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1.
J Med Syst ; 44(2): 54, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31927706

RESUMO

Sepsis mortality is heavily influenced by the quality of care in hospitals. Comparing risk-standardized mortality rate (RSMR) of sepsis patients in different states in the United States has potentially important clinical and policy implications. In the current study, we aimed to compare national sepsis RSMR using an interactive web-based dashboard. We analyzed sepsis mortality using the National Inpatient Sample Database of the US. The RSMR was calculated by the hierarchical logistic regression model. We wrote the interactive web-based dashboard using the Shiny framework, an R package that integrates R-based statistics computation and graphics generation. Visual summarizations (e.g., heat map, and time series chart), and interactive tools (e.g., year selection, automatic year play, map zoom, copy or print data, ranking data by name or value, and data search) were implemented to enhance user experience. The web-based dashboard (https://sepsismap.shinyapps.io/index2/) is cross-platform and publicly available to anyone with interest in sepsis outcomes, health inequality, and administration of state/federal healthcare. After extrapolation to the national level, approximately 35 million hospitalizations were analyzed for sepsis mortality each year. Eight years of sepsis mortality data were summarized into four easy to understand dimensions: Sepsis Identification Criteria; Sepsis Mortality Predictors; RSMR Map; RSMR Trend. Substantial variation in RSMR was observed for different states in the US. This web-based dashboard allows anyone to visualize the substantial variation in RSMR across the whole US. Our work has the potential to support healthcare transparency, information diffusion, health decision-making, and the formulation of new public policies.

2.
Environ Pollut ; 258: 113476, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31902537

RESUMO

Exposure to chemicals produced by petrochemical industrial complexes (PICs), such as benzene, ionizing radiation, and particulate matters, may contribute to the development of leukemia. However, epidemiological studies showed controversial results. This systematic review and meta-analysis aimed to summarize the association between residential exposure to PICs and the risk of leukemia incidence, focusing on exposure-response effects. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies published before September 1st, 2019. Observational studies investigating residential exposure to PICs and the risk of leukemia were included. The outcome of interest was the incidence of leukemia comparing to reference groups. Relative risk (RR) was used as the summary effect measure, synthesized by characteristics of populations, distance to PICs, and calendar time in meta-regression. We identified 7 observational studies, including 2322 leukemia cases and substantial reference groups, in this meta-analysis. Residential exposure to PICs within a maximal 8-km distance had a 36% increased risk of leukemia (pooled RR = 1.36, 95% CI = 1.14-1.62) compared to controls, regardless of sex and age. In terms of leukemia subtypes, residential exposure to PICs was associated with the risks of acute myeloid leukemia (AML, pooled RR = 1.61, 95% CI = 1.12-2.31) and chronic lymphocytic leukemia (CLL, pooled RR = 1.85, 95% CI = 1.11-6.42). In meta-regression, the positive association occurred after 10 years of follow-up with a pooled RRs of 1.21 (95% CI = 1.02-1.44) and then slightly increased to 1.77 (95% CI = 1.35-2.33) at 30 years after follow-up. No effect modification was found by sex, age, and geographic locations.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Benzeno/toxicidade , Exposição Ambiental/efeitos adversos , Leucemia/induzido quimicamente , Petróleo/toxicidade , Benzeno/efeitos adversos , Indústria Química , Humanos , Incidência , Leucemia/epidemiologia , Petróleo/efeitos adversos , Risco
3.
PLoS One ; 14(12): e0226637, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31881052

RESUMO

BACKGROUND: Although studies reported increased cardiovascular (CV) risks in patients treated with macrolides, the risks remain controversial among clarithromycin (CLR) users. We aimed to summarize the association between CLR use and the risks of mortality and CV events. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies with population exposed to CLR published until December 31st, 2018. These studies reported either all-cause mortality (primary outcome) or CV adverse events (secondary outcomes) based on multivariate models. Effect measures were synthesized by study design and follow-up duration (long-term, ≥ 1 year; short-term, ≤ 3 months; and immediate, ≤ 2 weeks). This study has been registered on PROSPERO (ID: CRD42018089605). RESULTS: This meta-analysis included 13 studies (3 RCTs and 10 observational studies) and 8,351,815 subjects (1,124,672 cases and 7,227,143 controls). Overall, CLR use was not associated with increased long-term all-cause mortality (pooled rate ratio RR = 1.09, 95% CI = 0.91-1.32), either among patients with or without comorbidities of cardiovascular diseases. Comparing CLR users to placebo, there is no additional risks of cardiac mortality (pooled RR = 1.03, 95% CI = 0.53-2.01), acute myocardial infarction (pooled RR = 1.29, 95% CI = 0.98-1.68), and arrhythmia (pooled RR = 0.90, 95% CI = 0.62-1.32). CONCLUSIONS: Our findings suggested no significant association between CLR use and subsequent long-term all-cause mortality, regardless having comorbidity of cardiovascular diseases or not. Further RCTs investigating the short-term CV risks of CLR use compared to alternative antibiotics are warranted, particularly in high-risk populations.


Assuntos
Antibacterianos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Claritromicina/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Humanos , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/epidemiologia , Fatores de Risco
4.
Environ Health ; 18(1): 52, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196209

RESUMO

Estimation of population attributable fraction (PAF) requires unbiased relative risk (RR) by using either Levin's or Miettinen's formula, on which decision depends on the available exposure information in reference group, not the types of studies. For ecological studies and studies with aggregated outcomes, once having unbiased RRs, Levin's and Miettinen's formulae would provide identical PAF estimates. PAF could also be applied to compare relative burdens of disease between countries across time, which is an additional information in consideration of country-level policies.

5.
J Vasc Surg ; 70(6): 1792-1800.e3, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31176640

RESUMO

OBJECTIVE: This study aimed to address the shortcomings of previous clinical trials that were inadequate to prove the superiority of thoracic endovascular aortic repair (TEVAR) in managing type B aortic dissection (TBAD) over open surgery (OS) or best medical treatment (BMT). The comparative effectiveness of these three treatments was analyzed using data of the National Inpatient Sample, a large U.S. database including patients from 4378 hospitals. METHODS: Adult patients diagnosed with a primary or secondary TBAD in the years 2005 to 2012 were included for analysis. Patients who had aortic aneurysm or received cardioplegia, valve repair, or operations on vessels of the heart were excluded. A three-category propensity score was created by using a multinomial logistic regression model, a three-way matching algorithm for 1:1:1 matching was applied, and a parallel outcome comparison between the three matched treatment groups was performed. RESULTS: Of a total of 54,971 patients included in the study, we matched 17,211 into three equal-size treatment groups (OS, 5755; TEVAR, 5695; BMT, 5761). No significant difference in the 22 baseline covariates was found in the matched cohort. We found TEVAR to have a much lower mortality rate than OS (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.46-0.79) or BMT (OR, 0.62; 95% CI, 0.47-0.83). Mortality rates between OS and BMT were similar (OR, 0.97; 95% CI, 0.74-1.27). We also found TEVAR to have a lower complication rate, shorter hospitalization, and lower medical cost compared with OS. CONCLUSIONS: TEVAR is superior to BMT or OS for treatment of TBAD in terms of mortality, complications, and cost.

6.
Pediatr Neonatol ; 59(6): 611-617, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29548703

RESUMO

BACKGROUND: Helicobacter pylori infection is associated with iron deficiency (ID) in children. Inflammatory cytokine reactions could influence the consequences of H. pylori infection. Hepcidin is an important regulator in iron homeostasis and could be induced by chronic inflammation. The relationship between hepcidin and cytokine levels in children infected with H. pylori remains controversial. METHODS: Based on serology testing for anti-H. pylori IgG, participants (43 seropositive and 43 seronegative) aged 10-18 years were enrolled. Serum hepcidin levels and iron profiles, including iron, ferritin, and total iron-binding capacity, were measured. ID is defined as iron saturation less than 15%. Seropositive children were divided into low hepcidin (n = 22) and high hepcidin (n = 21) groups. IL-1ß, IL-6, and IL-8 serum levels were compared. RESULTS: Serum IL-1ß and IL-6 levels were comparable between H. pylori seropositive and seronegative children, as were the median serum hepcidin levels (6.5 ng/mL versus 8.6 ng/mL; P = 0.1318). Median levels of serum iron, ferritin, and iron saturation were significantly lower in seropositive children with low hepcidin than in those with high hepcidin (P = 0.0123, P = 0.0001, and P = 0.0004, respectively). The prevalence of ID was significantly higher in those with low serum hepcidin levels (33.3% versus 4.5%; P = 0.015). Compared to the high hepcidin seropositive group, the low hepcidin group had significantly lower median serum levels of cytokines IL-1ß and IL-6, but not IL-8 (P = 0.0151 and P = 0.0015, respectively). CONCLUSIONS: Inflammatory cytokines IL-1ß and IL-6, but not IL-8, might be associated with increased hepcidin levels among H. pylori-seropositive children. Further studies are needed to clarify the role of hepcidin.


Assuntos
Infecções por Helicobacter/sangue , Hepcidinas/sangue , Interleucinas/sangue , Adolescente , Criança , Feminino , Ferritinas/sangue , Helicobacter pylori , Humanos , Ferro/sangue , Masculino , Taiwan
7.
J Paediatr Child Health ; 54(7): 776-783, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29424065

RESUMO

AIM: The aim of this study was to investigate the trend of incidence and outcome of paediatric sepsis in a population-based database. METHODS: Children with sepsis were identified from the 23 million nationwide health insurance claims database of Taiwan. Sepsis was defined by the presence of single ICD-9 code for severe sepsis or septic shock or a combination of ICD-9 codes for infection and organ dysfunction. We analysed the trend of incidence, mortality and source of infection in three age groups: infant (28 days to 1 year), child (1-9 years) and adolescent (10-18 years). RESULTS: From 2002 to 2012, we identified 38 582 paediatric patients with sepsis, of which 21.3% were infants, 52.8% were children and 25.8% were adolescents. The incidence of sepsis was 336.4 cases per 100 000 population in infants, 3.3 times higher than in children (101.5/100 000 cases) and 7.3 times higher than in adolescents (46.2/100 000 cases). While sepsis incidence decreased from 598.0 to 336.4 cases per 100 000 people in the infant population, it remained relatively unchanged in children and adolescents. For 90-day mortality, there were significant decreases in all three age groups (absolute decrease of 5.0% for infants, 3.7% for children and 14.4% for the adolescents). In the infant population, we observed a decrease in the incidence of lower respiratory tract infections, while the incidence of urinary tract infections remained unchanged. CONCLUSIONS: The incidence and mortality of sepsis among paediatric patients have decreased substantially between 2002 and 2012, especially among infants. The widespread use of Haemophilus influenzae and pneumococcal vaccines in infants could be a possible explanation.


Assuntos
Sepse/epidemiologia , Adolescente , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Incidência , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/prevenção & controle , Taxa de Sobrevida , Taiwan/epidemiologia
8.
J Surg Oncol ; 117(3): 497-505, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29284067

RESUMO

BACKGROUND: Population-based studies evaluating outcomes of different approaches for rectal cancer are scarce. METHODS: We conducted a retrospective cohort study using the Nationwide Inpatient Sample database between 2008 and 2012. We compared the outcomes and costs among rectal cancer patients undergoing robotic, laparoscopic, or open surgeries using propensity scores for adjusted and matched analysis. RESULTS: We identified 194 957 rectal cancer patients. Over the 5-year period, the annual admission number decreased by 13.9%, the in-hospital mortality rate decreased by 32.2%, while the total hospitalization cost increased by 13.6%. Compared with laparoscopic surgery, robotic surgery had significantly lower length of stay (LOS) (OR 0.69, 95%CI 0.57-0.84), comparable wound complications (OR 1.08, 95%CI 0.70-1.65) and higher cost (OR 1.42, 95%CI 1.13-1.79), while open surgery had significantly longer LOS (OR 1.38, 95%CI 1.19-1.59), more wound complications (OR 1.49, 95%CI 1.08-1.79), and comparable cost (OR 0.92, 95%CI 0.79-1.07). There were no difference in in-hospital mortality among three approaches. CONCLUSIONS: Laparoscopic surgery was associated with better outcomes than open surgery. Robotic surgery was associated with higher cost, but no advantage over laparoscopic surgery in terms of mortality and complications. Studies on cost-effectiveness of robotic surgery may be warranted.


Assuntos
Laparoscopia/estatística & dados numéricos , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Idoso , Estudos de Coortes , Análise Custo-Benefício , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Laparoscopia/economia , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Neoplasias Retais/economia , Neoplasias Retais/epidemiologia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/economia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Estados Unidos/epidemiologia
9.
J Pediatr Gastroenterol Nutr ; 66(2): e36-e40, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28727656

RESUMO

OBJECTIVE: Helicobacter pylori infection occurs predominantly in childhood. Host immune response gene polymorphism is reported to affect the susceptibility to H pylori infection and the outcome of H pylori-related gastric cancer. Not all H pylori-infected patients, however, exhibit iron deficiency (ID). The relationship between host genetic polymorphisms and ID mediated by H pylori infection is not well understood. METHODS: Subjects (n = 644) from the general population of age 10 to 18 years were divided into 2 groups based on serology testing for anti-H pylori IgG: seropositive study group; and seronegative control group. Five single nucleotide polymorphisms (SNPs) in IL1B (rs1143627 and rs16944), IL8 (rs4073), IL10 (rs1800896), and ABO (rs505922), were genotyped and the iron status of the 2 groups was compared. RESULTS: The seroprevalence rate for H pylori was 10.7% in this study. Infected subjects were significantly older and had lower serum iron levels than uninfected subjects (P = 0.0195 and 0.0059, respectively). Multivariate analysis revealed a significantly higher frequency of the T allele of rs505922 (odds ratio [OR] = 6.128; P < 0.001) and lower frequency of the T allele of rs1143627 (OR = 0.846; P = 0.014) in seropositive subjects. Among 59 seropositive subjects, the T allele frequency of rs1143627 was significantly higher in those with ID (OR = 3.156; P = 0.043), compared with those without ID. CONCLUSIONS: ABO (rs505922) and IL1B (rs1143627) may affect H pylori infection susceptibility, and IL1B (rs1143627) may also influence ID risk in infected children.


Assuntos
Anemia Ferropriva/genética , Infecções por Helicobacter/genética , Interleucina-1beta/genética , Sistema ABO de Grupos Sanguíneos/genética , Adolescente , Anemia Ferropriva/complicações , Estudos de Casos e Controles , Criança , Feminino , Predisposição Genética para Doença , Genótipo , Infecções por Helicobacter/complicações , Helicobacter pylori/imunologia , Humanos , Interleucina-10/genética , Interleucina-8/genética , Ferro/sangue , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Soroepidemiológicos , Taiwan
10.
PLoS One ; 12(9): e0183813, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28873440

RESUMO

BACKGROUND: Fluoroquinolone is a commonly prescribed antimicrobial agent, and up to 20% of its users registers adverse gastroenterological symptoms. We aimed to evaluate the association between use of fluoroquinolone and gastrointestinal tract perforation. METHODS: We conducted a nested case-control study on a national health insurance claims database between 1998 and 2011. The use of fluoroquinolones was classified into current (< 60 days), past (61-365 days prior to the index date) and any prior year use of fluoroquinolones. We used the conditional logistic regression model to estimate rate ratios (RRs), adjusting or matching by a disease risk score (DRS). RESULTS: We identified a cohort of 17,510 individuals diagnosed with gastrointestinal perforation and matched them to 1,751,000 controls. Current use of fluoroquinolone was associated with the greatest increase in risk of gastrointestinal perforations after DRS score adjustment (RR, 1.90; 95% CI, 1.62-2.22). The risk of gastrointestinal perforation was attenuated for past (RR, 1.33; 95% CI, 1.20-1.47) and any prior year use (RR, 1.46; 95% CI, 1.34-1.59). To gain insights into whether the observed association can be explained by unmeasured confounder, we compared the risk of gastrointestinal perforation between fluoroquinolone and macrolide. Use of macrolide, an active comparator, was not associated with a significant increased risk of gastrointestinal perforation (RR, 1.11, 95%CI, 0.15-7.99). Sensitivity analysis focusing on perforation requiring in-hospital procedures also demonstrated an increased risk associated with current use. To mitigate selection bias, we have also excluded people who have never used fluoroquinolone before or people with infectious colitis, enteritis or gastroenteritis. In both of the analysis, a higher risk of gastrointestinal perforation was still associated with the use of fluoroquinolone. CONCLUSIONS: We found that use of fluoroquinolones was associated with a non-negligible increased risk of gastrointestinal perforation, and physicians should be aware of this possible association.


Assuntos
Antibacterianos/efeitos adversos , Fluoroquinolonas/efeitos adversos , Gastroenteropatias/induzido quimicamente , Perfuração Intestinal/induzido quimicamente , Intestinos/efeitos dos fármacos , Administração Oral , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Intestinos/patologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Taiwan , Resultado do Tratamento
12.
Oncotarget ; 8(14): 22460-22476, 2017 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-27816970

RESUMO

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Colorretais/metabolismo , Hidroximetilglutaril-CoA Sintase/metabolismo , Mitocôndrias/fisiologia , Neoplasias Bucais/metabolismo , Animais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Movimento Celular , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Hidroximetilglutaril-CoA Sintase/genética , Camundongos , Camundongos SCID , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/mortalidade , PPAR alfa/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , RNA Interferente Pequeno/genética , Análise de Sobrevida , Células Tumorais Cultivadas
13.
Oral Oncol ; 66: 100-107, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28012797

RESUMO

OBJECTIVES: Relapse is the most serious problem affecting the morbidity and mortality rates of patients with head and neck squamous cell carcinoma (HNSCC). Although HNSCC has been studied for several decades, the exact mechanism of cancer recurrence remains unclear. MATERIALS AND METHODS: ataxia-telangiectasia mutated interactor (ATMIN) messenger RNA(mRNA) expression was detected in HNSCC samples by quantitative RT-PCR, and was analyzed with patients' clinical outcomes by Kaplan-Meier analyses. The ectopic ATMIN expression or ATMIN silencing on invasion ability was evaluated in HNSCC cell lines. Lymph node metastasis ability was investigated by buccal orthotopic implantation in vivo. All statistical tests were two-sided. RESULTS: ATMIN mRNA expression was positively correlated with patients' clinical outcomes. ATMIN blockage reduced invasion, migration, and metastasis abilities both in vitro and in vivo. Evidence from a buccal orthotopic implantation mice model showed that silenced ATMIN expression prolongs mice survival and reduced lymph node metastasis. In high-throughput microarray and bioinformative analyses, KRas was identified as a crucial downstream effector in ATMIN-mediated HNSCC metastasis and was positively associated with patients' clinical stages and ATMIN mRNA expression. CONCLUSIONS: The role of ATMIN and its regulatory mechanisms in HNSCC progression are reported for the first time. The study results improve our understanding of the ATMIN-KRas axis leading to HNSCC migration or invasion and metastasis and facilitates the identification of possible therapy targets of downstream genes for designing effective therapeutic strategies in personalized medicine.


Assuntos
Carcinoma de Células Escamosas/patologia , Genes ras , Neoplasias de Cabeça e Pescoço/patologia , Metástase Linfática/genética , Fatores de Transcrição/fisiologia , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Transcrição/genética
14.
Ann Surg Oncol ; 22(13): 4335-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25820997

RESUMO

BACKGROUND: To assess the correlations and functions of complement C1r/C1s, Uegf, Bmp1 domain-containing protein-1 (CDCP1) in identifying colorectal cancer (CRC) patients who are at high risk for metastasis. METHODS: Tumor specimens from 101 patients were analyzed by real-time polymerase chain reaction to detect CDCP1 expression. CDCP1 expression plasmids and shRNA were used to knock down CDCP1 expression in this study to investigate migratory and invasive abilities by Boyden chambers. The mRNA expression profiles in shCDCP1 transfectants were compared to those in control cells by conducting microarray analysis. Its downstream effectors were also invested in this study. RESULTS: CRC patients with a high CDCP1 expression had a statistically significant lower overall survival and disease-free survival compared to those exhibiting low CDCP1 expression. In vitro, knock-down CDCP1 expression significantly decreased migratory and invasive abilities in HCT116. Aberrant expression of CDCP1 increased cancer cell migration and invasion. By using integrated genomics, we identified ROCK1 (rho-associated, coiled-coil-containing protein kinase 1 pseudogene 1) as a downstream effector in CDCP1-mediated migration and as an invasion mediator. Clinically, ROCK1 and CDCP1 mRNA expression exhibited a strong positive correlation in CRC patient samples. CONCLUSIONS: Our results implicated CDCP1 as a key regulator of CRC migration and invasion, and suggest that it is a useful prognostic factor for patients with CRC. Improved identification of a high-risk subset of early metastatic patients may guide indications of individualized treatment in clinical practice.


Assuntos
Antígenos CD/genética , Biomarcadores Tumorais/genética , Moléculas de Adesão Celular/antagonistas & inibidores , Moléculas de Adesão Celular/genética , Movimento Celular , Neoplasias Colorretais/patologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/patologia , Idoso , Adesão Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Células Tumorais Cultivadas
15.
Oral Oncol ; 51(2): 170-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25435433

RESUMO

OBJECTIVES: MicroRNA (miRNA) machinery regulates cancer cell behavior, and has been implicated in patients' clinical status and prognosis. We found that microRNA-29b (miR-29b) increased significantly in advanced migratory cells. However, miR-29b controls the migration ability, and its regulatory mechanism in oral squamous cell carcinoma (OSCC) remains unknown. MATERIALS AND METHODS: We triggered miR-29b expression in OSCC patients and cell lines by conducting real-time quantitative PCR. We determined the functions of miR-29b in the migration of OSCC cells by using gain- and loss-of-function approaches. We elevated the target genes of miR29b through software predictions and a luciferase report assay. We used an orthotopic OSCC animal model to investigate the effects of miR29b on OSCC cell metastasis in vivo. RESULTS: The clinical data revealed that miR-29b expression was correlated with lymph node metastasis and an advanced tumor stage in 98 OSCC patients. Furthermore, multivariate analysis revealed that miR-29b expression was significantly correlated with recurrence, and indicated poor survival. MiR-29b promoted OSCC cell migration and downregulated CX3CL1, a cell-cell adhesion regulator, which plays an essential role in miR-29b-regulated OSCC cell migration machinery. Furthermore, we found that CX3CL1 expression was correlated with lymph node metastasis and an early tumor stage in OSCC patients, and negatively correlated with miR-29b expression. CONCLUSION: MiR-29b acts as an oncomir, promoting cell migration through CX3CL1 suppression, and could be a potential therapeutic target for preventing OSCC progression.


Assuntos
Carcinoma de Células Escamosas/patologia , MicroRNAs/fisiologia , Neoplasias Bucais/patologia , Metástase Neoplásica , Animais , Quimiocina CX3CL1/genética , Inativação Gênica , Humanos , Metástase Linfática , Camundongos , MicroRNAs/genética , Análise de Sobrevida
16.
J Pediatr Gastroenterol Nutr ; 57(2): 225-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23880628

RESUMO

OBJECTIVE: Gastrointestinal (GI) involvement in childhood Behçet disease (BD) is not well understood. We aimed to clarify the intestinal presentation in children with BD. METHODS: Medical records of 85 children with recurrent oral ulcers between 1990 and 2010 at the National Taiwan University Hospital were reviewed retrospectively. Twenty of them who fulfilled the Mason and Barnes criteria for the diagnosis of childhood BD were enrolled. The clinical and laboratory characteristics were analyzed. RESULTS: Among 20 patients, the median age at diagnosis was 13.2 years. The common presentations included oral ulcers (100%), genital ulcers (70%), skin lesions (65%), and GI symptoms (50%). Five of 10 patients with GI symptoms received endoscopic examinations and all had ulcers. Divided by the age of 10, patients younger than 10 years tended to have higher rates of GI symptoms initially and intestinal ulcers (P = 0.002 and 0.015, respectively). Platelet count was significantly lower in young patients (P = 0.0151). Patients without GI symptoms had higher rates of skin involvement than patients with GI symptoms (P = 0.019). CONCLUSIONS: Young children with BD tended to have more GI presentations. For children with BD younger than 10 years having GI symptoms, endoscopic examinations may be considered.


Assuntos
Síndrome de Behçet/patologia , Gastroenteropatias/etiologia , Boca/patologia , Úlceras Orais/etiologia , Dermatopatias/etiologia , Pele/patologia , Úlcera/etiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Endoscopia , Feminino , Gastroenteropatias/epidemiologia , Genitália/patologia , Humanos , Lactente , Masculino , Úlceras Orais/epidemiologia , Contagem de Plaquetas , Dermatopatias/epidemiologia , Taiwan/epidemiologia , Úlcera/epidemiologia
17.
Cancer Res ; 73(13): 4147-57, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23687336

RESUMO

The epithelial-mesenchymal transition (EMT) is a key mechanism in both embryonic development and cancer metastasis. The EMT introduces stem-like properties to cancer cells. However, during somatic cell reprogramming, mesenchymal-epithelial transition (MET), the reverse process of EMT, is a crucial step toward pluripotency. Connective tissue growth factor (CTGF) is a multifunctional secreted protein that acts as either an oncoprotein or a tumor suppressor among different cancers. Here, we show that in head and neck squamous cell carcinoma (HNSCC), CTGF promotes the MET and reduces invasiveness. Moreover, we found that CTGF enhances the stem-like properties of HNSCC cells and increases the expression of multiple pluripotency genes. Mechanistic studies showed that CTGF induces c-Jun expression through αvß3 integrin and that c-Jun directly activates the transcription of the pluripotency genes NANOG, SOX2, and POU5F1. Knockdown of CTGF in TW2.6 cells was shown to reduce tumor formation and attenuate E-cadherin expression in xenotransplanted tumors. In HNSCC patient samples, CTGF expression was positively correlated with the levels of CDH1, NANOG, SOX2, and POU5F1. Coexpression of CTGF and the pluripotency genes was found to be associated with a worse prognosis. These findings are valuable in elucidating the interplay between epithelial plasticity and stem-like properties during cancer progression and provide useful information for developing a novel classification system and therapeutic strategies for HNSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Fator de Crescimento do Tecido Conjuntivo/fisiologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Ativação Transcricional , Animais , Sítios de Ligação , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Movimento Celular , Intervalo Livre de Doença , Células HEK293 , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Nus , Proteína Homeobox Nanog , Invasividade Neoplásica , Transplante de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Proto-Oncogênicas c-jun/metabolismo , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Esferoides Celulares/metabolismo , Transcriptoma
18.
Oral Oncol ; 49(9): 923-931, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23602254

RESUMO

OBJECTIVES: Oral squamous cell carcinoma (OSCC) accounts for>90% oral cancer which is a leading cause of cancer death worldwide. Early diagnosis may well offer an opportunity to increase survival to this neoplasm. Micro(mi)RNA-interfered cancer progression is crucial, yet its migration machinery of OSCC is still unknown. To access whether the possible miRNA prognostic markers and underlying mechanisms, we developed a highly migratory TW2.6 MS-10 cells from TW2.6 cells to investigate the issue. MATERIALS AND METHODS: miRNA profiling was performed on TW2.6 and TW2.6 MS-10. Target miRNA was correlated to pathological status in OSCC patients by real-time RT-PCR. A downstream effector was identified using a bioinformatics analysis, and a 3'-untranslated region (UTR) reporter assay was used. RESULTS: An miRNA cluster, miR-17-92, including miR-17, miR-19b, miR-20a, and miR-92a, was found to be significantly down-regulated in TW2.6 MS-10 compared to TW2.6 cells. Overexpression of this cluster decreased the migratory ability of OSCC cell lines. We further demonstrated that miR-17 and miR-20a are the main miRNAs of miR-17-92 cluster which modulate OSCC migration. Clinically, miR-17/20a showed negative correlation with TNM stage and lymphatic metastasis. Through a bioinformatics screening analysis and 3'UTR reporter assay, we confirmed the integrin (ITG) ß8 as a direct target of miR-17/20a, and knockdown of ITGß8 reduced cell migratory capability of OSCC. CONCLUSIONS: miR-17/20a acts as a prognostic predictor of OSCC patients' outcome and a tumor migration suppressor miRNA.


Assuntos
Carcinoma de Células Escamosas/patologia , Movimento Celular , MicroRNAs/fisiologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Análise por Conglomerados , Humanos , Neoplasias Bucais/genética , Prognóstico
19.
J Pediatr ; 161(4): 626-31.e2, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22575253

RESUMO

OBJECTIVE: To assess the diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) by using high-resolution melting (HRM) analysis and a clinical scoring system. STUDY DESIGN: Genetic variations in the 18 coding exons were prescreened using HRM analysis and then confirmed by direct sequencing. To establish a scoring system, clinical features of 20 patients with NICCD diagnosed in Taiwan between the years 2000 and 2008 were compared with those of 47 patients with biliary atresia and 35 with infantile cholestasis. RESULTS: Eight types of mutations/polymorphisms were identified in patients with NICCD, including 5 mutations in the coding region or splice site (c.851del4, c.1638ins23, R553Q, IVS6+5G > A, IVS11+1G > A), and 3 single-nucleotide polymorphisms (IVS11+17C > G, IVS4+6A > G/rs6957975, and c.1194A > G/rs2301629). The 3 hotspot mutations (c.851del4, c.1638ins23, and IVS6+5G > A) comprised 33/35 (94.3%) mutated alleles. The patients with NICCD had a higher frequency of the rs6957975 polymorphism compared with 103 healthy controls (P < .0001). A 6-point scoring system was proposed according to clinical parameters. The patients with NICCD tended to score ≥ 4 points, whereas biliary atresia and other infantile cholestasis tended to score <4 points (P < .0001). CONCLUSIONS: HRM analysis was efficient and effective in detecting mutations. Three common mutations comprised the majority of mutations found in our patients. The IVS4+6A > G polymorphism was associated with NICCD. A scoring system may help to differentiate patients with NICCD from those with biliary atresia.


Assuntos
Citrulinemia/diagnóstico , Desnaturação de Ácido Nucleico , Citrulinemia/genética , Frequência do Gene , Humanos , Recém-Nascido , Proteínas de Transporte da Membrana Mitocondrial/genética , Mutação , Mutação de Sentido Incorreto , Polimorfismo de Nucleotídeo Único
20.
Ann Surg Oncol ; 19 Suppl 3: S385-94, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21681381

RESUMO

BACKGROUND: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been implicated in tumor development and progression. The aim of this study was to investigate the role of TWEAK in colorectal cancer (CRC) progression. METHODS: To investigate the involvement of TWEAK in the progression of human CRC, normal, and tumor specimens from 174 patients were analyzed immunohistochemically for the expression of TWEAK. TWEAK recombinant protein treatment, transfection of expression plasmids, and small interfering RNA to knockdown TWEAK expression were performed to test invasive ability with a Boyden chamber. The mRNA expression profile in recombinant TWEAK treatment was compared to a control group by microarray analysis. To identify downstream effectors, Raf kinase inhibitor (RKIP) and its correlation with TWEAK in vitro and in vivo were examined by quantitative real-time polymerase chain reaction and invasion assays. RESULTS: CRC patients whose tumors displayed high TWEAK expression had a statistically significantly higher overall survival and a disease-free advantage over those with a low TWEAK expression. In in vitro invasion assays, alterations in TWEAK expression in CRC cell lines inversely modulated their invasive ability. By means of integrated genomics, we identified RKIP as a downstream effector in TWEAK-mediated invasion inhibition. Knockout of RKIP expression in HCT116 cells by short hairpin RNA (shRKIP) resulted in increased invasiveness. Clinically, RKIP and TWEAK mRNA expression showed strong positive correlations in CRC patient samples. CONCLUSIONS: Our results implicate TWEAK as a key regulator of CRC invasion, and it appears to be a useful prognostic factor for patients with CRC.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Recidiva Local de Neoplasia/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Fatores de Necrose Tumoral/metabolismo , Idoso , Neoplasias Colorretais/genética , Citocina TWEAK , Intervalo Livre de Doença , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Feminino , Técnicas de Inativação de Genes , Células HCT116 , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Proteína de Ligação a Fosfatidiletanolamina/genética , Plasmídeos , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Transfecção , Fatores de Necrose Tumoral/genética , Fatores de Necrose Tumoral/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
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