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BACKGROUND: Currently, little information is available on childhood cancer incidence rates in Eastern Asia. The objective of this study was to report the first population-based cancer surveillance of children and adolescents in Taiwan. METHODS: Data from the Taiwan Cancer Registry were examined for cancer frequencies and incidence rates among individuals ages birth to 19 years from 1995 to 2009. Types of cancers were grouped according to the International Classification of Childhood Cancer. Rates were compared by sex and age. For further comparisons with other countries, rates were age standardized to the 2000 world standard population in 5-year age groups. Trends in incidence rates also were evaluated. RESULTS: In total, 12,315 individuals were diagnosed with childhood cancers, for an age-standardized incidence rate (ASR) of 132.1 per million person-years from 1995 to 2009. The male-to-female incidence rate ratio was 1.19. Overall, leukemias were the most common cancer (ASR, 39.1 per million person-years), followed by central nervous system neoplasms (15.8 per million person-years), and lymphomas (15.3 per million person-years). During the 15-year study period, the incidence rates increased by 1% annually. Compared with other countries, the rate of hepatic tumors was 2 times greater in Taiwan. The rate of germ cell neoplasms in Taiwan was similar to that in the United States and was 1.3 to 1.9 times greater compared with Canada, Brazil, Israel, and Japan. CONCLUSIONS: Based on the current data, the observed increase in overall incidence rates was attributable only marginally to improvements in case ascertainment and diagnostic procedures. The high rates of malignant hepatic tumors and germ cell neoplasms in Taiwan suggest variations in the background risk factors.
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Neoplasias/epidemiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Taiwan/epidemiologia , Fatores de TempoRESUMO
BACKGROUND/AIM: The capacity for non-homologous end-joining (NHEJ) repair plays a pivotal role in maintaining genome stability and in carcinogenesis. However, there is little literature on the involvement of NHEJ-related genes in childhood acute lymphocytic leukemia (ALL). Our study aimed to elucidate the impact of polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) (rs6869366, rs2075685, rs2075686, rs28360071, rs3734091, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and DNA ligase IV (LIG4) rs1805388, on the odds of childhood ALL. MATERIALS AND METHODS: Genotypes NHEJ-related genes of 266 cases and 266 controls were determined, and the genotype-phenotype correlation was investigated by examining mRNA transcript expression and the capacity for overall and precise NHEJ repair. RESULTS: The variant genotypes of XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 were significantly associated with increased odds of childhood ALL. Further analysis based on susceptibility genotypes showed no significant differences in mRNA transcript expression levels among childhood ALL cases with various putative high-risk genotypes, except XRCC6 rs5751129. Moreover, the overall NHEJ repair capacity was similar among carriers of different XRCC4, XRCC5, and XRCC6 genotypes. However, it is worth noting that individuals carrying the variant C allele at XRCC6 rs5751129 exhibited lower precise NHEJ repair capacity compared to those with the wild-type T allele. CONCLUSION: Our study identified significant associations between XRCC4 rs3734091, rs28360071, XRCC5 rs828907, and XRCC6 rs5751129 genotypes and childhood ALL. Notably, lower transcriptional expression and reduced precise NHEJ repair capacity were observed in patients carrying the C allele of XRCC6 rs5751129. Further investigations are required to gain deeper insights into childhood ALL development.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Genótipo , Alelos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Reparo do DNA/genética , RNA Mensageiro/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND/AIM: Interleukin 8 (IL-8) is highly expressed in refractory acute lymphocytic leukemia (ALL) cells. This study aimed to investigate the contribution of IL-8 polymorphisms to the risk of childhood ALL. MATERIALS AND METHODS: The genotypes of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were determined in 266 childhood ALL cases and 266 controls using the PCR-RFLP method. Additionally, we assessed whether the interactions of these genotypes with age and sex contributed to childhood ALL risk. RESULTS: The distributions of genotypic and allelic frequencies of IL-8 rs4073, rs2227306, rs2227543, and rs1126647 were not significantly different between childhood ALL cases and controls (all p>0.05). However, carriers of the variant AA genotype at IL-8 rs4073 had a significantly higher risk of childhood ALL among those aged ≤3.5 years and among girls (OR=2.39 and 3.32, 95%CI=1.21-4.73 and 1.51-7.30, p=0.0182 and 0.0042, respectively). In the stratification analysis, IL-8 rs4073 AT and AA genotypes were associated with higher childhood ALL risk classification and shorter survival time (OR=2.21 and 4.13, 95%CI=1.29-3.78 and 1.87-9.10, p=0.0054 and 0.0002, respectively). There was no positive association for rs2227306, rs2227543, or rs1126647 (all p>0.05). CONCLUSION: The A allele of IL-8 rs4073 can serve as a diagnostic predictor for childhood ALL, but only in girls and patients younger than or equal to 3.5 years old. More importantly, it can serve as a prognostic marker for high-risk classification and shorter survival time. Further validation studies can help extend the use of this prognostic predictor in clinical practice.
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Interleucina-8 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Feminino , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Interleucina-8/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , PrognósticoRESUMO
BACKGROUND/AIM: Arsenic trioxide (As2O3), a potent toxin in traditional Chinese medicine, has been utilized as an anticancer agent in Chinese culture for over a millennium. Betulin, commonly extracted from the bark of birch trees, has been identified for its pharmacological properties, including antibacterial, anti-inflammatory, antitumor, and antiviral activities. The aim of this study was to determine the efficacy and underlying anticancer signaling cascade induced by As2O3 and betulin in neuroblastoma cells. MATERIALS AND METHODS: SK-N-SH cells were treated with As2O3 with or without betulin. Cell viability and apoptotic signaling were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, measurement of mitochondrial membrane potential (MMP) loss and reactive oxygen species (ROS), and quantitative western blotting analysis. Student's t-test in addition to one- or two-way analysis of variance was used to examine significant differences between comparison groups. RESULTS: The combined treatment of As2O3 plus betulin was more effective than single treatments in suppressing cell viability and induction of apoptosis, which correlated well with elevated ROS levels. The apoptotic signaling cascade of As2O3 plus betulin was revealed as ROS elevation and relative loss of MMP, leading to the cleavage of caspase-3 and -9. As2O3 plus betulin treatment also reduced the expression of BCL2 apoptosis regulator, BH3-interacting domain death agonist, and BCL2-like-1. CONCLUSION: The novel combination of As2O3 plus betulin has the potential to serve as a practical anti-neuroblastoma drug.
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Antineoplásicos , Arsenicais , Humanos , Trióxido de Arsênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Óxidos/farmacologia , Óxidos/uso terapêutico , Arsenicais/farmacologia , Linhagem Celular Tumoral , Apoptose , Antineoplásicos/farmacologia , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
Background and Aims: Krüppel-like factor (KLF) has a role in the occurrence, development and metabolism of cancer. We aimed to explore the role and potential molecular mechanism of KLF13 in the growth and migration of liver cancer cells. Methods: The expression of KLF13 in hepatocellular carcinoma (HCC) tissues was higher than that in normal tissues according to analysis of The Cancer Genome Atlas (TCGA) database. Lentiviral plasmids were used for overexpression and plasmid knockdown of KLF13. Real-time quantitative polymerase chain reaction (qPCR) and western blotting were used to detect mRNA and protein expression in HCC tissues and cells. Cell counting kit-8 (CCK-8), colony formation, cell migration and invasion, and flow cytometry assays were used to assess the in vitro function of KLF13 in HCC cells. The effect of KLF13 on xenograft tumor growth in vivo was evaluated. The cholesterol content of HCC cells was determined by an indicator kit. A dual-luciferase reporter assay and chromatin immunoprecipitation sequencing (ChIP-seq) revealed the binding relationship between KLF13 and HMGCS1. Results: The expression of KLF13 was upregulated in HCC tissues and TCGA database. KLF13 knockdown inhibited the proliferation, migration and invasion of HepG2 and Huh7 cells and increased the apoptosis of Huh7 cells. The opposite effects were observed with the overexpression of KLF13 in SK-Hep1 and MHCC-97H cells. The overexpression of KLF13 promoted the growth of HCC in nude mice and KLF13 transcription promoted the expression of HMGCS1 and the biosynthesis of cholesterol. KLF13 knockdown inhibited cholesterol biosynthesis mediated by HMGCS1 and inhibited the growth and metastasis of HCC cells. Conclusions: KLF13 acted as a tumor promoter in HCC by positively regulating HMGCS1-mediated cholesterol biosynthesis.
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BACKGROUND/AIM: Acute lymphoblastic leukemia (ALL) is frequent among children. Few studies have researched the relationship between maternally expressed gene 3 (MEG3) and cancer risk. We hypothesized long non-coding RNA MEG3 polymorphisms might influence the risk of childhood ALL. MATERIALS AND METHODS: In a total of 266 patients with childhood ALL and 266 healthy controls, genotypes of MEG3 rs7158663, rs3087918, rs11160608 and rs4081134 single nucleotide polymorphisms were investigated for their associations with childhood ALL. RESULTS: MEG3 rs7158663 AG and AA genotypes were significantly associated with ALL [odds ratio=1.61 (95% confidence interval=1.12-2.31) and 2.21 (1.16-4.22), respectively]. The A allele also exhibited a statistical association with higher risk of ALL (p=0.0015). There was no positive association as for rs3087918, rs11160608 or rs4081134. Interestingly, a significant interaction between MEG3 rs7158663 and age (≥3.5 years) and gender (male) was found. CONCLUSION: MEG3 rs7158663 AG/AA genotypes were associated with higher susceptibility to childhood ALL. These novel findings should be validated in larger populations and different ethnicities.
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Biomarcadores Tumorais/genética , Predisposição Genética para Doença , Leucemia/genética , RNA Longo não Codificante/genética , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Humanos , Leucemia/epidemiologia , Masculino , Polimorfismo de Nucleotídeo Único , Medição de Risco/métodosRESUMO
BACKGROUND/AIM: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk. MATERIALS AND METHODS: In 266 childhood ALL cases and 266 healthy controls, the CDKN1B rs34330 and 2066827 polymorphisms were genotyped, and the association of CDKN1B genotypes with childhood ALL risk were analyzed. RESULTS: The genotypes of CDKN1B rs34330 and 2066827 were similarly distributed between the control and case groups (p for trend=0.8718 and 0.4030, respectively). The allelic frequency also exhibited no statistical difference (p=1.0000 and 0.6666, respectively). There was no significant interaction between CDKN1B genotypes and age or sex. CONCLUSION: CDKN1B genotypes were not found to be minor contributors to childhood ALL susceptibility in Taiwan.
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Inibidor de Quinase Dependente de Ciclina p27 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Inibidor de Quinase Dependente de Ciclina p27/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , TaiwanRESUMO
BACKGROUND/AIM: Evidence has shown that interleukin-18 (IL-18) has both antitumor and pro-tumor effects in various types of leukemia. The current study aimed at investigating the contribution of IL-18 polymorphisms to the risk of childhood acute lymphocytic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: IL-18 promoter -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 266 childhood ALL cases and 266 controls were determined by polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 rs1946519, rs1946518 or rs187238, were not significantly different between childhood ALL cases and controls (all p>0.05). However, in the stratification analysis among the cases, IL-18 rs187238 GC and CC genotypes were associated with increased childhood ALL risk and shorter survival (OR=4.19 and 2.93, 95%CI=2.04-8.64 and 1.19-7.23, p=0.0001 and 0.0250, respectively). No association was found with rs1946519 and rs1946518 (all p>0.05). CONCLUSION: IL-18 rs187238 GC and CC genotypes can serve as predictors for childhood ALL prognosis among Taiwanese. Validation in larger and various populations can greatly extend the feasibility of this novel predictor.
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Interleucina-18 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , TaiwanRESUMO
The purpose of our study was to investigate whether genetic variations in lncRNA H19 were associated with susceptibility to childhood leukemia. Two hundred and sixty-six childhood leukemia patients and 266 healthy controls were enrolled in Taiwan, and two single nucleotide polymorphisms (SNPs), rs2839698 and rs217727, in H19 were genotyped and analyzed. There was a significant difference in the genotypic distribution of rs2839698 between patients and healthy controls (p = 0.0277). Compared to the wild-type CC genotype, the heterozygous variant CT and homozygous variant TT genotypes were associated with significantly increased risks of childhood leukemia with an adjusted odd ratio (OR) of 1.46 (95% confidence interval (CI), 1.08-2.14, p = 0.0429) and 1.94 (95%CI, 1.15-3.31, p = 0.0169), respectively (pfor tread = 0.0277). The difference in allelic frequencies between childhood leukemia patients and controls was also significant (T versus C, adjusted OR = 1.53, 95%CI, 1.13-1.79, p = 0.0077). There were no significant differences in the genotypic and allelic distributions of rs217727 between cases and controls. Interestingly, the average level of H19 rs2839698 was statistically significantly higher for patients with CT and TT genotypes than from those with the CC genotype (p < 0.0001). Our results indicate that H19 SNP rs2839698, but not rs217727, may serve as a novel susceptibility marker for childhood leukemia.
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BACKGROUND/AIM: This study investigated whether genetic variations in cyclin D1 (CCND1) are associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: A total of 266 childhood ALL cases and 266 healthy controls were genotyped for CCND1 rs9344 and rs678653. RESULTS: There was a significant difference in the genotypic distribution of rs9344 between childhood ALL patients and healthy controls (p=0.0077). Compared to the AA genotype, AG and GG genotypes were associated with significantly decreased risks of childhood ALL with odds ratio (OR) of 0.65 [95% confidence interval (CI)=0.44-0.94, p=0.0234] and 0.45 (95%CI=0.26-0.78, p=0.0040), respectively. Supporting this, allelic frequency distributions between childhood ALL patients and controls was significantly different (OR=0.68, 95%CI=0.53-0.88, p=0.0025). There was no significant difference in the genotypic and allelic distributions of rs678653 between cases and controls. CONCLUSION: CCND1 rs9344, but not rs678653, may serve as a predictive marker of susceptibility for childhood ALL.
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Ciclina D1/genética , Predisposição Genética para Doença/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Alelos , Criança , Pré-Escolar , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND/AIM: The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. CONCLUSION: The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.
Assuntos
Povo Asiático/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Idade de Início , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , TaiwanRESUMO
BACKGROUND/AIM: Mounting evidence has shown that miRNAs play a critical role in the regulation of hematopoiesis of cell proliferation and apoptosis as well as in tumorigenesis. The miR146a rs2910164 polymorphism, which is closely responsive for its expression, has been reported to associate with the risk of several solid cancers. The study aimed at examining the association of the it with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: We recruited 266 patients with childhood ALL and 266 healthy controls, and rs2910164 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The allele G was associated with decreased childhood ALL risk (OR=0.66, 95%CI=0.52-0.85, p=0.0011). Consistently, the GG genotype was associated with a decreased susceptibility (OR=0.40, 95%CI=0.23-0.67, p=0.0004). Patients with CG and GG genotypes were of earlier onset than those with CC genotype (p=0.0255 and p=0.0001). CONCLUSION: MiR146a rs2910164 G allele serves as a protective marker for childhood ALL in Taiwan.
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MicroRNAs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , TaiwanRESUMO
BACKGROUND/AIM: The association of matrix metalloproteinase-2 (MMP-2) genotypes with adult leukemia has been reported only once, but never for childhood leukemia. This study aimed to determine the role of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes in childhood leukemia risk. MATERIALS AND METHODS: This case-control study included 266 patients and 266 age- and gender-matched healthy controls. The polymorphic sites of MMP-2 were genotyped by typical polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The CC, CT and TT of rs243865 genotype were 75.2, 23.7 and 1.1% in the case group and 69.2, 28.9 and 1.9% in the control group, respectively. The CT and TT genotypes caused a 0.75- and 0.55-fold increase in the risk of childhood leukemia, respectively. There was no differential distribution of rs2285053 genotypes. Allelic frequency analysis showed that the T allele of MMP-2 promoter -1306 and -735 conferred lower susceptibility than the C allele. CONCLUSION: The MMP-2 promoter genotypes play a minor role in determining personal susceptibility to childhood leukemia among the Taiwanese.
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Povo Asiático/genética , Metaloproteinase 2 da Matriz/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Regiões Promotoras Genéticas , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND/AIM: Cells suffer from oxidative DNA damage which leads to the accumulation of 8-oxoguanine (8-oxoG) adducts in our genome that can become carcinogenic. The human 8-oxoG DNA glycosylase 1 (hOGG1) plays a central role in repairing these 8-oxoGs via the base excision repair pathway. Mounting evidence has suggested that hOGG1 polymorphisms may affect the activity of hOGG1 and serve as genomic markers for the prediction of personal susceptibility to several cancers. To determine whether the commonly examined hOGG1 rs1052133 (Ser326Cys) polymorphism is associated with the risk of childhood acute lymphoblastic leukemia (ALL) among Taiwanese children, we genotyped the hOGG1 rs1052133 (Ser326Cys) in 266 cases and 266 controls. RESULTS: The distributions of the GG, CG and CC genotypes at the hOGG1 rs1052133 were 49.2, 39.1 and 11.7% in the control group and 48.1, 36.1 and 15.8% in the case group (p=0.3656). The combined genotypes CG+CC were not associated with increased risk of childhood ALL (odds ratio [OR]=1.05, 95% confidence interval [CI]=0.74-1.47, p=0.7947). CONCLUSION: The hOGG1 rs1052133 polymorphism is not associated with susceptibility to childhood ALL in the Taiwanese population.
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Alelos , DNA Glicosilases/genética , Predisposição Genética para Doença , Genótipo , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Povo Asiático/genética , Estudos de Casos e Controles , Criança , Feminino , Frequência do Gene , Humanos , Masculino , Razão de Chances , Vigilância da População , Medição de Risco , Fatores de Risco , Taiwan/epidemiologiaRESUMO
PURPOSE: A growing body of evidence shows an association between DNA repair protein genotypes and susceptibility to various cancers. However, few studies have assessed the contribution of the genotype of XRCC3, a homologous repair gene, to the occurrence or prognosis of childhood acute lymphoblastic leukemia (ALL). In this study, we investigated the contribution of seven XRCC3 polymorphisms to childhood ALL. PATIENTS AND METHODS: We recruited 266 patients with childhood ALL and 266 healthy controls. Genomic DNA was isolated from peripheral blood samples. The XRCC3 rs1799794, rs45603942, rs1799796, rs861530, rs28903081, rs861539, and rs3212057 polymorphic genotypes of each subject were determined through conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Genotypes with the rs861539 polymorphism were significantly associated with the risk of childhood ALL. The allelic distribution analyses suggested a significant association between the T allele at rs861539 with an increased risk of childhood ALL in the Taiwanese population. Polymorphic variants of XRCC3 at rs3212057 or rs28903081 did not exist in the study population. XRCC3 rs1799794, rs45603942, rs1799796, and rs861530 were not significantly associated with the risk of childhood ALL in the Taiwanese population. CONCLUSION: Our findings suggest that XRCC3 genotypes with polymorphisms at rs861539 may play a role in determining individual susceptibility to childhood ALL in this Taiwanese population. The polymorphism may be a potential detector and predictor of childhood ALL.
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That both infiltrating macrophages and resident mesangial cells express inducible nitric oxide synthase (iNOS) and produce nitric oxide (NO) excessively is crucial to the progress of glomerulonephritis. Although several reports have mentioned the protective impacts of conjugated linoleic acid (CLA) in stimulated macrophages, the role of CLA in glomerular mesangial cells is unknown. The aim of the present study was to explore the ability of CLA to regulate iNOS expression and NO production in stimulated glomerular mesangial cells. Additionally, we evaluated the effect of CLA on activation of transcription factors which mediate iNOS expression. Exogenous CLA dose-dependently diminished iNOS mRNA and protein expression as well as NO production in lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-stimulated SV-40-transformed mouse mesangial cells. Electrophoretic mobility shift assay experiments demonstrated that CLA (100 microM) dramatically reduced activation of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1) and cAMP response element binding protein (CREB) induced by LPS/IFN-gamma. Moreover, addition of 100 microM CLA significantly diminished LPS-IFN-gamma-induced protein degradation of inhibitor kappaB-alpha (IkappaB-alpha) and the protein expression of phosphorylated IkappaB-alpha in the cytosolic fraction as well as nuclear p65 expression (P < 0.05). In summary, inhibition of NF-kappaB, AP-1 and CREB activation by CLA may be associated with the molecular basis for which CLA suppresses iNOS expression and NO production in stimulated mesangial cells.
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Ácidos Linoleicos Conjugados/farmacologia , Células Mesangiais/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Animais , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática , Regulação Enzimológica da Expressão Gênica , Glomerulonefrite/genética , Glomerulonefrite/metabolismo , Interferon gama/toxicidade , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/enzimologia , Camundongos , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Fator de Transcrição AP-1/metabolismoRESUMO
This study aimed to describe cancer incidence rates and trends specifically for adolescents aged 15-19 years during 1995-2009 in Taiwan. The incidence counts and census data were obtained from the population-based Taiwan Cancer Registry. During the 15-year study period, 4122 adolescents were diagnosed with cancer. The overall incidence rate was 155.2 per million person-years. Other epithelial tumors were the most frequently diagnosed cancer group (23.7%), followed by leukemias (18.0%) and lymphomas (13.9%). When compared to rates in Western countries, a significantly low rate of lymphomas was found. Moreover, rates of the subtypes of melanomas and nasopharyngeal carcinomas being 1/10- and 4-times rates in Western countries were the most striking variations. During 1995-2009, the overall rate of adolescent cancer did not significantly change. However, the most significant upward and declining trends in incidence rates were found for male germ cell neoplasms (annual percent change, APC, 6.4%) and hepatic tumors (APC, -11.1%), respectively. Further investigation and enhancement of the public discourse of possible lifestyle and environmental risk factors associated with increasing trends of certain adolescent cancers should be carried out in Taiwan.
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Neoplasias/epidemiologia , Adolescente , Distribuição por Idade , Feminino , Humanos , Incidência , Masculino , Neoplasias/diagnóstico , Sistema de Registros , Fatores de Risco , Distribuição por Sexo , Taiwan/epidemiologia , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND AND AIMS: There have been rapid advances in the area of interventional bronchoscopy over the past 15 years, but associated complications have been rarely discussed. A longitudinal evaluation of the same operator's performance at a cancer center is reported. METHODS: A detailed record review of diagnostic and therapeutic bronchoscopy between January 1997 and March 2013 was conducted. RESULTS: Among the 1358 diagnostic bronchoscopies, there were nine major complications requiring premature termination and three pneumothoraces found during follow-up (0.88%). An escalation in the level of care was required for four patients with massive bleeding, asthma attack, sedation intoxication and myocardial ischemia, respectively. Six cases occurred after brushing (0.71%), and five cases before any sampling procedure was conducted. The complication rate was highest for peripheral lesions (1.03%). Among the 109 therapeutic bronchoscopies, no major patient-specific complication occurred except for excessive granulation tissue formation following metallic stenting in one patient with benign tracheal stenosis. CONCLUSION: The complication rate with regard to bronchoscopy is comparable with historical controls according to the related literature, and their occurrence appears to be sporadic, not relevant to patient characteristics and mostly related to the bronchoscopy itself rather than the introduction of new techniques. Bronchoscopy remains safe along with technical innovations. However, risk recognition and effective prevention is essential.
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Broncoscopia/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia/efeitos adversos , Criança , China/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pneumotórax/epidemiologia , Pneumotórax/etiologia , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Adulto JovemRESUMO
To identify the prognostic factors and long-term outcome of the Ewing sarcoma family of tumors (ESFT), data on 50 patients with ESFT treated at Taipei Veterans General Hospital between February 1991 and March 2014 were retrospectively considered. The influence of patient demographics, tumor features, and clinical and therapeutic parameters on overall survival (OS) and progression-free survival (PFS) rates were assessed. The results revealed that 21 of the 50 patients (42%) were metastatic at diagnosis. The median follow-up time was 1.8 years. The 5-year OS and PFS for patients who were nonmetastatic were 61.6% and 55.5%, respectively, and 18.8% and 15.4% for patients who were metastatic, respectively. The key adverse prognostic factor was metastasis at diagnosis. Radiotherapy for local control was associated with improved PFS. The high rate of primary metastasis and poorer outcomes of nonmetastatic ESFT compared with results from Western studies, along with previously reported low rates of ESFT in Taiwanese people, suggest that genetic factors play a role in the pathogenesis of ESFT and chemotherapy pharmacokinetics and pharmacodynamics. Radiotherapy in local treatment should be considered more aggressively in Taiwanese patients with ESFT.
Assuntos
Neoplasias Ósseas/patologia , Sarcoma de Ewing/patologia , Adolescente , Adulto , Fatores Etários , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Feminino , Humanos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia , Fatores Sexuais , Taxa de Sobrevida , Taiwan , Carga Tumoral , Adulto JovemRESUMO
We report on the first electrical characterizations of single-crystalline TiSi nanowires (NWs) synthesized by chemical vapor deposition reactions. By utilizing the focused-ion-beam-induced deposition technique, we have delicately made four-probe contacts onto individual NWs. The NW resistivities have been measured between 2 and 300 K, which reveal overall metallic conduction with small residual resistivity ratios in the NWs. Surprisingly, we find that the effect due to the interference processes between the elastic electron scattering and the electron-phonon scattering largely dominates over the usual Boltzmann transport even at room temperature. Such prominent electron-phonon-impurity interference effect is ascribed to the presence of large amounts of disorder and high Debye temperatures in TiSi NWs.