide suppresses gastric cancer growth. LL-37 lowered gastric cancer cell proliferation and delayed G(1)-S transition in vitro and inhibits the growth of gastric cancer xenograft in vivo. In this connection, LL-37 increased the tumor-suppressing bone morphogenetic protein (BMP) signaling, manifested as an increase in BMP4 expression and the subsequent Smad1/5 phosphorylation and the induction of p21(Waf1/Cip1). The anti-mitogenic effect, Smad1/5 phosphorylation, and p21(Waf1/Cip1) up-regulation induced by LL-37 were reversed by the knockdown of BMP receptor II. The activation of BMP signaling was paralleled by the inhibition of chymotrypsin-like and caspase-like activity of proteasome. In this regard, proteasome inhibitor MG-132 mimicked the effect of LL-37 by up-regulating BMP4 expression and Smad1/5 phosphorylation. Further analysis of clinical samples revealed that LL-37 and p21(Waf1/Cip1) mRNA expressions were both down-regulated in gastric cancer tissues and their expressions were positively correlated. Collectively, we describe for the first time that LL-37 inhibits gastric cancer cell proliferation through activation of BMP signaling via a proteasome-dependent mechanism. This unique biological activity may open up novel therapeutic avenue for the treatment of gastric cancer.
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BACKGROUND: A simple and meaningful health-related quality of life (HRQoL) questionnaire for gastro-oesophageal reflux disease (GERD) patients is lacking. AIM: To develop and validate a disease-specific HRQoL instrument (GERD-QOL)...
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BACKGROUND: A simple and meaningful health-related quality of life (HRQoL) questionnaire for gastro-oesophageal reflux disease (GERD) patients is lacking. AIM: To develop and validate a disease-specific HRQoL instrument (GERD-QOL) for GERD patients. METHODS: An 18-item questionnaire was generated to measure the impact of GERD on sleep, exercise, diet, need for medication, sex life, work, social activity and psychological well-being. GERD patients were invited to complete the GERD-QOL, a visual analogue scale (VAS) and a validated Chinese generic QoL (SF-36) questionnaire before and after esomeprazole treatment. Factor analysis was performed for item selection and psychometric properties were measured. An English version was developed by a forward-backward translation process. RESULTS: A final 16-item GERD-QOL questionnaire was developed. The items were grouped into four subscales (Daily activity, Treatment effect, Diet, and Psychological well-being) after factor analysis. GERD-QOL had good item-internal consistency (Cronbach's alpha: 0.64-0.88), high test-retest reliability (intraclass correlation coefficient: 0.73-0.94, P < 0.001). Its subscale scores were correlated with SF-36 and VAS, which demonstrated high construct validity (P < 0.001). Discriminant validity was verified by correlating GERD-QOL scores with symptom severity (P < 0.001). Responsiveness after esomeprazole treatment was significant (paired-t-test P < 0.001). An English version of GERD-QOL was developed. CONCLUSION: The instrument, GERD-QOL, is valid and reliable.
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OBJECTIVE: The aim of this study is to determine whether a changed expression ratio of PAR-1 and PAR-2 in the colon is associated with diarrhea-predominant IBS patients. METHODS: PAR-1, -2, thrombin, mast cell tryptase, tryptophan...
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OBJECTIVE: The aim of this study is to determine whether a changed expression ratio of PAR-1 and PAR-2 in the colon is associated with diarrhea-predominant IBS patients. METHODS: PAR-1, -2, thrombin, mast cell tryptase, tryptophan hydroxylase (TPH), and chromgranin A (ChrA) in colonic biopsy samples from 10 diarrhea-predominant IBS patients and 13 healthy control subjects were semiquantified with immunofluorescence and image analysis. Serotonin concentrations in biopsy samples were evaluated by capillary electrophoresis. RESULTS: Significantly lower expression of PAR-1 and higher expression of mast cell tryptase was detected in the colons of patients, with statistically unchanged expression of PAR-2. Thrombin-, TPH-, and ChrA-positive cells were markedly increased in IBS patients, but no significant difference in serotonin concentration existed in the colons between two groups. The ratio of PAR-1/PAR-2 expression was significantly decreased in patients (0.33+/-0.19 versus 0.66+/-0.22, P=0.001) and negatively correlated to ChrA-positive cells. CONCLUSIONS: Changed expression ratio of PAR-1 to PAR-2 in the colon is connected with diarrhea-predominant IBS patients. Methods to restore an appropriate balance of PAR-1 and PAR-2 activation in the colon may offer a promising future therapeutic strategy for IBS patients.
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BACKGROUND & AIMS: Liver stiffness measurement (LSM) with transient elastography (Fibroscan) can accurately diagnose advanced liver fibrosis, but its performance in early liver fibrosis is less satisfactory. We aimed to study the diagnostic performance of LSM for histologic bridging fibrosis and cirrhosis in various chronic liver diseases and to investigate the effects of liver fibrosis distribution on LSM. METHODS: We prospectively studied consecutive patients with chronic liver diseases undergoing liver biopsy and transient elastography examinations. Morphometric analysis was performed to evaluate the distribution of liver fibrosis. RESULTS: One hundred thirty-three patients (50% chronic hepatitis B, 14% chronic hepatitis C, and 24% nonalcoholic fatty liver disease) were studied. Morphometric analysis revealed a higher correlation between LSM and pericellular fibrosis (r = 0.43) than periportal (r = 0.21) or perivenular fibrosis (r = 0.25). Area under receiver operating characteristic curve (ROC) of LSM for bridging fibrosis was 0.87 (95% confidence interval, 0.81-0.93) and for cirrhosis was 0.89 (95% confidence interval, 0.83-0.94). Higher LSM was associated with higher serum ALT level. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM. The area under ROC curve of LSM for cirrhosis was lower among patients who had ALT above the upper limit of normal (0.86) as compared with that of patients with normal ALT levels (0.93, P = .03). CONCLUSIONS: Transient elastography can diagnose severe fibrosis because of its good correlation with pericellular fibrosis. Transient elastography might overestimate liver fibrosis when ALT is elevated....
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BACKGROUND & AIMS: Liver stiffness measurement (LSM) with transient elastography (Fibroscan) can accurately diagnose advanced liver fibrosis, but its performance in early liver fibrosis is less satisfactory. We aimed to study the diagnostic performance of LSM for histologic bridging fibrosis and cirrhosis in various chronic liver diseases and to investigate the effects of liver fibrosis distribution on LSM. METHODS: We prospectively studied consecutive patients with chronic liver diseases undergoing liver biopsy and transient elastography examinations. Morphometric analysis was performed to evaluate the distribution of liver fibrosis. RESULTS: One hundred thirty-three patients (50% chronic hepatitis B, 14% chronic hepatitis C, and 24% nonalcoholic fatty liver disease) were studied. Morphometric analysis revealed a higher correlation between LSM and pericellular fibrosis (r = 0.43) than periportal (r = 0.21) or perivenular fibrosis (r = 0.25). Area under receiver operating characteristic curve (ROC) of LSM for bridging fibrosis was 0.87 (95% confidence interval, 0.81-0.93) and for cirrhosis was 0.89 (95% confidence interval, 0.83-0.94). Higher LSM was associated with higher serum ALT level. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM. The area under ROC curve of LSM for cirrhosis was lower among patients who had ALT above the upper limit of normal (0.86) as compared with that of patients with normal ALT levels (0.93, P = .03). CONCLUSIONS: Transient elastography can diagnose severe fibrosis because of its good correlation with pericellular fibrosis. Transient elastography might overestimate liver fibrosis when ALT is elevated.
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BACKGROUND AND OBJECTIVES: Optic neuritis or longitudinally extensive myelitis in Sjogren syndrome (SS) suggests a neuromyelitis optica spectrum disorder (NMOSD). However, brain abnormalities of SS remain to be elucidated for the ...
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BACKGROUND AND OBJECTIVES: Optic neuritis or longitudinally extensive myelitis in Sjogren syndrome (SS) suggests a neuromyelitis optica spectrum disorder (NMOSD). However, brain abnormalities of SS remain to be elucidated for the association with neuromyelitis optica (NMO). METHODS: Twelve primary SS patients (all women, 42 +/- 13.2 years) who had recurrent central nervous system (CNS) manifestations with brain involvement were retrospectively identified. Brain MRI, and neurologic and serologic findings were analyzed with the measurement of anti-aquaporin-4 antibody (AQP4-Ab). RESULTS: All patients showed brain lesions characteristic of NMO as follows: 1) the involved sites adjacent to the third and fourth ventricles and in the posterior limb of the internal capsule, 2) unique configurations, such as the longitudinal course from the internal capsule to the midbrain, large cerebral or cerebellar lesions over 3 cm, and cavity-like formations. AQP4-Ab was positive in six of eight patients tested, and all the seropositive patients showed lesions with increased diffusion, suggestive of vasogenic edema. Four patients met the revised criteria of NMO, and nine had features of NMOSDs. Of the remaining three patients showing only brain involvement, one had AQP4-Ab. CONCLUSIONS: This study demonstrates that SS patients with recurrent CNS involvement have brain abnormalities characteristic of NMO and AQP4-Ab in Korea. The presence of AQP4-Ab in one SS patient with only brain involvement may suggest that the coexistence of NMO should be explored in SS patients with recurrent CNS manifestations, even without optic neuritis or myelitis.
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BACKGROUND AND OBJECTIVE: Agents such as Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila are recognized as important causes of community-acquired pneumonia (CAP) worldwide. This study examined the role o...
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BACKGROUND AND OBJECTIVE: Agents such as Mycoplasma pneumoniae, Chlamydophila pneumoniae and Legionella pneumophila are recognized as important causes of community-acquired pneumonia (CAP) worldwide. This study examined the role of these 'atypical pathogens' (AP) among adult hospitalized patients with CAP. METHODS: A prospective, observational study of consecutive adult CAP (clinico-radiological diagnosis) patients hospitalized during 2004-2005 was conducted. Causal organisms were determined using cultures, antigen testing and paired serology. Clinical/laboratory/radiological variables and outcomes were compared between different aetiologies, and a clinical prediction rule for AP was constructed. RESULTS: There were 1193 patients studied (mean age 70.8 +/- 18.0 years, men 59.3%). Causal organisms were identified in 468 (39.2%) patients: 'bacterial' (48.7%), 'viral' (26.9%), 'AP' (28.6%). The AP infections comprised Mycoplasma or Chlamydophila pneumoniae (97.8%) and co-infection with bacteria/virus (30.6%). The majority of AP infections involved elderly patients (63.4%) with comorbidities (41.8%), and more than one-third of patients were classified as 'intermediate' or 'high' risk CAP on presentation (pneumonia severity index IV-V (35.1%); CURB-65 2-5 (42.5%)). Patients with AP infections had disease severities and outcomes similar to patients with CAP due to other organisms (oxygen therapy 29.1% vs 29.8%; non-invasive ventilation 3.7% vs 3.3%; admission to the intensive care unit 4.5% vs 2.7%; length of hospitalization 6 day vs 7 day; 30-day mortality: 2.2% vs 6.0%; overall P > 0.05). Age <65 years, female gender, fever > or =38.0 degrees C, respiratory rate <25/min, pulse rate <100/min, serum sodium >130 mmol/L, leucocyte count <11 x 10(9)/L and Hb < 11 g/dL were features associated with AP infection, but the derived prediction rule failed to reliably discriminate CAP caused by AP from bacterial CAP (area under the curve 0.75). CONCLUSIONS: M. pneumoniae and C. pneumoniae as single/co-pathogens are important causes of severe pneumonia among older adults. No reliable clinical indicators exist, so empirical antibiotic coverage for hospitalized CAP patients may need to be considered.
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Chronic inflammation is the hallmark of the pathogenesis of Helicobacter pylori-induced gastric cancer. Interleukin (IL)-17A and IL-17F are inflammatory cytokines expressed by a novel subset of CD4+ Th cells and play critical func...
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Chronic inflammation is the hallmark of the pathogenesis of Helicobacter pylori-induced gastric cancer. Interleukin (IL)-17A and IL-17F are inflammatory cytokines expressed by a novel subset of CD4+ Th cells and play critical function in inflammation and probably in cancer. We conducted a case-control study including 1,010 gastric cancer patients and 800 healthy controls to assess the association between IL-17A G197A and IL-17F A7488G polymorphisms and risk of gastric cancer. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. Logistic regression and Cox-proportional hazards analyses were used to evaluate the associations between polymorphisms and gastric cancer susceptibility, clinicopathological features and survival. After adjusted for age and gender, IL-17F 7488GA and GG genotypes were associated with an increased risk of gastric cancer compared with AA genotype [OR 1.51, 95% confidence interval (CI): 1.22-1.87 for GA; OR 1.61, 95% CI: 1.03-2.51 for GG]. Further stratification analyses indicated that the effect of IL-17F 7488GA genotype was noteworthy in gastric cancer patients of noncardia, intestinal type, poorly and moderately differentiated, age older than 40, large tumor size and lymph node metastasis. IL-17A 197AG genotype was associated with increased risk of poorly differentiated, TNM I/II, age of 40-65-year subtypes of gastric cancer, but not with total gastric cancer risk (p = 0.098). No significant relationship was observed between polymorphisms and survival of gastric cancer patients. These findings suggest that polymorphism of IL-17F 7488 involved in susceptibility to gastric cancer, which also influenced certain subtypes according to clinicopathological features, whereas IL-17A 197 may be less relevant.
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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily which form heterodimers with retinoid X receptors (RXRs) in nucleus and bind to the PPAR response elements (PPREs) of targ...
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Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily which form heterodimers with retinoid X receptors (RXRs) in nucleus and bind to the PPAR response elements (PPREs) of target genes, leading to a wide spectrum of physiological functions. With an improved understanding of its physiological role, PPARdelta and its agonist have been gaining attention in cancer research in recent years. Despite the paucity of research concerning the direct relationship between PPARdelta and gastric cancer, there is substantial evidence that PPARdelta may play a role in the development of gastric cancer. This review focuses on recent literature describing the role of PPARdelta, especially in its association with nuclear factor-kappaB (NF-kappaB), interleukin-1beta (IL-1beta), cyclooxygenase-2 (COX-2) and Wnt-beta-catenin/TCF-4 pathways on gastric tumorigenesis and highlights critical discrepancies that need to be resolved for a more comprehensive understanding of how this receptor modulates gastric tumorigenesis. The potential role of PPARdelta as a therapeutic target in the treatment of gastric cancer deserves further research focus.
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