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OBJECTIVE: To observe the regulatory effect of electroacupuncture (EA) on small airway function and exercise tolerance in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: A total of 62 patients with stable COPD were randomized into an observation group (31 cases, 1 case dropped off) and a control group (31 cases, 5 cases dropped off). On the base of routine medication and aerobic exercise, the patients of the two groups all received EA at Danzhong (CV 17), Rugen (ST 18), Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25) and Yingchuang (ST 16). In the observation group, filiform needles were used and inserted perpendicularly, 3 mm in depth. In the control group, the placebo needling method was performed, in which the needle was not inserted through skin at each point. In both groups, electric stimulation with low-frequency electronic pulse instrument was exerted, with continuous wave, 2 Hz in frequency, lasting 30 min each time in the two groups. The treatment was given once every other day, 3 times a week, for 14 treatments totally. Before and after treatment, the following indexes were compared in patients between the two groups, i.e. the lung function indexes (forced expiratory volume in first second [FEV1], forced vital capacity [FVC], the ratio of FEV1 to FVC [FEV1/FVC], maximal voluntary ventilation [MVV], the percentage of maximal expiratory flow [MEF] at 25% of FVC exhaled [MEF25], MEF50 and MEF75 in predicted value), cardiopulmonary exercise test indexs (metabolic equivalent [METS], oxygen uptake per kg body weight [VO2/kg], minute ventilation [VE], the percentage of oxygen pulse [VO2/HR] in predictd value, maximal minute ventilation [VEmax], ventilatory equivalent for oxygen [VE/VO2], ventilatory equivalent for carbon dioxide [VE/VCO2]), 6-minute walk distance (6MWD), the total score of COPD assessment test (CAT), the modified British Medical Research Council (mMRC) score and COPD comprehensive grade. RESULTS: After treatment, FVC%, MVV%, MEF75%, MEF50%, VO2/kg%, METs%, VEmax, VO2/HR%, 6MW and the total CAT score were all improved as compared with those before treatment in the observation group (P<0.05, P<0.01). After treatment, MEF75% and the total CAT score were reduced as compared with those before treatment in the control group (P<0.05). After treatment, MVV%, MEF50%, VO2/kg%, METs%, VEmax and 6MWD in the observation group were all better than those in the control group (P<0.05, P<0.01). CONCLUSION: Electroacupuncture can improve the respiratory function and exercise tolerance in COPD patients through removing small airway obstruction and increasing ventilation.
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Eletroacupuntura , Doença Pulmonar Obstrutiva Crônica , Tolerância ao Exercício , Volume Expiratório Forçado , Humanos , Doença Pulmonar Obstrutiva Crônica/terapia , Testes de Função RespiratóriaRESUMO
Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and posttranscriptional levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA sequencing data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values. The expression levels of circMAN1A2 were detected by quantitative real-time PCR, and the correlations of clinical features with circMAN1A2 expression were analyzed by χ2 tests. Receiver operating characteristic curves were used to evaluate the clinical applications of circMAN1A2. The results showed that circMAN1A2 was upregulated in nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer, with areas under the curves of 0.911, 0.779, 0.734, 0.694, and 0.645, respectively, indicating the good diagnostic value of circMAN1A2. Overall, our findings suggested that circMAN1A2 could be a serum biomarker for malignant tumors, providing important insights into diagnostic approaches for malignant tumors. Further studies are needed to elucidate the mechanisms of circMAN1A2 in the pathogenesis of cancer.
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Biomarcadores Tumorais/sangue , Neoplasias/genética , RNA/genética , Regulação para Cima , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Neoplasias Bucais/sangue , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/genética , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , RNA Circular , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Sequenciamento do ExomaRESUMO
Actin filament-associated protein 1-antisense RNA1 (AFAP1-AS1), a cancer-related long non-coding RNA, has been found to be upregulated in multiple types of cancers. AFAP1-AS1 is important for the initiation, progression and poor prognosis of many cancers, including nasopharyngeal carcinoma (NPC). However, the mechanism underlying the regulation of AFAP1-AS1 expression is not well-understood. In our study, the potential promoter region of AFAP1-AS1 was predicted by comprehensive bioinformatics analysis. Moreover, promoter deletion analysis identified the sequence between positions -359 and -28 bp as the minimal promoter region of AFAP1-AS1. The ChIP assay results indicate that the AFAP1-AS1 promoter is responsive to the transcription factor c-Myc, which can promote high AFAP1-AS1 expression. This study is the first to clone and characterize the AFAP1-AS1 promoter region. Our findings will help to better understand the underlying mechanism of high AFAP1-AS1 expression in tumorigenesis and to develop new strategies for therapeutic high expression of AFAP1-AS1 in NPC.
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Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/metabolismo , Autoantígenos/metabolismo , Proteínas de Ligação a Ácido Graxo , Glicoproteínas/metabolismo , Humanos , Imunidade Inata/imunologia , Lactoferrina/metabolismo , Fosfoproteínas/metabolismo , Proteínas/metabolismoRESUMO
Long noncoding RNAs (lncRNAs) play an important role in lung adenocarcinoma (LUAD) metastasis. Here, we found that lncRNA chromatin-associated RNA 10 (CAR10) was upregulated in the tumor tissue of patients with LUAD and enhanced tumor metastasis in vitro and in vivo. Mechanistically, CAR10 induced epithelial-to-mesenchymal transition (EMT) by directly binding with miR-30 and miR-203 and then regulating the expression of SNAI1 and SNAI2. CAR10 overexpression was positively correlated with a poor prognosis in LUAD patients, whereas overexpression of both CAR10 and SNAI was correlated with even worse clinical outcomes. In conclusion, the CAR10/miR-30/203/SNAI axis is a novel and potential therapeutic target for LUAD.
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Adenocarcinoma de Pulmão/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Fatores de Transcrição da Família Snail/genética , Células A549 , Animais , Linhagem Celular , Linhagem Celular Tumoral , Cromatina/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Neoplasias Pulmonares/genética , Células MCF-7 , Melanoma Experimental/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Prognóstico , Regulação para Cima/genéticaRESUMO
Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body's immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects the biological characteristics of the cells infiltrating them. Regulatory T cells (Tregs) are a subset of T cells that regulate immune responses in the body. They exist in large quantities in the tumor microenvironment and exert immunosuppressive effects. The main effect of tumor microenvironment on Tregs is to promote their differentiation, proliferation, secretion of immunosuppressive factors, and chemotactic recruitment to play a role in immunosuppression in tumor tissues. This review focuses on cell metabolism reprogramming and the most significant features of the tumor microenvironment relative to the functional effects on Tregs, highlighting our understanding of the mechanisms of tumor immune evasion and providing new directions for tumor immunotherapy.
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Neoplasias/metabolismo , Neoplasias/patologia , Linfócitos T Reguladores/metabolismo , Microambiente Tumoral/fisiologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Linfócitos T Reguladores/patologiaRESUMO
OBJECTIVE: To observe the immunoregulatory effect of electroacupuncture (EA) intervention for muscular dystrophy chronic obstructive pulmonary disease (COPD) rats, so as to investigate its underlying mechanism in improving respiratory function. METHODS: Forty male SD rats were randomly divided into 5 groups: normal, model, EA, exercise, and EA+ exercise (n=8 in each). The muscular dystrophy COPD model was established by placing the rats in a closed box to be exposed to cigarette smoke (3-10 cigarettes/time) for 60 min, twice daily, 6 days a week for 90 days. The EA, exercise and EA+exercise interventions were given beginning from day 80 after exposure to cigarette smoke. EA (2 Hz/40 Hz, 6 mA) was applied to "Danzhong" (CV 17), "Qihai" (CV 6), "Zhongwan" (CV 12), "Liangmen" (ST 21) and bilateral "Quchi" (LI 11) for 10 min, once every other day, for 20 times. The swimming exercise was conducted by forcing the rat to swim in a water box for 10 min, once every other day, for 20 times. The rat's lung function including the resistance of inspiration (RI), functional residual capacity(FRC), pulmonary dynamic compliance (Cdyn), etc., was detected under anesthesia. Pathological changes of the lung tissue were detected by H.E. staining, and the contents of serum TNF-alpha, IL-6 and IL-1 beta assayed by ELISA. RESULTS: After 80 days' exposure to the cigarette smoke, the rats' body weight values in the model, EA, exercise and EA+exercise groups were significantly lower than that of the normal group(P<0.05). Moreover, the RI and FRC levels were significantly increased, and the Cdyn level was remarkably decreased in the model group relevant to the normal group (P<0.01). Following the intervention, both RI and FRC levels were significantly down-regulated in the EA, exercise and EA+exercise groups relevant to the model group (P<0.05), suggesting an improvement of the lung function. But the decreased Cdyn level had no marked improvement in the 3 treatment groups relevant to the model group (P>0.05). The numbers of monocytes and lymphocytes of the lung tissue, and the contents of serum TNF-α, IL-6 and IL-1 ß were significantly higher in the model group than in the normal group (P< 0.01), and significantly lower in the EA, exercise and EA+exercise groups than in the model group (P<0.05), except monocytes in the exercise group (P>0.05). No significant differences were found among the EA, exercise and EA+exercise groups in the levels of RI and FRC, pulmonary monocytes and serum IL-6 and IL-1 ß (P>0.05). The body weight was significantly higher in the exercise and EA+exercise groups than in the EA group, and the pulmonary lymphocytes and serum TNF-α obviously lowered in the EA group than in the exercise group (P<0.05). H.E. staining showed deformation of the bronchial tube cavity, detachment and flattening of the bronchial mucosal epithelial cilia, hyperplasia of Goblet cells, infiltration of abundant inflammatory cells in the submucosal layer and muscular layer, more secretions in the bronchovascular cavity, incomplete alveolar structure, thinning and rupture of the alveolar wall, and expansion of the alveolar cavity to form large pulmonary vesicles after modeling, which was obviously milder in the 3 treatment groups. CONCLUSION: EA intervention can improve the pulmonary function and pathological changes in pulmonary muscular dystrophy COPD rats, which is associated with its effects in reducing pulmonary monocytes and lymphocytes and serum TNF-α, IL-6 and IL-1 ß contents, suggesting an enhancement of immunoregulation.
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Eletroacupuntura , Doença Pulmonar Obstrutiva Crônica , Pontos de Acupuntura , Animais , Interleucina-1beta , Pulmão , Masculino , Doença Pulmonar Obstrutiva Crônica/terapia , Ratos , Ratos Sprague-DawleyRESUMO
An increasing number of studies has confirmed that many cells can secrete vesicles or exosomes in eukaryotes, which contain important nucleic acids, proteins and lipids and play important roles in cell communication and tumor metastasis. This paper summarizes the comprehensive function of exosomal non-coding RNAs. Although some studies have shown that exosomes mediate tumor signal transduction, the functional mechanism of the tumor metastasis remains to be elucidated. In this paper, we reviewed the role of exosomal non-coding RNAs in mediating cancer metastasis in the tumor microenvironment to provide new ideas for the study of tumor pathophysiology.
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MicroRNA expression profiling assays have shown that miR-34b/c and miR-449a are down-regulated in nasopharyngeal carcinoma (NPC); however, the targets and functions of miR-34b/c and miR-449a in the pathologenesis of NPC remain elusive. In this study, we verified miR-34b/c and miR-449a were significantly reduced with the advance of NPC. Overexpression of miR-34b-3 and miR-449a suppressed the growth of NPC cells in culture and mouse tumor xenografts. Using tandem mass tags for quantitative labeling and LC-MS/MS analysis to investigate protein changes after restoring expression of miR-34b-3, 251 proteins were found to be down-regulated after miR-34b-3 transfection. Through 3 replicate experiments, we found that miR-34b-3 regulated the expression of 15 potential targeted genes mainly clustered in the key enzymes of glycolysis metabolism, including lactate dehydrogenase A (LDHA). Further investigation revealed that miR-34b-3 and miR-449a negatively regulated LDHA by binding to the 3' untranslated regions of LDHA. Furthermore, LDHA overexpression rescued the miR-34b-3 and miR-449a induced tumor inhibition effect in CNE2 cells. In addition, miR-34b-3 and miR-449a suppressed LDH activity and reduced LD content, which were directly induced by downregulation of the LDHA. Our findings suggest that miR-34b-3 and miR-449a suppress the development of NPC through regulation of glycolysis via targeting LDHA and may be potential therapeutic targets for the treatment of NPC.
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Regulação Neoplásica da Expressão Gênica , L-Lactato Desidrogenase/genética , MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Regiões 3' não Traduzidas/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Cromatografia Líquida , Progressão da Doença , Glicólise/genética , Humanos , Isoenzimas/genética , Isoenzimas/metabolismo , L-Lactato Desidrogenase/metabolismo , Lactato Desidrogenase 5 , Camundongos Nus , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Proteoma/análise , Proteômica/métodos , Espectrometria de Massas em Tandem , Transplante HeterólogoRESUMO
OBJECTIVE: To compare the positions of the mandibular premolars in Angle Class I subjects according to vertical facial type. The results will provide a theoretical basis for predicting effective tooth movement in orthodontic treatment. METHODS: Cephalometric parameters were determined using cone-beam computed tomography in 120 Angle Class I subjects. Subjects were categorized as short, normal, and long face types according to the Frankfort mandibular angle. Parameters indicating the position of the mandibular right premolars and the mandible were also measured. RESULTS: The angle between the mandibular first premolar axis and buccal cortex, the distance between the root apex and buccal cortex, angle of vestibularization, arc of vestibularization, and root apex maximum movable distance were significantly greater in the short face type than in the long and norm face types. The angle between the mandibular second premolar axis and buccal cortex, the distance from root apex to buccal cortex, and the arc of vestibularization were significantly greater in the short face type than in the normal face type. CONCLUSIONS: There are significant differences in the mandibular premolar positions in Class I subjects according to vertical facial type.
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OBJECTIVE: To verify the regulatory effects of acupuncture on exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) at stable phase. METHODS: Thirty cases of COPD were randomly divided into a treatment group (16 cases) and a placebo group (14 cases). Based on specified aerobic exercise, acupuncture was applied in the treatment group and placebo acupuncture was used in the placebo group. The acupoints included Danzhong (CV 17), Rugen (ST 18), Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25) and so on. The needle did not penetrate into the skin for the placebo group. The treatment was required for 2 to 3 times per week for totally 5 weeks. The indices of exercise tolerance, including 6-min walking distance (6-MWD), exercise time, maximum oxygen uptake (VO2max) forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC), maximum ventilatory volume (MVV), St. George respiratory questionnaire (SGRQ) were observed in two groups before and after treatment. RESULTS: (1) Exercise tolerance: the differences of 6-MWD and exercise time were statistically significant between groups, which were more superior in the treatment group (both P<0.01); the VO2max was significantly increased after treatment in the treatment group (P<0.05), but there was no difference between two groups (P>0.05). (2) Pulmonary ventilation function: the differences of FEV1%, FEV1/FVC and MVV% were statistically significant between groups, which were more superior in the treatment group (P<0.05, P<0.01); (3) SGRQ: the SGRQ was significantly improved after treatment in the treatment group (P<0.05), but there was no difference between two groups (P>0.05). CONCLUSION: The acupuncture could improve the exercise tolerance in patients with chronic obstructive pulmonary disease at stable phase, and shorten the onset time of aerobic exercise. Besides, acupuncture combined with aerobic exercise could effectively improve the pulmonary function.
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Terapia por Acupuntura , Tolerância ao Exercício , Doença Pulmonar Obstrutiva Crônica/terapia , Pontos de Acupuntura , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/fisiopatologiaRESUMO
Epstein-Barr virus (EBV) is a human herpesvirus associated with important human diseases, including infectious mononucleosis syndrome, malignant lymphoma, and nasopharyngeal carcinoma. The mechanism of EBV entry into host cells remains a subject of intensive research. After decades of study, researchers have identified several key proteins and different patterns of EBV intrusion into host cells. The viral surface glycoproteins, gp350/220, gp42, gB, gH, and gL, are involved in interactions with the CR2 receptor on the surface of B lymphocytes during viral entry. However, the majority of epithelial cells lack CR2 receptor expression, which makes viral invasion much more complex than in B lymphocytes. Three different models have been proposed to explain how EBV enters epithelial cells: (1) "transfer of infection", mediated by B lymphocytes or Langerhans cells; (2) EBV utilizes its own proteins during the process of fusion with the cell membrane; and (3) progeny virions arising from EBV-infected epithelial cells cross lateral membranes into adjacent epithelial cells. This review will discuss the relevant mechanism of viral entry into B lymphocytes and epithelial cells during EBV infection.
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Linfócitos B/virologia , Células Epiteliais/virologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/fisiologia , Internalização do Vírus , Animais , Herpesvirus Humano 4/genética , Humanos , Proteínas Virais/genética , Proteínas Virais/metabolismoRESUMO
Proliferation of vascular smooth muscle cells (VSMCs) contributes to the development of atherosclerosis. Ezetimibe is a new lipid lowering agent that inhibits cholesterol absorption. In the present study we attempted to investigate whether ezetimibe has any effect on VSMC proliferation and the potential mechanisms involved. Our data showed ezetimibe abrogated the proliferation and migration of primary rat VSMCs induced by Chol:MßCD. Mechanically, we found that ezetimibe was capable of abolishing cyclin D1, CDK2, phospho-Rb (p-Rb), and E2F protein expressions that were upregulated by Chol:MßCD treatment. In addition, Ezetimibe was able to reverse cell cycle progression induced by Chol:MßCD, which was further supported by its down-regulation of cyclin D1 promoter activity in the presence of Chol:MßCD. Furthermore, ezetimibe abrogated the increment of phospho-ERK1/2 (p-ERK1/2) and nuclear accumulation of ERK1/2 in VSMCs induced by Chol:MßCD. Inhibition of the MAPK pathway by using ERK1/2 inhibitor PD98059 attenuated the reduction effect of ezetimibe on the expressions of phosphor-MEK1 (p-MEK1), p-ERK1/2, and cyclin D1. Taken together our data suggest that ezetimibe inhibits Chol:MßCD-induced VSMCs proliferation and leads to cell cycle arrest at the G0/G1 phase by suppressing cyclin D1 expression via the MAPK signaling pathway. These novel findings support the potential pleiotropic effect of ezetimibe in cardiovascular disease.
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Anticolesterolemiantes/farmacologia , Azetidinas/farmacologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Ciclina D1/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Músculo Liso Vascular/citologia , Animais , Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/genética , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Depressão Química , Ezetimiba , Masculino , Terapia de Alvo Molecular , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacosRESUMO
Previous studies have focused on the association of signal-induced proliferation associated 1 gene (SIPA1) with carcinogenesis of many cancers, including breast cancer. It has been suggested that SIPA1 polymorphisms are associated with susceptibility to breast cancer. In the present study, we performed a meta-analysis to systematically summarize the possible association between SIPA1 and the risk for breast cancer. We conducted a search of case-control studies on the associations of SPIA1 with susceptibility to breast cancer in PubMed, Embase, International Statistical Institute Web of Science, Wanfang Database in China, and Chinese National Knowledge Infrastructure databases. Data from eligible studies were extracted for meta-analysis. Breast cancer risk associated with SIPA1 was estimated by pooled odds ratios and 95% confidence intervals. Four studies on SIPA1 and breast cancer were included in our meta-analysis. Our results showed that rs746429 was associated with the risk of breast cancer. However, rs931127 and rs3741378 were not found to be associated with breast cancer in our analysis. This meta-analysis suggests that rs746429 is associated with the risk of breast cancer. Well-designed studies with larger sample size and more ethnic groups are required to further validate the results.
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Neoplasias da Mama/genética , Proteínas Ativadoras de GTPase/genética , Estudos de Associação Genética , Proteínas Nucleares/genética , Polimorfismo Genético , Alelos , Neoplasias da Mama/etnologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , RiscoRESUMO
BACKGROUND/AIMS: Glutathione S-transferase T1 (GSTT1), a phase-II enzyme, plays an important role in detoxification of carcinogen electrophiles. Many studies have investigated the association between GSTT1 polymorphism and esophageal cancer risk in Asian populations, but its actual impact is not clear owing to apparent inconsistencies among those studies. Thus, a meta-analysis was performed to explore the effect of GSTT1 polymorphism on the risk of developing esophageal cancer. METHODS: A literature search of PubMed, Embase, and Wanfang databases up to August 2012 was conducted and 15 eligible papers were finally selected, involving a total of 1,626 esophageal cancer cases and 2,216 controls. We used the pooled odds ratio (OR) with its corresponding 95% confidence interval (95%CI) to estimate the association of GSTT1 polymorphism with esophageal cancer risk. Subgroup analyses and sensitivity analyses were performed to further identify the association. RESULTS: Meta-analysis of total studies showed the null genotype of GSTT1 was significantly associated with an increased risk of esophageal cancer in Asians (OR=1.26, 95%CI=1.05-1.52, POR=0.015, I2=42.7%). Subgroup analyses by sample size and countries also identified a significant association. Sensitivity analysis further demonstrated a relationship of GSTT1 polymorphism to esophageal cancer risk in Asians. CONCLUSIONS: The present meta-analysis of available data showed a significant association between the null genotype of GSTT1 and an increased risk of esophageal cancer in Asians, particularly in China.
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Povo Asiático/genética , Neoplasias Esofágicas/etiologia , Predisposição Genética para Doença , Glutationa Transferase/genética , Polimorfismo Genético/genética , Ásia/epidemiologia , Estudos de Casos e Controles , Neoplasias Esofágicas/epidemiologia , Humanos , Prognóstico , Fatores de RiscoRESUMO
Although several miRNAs have been identified to be involved in glioblastoma tumorigenesis, little is known about the global expression profiles of miRNAs and their functional targets in astrocytomas at earlier stages of malignancy. In this study the global expression of miRNAs and mRNAs in normal brain tissue samples and grade I-III astrocytomas were analyzed parallelly using microarrays, and the grade-specific expression profiles of them were obtained by unsupervised hierarchical clustering. It was also confirmed that miR-107, miR-124, miR-138, and miR-149 were downregulated significantly in grade I-IV astrocytomas, and overexpression of miR-124 and miR-149 inhibited glioblastoma cell proliferation and migration. Furthermore, grade-specific changes were discovered in the central biological processes, regulatory networks, and signaling pathways associated with dysregulated genes, and a regulatory network of putative functional miRNA-mRNA pairs was defined. In conclusion, our results may contribute to a better understanding of the molecular mechanisms involved in astrocytoma tumorigenesis and malignant progression.
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Astrocitoma/genética , Neoplasias Encefálicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , RNA Mensageiro/metabolismo , Adulto , Astrocitoma/metabolismo , Astrocitoma/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Simulação por Computador , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Redes e Vias Metabólicas/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Modelos Genéticos , Gradação de Tumores , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de Sinais/genéticaRESUMO
BACKGROUND: Serum peptidome profile is a promising tool to identify physiologic or pathologic conditions. Stable serum peptidome profiles with high quality are essential for serum peptidome research. The aim of this study is to examine the impact of experimental and demographic variables in serum peptide profiling. METHODS: Magnetic bead combined with MALDI-TOF mass spectrometry was performed to evaluate the efficacy of various variables including the treatment of blood, the pretreatment of serum (magnetic beads and ultrafiltrate centrifugal filters), the mass spectrometry and the data handling. The influence of age and gender on serum peptidome was also analyzed in 123 healthy volunteers. RESULTS: The results showed that the sampling processing procedures were crucial for the serum peptidome profiles. There were obvious differences on the serum peptidome profiles between the age groups younger and older than 30. There was no difference between gender groups. CONCLUSIONS: A number of optimized and standardized variables should be defined in serum peptidome research based on magnetic beads and MALDI-TOF mass spectrometry. An extremely strict standard procedure and considerate arrangement should be applied.
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Análise Química do Sangue/métodos , Demografia , Magnetismo , Peptídeos/sangue , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Adulto , Fatores Etários , Análise Química do Sangue/normas , Fracionamento Químico , Cristalização , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Peptídeos/isolamento & purificação , Padrões de Referência , Fatores Sexuais , Manejo de Espécimes/normas , Fatores de TempoRESUMO
Transcription factors (TFs) are crucial modulators of gene regulation during the development and progression of tumors. We previously reported the activation of TFs in nasopharyngeal carcinoma (NPC) cell lines. In this study, we explored the activity profiles of TFs in Protein/DNA array data of a 12-tissue independent set and a 13-tissue pooled set of NPC that included different clinical stages. TFs associated with tumor progression were revealed using a generalized linear model-based regression analysis. Immunohistochemical analysis of clinical NPC samples was used to validate the results of array analysis. We identified 26 TFs that showed increased activities. Of these 26 TFs, 16 were correlated with clinical stages. Activity changes of AP2 and ATF/CREB were confirmed by electrophoretic mobility shift assay (EMSA), and increased expression of AP2α, ß, γ, ATF2, and ATF1 in nuclei of tumor cells was associated with clinical stages. In addition, the expressions of AP2α, ATF2, and ATF1 were correlated with those of their target genes (epithelia growth factor receptor (EGFR) and matrix metalloproteinase 2 (MMP-2), respectively). This study provides data and valuable clues that can be used to further investigate the laws of gene transcription regulation in NPC and to identify suitable targets for the development of TF-targeted antitumor agents.
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Neoplasias Nasofaríngeas/metabolismo , Proteínas de Neoplasias/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Transcrição/metabolismo , Sequência de Bases , Western Blotting , Sondas de DNA , Progressão da Doença , Ensaio de Desvio de Mobilidade Eletroforética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
OBJECTIVE: to investigate the effects of clotrimazole on the growth of oral squamous cell carcinoma (OSCC). METHODS: OSCC-25 cells growing in log phase were treated with various doses of clotrimazole. The concentration of IC(50), cell cycle and cell cycle related protein were examined. RESULTS: the concentration of clotrimazole for inhibiting OSCC was IC(50) 8.51 µmol/L. Clotrimazole induced cell cycle arrest in the G(0)-G(1) cell cycle phase, with a concomitant decrease of cells in the G(2)-M and S-phase. Furthermore, clotrimazole significantly decreased the levels of cyclin D, cyclin E and CDK-4. CONCLUSIONS: clotrimazole inhibits the growth of OSCC.
Assuntos
Carcinoma de Células Escamosas/patologia , Clotrimazol/farmacologia , Neoplasias Bucais/patologia , Ciclo Celular , Pontos de Checagem do Ciclo Celular , Divisão Celular , Linhagem Celular Tumoral , Ciclina E , Humanos , Proteínas OncogênicasRESUMO
Hypercholesterolemia contributes to cardiovascular diseases, but its direct effect on lung is little known. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to exert numerous effects that are dependent and independent of their cholesterol-lowering property. The authors hypothesized that atorvastatin would attenuate hypercholesterolemia-induced lesion in lung. Fifteen rabbits were randomly divided into control group, high-cholesterol forage group, and atrovastatin treatment group. Body weight and blood lipid were measured. All lung tissue and pulmonary arteries were collected for histopathology and immunohistochemistry. Alveolar macrophages (AMs) were cultured and activation of nuclear factor (NF)-κB was detected. Concentrations of interleukin (IL)-6 were measured in serum, bronchoalveolar lavage fluid (BALF), and culture supernatants of AMs. Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) of high-cholesterol forage group were higher than control group (P < .05). There were infiltrating of AMs and lymphocytes in lung tissue of high-cholesterol forage group. NF-κB activity in AMs and concentrations of IL-6 in serum, BALF, and culture supernatants of AMs were higher than those of control group (P < .01), and so were all vascular remodeling indexes. TC and LDL-C and other indexes of atrovastatin treatment group were decreased (P < .05). Hypercholesterolemia induced pulmonary inflammatory Infiltration and vascular remodeling. Atorvastatin attenuated inflammatory infiltration and vascular remodeling in lung of hypercholesterolemia rabbits.