Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
Appl Ergon ; 106: 103899, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36191404

RESUMO

Night foggy road conditions limit visibility distance of drivers and are associated with higher accident and fatality rates than other weather conditions. Therefore, ensuring road visibility in night foggy road is critical. However, it is difficult to reproduce fog on a real road and only a few studies have researched foggy road conditions and visibility in a laboratory as a small scale. Previous studies have suggested that a color temperature of road lighting is related to visibility. However, many have only investigated the effects of relative transmittance in limited indoor experiments, and the impacts of differences in transmittance on visibility have thus far not been studied in real-scale conditions. In this study, a real-scale test involving 91 subjects was conducted to investigate how the visibility distance under night foggy conditions is affected by different lighting color temperatures. Based on the real scale experiments, the correlation between the visibility distance and lighting color temperature was derived. Road lighting with a low color temperature (i.e., yellow) was found to provide longer visibility distances than that with high color temperatures under night foggy conditions having measured visibility of approximately 102m. The impact of the differences in lighting color increased as the visibility distance decreased. In contrast, road lighting with a high color temperature (i.e., white) improved driver visibility in higher-visibility conditions. Therefore, this study confirmed the correlation between lighting color temperature and visibility distance for different visibility conditions and could serve as a foundation for the development of roadway design standards as well as future studies.


Assuntos
Acidentes de Trânsito , Iluminação , Humanos , Temperatura , Tempo (Meteorologia)
2.
Histol Histopathol ; 37(12): 1177-1184, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35673779

RESUMO

The protein p110γ is an isoform of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration and have been implicated in the oncogenesis of various cancers. In this study, p110γ expression in non-small cell lung cancer (NSCLC) and its association with clinicopathological factors and patient survival were evaluated. A total of 230 NSCLC tumors were immunohistochemically stained for p110γ. Of these, 174 (75.7%) and 56 (24.3%) were placed in the low and high expression groups, respectively. The positive rate of p110γ was significantly higher in adenocarcinoma than in squamous cell carcinoma (p⟨0.001). Advanced stage NSCLCs showed higher p110γ expression than those at an early stage (p=0.002). Irrespective of the histological tumor type, the patients with high p110γ expression had significantly worse overall survival than those with low p110γ expression (p=0.004). p110γ expression was an independent poor prognostic factor in the multivariate analysis. Our results suggest that p110γ may be involved in the development and progression of NSCLC, and that p110γ has promising potential as a prognostic factor or novel therapeutic target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinase , Neoplasias Pulmonares/metabolismo , Isoformas de Proteínas , Prognóstico
3.
Materials (Basel) ; 15(10)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35629441

RESUMO

Powder-based 3D printing is an excellent technique for the fabrication of complex structural shapes. The outstanding bone remodeling capacity of calcium phosphate bioceramics is a desirable characteristic for such fabrication. Whitlockite (WH) is a calcium phosphate-based ceramic that contains Mg ions and possesses good mechanical properties, rapid resorbability, and promotes osteogenesis. The aim of this study was to fabricate 3D-printed scaffolds using marine plankton-derived WH (MP-WH) powder. The surface morphology and composition of the fabricated scaffolds were characterized by scanning electron microscopy and X-ray diffraction. The biocompatibility and osteogenic effects were evaluated using human mesenchymal stem cells. We successfully obtained a 3D porous scaffold using MP-WH. The MP-WH 3D scaffold showed improved compressive strength compared to the tricalcium phosphate (TCP) 3D scaffold. The in vitro results showed that compared with TCP 3D scaffolds, MP-WH 3D scaffolds were biocompatible and enhanced cell proliferation and adhesion. In addition, alkaline phosphatase activity and real-time polymerase chain reaction assays demonstrated that osteoblast differentiation was improved on the MP-WH scaffold. These results suggest that marine plankton-derived WH is useful for fabricating 3D-printed scaffolds for bone tissue engineering applications.

4.
Biomolecules ; 10(3)2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143496

RESUMO

As mesothelin is overexpressed in various types of cancer, it is an attractive target for therapeutic antibodies. T-cell bispecific antibodies bind to target cells and engage T cells via binding to CD3, resulting in target cell killing by T-cell activation. However, the affinity of the CD3-binding arm may influence CD3-mediated plasma clearance or antibody trapping in T-cell-containing tissues. This may then affect the biodistribution of bispecific antibodies. In this study, we used scFab and knob-into-hole technologies to construct novel IgG-based 1 + 1 MG1122-A and 2 + 1 MG1122-B bispecific antibodies against mesothelin and CD3ε. MG1122-B was designed to be bivalent to mesothelin and monovalent to CD3ε, using a 2 + 1 head-to-tail format. Activities of the two antibodies were evaluated in mesothelin-positive tumor cells in vitro and xenograft models in vivo. Although both antibodies exhibited target cell killing efficacy and produced regression of xenograft tumors with CD8+ T-cell infiltration, the antitumor efficacy of MG1122-B was significantly higher. MG1122-B may improve tumor targeting because of its bivalency for tumor antigen. It may also reduce systemic toxicity by limiting the activation of circulating T cells. Thus, MG1122-B may be useful for treating mesothelin-positive solid tumors.


Assuntos
Anticorpos Biespecíficos , Antineoplásicos Imunológicos , Proteínas Ligadas por GPI/imunologia , Imunoglobulina G , Proteínas de Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Linfócitos T/imunologia , Animais , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/farmacologia , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/farmacologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/farmacologia , Células Jurkat , Mesotelina , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias/imunologia , Neoplasias/patologia , Linfócitos T/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Artigo em Inglês | MEDLINE | ID: mdl-32155755

RESUMO

(1) Background: Cervical cancer is one of the most common cancers in Korean women. This study was performed to discover the utility of HPV (Human Papillomavirus) testing in screening of cervical lesions and to provide the prevalence of HPV and the genotype distribution in a single center of Korea. (2) Methods: A total of 15,141 women who underwent both HPV testing and cervical cytology were enrolled in this retrospective medical record review study. (3) Results: HPV testing showed higher sensitivity than cytology for the detection of histological high-grade squamous lesions. Furthermore, the sensitivity and specificity of HPV testing varied depending on the method used. The BD Onclarity™ HPV assay had higher sensitivity (90%) than the MyHPV CHIP™ kit (all types of HPV: 82%; high-risk HPV: 76%) for high-grade squamous lesions. A combination of MyHPV CHIP™ and cytology detected 90.9% (30/33) of histological high-grade squamous lesions. A combination of BD Onclarity™ HPV assay and cytology detected 96.55% (84/87) of histological high-grade squamous lesions. In addition, HPV prevalence and genotype distribution were different depending on the HPV testing method used. (4) Conclusion: HPV testing showed higher sensitivity than cytology, but the sensitivity and specificity of HPV testing had variation depending on the method used.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Idoso , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , República da Coreia , Estudos Retrospectivos , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia
6.
Int J Clin Exp Pathol ; 12(3): 978-986, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933908

RESUMO

Heat shock protein 90 (HSP90), a molecular chaperone, plays critical roles in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. HSP90 has four human isoforms; HSP90α, HSP90ß, glucose related protein 94 (GRP94), and tumor necrosis factor (TNF) receptor-associated protein 1 (TRAP1). We evaluated the differential expression of these HSP90 isoforms in colorectal cancer (CRC) and correlated their expression levels with clinicopathological factors and patient survival rates. We performed immunohistochemical staining for HSP90α, HSP90ß, GRP94, and TRAP1 in 129 CRC tumor samples and found that HSP90α expression was significantly associated with advanced pT stage (P = 0.011) and shorter recurrence-free survival (RFS) (P = 0.010), whereas GRP94 expression was correlated with low grade (P = 0.029) and better RFS (P < 0.001). HSP90ß and TRAP1 had no prognostic impact, although HSP90ß expression was positively correlated with tumor size (P = 0.008). Based on our results, HSP90α and GRP94 are potential prognostic biomarkers of CRC. In addition, the differences in expression and functional activities among four HSP90 isoforms imply that isoform selectivity should be seriously considered when HSP90 inhibitors are studied or adopted for the treatment of CRC.

7.
Environ Res ; 155: 175-181, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28226276

RESUMO

Epidemiologic studies have indicated that albuminuria is associated with mortality from all causes and cardiovascular disease (CVD), with substantial heterogeneity. We evaluated if the associations of urine albumin creatinine ratio (ACR) with all-cause and CVD mortality differed depending on serum concentrations of persistent organic pollutants (POPs), strong lipophilic chemical mixtures with very long half-lives, which are recently linked to many degenerative diseases. Study subjects were participants of the National Health and Nutrition Examination Survey 1999-2004 who were 60 years or older at baseline (n=1215 and 1067 for organochlorine pesticides (OCPs) and other POPs, respectively). They were followed-up through 2011 (mean follow-up periods: 8.1 and 8.0 years for OCPs and other POPs, respectively). The associations between the ACR and all-cause mortality significantly differed by the serum levels of POPs, especially organochlorine pesticides (OCPs; Pinteraction<0.01). Stratified analyses indicated that the associations between ACR and all-cause mortality became stronger as the serum levels of OCPs increased. Among the elderly with the highest tertile of OCPs, the adjusted hazard ratios were 1.0, 1.1, and 2.9 (Ptrend<0.01) across the categories of ACR (<10, 10-<30, and ≥30mg/g); however, ACR was not clearly related to mortality among the elderly with the lowest tertile of OCPs. CVD mortality showed similar interactions, as noted for all-cause mortality (Pinteraction<0.01). The different associations between albuminuria and mortality by the serum OCP levels and the little association among the elderly with low serum OCPs levels suggest that OCPs play an important role in albuminuria-related death risk. However, these findings need to be replicated in other cohort studies.


Assuntos
Albuminúria/sangue , Albuminúria/mortalidade , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Poluentes Ambientais/sangue , Hidrocarbonetos Clorados/sangue , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais
9.
Proc Natl Acad Sci U S A ; 113(45): 12780-12785, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27791177

RESUMO

Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibily other cell-surface receptors in human tumors.

10.
Patient Prefer Adherence ; 10: 1979-1989, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27729776

RESUMO

PURPOSE: We assessed medication nonadherence, categorized as intentional or unintentional, and related factors in elderly patients with hypertension, correlating the data with measurement of blood pressure as the final target of medication adherence and other possible influencing factors, such as lifestyle. PATIENTS AND METHODS: Subjects were aged ≥65 years, resided in a rural area, and were taking antihypertensive drugs. The survey was conducted in July 2014. Participants were divided into the following three groups: "Adherence", "Unintentional nonadherence", and "Intentional nonadherence". Individual cognitive components, such as necessity and concern as well as self-efficacy and other related factors, were compared according to adherence groups. The interrelationships between those factors and nonadherence were tested using structural equation modeling analysis. RESULTS: Of the 401 subjects, 182 (45.6%) were in the adherence group, 107 (26.7%) in the unintentional nonadherence group, and 112 (27.9%) in the intentional nonadherence group. Necessity and self-efficacy were found to have a significant direct influence on unintentional nonadherence behaviors (necessity ß=-0.171, P=0.019; self-efficacy ß=-0.433, P<0.001); concern was not statistically significant (ß=-0.009, P=0.909). Necessity was found to have significant direct and indirect impact on intentional nonadherence (direct ß=-0.275, P=0.002; indirect ß=-0.113, P=0.036). Self-efficacy had no significant direct effect on intentional nonadherence though it had the only significant indirect effect on intentional nonadherence (direct ß=-0.055, P=0.515; indirect ß=-0.286, P<0.001). Concern had no significant influence on intentional or on unintentional nonadherence (direct ß=0.132 0.132, P=0.151; indirect ß=-0.006, P=0.909). CONCLUSION: Unintentional nonadherence should be regularly monitored and managed because of its potential prognostic significance. Interventions addressing cognitive factors, such as beliefs about medicine or self-efficacy, are relatively difficult to implement, but are essential to improve medication adherence.

11.
Ground Water ; 54(3): 448-458, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26375720

RESUMO

The "Four Major Rivers Restoration Project" was conducted to secure sufficient water resources, introduce comprehensive flood control measures, improve water quality, and restore river ecosystems in Korea. As a part of the project, 16 sites were dredged and weirs were installed in the Han, Geum, Yeongsan, and Nakdong Rivers from late 2010 to early 2012. Groundwater data were obtained from 213 groundwater monitoring wells near the four major rivers to analyze the impacts of weir construction on the nearby groundwater flow system. The groundwater level and chemical characteristics were analyzed to investigate how the groundwater flow system and water quality changed following weir construction. Our results show that the groundwater level immediately increased with increased river levels following weir construction. In addition, the hydrologic condition of some rivers upstream of the weirs was changed from gaining to losing streams. Consequently, the direction of groundwater flow changed from perpendicular to parallel to the river, and groundwater downstream of the weir became recharged from the area upstream of the weir. This should affect groundwater quality, which should become similar to the river water; however, this change has not yet been observed. Therefore, both further monitoring of the groundwater quality and further hydrogeochemical analysis are required for quantitative evaluation of the effects of weir construction in the study area.

12.
Environ Res ; 138: 1-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25682252

RESUMO

BACKGROUND: We investigated if certain persistent organic pollutants (POPs), namely polychlorinated biphenyls (PCBs) and organochlorine (OC) pesticides, predicted total, cardiovascular disease (CVD), and cancer mortality among the elderly, with the hypothesis that associations differ by the amount of fat mass. METHODS: We studied serum concentrations of 11 PCBs in 633 elders (age≥70 years) and of 5 OC pesticides in 675 elders within the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Mean follow-up was 4.1-years. RESULTS: Neither PCBs nor OC pesticides were associated with total mortality when fat mass was not considered in analyses. However, associations of PCBs and OC pesticides with total mortality depended on fat mass (Pinteraction<0.01 and 0.06, respectively). PCBs associated inversely with total mortality for high fat mass, but not for lower fat mass. On the contrary, OC pesticides associated positively with total mortality for low fat mass and this association weakened at higher fat mass. The interaction was also observed with CVD mortality. In elders with low fat mass, higher PCBs associated with 2-3 fold higher risk of CVD mortality, while this association was absent in elders with more fat mass (Pinteraction=0.03). The positive association between OC pesticides and CVD mortality was also observed only among elderly with low fat mass (Pinteraction=0.03). CONCLUSIONS: The possibility of interaction between POPs and the amount of fat mass on risk of mortality from chronic diseases is clinically important in modern societies with an obesity epidemic and requires confirmation in other studies with larger sample size.


Assuntos
Doenças Cardiovasculares/mortalidade , Exposição Ambiental , Hidrocarbonetos Clorados/sangue , Neoplasias/mortalidade , Praguicidas/sangue , Bifenilos Policlorados/sangue , Absorciometria de Fóton , Adiposidade , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/induzido quimicamente , Poluentes Ambientais/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Neoplasias/induzido quimicamente , Inquéritos Nutricionais , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia
13.
Biomarkers ; 20(2): 136-42, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25585924

RESUMO

Promoter hypermethylation of the O(6)-methylguanine-DNA methyltransferase (MGMT) DNA repair gene is important during carcinogenesis. We explored whether organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), were associated with hypermethylation of the MGMT gene promoter in peripheral leukocytes among 368 Koreans without cancer. Hypermethylation decreased as OCPs increased (Ptrend = 0.02), while PCB concentrations showed an inverted U-shaped association (Pquadratic < 0.01). The prevalence of MGMT promoter hypermethylation was highest within the 2nd quintile of the PCB summary score (28.4%), while it was only 2.7% in the upper 10% score. Chronic exposure to these chemicals may affect methylation of the MGMT promoter, with possibly non-monotonic dose response relationships.


Assuntos
Metilação de DNA , Hidrocarbonetos Clorados/sangue , Praguicidas/sangue , Bifenilos Policlorados/sangue , Estudos de Casos e Controles , Poluentes Ambientais/sangue , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , O(6)-Metilguanina-DNA Metiltransferase/genética , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas/genética , Inquéritos e Questionários
14.
Environ Int ; 75: 87-92, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25461417

RESUMO

There is limited evidence about whether background exposure to organochlorine pesticides is related to impairment of cognitive function in general populations. This study was performed to investigate cross-sectional associations between serum concentrations of organochlorine pesticides and cognitive function, a predictor of dementia, among U.S. elders without overt dementia. Study subjects were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. We selected 6 organochlorine pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethylene (DDE), trans-nonachlor, oxychlordane, heptachlor epoxide, and ß-hexachlorocyclohexane) which were commonly detected in current general population. Cognitive function was assessed with the Digit-Symbol Substitution Test. All 6 compounds showed statistically significant or marginally significant inverse associations with cognitive score after adjusting for covariates including education levels. The strongest association was observed with p,p'-DDT. With the outcome of low cognitive score defined as <25th percentile, elders in the highest quartile of p,p'-DDT, p,p'-DDE, and ß-hexachlorocyclohexane had 2 to 3 times higher risks than those in the lowest quartile. In particular, when their concentrations were further divided with the cutoff points of 90th and 95th percentiles, p,p'-DDT in the highest 5th percentile showed 6.5 (95% confidence interval: 2.6-16.3) times higher risk of low cognitive score. On the other hand, non-persistent pesticides like organophosphates or pyrethroid showed little association with this cognitive score. The potential role of background exposure to organochlorine pesticides in the development of dementia should be explored in future prospective studies and in-vitro/in-vivo experimental studies.


Assuntos
Cognição/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Hidrocarbonetos Clorados/toxicidade , Inquéritos Nutricionais , Praguicidas/sangue , Adulto , Idoso , Humanos , Masculino , Praguicidas/toxicidade , Estados Unidos
15.
J Gerontol A Biol Sci Med Sci ; 70(7): 847-53, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25326285

RESUMO

BACKGROUND: Insulin resistance is linked to many human chronic diseases. Paradoxically, however, impaired insulin signaling contributes to longevity in various organisms and is suggested as an adaptive mechanism against external stressors, including obesity. We formulated a novel hypothesis that insulin resistance can be beneficial in obese humans, insofar as it does not cause glucose dysmetabolism. METHODS: N = 5,241 participants aged ≥40 with normal fasting glucose were combined across the 1988-1994 and 1999-2004 National Health and Nutrition Examination Survey datasets. Mean follow-up period was 6.6 years. Insulin resistance was measured with homeostasis model assessment (HOMA-IR). Outcomes were all causes (n = 724), cardiovascular diseases (CVD, n = 316), and cancer mortality (n = 190). RESULTS: Supporting the hypothesis, obese persons with high HOMA-IR showed a decreased risk of total and CVD mortality compared to those with the lowest HOMA-IR. Adjusted hazard ratios were 1.0, 0.8, 0.4, and 0.4 (p(trend) = .02) for all death and 1.0, 0.6, 0.2, and 0.2 (p(trend) < .01) for CVD death. On the other hand, lean persons with high HOMA-IR showed about twice the total and CVD mortality compared to persons with the lowest HOMA-IR (p(trend) < .01, respectively). CONCLUSIONS: Insulin resistance in obese individuals may begin as an adaptive mechanism and can be beneficial if it is not associated with glucose dysmetabolism. In contrast, insulin resistance in lean individuals associated with higher risk of total and CVD mortality. Insulin resistance may be multifaceted and conventional approaches to regard insulin resistance itself as a pathological condition may be reconsidered in this light.


Assuntos
Doenças Cardiovasculares/mortalidade , Resistência à Insulina/fisiologia , Obesidade/metabolismo , Obesidade/mortalidade , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Feminino , Humanos , Longevidade , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/complicações , Neoplasias/mortalidade , Inquéritos Nutricionais , Obesidade/complicações , Estados Unidos
16.
Sci Total Environ ; 496: 219-225, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25089684

RESUMO

OBJECTIVE: Exposure to persistent organic pollutants (POPs) has recently been linked to metabolic syndrome (MetS) and some MetS components. However, prospective evidence in humans is scarce, and the nature of the dose-response relationship is unclear. We evaluated the association between POPs and MetS using a nested-case control study within a community-based Korean cohort. METHOD: The study subjects were 64 patients newly diagnosed with MetS during a 4-year follow-up, and the controls were 182 subjects without MetS. Concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) were measured in stored serum collected at baseline. RESULTS: The concentrations of most PCBs and some OCPs such as ß-hexachlorocyclohexane, hexachlorobenzene, oxychlordane, and heptachlor epoxide predicted the risk for MetS. The POP exposure and MetS showed an inverted U-shaped or a linear association with plateau rather than a linear dose-response association. When the summary measure of the PCBs and OCPs was used, the adjusted odds ratios (ORs) across the quartiles of the summary measure were 1.0, 1.3, 3.8 (95% confidence interval, 1.3-10.7), and 2.1 (Pquadratic=0.013) after adjusting for potential confounders. In the analyses of each of the five MetS components, POP exposure was mainly associated with an increased risk for glucose and lipid metabolism disturbances. CONCLUSION: This study demonstrated that chronic exposure to a mixture of PCBs and OCPs can increase the risk for MetS within the low-dose background exposure range of POPs. As the findings of this study suggest a nonmonotonic dose-response relationship, in vitro and in vivo experimental studies are needed to understand the underlying mechanisms.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/sangue , Síndrome Metabólica/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Hidrocarbonetos Clorados/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Praguicidas/sangue , Bifenilos Policlorados/sangue
17.
BMC Endocr Disord ; 14: 57, 2014 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-25015117

RESUMO

BACKGROUND: Despite the consistent relationship between serum γ-glutamyltransferase (GGT) and type 2 diabetes (T2D), one unsolved issue is the role of serum GGT in the well-known association between obesity and T2D. This study was performed to investigate whether the association between body mass index (BMI) and impaired fasting glucose (IFG) differed depending on serum GGT levels within the normal range. METHODS: Study subjects were 2,424 men and 3,652 women aged ≥ 40, participating in the Fifth Korean National Health and Nutrition Examination Survey. Serum GGT levels within the normal range were classified into gender-specific tertiles. RESULTS: Among men and women belonging to the lowest tertile of serum GGT, BMI showed statistically non-significant weak associations with the risk of IFG. However, among persons in the highest tertile of serum GGT, the risk of IFG was 3 - 4 times higher among persons with BMI ≥ 25 kg/m2 than those with BMI < 23 kg/m2 (Pinteraction = 0.032 in men and 0.059 in women). CONCLUSIONS: The well-known strong association between BMI and IFG was observed mainly among persons with elevation of serum GGT to certain physiological levels, suggesting a critical role of serum GGT in the pathogenesis of IFG. This finding has an important clinical implication because serum GGT can be used to detect high-risk obese persons.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Intolerância à Glucose/sangue , Obesidade/complicações , gama-Glutamiltransferase/sangue , Glicemia/análise , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etiologia , Feminino , Seguimentos , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/fisiopatologia , Prognóstico , Valores de Referência , Fatores de Risco
18.
Mol Cancer Ther ; 13(3): 651-61, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24435448

RESUMO

The limited localization and penetration of monoclonal antibodies (mAb) into solid tumors restricts their antitumor efficacy. Here, we describe a solid tumor-targeting antibody with enhanced tumor penetration activity. We designed a 22-residue peptide (A22p), which was extracted from the C-terminal basic region of semaphorin 3A (Sema3A) but modified to have higher affinity with neuropilin receptors (NRP), and genetically fused it to the C-terminus of Fc of human immunoglobulin G1 via a 15-residue (G4S)3 linker, generating Fc-A22p, for the bivalent binding to NRPs. In contrast to Fc or the monovalent A22p peptide alone, Fc-A22p homed to tumor vessels and induced vascular permeability through VE-cadherin downregulation and penetrated tumor tissues by interacting with NRPs in mice bearing human tumor xenografts. We extended the Fc-A22p platform by generating mAb-A22p antibodies of two clinically approved solid tumor-targeting mAbs, the anti-EGF receptor mAb cetuximab (erbitux), and the anti-Her2 mAb trastuzumab (herceptin). The mAb-A22p antibodies retained the intrinsic antigen binding, natural Fc-like biophysical properties, and productivity in mammalian cell cultures, comparable with those of the parent mAbs. In mouse xenograft tumor models, the mAb-A22p antibodies more efficiently homed to tumor vessels and spread into the extravascular tumor parenchyma, which significantly enhanced antitumor efficacy compared with the parent mAbs. Our results suggest that mAb-A22p is a superior format for solid tumor-targeting antibodies due to its enhanced tumor tissue penetration and greater antitumor efficacy compared with conventional mAbs.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/genética , Peptídeos Penetradores de Células/genética , Neuropilinas/genética , Proteínas Recombinantes de Fusão/genética , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Antígenos CD/efeitos dos fármacos , Antígenos CD/genética , Caderinas/efeitos dos fármacos , Caderinas/genética , Linhagem Celular Tumoral , Peptídeos Penetradores de Células/administração & dosagem , Cetuximab , Feminino , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neuropilinas/administração & dosagem , Transporte Proteico/genética , Proteínas Recombinantes de Fusão/administração & dosagem , Trastuzumab
19.
Chemosphere ; 94: 151-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24161582

RESUMO

Background exposure to organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs) has been linked to type 2 diabetes. As OC pesticides and PCBs mainly accumulate in adipose tissue and there are physiological and clinical differences between visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), we explored if there were associations of OC pesticides and PCBs in VAT or SAT with type 2 diabetes and insulin resistance. Participants were 50 patients with or without type 2 diabetes who underwent surgery for either cancer or benign liver or gallbladder lesions. We analyzed 14 OC pesticides and 22 PCB congeners in both VAT and SAT. Insulin resistance was estimated using homeostasis model assessment (HOMA). Although concentrations of OC pesticides and PCBs were strongly correlated between VAT and SAT, absolute concentrations differed substantially between them. In particular, concentrations of all PCBs were consistently about 5-10 times higher in VAT than SAT, but these patterns were independent of diabetes status. Some OC pesticides or PCBs, such as dichlorodiphenyltrichloroethanes (DDTs), chlordanes, and PCBs with 5 or less chlorides showed significant associations with diabetes or insulin resistance. For example, when tertiles of concentration-based summary measures were used, adjusted ORs were 1.0, 2.3, and 9.0 (P trend=0.02) for DDTs in VAT and 1.0, 2.1, and 5.7 (P trend=0.08) for PCBs with 5 or less chlorides. This study generally confirmed previous findings using serum concentrations. It would be useful to study pharmacodynamics of POPs in VAT and SAT further.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Hidrocarbonetos Clorados/metabolismo , Resistência à Insulina/fisiologia , Praguicidas/metabolismo , Bifenilos Policlorados/metabolismo , Gordura Subcutânea/metabolismo , Adulto , Idoso , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Prev Med Public Health ; 45(3): 196-203, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22712047

RESUMO

OBJECTIVES: Even though experimental studies have suggested that iron can be involved in generating oxidative stress, epidemiologic studies on the association of markers of body iron stores with cardiovascular disease or cancer remain controversial. This study was performed to examine the association of serum ferritin and transferrin saturation (%TS) with all-cause, cancer, and cardiovascular mortality. METHODS: The study subjects were men aged 50 years or older and postmenopausal women of the Third National Health and Nutrition Examination Survey 1988-1994. Participants were followed-up for mortality through December 31, 2006. RESULTS: Serum ferritin was not associated with all-cause, cancer, or cardiovascular mortality for either men or postmenopausal women. However, all-cause, cancer, and cardiovascular mortality were inversely associated with %TS in men. Compared with men in the lowest quintile, adjusted hazard ratios for all-cause, cancer, and cardiovascular mortality were 0.85, 0.86, 0.76, and 0.74 (p for trend < 0.01), 0.82, 0.73, 0.75, and 0.63 (p for trend < 0.01), and 0.86, 0.81, 0.72, and 0.76 (p for trend < 0.01), respectively. For postmenopausal women, inverse associations were also observed for all-cause and cardiovascular mortality, but cancer mortality showed the significantly lower mortality only in the 2nd quintile of %TS compared with that of the 1st quintile. CONCLUSIONS: Unlike speculation on the role of iron from experimental studies, %TS was inversely associated with all-cause, cancer and cardiovascular mortality in men and postmenopausal women. On the other hand, serum ferritin was not associated with all-cause, cancer, or cardiovascular mortality.


Assuntos
Doenças Cardiovasculares/mortalidade , Ferritinas/sangue , Neoplasias/mortalidade , Transferrinas/sangue , Idoso , Doenças Cardiovasculares/sangue , Causas de Morte , Feminino , Seguimentos , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...