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1.
Artigo em Inglês | MEDLINE | ID: mdl-39008330

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the two most common druggable targets in non-small cell lung cancer (NSCLC). To investigate whether the EGFR mutation and ALK rearrangement could be predicted by the combination of FDG avidity, tumor markers and Ki-67 Index. METHODS: A total of 168 newly diagnosed NSCLC patients who had undergone 18F-FDG PET/CT for staging were enrolled. PET/CT parameters of primary tumors including maximum standardized uptake value (pSUVmax), metabolic tumor volume (pMTV) and total lesion glycolysis (pTLG) were measured. Five serous tumor markers for lung cancer were recorded. Ki-67 labeling index was counted by immunohistochemical staining. EGFR mutation and ALK status were detected by ARMS-PCR and RT-PCR, respectively. Univariate and multivariate analyses were applied to identify the predictors of EGFR mutation and ALK positivity. RESULTS: EGFR mutation rate was 38.1% (64/168), which were found more frequently in female, ≤60 years old, non-smokers and adenocarcinoma patients, and were not related to lymph node involvements, distant metastases, stage and serum tumor markers. Low pSUVmax, pMTV, pTLG and Ki-67 were significantly associated with EGFR mutation. Logistic regression demonstrated that pSUVmax <6.75 and gender (female) were the independent factors affecting EGFR mutation, and the combination of them had a certain predictive value with the area under the curve of 0.784. ALK positive rate was 6.0% (10/168), all of them were adenocarcinoma patients, which were more common in non-smokers, low serum cytokeratin-19 fragment antigen (CYFRA21-1) and low Ki-67, and were not related to FDG activity. No independent factor for ALK positivity was found on Logistic regression. CONCLUSIONS: Low pSUVmax, rather than tumor markers or Ki-67, was correlated with EGFR mutation independently, which could be integrated with gender (female) to improve the identification for EGFR mutation in NSCLC patients.

2.
J Asian Nat Prod Res ; 26(7): 812-823, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38477295

RESUMO

Nineteen isosteviol derivatives were designed and synthesized by C-16, C-19 and D-ring modifications of isosteviol. These compounds were screened for their cytotoxic activities against Hela and A549 cells in vitro. Among them, the inhibitory effect of compounds 3b and 16 on Hela cells was comparable to that of the positive control gefitinib, and the compounds 3b (IC50=7.84 ± 0.84 µM) and 7a (IC50=6.89 ± 0.33 µM) exhibited significant cytotoxicity superior to gefitinib (IC50=11.02 ± 3.27 µM) against A549 cells.


Assuntos
Diterpenos do Tipo Caurano , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Diterpenos do Tipo Caurano/farmacologia , Diterpenos do Tipo Caurano/síntese química , Diterpenos do Tipo Caurano/química , Estrutura Molecular , Células HeLa , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Células A549 , Gefitinibe/farmacologia , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Quinazolinas/farmacologia , Quinazolinas/química , Quinazolinas/síntese química
3.
Int J Mol Sci ; 25(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38791591

RESUMO

Multidrug resistance (MDR) is frequently induced after long-term exposure to reduce the therapeutic effect of chemotherapeutic drugs, which is always associated with the overexpression of efflux proteins, such as P-glycoprotein (P-gp). Nano-delivery technology can be used as an efficient strategy to overcome tumor MDR. In this study, mesoporous silica nanoparticles (MSNs) were synthesized and linked with a disulfide bond and then coated with lipid bilayers. The functionalized shell/core delivery systems (HT-LMSNs-SS@DOX) were developed by loading drugs inside the pores of MSNs and conjugating with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and hyaluronic acid (HA) on the outer lipid surface. HT-LMSNs-SS and other carriers were characterized and assessed in terms of various characteristics. HT-LMSNs-SS@DOX exhibited a dual pH/reduction responsive drug release. The results also showed that modified LMSNs had good dispersity, biocompatibility, and drug-loading capacity. In vitro experiment results demonstrated that HT-LMSNs-SS were internalized by cells and mainly by clathrin-mediated endocytosis, with higher uptake efficiency than other carriers. Furthermore, HT-LMSNs-SS@DOX could effectively inhibit the expression of P-gp, increase the apoptosis ratios of MCF-7/ADR cells, and arrest cell cycle at the G0/G1 phase, with enhanced ability to induce excessive reactive oxygen species (ROS) production in cells. In tumor-bearing model mice, HT-LMSNs-SS@DOX similarly exhibited the highest inhibition activity against tumor growth, with good biosafety, among all of the treatment groups. Therefore, the nano-delivery systems developed herein achieve enhanced efficacy towards resistant tumors through targeted delivery and redox-responsive drug release, with broad application prospects.


Assuntos
Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , Bicamadas Lipídicas , Nanopartículas , Oxirredução , Dióxido de Silício , Dióxido de Silício/química , Humanos , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas/química , Camundongos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Bicamadas Lipídicas/química , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Sistemas de Liberação de Medicamentos , Apoptose/efeitos dos fármacos , Porosidade , Feminino , Células MCF-7 , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Ácido Hialurônico/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Camundongos Nus
4.
Microcirculation ; 30(4): e12803, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36916460

RESUMO

BACKGROUND: Impaired microcirculation in acute coronary syndrome (ACS) patients manifests inadequate recovery and adverse clinical outcome. Here, we analyzed correlations between peripheral microcirculation and heart function in ACS patients. METHODS: Opisthenar microvessel area (OMA) were measured with optical coherence tomography angiography (OCTA), cardiac functional indexes (echocardiograph) were assessed 48-72 h after therapeutic interventions. RESULTS: Results showed that OMA normalized with heart rate (OMA-HR) were significantly greater in ACS patients with percutaneous intervention (ACS-PCI, n = 25, stenosis >80%) compared to those with pharmacological intervention (ACS-PI, n = 23, stenosis <50%, p = .02). Ejection fraction (EF) and fractional shortening (FS), which were not different between two groups, showed negative correlations with OMA-HR in ACS-PCI (EF: r = -0.512, p = .009; FS: r = -0.594, p = .002). Cardiac output (CO) inversely correlated with OMA-HR in both groups (r = -0.697, p < .0001; r = -0.527, p = .01). Neutrophil to lymphocyte ratio (NLR) on admission was greater in ACS-PCI group. NLR, which was negatively associated with EF or FS, was positively associated with OMA-HR in all patients. The area under the curve (AUC) for OMA-HR was 0.683 (specificity 0.696 and sensitivity 0.72, p = .02). OMA-HR at >376.5 µm2 predicts reduced FS and CO (p = .002, p = .005, respectively). Summary OMA-HR predicts inadequate recovery of the heart in severe ACS patients post-PCI.


Assuntos
Síndrome Coronariana Aguda , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/etiologia , Microcirculação , Intervenção Coronária Percutânea/efeitos adversos , Constrição Patológica/etiologia , Coração/diagnóstico por imagem
5.
J Transl Med ; 21(1): 586, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658364

RESUMO

BACKGROUND: As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy. METHODS: The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature. RESULTS: The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs' marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer. CONCLUSIONS: The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.


Assuntos
Síndrome de DiGeorge , Neoplasias Ovarianas , Feminino , Animais , Camundongos , Humanos , Receptor beta de Fator de Crescimento Derivado de Plaquetas , Prognóstico , Neoplasias Ovarianas/tratamento farmacológico , Imunossupressores , Imunoterapia , Microambiente Tumoral
6.
Hum Genomics ; 15(1): 30, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034810

RESUMO

UDP-glucuronosyltransferases (UGTs) are the main phase II drug-metabolizing enzymes mediating the most extensive glucuronidation-binding reaction in the human body. The UGT1A family is involved in more than half of glucuronidation reactions. However, significant differences exist in the distribution of UGT1As in vivo and the expression of UGT1As among individuals, and these differences are related to the occurrence of disease and differences in metabolism. In addition to genetic polymorphisms, there is now interest in the contribution of epigenetics and noncoding RNAs (especially miRNAs) to this differential change. Epigenetics regulates UGT1As pretranscriptionally through DNA methylation and histone modification, and miRNAs are considered the key mechanism of posttranscriptional regulation of UGT1As. Both epigenetic inheritance and miRNAs are involved in the differences in sex expression and in vivo distribution of UGT1As. Moreover, epigenetic changes early in life have been shown to affect gene expression throughout life. Here, we review and summarize the current regulatory role of epigenetics in the UGT1A family and discuss the relationship among epigenetics and UGT1A-related diseases and treatment, with references for future research.


Assuntos
Epigênese Genética/genética , Glucuronosiltransferase/genética , Inativação Metabólica/genética , Glucuronosiltransferase/metabolismo , Humanos , MicroRNAs/genética , Família Multigênica/genética
7.
Environ Res ; 215(Pt 3): 114390, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36154857

RESUMO

Take-out food has become increasingly prevalent due to the fast pace of people's life. However, few study has been done on microplastics in take-out food. Contacting with disposable plastic containers, take-out food may be contaminated with microplastics. In the present study, abundance and characteristics of microplastics in total of 146 take-out food samples including solid food samples and beverage samples (bubble tea and coffee) were determined and identified. The mean abundance of microplastics in take-out food was 639 items kg-1, with the highest value in rice and the lowest value in coffee. Fragments shape, transparent color and sizes ≤ 500 µm were the main characteristics of microplastics in those food, and polyethylene was the main polymer type. Our results indicated that microplastics in take-out food was influenced by food categories and cooking methods, as well as food packaging materials. Approximately 170-638 items of microplastics may be consumed by people who order take-out food 1-2 times weekly.


Assuntos
Microplásticos , Poluentes Químicos da Água , Café , Monitoramento Ambiental , Humanos , Plásticos , Polietileno , Polímeros , Chá , Poluentes Químicos da Água/análise
8.
Neoplasma ; 69(1): 80-94, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34818027

RESUMO

Glioblastoma (GBM) is the most universal and devastating primary intracranial neoplasm in the central nervous system. Urolithin A (UA) possesses many pharmacological and biological activities, but its function in GBM is not clear. CCK-8 and colony formation test were used to measure the anti-proliferative potency of UA against GBM cells. Flow cytometry was applied to evaluate cell cycle arrest and apoptosis of U251 and U118 MG cells upon UA incubation. Quantitative real-time PCR and western blotting were conducted to test the regulatory effect of UA on the expression of Sirt1 and FOXO1. Immunodeficient mice were implanted with GBM cells for in vivo validation of the anti-cancer effect of UA. We found UA repressed the proliferation, migration and invasion of glioblastoma cells, while also inhibiting the induction of colony formation ability and epithelial to mesenchymal transition (EMT) in a time- or dose-dependent manner. The does-dependent relationship of UA inducing the cell cycle arrest and apoptosis of glioblastoma cells was identified. Furthermore, UA could enhance the expression levels of Sirt1 and FOXO1 and the knockdown of Sirt1 blocked the inhibitory effects of UA on the proliferation and migration of glioblastoma cells and correspondingly modified the expression level of FOXO1. Overexpression of Sirt1 restored the despaired inhibitory effect of UA induced by Sirt1 knockout on the proliferation and migration of glioblastoma cells. In animal experiments, UA decreased the tumor size and weight of glioblastoma in xenograft nude mice and promoted the expression of Sirt1 and FOXO1 in transplanted tumors. Our findings presented in this study indicate that UA exerts a repressive effect on glioblastoma cells in vivo and in vitro by regulating the Sirt1-FOXO1 axis via the ERK and AKT pathways, indicating that UA is a new novel therapeutic candidate for the treatment of glioblastoma.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Apoptose , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Cumarínicos , Transição Epitelial-Mesenquimal , Proteína Forkhead Box O1/genética , Glioblastoma/tratamento farmacológico , Humanos , Camundongos , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Sirtuína 1/genética
9.
BMC Public Health ; 22(1): 250, 2022 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130854

RESUMO

BACKGROUND: Decreased physical activity had been reported to be a common causal and modifiable risk factor for major vascular events. However, the relationship of physical activity and sedentary leisure time with carotid atherosclerosis in population with high risk for cardiovascular diseases (CVDs) is still inconclusive. We aimed to evaluate the association of physical activity and sedentary leisure time with the risk of carotid atherosclerosis, and investigate any possible effect modifiers in population with high risk for CVDs. METHODS: The study population was drawn from the China Patient-Centered Evaluative Assessment of Cardiac Events (PEACE) Million Persons Project-Jiangsu project, which is a population-based screening project that included permanent residents aged 35-75 years from 6 surveillance cities in Jiangsu Province. Linear regression models were used to evaluate the association of physical activity and sedentary leisure time with carotid intima-media thickness (CIMT). The risks of abnormal carotid artery and carotid plaque (CP) were estimated by odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. RESULTS: Overall, a total of 10,920 participants were enrolled in the final analysis. There was a significant inverse association of physical activity level with CIMT (per SD increase: ß=-0.0103; 95%CI: -0.0154, -0.0053). The risk of abnormal carotid artery and CP decreased significantly with the increase of physical activity level (per SD increase: OR=0.908, 95%CI: 0.869-0.948; OR=0.900, 95%CI: 0.857-0.945, respectively). When physical activity level was categorized as quartiles, a significantly lower risk of abnormal carotid artery and CP was found in quartiles 2-4 with quartile 1 as reference (P<0.05 for all). Furthermore, the inverse association were stronger in participants with age ≥60 years (vs. <60 years, Pinteraction<0.001 for both). However, there were no significant association of sedentary leisure time with CIMT, abnormal carotid artery and CP. CONCLUSIONS: In population with high risk for CVDs, physical activity was inversely associated with CIMT, abnormal carotid artery and CP, particularly among the elders. Sedentary leisure time was not associated with them. These results suggested that physical activity is important for carotid vascular health, and perhaps especially in elder population.


Assuntos
Doenças Cardiovasculares , Doenças das Artérias Carótidas , Placa Aterosclerótica , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças das Artérias Carótidas/epidemiologia , Espessura Intima-Media Carotídea , Estudos Transversais , Exercício Físico , Humanos , Fatores de Risco , Comportamento de Redução do Risco
10.
J Asian Nat Prod Res ; 24(8): 746-753, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35137660

RESUMO

Two new stilbene glucosides, trans-3,5-dihydroxy-4-methoxystilbene 3-O-ß-D-glucopyranoside (1), cis-3,5-dihydroxy-4-methoxystilbene 3-O-ß-D-glucopyranoside (2), one new benzoic acid derivative, cis-4-hydroxy-3-hydroxymethyl-2-butenyl benzoate 4-O-ß-D-glucopyranoside (3), and four known compounds (4 - 7) were isolated from Tournefortia sibirica L. The structures of these compounds were elucidated on the basis of spectral data. Anti-inflammatory effects of compounds (1 - 7) were evaluated in terms of inhibition on production of NO, TNF-α and IL-6 in LPS-induced RAW 264.7 cells. Compounds 1, 2 and 5 - 7 could inhibit the levels of NO, TNF-α and IL-6 in LPS-induced RAW264.7 cells with IC50 values ranging from 40.96 to 88.76 µM.


Assuntos
Boraginaceae , Estilbenos , Ácido Benzoico/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Interleucina-6 , Lipopolissacarídeos/farmacologia , Estrutura Molecular , Estilbenos/química , Estilbenos/farmacologia , Fator de Necrose Tumoral alfa
11.
Curr Ther Res Clin Exp ; 96: 100670, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35515958

RESUMO

Background: The presence of left atrial/left atrial appendage thrombosis is associated with a higher risk of thromboembolic events in patients with atrial fibrillation. The optimal antithrombotic strategy is not established to date. Objective: Our aim was to compare the efficacy and safety profile of novel oral anticoagulants with warfarin in the treatment of left atrial/left atrial appendage thrombosis. Methods: We conducted a systematic search in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and 3 Chinese databases for all randomized controlled trials and cohort studies (PROSPERO, CRD42021238952) from inception to 7 May 2021. Two authors independently performed the articles selection, data extraction, and quality assessment. The efficacy outcome was the resolution of left atrial/left atrial appendage thrombosis, and the safety outcomes were bleeding and stroke/transient ischemic attack. Results: One randomized controlled trial and 5 cohort studies were included, with a total of 353 patients. Compared with warfarin, novel oral anticoagulants were associated with increased probability of left atrial/left atrial appendage thrombosis resolution (OR = 2.20; 95% CI, 1.35-3.60; I 2 = 0%). Compared with warfarin, novel oral anticoagulants had a similar risk of bleeding (OR = 0.91; 95% CI, 0.39-2.13; I 2 = 0%). There was no evidence of increased risk of stroke/transient ischemic attack (OR = 0.42; 95% CI, 0.12-1.45; I 2 = 0%). Conclusions: Novel oral anticoagulants were more effective than warfarin in promoting the resolution of left atrial/left atrial appendage thrombosis, without increased risks of bleeding and stroke/transient ischemic attack. Our study provides valuable insight into clinical practice. Further well-designed randomized controlled trials are needed to fully evaluate the benefits and risks in these patients. PROSPERO Registration No.: CRD42021238952.

12.
Wei Sheng Yan Jiu ; 51(6): 975-980, 2022 Nov.
Artigo em Zh | MEDLINE | ID: mdl-36539877

RESUMO

OBJECTIVE: To explore the effect of intake of milk and milk products on high risk of cardiovascular disease. METHODS: Six districts in Jiangsu Province were selected as project sites by using cluster sampling method. The residents aged 35-75 years old in the districts were screened at early stage for high risk population of cardiovascular diseases from June 2015 to September 2017, and the risk of cardiovascular diseases was assessed, a total of 40 234 subjects were classified as high-risk subjects of cardiovascular disease((57.30±9.44) years old, 24 608 female(61.15%), 20 412 rural residents(50.72%)). Through questionnaire, physical examination, laboratory test, and propensity score matching, 35 104 subjects were finally included in this study. The t test, χ~2 test, multivariate Logistic regression and additive interaction analysis were used to analyze the data with software of SPSS 23.0. RESULTS: There were 67.30%(n=23 607) of subjects with milk and product consumption<1 d/week. With the frequency as a reference, adjusted urban and rural areas, educational level, occupation, annual family income, drinking, BMI, abdominal obesity, and intake of vegetables and fruits, multiple Logistic regression analysis showed that the risk of cardiovascular disease decreased with the increase of intake frequency of milk and milk products(P<0.001), the frequency of 4-6 d/week was the lowest(OR=0.608, 95% CI 0.546-0.677). Additive interaction analysis found that combination with vegetable consumption significantly reduced the high risk of cardiovascular diseases(P<0.05). While the high risk of cardiovascular disease was reduced by increasing fruit intake frequency at the same intake frequency of milk and products. CONCLUSION: More intake milk and product can reduce the high-risk of cardiovascular diseases. Combination with vegetables or fruits could synergistically reduce the high risk, the effect is stronger with vegetables than that with fruits.


Assuntos
Doenças Cardiovasculares , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Verduras , Obesidade/epidemiologia , Frutas , Fatores de Risco , Dieta
13.
Q J Nucl Med Mol Imaging ; 65(2): 172-177, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30916535

RESUMO

BACKGROUND: 18F-FDG PET/CT metabolic characteristics provide the crucial biologic and molecular information for tumors. To explore the relationships between 18F-FDG PET/CT derived parameters such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG) of primary tumor and clinical stage in different histopathologic subtypes of lung cancer. METHODS: A total of 97 newly diagnosed lung cancer patients (69 males, 28 females; average age 65.1 years) with pathologically proven were retrospectively analyzed, who had undergone 18F-FDG PET/CT scan before treatment from September 2016 to November 2017. SUVmax, MTV and TLG of primary tumor were measured. Clinical stage was mainly determined by 18F-FDG PET/CT, in conjunction with conventional imaging and endoscopic biopsy. Mann-Whitney U test, χ2 test, Spearman correlation test and ROC curve analysis were used for statistical analysis. RESULTS: There were 53 adenocarcinomas (AC), 28 squamous carcinomas (SCC), 13 small cell carcinomas (SCLC), one adenosquamous carcinoma, one mucoepidermoid carcinoma, and one sarcomatoid carcinoma in 97 patients. Both AC and SCLC revealed more cases in stage IV than in stage I-III (P<0.01). There was no significant difference in four stages of SCC (P>0.05). Metabolic parameters of SCC were higher than AC including SUVmax, MTV and TLG (P<0.01). SCLC showed a higher value than AC in TLG (P<0.05). No significant differences were found between AC and SCLC in SUVmax and MTV, also between SCC and SCLC in SUVmax, MTV and TLG (P>0.05). MTV and TLG except SUVmax were positively correlated with stage in AC (P≤0.001). Only MTV showed a positive correlation with stage in SCC (P<0.05). Whereas there were no definitive relationships between metabolic parameters and stage in SCLC (P>0.05). AC with a higher MTV (MTV≥5.965 cm3) indicated a significantly higher rate of distant metastasis than those with a lower MTV (77.5% (31/40) vs. 30.8% (4/13), χ2=9.553, P<0.01), as well as AC with a higher TLG (TLG≥46.922) than those with a lower TLG (88.5% (23/26) vs. 44.4% (12/27), χ2=11.422, P<0.01). CONCLUSIONS: Histopathologic subtypes have a significant influence on the relationships between MTV/TLG not SUVmax of primary foci and stage in lung cancer. Primary MTV/TLG is related to clinical stage closely in AC, and a higher MTV/TLG results in a higher risk of distant metastasis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma de Células Escamosas/diagnóstico por imagem , Fluordesoxiglucose F18/química , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glicólise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Carga Tumoral
14.
Public Health Nutr ; 24(15): 4918-4928, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33256868

RESUMO

OBJECTIVE: To determine if specific dietary patterns are associated with breast cancer (BC) risk in Chinese women. DESIGN: Latent class analysis (LCA) was performed to identify generic dietary patterns based on daily food-frequency data. SETTING: The Chinese Wuxi Exposure and Breast Cancer Study (2013-2014). PARTICIPANTS: A population-based case-control study (695 cases, 804 controls). RESULTS: Four dietary patterns were identified, Prudent, Chinese traditional, Western and Picky; the proportion in the controls and cases was 0·30/0·32/0·16/0·23 and 0·29/0·26/0·11/0·33, respectively. Women in Picky class were characterised by higher extreme probabilities of non-consumption of specific foods, the highest probabilities of consumption of pickled foods and the lowest probabilities of consumption of cereals, soya foods and nuts. Compared with Prudent class, Picky class was associated with a higher risk (OR = 1·42, 95 % CI 1·06, 1·90), while the relevant association was only in post- (OR = 1·44, 95 % CI 1·01, 2·05) but not in premenopausal women. The Western class characterised by high-protein, high-fat and high-sugar foods, and the Chinese traditional class characterised by typical consumption of soya foods and white meat over red meat, both of them showed no difference in BC risk compared with Prudent class did. CONCLUSIONS: LCA captures the heterogeneity of individuals embedded in the population and could be a useful approach in the study of dietary pattern and disease. Our results indicated that the Picky class might have a positive association with the risk of BC.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , China/epidemiologia , Dieta , Feminino , Humanos , Análise de Classes Latentes , Fatores de Risco
15.
Am J Physiol Cell Physiol ; 319(6): C1082-C1096, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32938225

RESUMO

Endogenous hydrogen sulfide (H2S) affects cholesterol homeostasis and liver X receptor α (LXRα) expression. However, whether low-density lipoprotein (LDL) receptor (LDLR), a key player in cholesterol homeostasis, is regulated by exogenous H2S through LXRα signaling has not been determined. We investigated the effects of sodium hydrosulfide (NaHS, H2S donor) on LDLR expression in the presence or absence of LXR agonists, T0901317 or GW3965 in HepG2 cells. We found that H2S strongly accumulated LDLR precursor in the presence of T0901317. Hence, LDLR transcription and the genes involved in LDLR precursor maturation and degradation were studied. T0901317 increased the LDLR mRNA level, whereas H2S did not affect LDLR transcription. H2S had no significant effect on the expression of LXRα and inducible degrader of LDLR (IDOL). H2S and T0901317 altered mRNA levels of several enzymes for N- and O-glycosylation and endoplasmic reticulum (ER) chaperones assisting LDLR maturation, but did not affect their protein levels. H2S decreased proprotein convertase subtilisin/kexin type 9 (PCSK9) protein levels and its mRNA level elevated by T0901317. T0901317 with PCSK9 siRNA also accumulated LDLR precursor as did T0901317 with H2S. High glucose increased PCSK9 protein levels and attenuated LDLR precursor accumulation induced by T0901317 with H2S. Taken together, H2S accumulates LDLR precursor by downregulating PCSK9 expression but not through the LXRα-IDOL pathway, LDLR transcriptional activation, or dysfunction of glycosylation enzymes and ER chaperones. These results also indicate that PCSK9 plays an important role in LDLR maturation in addition to its well-known effect on the degradation of LDLR mature form.


Assuntos
Sulfeto de Hidrogênio/metabolismo , Receptores X do Fígado/metabolismo , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/metabolismo , Benzoatos/farmacologia , Benzilaminas/farmacologia , Linhagem Celular Tumoral , Colesterol/metabolismo , Retículo Endoplasmático/fisiologia , Glicosilação/efeitos dos fármacos , Células Hep G2 , Homeostase/fisiologia , Humanos , Hidrocarbonetos Fluorados/farmacologia , Receptores X do Fígado/agonistas , Pró-Proteína Convertase 9/genética , Interferência de RNA , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Sulfetos/farmacologia , Sulfonamidas/farmacologia , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional/genética
16.
Mol Pharm ; 17(6): 1910-1921, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32223247

RESUMO

The surface charge of nanocarriers inevitably affects drug delivery efficiency; however, the cancer cell specificity, anti-inflammatory effects, and charge-reversal points remain to be further addressed in biomedical applications. The aim of this study was to comprehensively assess the cancer cell specificity of DOX-loaded mesoporous silica-chitosan oligosaccharide-carboxymethyl chitosan nanoparticles (DOX@MSNs-COS-CMC) in MCF-7 and HeLa cells, inhibit the production of inflammatory cytokines, and improve the drug accumulation in the tumor site. Intracellular results reveal that the retention time prolonged to 48 h in both HeLa and MCF-7 cells at pH 7.4. However, DOX@MSNs-COS-CMC exhibited a cell type-dependent cytotoxicity and enhanced intracellular uptake in HeLa cells at pH 6.5, due to the clathrin-mediated endocytosis and macropinocytosis in HeLa cells in comparison with the vesicular transport in MCF-7 cells. Moreover, Pearson's correlation coefficient value significantly decreased to 0.25 after 8 h, prompting endosomal escape and drug delivery into the HeLa nucleus. After the treatment of MSNs-COS-CMC at 200 µg/mL, the inflammatory cytokines IL-6 and TNF-α level decreased by 70% and 80%, respectively. Tumor inhibition of DOX@MSNs-COS-CMC was 0.4 times higher than free DOX, alleviating cardiotoxicity and inflammation in the HeLa xenograft tumor model. Charge-reversible DOX@MSNs-COS-CMC could be a possible candidate for clinical therapy of cervical carcinoma.


Assuntos
Anti-Inflamatórios/metabolismo , Quitosana/química , Neoplasias do Colo do Útero/metabolismo , Endocitose/fisiologia , Feminino , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Interleucina-6/metabolismo , Células MCF-7 , Modelos Biológicos , Fator de Necrose Tumoral alfa/metabolismo
17.
Mediators Inflamm ; 2020: 3050487, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32410849

RESUMO

OBJECTIVE: This study aimed at investigating the therapeutic effect and mechanism of pioglitazone metformin complex preparation (PM) in polycystic ovary syndrome (PCOS) comorbid psychological distress. METHODS: Seventy-five patients with PCOS comorbid psychological distress were randomly allocated into the PM, metformin, and placebo groups. The primary efficacy measure was the change from baseline to week 12 on the Symptom Checklist 90-R (SCL-90-R) scores. NLRP3 inflammasome, IL-1ß, IL-6, TNF-α, and biochemical parameters were determined at baseline and at week 12. The participants were required to meet the criteria for PCOS (Rotterdam, NIH) and psychological distress (any factor scores of SCL - 90 - R > 2). RESULTS: The participants had significantly high scores on the SCL-90-R scales of anxiety and depression. PM significantly decreased anxiety and depression symptom severity (from 2.31 ± 0.75 to 1.65 ± 0.38, p < 0.001, and from 2.08 ± 0.74 to 1.61 ± 0.46, p = 0.010, at week 12, respectively). PM significantly decreased the expression of NRPL3 and caspase-1. Patients in the PM group experienced a significant reduction in IL-1ß (from 98.42 ± 14.38 to 71.76 ± 13.66, p = 0.02), IL-6 (from 87.51 ± 8.74 to 71.98 ± 15.87, p = 0.02), and TNF-α (from 395.33 ± 88.55 to 281.98 ± 85.69, p = 0.04). PM was superior to metformin in reducing total testosterone (2.24 ± 0.74 versus 3.06 ± 0.83, p = 0.024, at week 12). CONCLUSIONS: This study is the first to reveal that PM alleviates psychological distress via inhibiting NLRP3 inflammasome and improves several markers, including total testosterone.


Assuntos
Metformina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Pioglitazona/farmacologia , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/psicologia , Angústia Psicológica , Adulto , Ansiedade/complicações , Ansiedade/tratamento farmacológico , Comorbidade , Depressão/complicações , Depressão/tratamento farmacológico , Feminino , Humanos , Inflamassomos , Pacientes Ambulatoriais , Síndrome do Ovário Policístico/complicações , Estudos Prospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
18.
J Clin Lab Anal ; 34(8): e23305, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32207862

RESUMO

BACKGROUND: To detect the mutations of KRAS gene in colorectal cancer patients and other cancer patients, it is of value to develop non-invasive, sensitive, specific, easy, and low-cost assays. METHODS: Templates harboring hotspot mutations of the KRAS gene were constructed, and primers were designed for evaluation of the specificity, and sensitivity of detection system consisted of exonuclease polymerase-mediated on/off switch; then, gel electrophoresis and real-time PCR were performed for verification. The assay was verified by testing the DNA pool of normal controls and circulating DNA (ctDNA) samples from 14 tumor patients, as compared to Sanger sequencing. RESULTS: A specific and sensitive assay consisted of exonuclease polymerase-mediated on/off switch, and multiplex real-time PCR method has been established. This assay could detect <100 copies of KRAS mutation in more than 10 million copies of wild-type KRAS gene fragments. This assay was applied to test KRAS gene mutations in three cases of fourteen ctDNA samples, and the results were consistent with Sanger sequencing. However, this PCR-based assay was more sensitive and easier to be interpreted. CONCLUSION: This assay can detect the presence of KRAS hotspot mutations in clinical circulating tumor DNA samples. The assay has a potential to be used in early diagnosis of colorectal cancer as well as other types of cancer.


Assuntos
DNA Tumoral Circulante/genética , Neoplasias Colorretais/diagnóstico , Mutação Puntual/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , DNA Tumoral Circulante/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Análise Mutacional de DNA , Humanos , Sensibilidade e Especificidade
19.
Breast Cancer Res Treat ; 173(3): 647-655, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30368743

RESUMO

PURPOSE: The accumulating evidence indicates that weight gain in adulthood is more predictive of breast cancer risk than absolute body weight. However, the relative impact of timing of weight gain in adulthood on breast cancer as well as other characteristics of the association between weight and breast cancer has not been well documented. METHODS: This population-based case-control study of breast cancer included 818 patients with newly diagnosed primary breast cancer and 935 residence and age-matched healthy controls. The body weight values at 18 years old, 1 year before diagnosis, and at menopause were obtained during in-person interviews. Unconditional logistic regression was used to estimate the effects of the weight change over adulthood on breast cancer risk. Linear mixed-effects regression was also applied as a secondary analysis. RESULTS: We found that the increased risk of breast cancer was associated with the weight gain in adulthood among postmenopausal women (OR 1.23; 95% CI 1.10-1.37 per 5 kg increase) but not in the premenopausal women. The risk associated with weight gain since menopause (OR 1.65; 95% CI 1.28-2.14 a 5-kg increase) was higher than that from age 18 to menopause (OR 1.14; 95% CI 1.02, 1.28 a 5-kg increase). The association tended to be stronger in those with higher waist circumference and who had never used hormone replacement therapy (HRT). Women who had never used HRT, the increased risk of breast cancer associated with weight gain was more consistent in leaner women at age 18 (BMI < 18.5) or at menopause (BMI < 24). CONCLUSIONS: Our findings indicated that weight gain has significant impact on postmenopausal breast cancer risk. The time periods of weight gain, central body fat, and HRT may affect the observed association, which should be further studied.


Assuntos
Peso Corporal , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Pós-Menopausa , Pré-Menopausa , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Terapia de Reposição Hormonal , Humanos , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Recidiva , Medição de Risco , Fatores de Risco , Resultado do Tratamento
20.
Circ J ; 83(12): 2537-2546, 2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31645525

RESUMO

BACKGROUND: Given that cathepsin S (CatS) gained attention due to its enzymatic and non-enzymatic functions in signaling, the role of CatS in ischemia-induced angiogenesis of aged mice was explored.Methods and Results:To study the role of CatS in the decline in aging-related vascular regeneration capacity, a hindlimb ischemia model was applied to aged wild-type (CatS+/+) and CatS-deficient (CatS-/-) mice. CatS-/-mice exhibited impaired blood flow recovery and capillary formation and increased levels of p-insulin receptor substrate-1, Wnt5a, and SC35 proteins and decreased levels of phospho-endothelial nitric oxide synthase (p-eNOS), p-mTOR, p-Akt, p-ERK1/2, p-glycogen synthase kinase-3α/ß, and galatin-3 proteins, as well as decreased macrophage infiltration and matrix metalloproteinase-2/-9 activities in the ischemic muscles. In vitro, CatS knockdown altered the levels of these targeted essential molecules for angiogenesis. Together, the results suggested that CatS-/-leads to defective endothelial cell functions and that CatS-/-is associated with decreased circulating endothelial progenitor cell (EPC)-like CD31+/c-Kit+cells. This notion was reinforced by the study finding that pharmacological CatS inhibition led to a declined angiogenic capacity accompanied by increased Wnt5a and SC35 levels and decreased eNOS/Akt-ERK1/2 signaling in response to ischemia. CONCLUSIONS: These findings demonstrated that the impairment of ischemia-induced neovascularization in aged CatS-/-mice is due, at least in part, to the attenuation of endothelial cell/EPC functions and/or mobilization associated with Wnt5a/SC35 activation in advanced age.


Assuntos
Catepsinas/metabolismo , Células Progenitoras Endoteliais/enzimologia , Isquemia/enzimologia , Músculo Esquelético/irrigação sanguínea , Fatores de Processamento de Serina-Arginina/metabolismo , Proteína Wnt-5a/metabolismo , Fatores Etários , Animais , Catepsinas/deficiência , Catepsinas/genética , Células Cultivadas , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Membro Posterior , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Isquemia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neovascularização Fisiológica , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
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