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OBJECTIVE: Hyperandrogenism is frequently observed in patients with polycystic ovary (PCO). The purpose of this study was to develop an easy-to-use tool for predicting polycystic ovary syndrome (PCOS) and to evaluate and compare the value of androstenedione (Andro) and other hormone indicators in the diagnosis of patients with hyperandrogenic PCOS. METHODS: This study included 139 women diagnosed with hyperandrogenic PCOS according to the Rotterdam criteria and 74 healthy control women from Shanghai Tenth People's Hospital. The serum hormone levels of the patients and controls were measured using a chemiluminescence immunoassay and incorporated for further analysis. RESULTS: Total testosterone (TT), Andro, dehydroepiandrosterone sulfate (DHEAS), and free androgen index (FAI) were significantly higher in the PCOS group than the control group. Further, Andro, follicle-stimulating hormone (FSH), luteinizing hormone (LH), TT, FAI, and LH/FSH in the hyperandrostenedione group were higher than the normal Andro group. The Youden index was the highest for Andro (0.65), with 81.82% sensitivity and 83.16% specificity. Correlation analysis showed that FSH, LH, TT, FAI, insulin sensitivity index, and LH/FSH were positively correlated with Andro, while fasting blood glucose and 2-hour postprandial blood glucose were negatively correlated with Andro. CONCLUSIONS: The model using Andro, TT, and FAI may help to identifying women with undiagnosed PCOS. Serum Andro is a meaningful biomarker for hyperandrogenism in PCOS patients and may further aid disease diagnosis.
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Hiperandrogenismo , Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/diagnóstico , Testosterona , Androstenodiona , Hiperandrogenismo/diagnóstico , Glucemia , China , Hormona Luteinizante , Hormona Folículo EstimulanteRESUMEN
BACKGROUND: Serum thyrotropin (TSH) has been recommended for the initial assessment of patients with thyroid nodules to exclude functional thyroid nodules (FTN). However, the sensitivity of TSH is very low. The increased level of thyroid peroxidase antibody (TPOAb) is considered to be one of the reasons. OBJECTIVE: To investigate whether normalized TSH (nTSH) can improve diagnostic efficiency by removing TPOAb interference in the first evaluation of thyroid nodules compared with traditional TSH strategy. METHODS: Thyroid nodules were retrospectively analysed in 90 patients with FTN and 1038 patients with non-functioning thyroid nodules (non-FTN). The regression coefficient (ß) of TPOAb affecting the TSH levels was assessed in patients with thyroid nodules, and then, the nTSH level was calculated based on the following formula: nTSH = TSH-ß*TPOAb. We used nTSH levels to initially evaluate the thyroid nodules instead of the traditional TSH values and finally compared the results of the two strategies. RESULTS: The sensitivity, specificity, accuracy, positive prediction rate (PPV) and negative prediction rate (NPV) of nTSH for accessing FTN were 50.00%, 87.70%, 84.67%, 26.01% and 95.29%, respectively, which were better than the values of 48.90%, 78.70%, 76.33%, 16.60% and 94.67% associated with TSH, respectively (p < 0.001). CONCLUSION: Serum TPOAb testing is recommended for the first assessment of thyroid nodules. Normalized TSH levels can improve assessment efficiency compared to traditional TSH assessment, increase the specificity and reduce an unnecessary 99mTc-TS test.
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Nódulo Tiroideo , Humanos , Nódulo Tiroideo/diagnóstico , Estudios Retrospectivos , Tirotropina , Autoanticuerpos , Yoduro PeroxidasaRESUMEN
OBJECTIVE: The lungs are the distant organ most frequently having metastases from differentiated thyroid cancer (DTC). Positive fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan can detect pulmonary metastases (PM) and thus suggest prognosis in DTC patients. The prognostic value of such a positive scan in DTC patients has not been specified. In this paper we studied the prognostic value of 18F-FDG PET/CT scan uptake and also of iodine-131 (131I) in DTC patients with PM. SUBJECTS AND METHODS: Out of 4500 DTC patients we retrospectively studied 83 patients having PM and treated with thyroidectomy and 131I ablation. Clinical data were also studied. Therapeutic response assessment was based on serum thyroglobulin (Tg) levels, Tg antibodies (TgAb) and tumor size on CT before and after 131I treatment. The mean follow-up period after the diagnosis of PM was 111.9±91.6 months (range: from 15 to 159 months). Sixty two (62/83) patients with PM were diagnosed soon after 131I ablation,8 patients at 6 months, 6 at 12 months and 4 at 18 months after 131I ablation. The remaining 3 patients were diagnosed at 30, 36 and 60 months after 131I ablation, respectively. The progression-free survival was estimated by the Kaplan-Meier method. RESULTS: Out of the 83 patients, 25 showed 18F-FDG uptake in PM of DTC with elevated Tg. Weak significant difference in the primary tumor size was found between 18F-FDG- positive and negative PM of DTC (P=0.05). After 131I ablation 57/83 patients had positive to 131I PM and also positive Tg. These patients were not statistically related to patients with positive or negative 18F-FDG PM according to CT and Tg levels (P=0.35, 0.47).The presence of 131I uptake in the lung lesions and the absence of 18F-FDG uptake in these lesions were independently related to a better progression-free survival (P=0.00). CONCLUSION: So, we conclude that 18F-FDG avidity predicates poor therapeutic effect on tumor size, high risk of disease progression and less favorable prognosis. Iodine-131 avidity remains the key factor suggesting a positive therapeutic effect on PM.
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Fluorodesoxiglucosa F18/metabolismo , Radioisótopos de Yodo/metabolismo , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones , Supervivencia sin Progresión , Neoplasias de la Tiroides/patología , Adolescente , Adulto , Anciano , Transporte Biológico , Niño , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tiroglobulina/sangre , Neoplasias de la Tiroides/sangre , Carga Tumoral , Adulto JovenRESUMEN
Octreotide is a somatostatin (SST) analogue currently used in the treatment of neuroendocrine tumors (NETs) with high binding affinity for the somatostatin receptor-2 (SSTR2) that is also overexpressed in non-small cell lung cancer cell (NSCLC). Alpha-particle-emitting astatine-211 (211At) is a promising radionuclide with appropriate physical and chemical properties for use in targeted anticancer therapies. To obtain an additional pharmacological agent for the treatment of NSCLC, we present the first investigation of the possible use of 211At-labeled octreotide as a potential alpha-radionuclide therapeutic agent for NSCLC treatment. 211At-SPC-octreotide exhibited observable higher uptake in lung, spleen, stomach and intestines than in other tissues. Through histological examination, 211At-SPC-octreotide demonstrated much more lethal effect than control groups (PBS, octreotide and free 211At). These promising preclinical results suggested that 211At labeled octreotide deserved to be further developed as a new anticancer agent for NSCLC.
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Antineoplásicos/química , Octreótido/análogos & derivados , Radiofármacos/química , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Astato/química , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Octreótido/farmacocinética , Octreótido/uso terapéutico , Radiofármacos/síntesis química , Radiofármacos/farmacocinética , Distribución Tisular , Trasplante HeterólogoRESUMEN
OBJECTIVE: The use of thyrotropin (TSH) in the initial assessment of thyroid nodules is inefficient and leads to unnecessary assessment costs. We compared the total costs of thyroid nodule assessment with or without the use of TSH in the initial assessment. METHODS: A total of 1808 patients with thyroid nodules received TSH, fine-needle aspiration (FNA) and thyroid scintigraphy (TS) assessment, including 83 autonomously functioning thyroid nodule (AFTN) cases and 1725 non-AFTN cases. The total costs of the TSH strategy and non-TSH strategies were compared. The ratio of single-use costs of FNA to TS (CFNA/TS ) was used as the main outcome measure. RESULTS: Only when 6·03 ≤ CFNA/TS ≤ 27·17, the lowest total costs were associated with using the conventional TSH strategy. When CFNA/TS <6·03 or CFNA/TS >27·17, the lowest costs were found with FNA and TS, respectively. CONCLUSION: From the perspective of cost economics, in iodine-sufficient areas, we recommend that the decision on the use of TSH for the initial assessment of thyroid nodules should be based on the testing costs of FNA and TS in that medical unit.
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Nódulo Tiroideo/diagnóstico , Nódulo Tiroideo/economía , Tirotropina/administración & dosificación , Biopsia con Aguja Fina , Costos y Análisis de Costo , Toma de Decisiones , Femenino , Humanos , Masculino , Curva ROC , Cintigrafía/economía , Sensibilidad y Especificidad , Nódulo Tiroideo/diagnóstico por imagen , Tirotropina/economíaRESUMEN
BACKGROUND: This study aimed to investigate the relationship between miR-506 and proliferation and migration of breast cancer cells. MATERIAL AND METHODS: MiR-506 mimics, inhibitor, and negative control (NC) were transfected into MDA-MB-231 breast cancer cells. Cell proliferation, cell counting, colony formation assay, and Transwell assay were applied to evaluate the proliferation and migration of breast cancer cells. Data are shown as mean ± standard deviation and the experiment was performed 3 times. Statistical analyses were performed with SPSS version 10.0. RESULTS: At 1 day after transfection, cell proliferation detected by CCK-8 assay was significantly promoted in miR-506 inhibitor when compared with the miR-506 mimics group and the NC group (P<0.05). At 3 days or 5 days after transfection, cell proliferation was markedly inhibited in the miR-506 mimics group, and miR-506 inhibitor was still significantly promoted. Cell counting with a hemocytometer showed similar results to cell proliferation. Colony formation assay showed that the number of colonies in the miR-506 mimics group was significantly smaller than that in the miR-506 inhibitor group and NC group. Transwell assay revealed that the number of migrated cells in miR-506 mimics was markedly smaller than that in the miR-506 inhibitor group and NC group. CONCLUSIONS: MiR-506 over-expression significantly inhibits the proliferation, colony formation, and migration of breast cancer cells. miR-506 over-expression may thus be able to improve the malignant phenotype of breast cancer cells.
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Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/fisiopatología , Proliferación Celular/fisiología , Regulación Neoplásica de la Expresión Génica/genética , MicroARNs/metabolismo , Metástasis de la Neoplasia/fisiopatología , Recuento de Células , Línea Celular Tumoral , Movimiento Celular/fisiología , Femenino , Humanos , Técnicas In Vitro , Lípidos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Imitación Molecular/genética , Transfección , Ensayo de Tumor de Célula MadreRESUMEN
BACKGROUND: To investigate the in vitro inhibitory effects of PEI-RGD/125I-(αv)ASODN (PEI, polyethylenimine; RGD, Arg-Gly-Asp; ASODN, antisense oligodeoxynucleotide) on the growth and invasion of HepG2 cells. MATERIAL AND METHODS: ASODN of the integrin αv-subunit was marked with 125I and underwent complexation with PEI-RGD, a PEI derivative. Next, PEI-RGD/125I-(αv) ASODN was introduced into HepG2 cells via receptor-mediated transfection, and its inhibition rate on HepG2 cell growth was tested using the methyl thiazolyl tetrazolium (MTT) method. The effects of PEI-RGD/125I-(αv) ASODN on HepG2 cell invasion ability were evaluated using the Boyden chamber assay. RESULTS: 1) The 125I marking rate of (αv) ASODN was 73.78±4.09%, and the radiochemical purity was 96.68±1.38% (greater than 90% even after a 48-h incubation period at 37°C), indicating high stability. 2) The cytotoxicity assays showed that the cell inhibition rates did not differ significantly between the PEI-RGD/125I-(αv)ASODN group and the PEI-RGD/(αv) ASODN group, but they were both significantly higher than in the other groups and were positively correlated (r=0.879) with the dosage within a certain range. 3) The invasion assays showed that the inhibition rate was significantly greater in the PEI-RGD/125I-(αv) ASODN group compared to the other groups. CONCLUSIONS: PEI-RGD/125I-(αv) ASODN can efficiently inhibit the growth and proliferation of HepG2 cells and can also weaken their invasive ability.
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Integrina alfaV/genética , Radioisótopos de Yodo/administración & dosificación , Oligodesoxirribonucleótidos Antisentido/administración & dosificación , Oligodesoxirribonucleótidos Antisentido/genética , Oligopéptidos/administración & dosificación , Polietileneimina/análogos & derivados , Secuencia de Bases , Proliferación Celular/efectos de los fármacos , Proliferación Celular/genética , Proliferación Celular/efectos de la radiación , Células Hep G2 , Humanos , Invasividad Neoplásica , Polietileneimina/administración & dosificaciónRESUMEN
Hsp90 interacts with proteins that mediate signaling pathways involved in the regulation of essential processes such as proliferation, cell cycle control, angiogenesis and apoptosis. Hsp90 inhibition is therefore an attractive strategy for blocking abnormal pathways that are crucial for cancer cell growth. In the present study, the role of Hsp90 in human breast cancer MCF-7 cells was examined by stably silencing Hsp90 gene expression with an Hsp90-silencing vector (Hsp90-shRNA). RT-PCR and Western blot analyses showed that Hsp90-shRNA specifically and markedly down-regulated Hsp90 mRNA and protein expression. NF-kB and Akt protein levels were down-regulated in Hsp90-shRNA transfected cells, indicating that Hsp90 knockout caused a reduction of survival factors and induced apoptosis. Treatment with Hsp90-shRNA significantly increased apoptotic cell death and caused cell cycle arrest in the G1/S phase in MCF-7 cells, as shown by flow cytometry. Silencing of Hsp90 also reduced cell viability, as determined by MTT assay. In vivo experiments showed that MCF-7 cells stably transfected with Hsp90-shRNA grew slowly in nude mice as compared with control groups. In summary, the Hsp90-shRNA specifically silenced the Hsp90 gene, and inhibited MCF-7 cell growth in vitro and in vivo. Possible molecular mechanisms underlying the effects of Hsp90-shRNA include the degradation of Hsp90 breast cancer-related client proteins, the inhibition of survival signals and the upregulation of apoptotic pathways. shRNA-mediated interference may have potential therapeutic utility in human breast cancer.
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Apoptosis/genética , Neoplasias de la Mama/terapia , Silenciador del Gen , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , ARN Interferente Pequeño/genética , Animales , Línea Celular Tumoral , Proliferación Celular , Femenino , Técnicas de Silenciamiento del Gen , Proteínas HSP90 de Choque Térmico/genética , Humanos , Ratones , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Indoleamine 2,3-dioxygenase (IDO) converts tryptophan to l-kynurenine, and it is noted as a relevant molecule in promoting tolerance and suppressing adaptive immunity. In this study, to investigate the effects of IDO in carbon tetrachloride (CCl(4) )-induced hepatitis model, the levels of IDO enzymic activities in the mock group, the control group and the 1-methyl-D-tryptophan (1-MT)-treated group were confirmed by determination of l-kynurenine concentrations. Serum alanine aminotransferase levels in 1-MT-treated rats after CCl(4) injection significantly increased compared with those in mock and control groups. In CCl(4)-induced hepatitis models, tumour necrosis factor-α (TNF-α) is critical in the development of liver injury. The mRNA expression and secretion levels of TNF-α in the liver from 1-MT-treated rats were more enhanced compared with those in the mock and the control groups. Moreover, the levels of cytokine and chemokine from mock, control group and 1-MT-treated rats after treated with CCl(4) were analyzed by ELISA, and the level of interleukin-6 was found to increase in 1-MT-treated rats. It was concluded that the deficiency of IDO exacerbated liver injury in CCl(4)-induced hepatitis and its effect may be connected with TNF-α and interleukin-6.
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Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Alanina Transaminasa/sangre , Animales , Tetracloruro de Carbono/toxicidad , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/genética , Citocinas/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Quinurenina/sangre , Hígado/efectos de los fármacos , Masculino , Ratas , Triptófano/análogos & derivados , Triptófano/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cageless ball bearings with discrete grooves in the outer raceway enable the dispersion of rolling elements. Once worn, the discrete groove can cause the rolling element to discretely fail. This paper presents the discrete element method to investigate the wear of discrete grooves in cageless bearings from the standpoint of bond fracture. In conjunction with the structural characteristics of bearing races with discrete slots, we propose a hexagonal close-spaced spherical particle arrangement, in which the discrete slots are discretized into particles of the same size that are connected by bonds. The contact model and contact force equation between the rolling elements and the aggregate elements are established, and the external force on the aggregate elements is calculated. Under the influence of an external force and the arrangement of particles in the aggregate element, the internal force transfer equation of different layers and different particles is derived, and the internal force of the particles in the aggregate unit is calculated. In accordance with Hertz-Mindline theory, the bonding model of discrete groove particles is established, the size of the particle shedding cohesive force during bond fracture is determined, and the wear degree of discrete grooves is characterized by comparing the cohesive force and internal force. Numerical solutions and wear tests are combined. Bond fracture can accurately characterize the wear of discrete grooves. This approach offers theoretical guidance for cageless bearing design.
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Objective: To investigate the effects of 99Tc-methylene diphosphonate (99Tc-MDP) on osteoporosis (OS) in postmenopausal patients with differentiated thyroid cancer (DTC) under thyroid stimulating hormone (TSH) suppression. Patients and Methods: Patients (n = 142) were divided into two groups: (1) 99Tc-MDP (n = 70) and (2) alendronate (n = 72) treatments (NCT02304757). Bone mineral density (BMD) in the lumbar spine and hip was evaluated by DXA, along with bone turnover markers, safety, and quality of life (QOL) using SF-36 at three time points: before treatment and at 6 and/or 12 months after treatment. Results: The percentage change of BMD in total lumbar spine or hip showed no significant difference throughout the study (P > 0.025). 99Tc-MDP and alendronate treatment alone significantly increased BMD in the lumbar spine, but alendronate treatment also significantly increased BMD in total hip at 6 and 12 months, as compared with the baseline. There were no significant differences in the results of the SF-36 scores between the two treatment groups at any time during the whole study period. 99Tc-MDP significantly increased bone formation markers of osteocalcin at 6 and 12 months (P all < 0.05), PINP at 12 months (P = 0.001), and bone resorption markers of ß-CTX at 6 and 12 months (p < 0.05) as compared with the alendronate treated group. No adverse event was observed in the 99Tc-MDP treatment group compared with alendronate (P = 0.014). Conclusion: 99Tc-MDP was as efficacious as alendronate in the improvement of lumbar BMD for DTC patients with OS under TSH stimulation. 99Tc-MDP was shown to be safe and improved patients' QOL.
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Objective: Patients receiving radionuclide 131I treatment expose radiation to others, and there was no clinical trial to verify the effectiveness and safety of mobile robots in radionuclide 131I isolation wards. The objective of this randomized clinical trial was to evaluate the effectiveness and safety of mobile robots in providing vital signs (body temperature and blood pressure) and radiation dose rate monitoring for patients receiving radionuclide therapy. Methods: An open-label, multicenter, paired, randomized clinical trial was performed at three medical centers in Shanghai and Wuhan, China, from 1 April 2018 to 1 September 2018. A total of 72 participants were assigned to the group in which vital signs and radiation doses were both measured by mobile robots and conventional instruments. Intergroup consistency, completion rate, and first success rate were the primary effectiveness measures, and vital sign measurement results, the error rate of use, and subjective satisfaction were secondary indicators. Adverse events related to the robot were used to assess safety. Results: Of the 72 randomized participants (median age, 39.5; 27 [37.5%] male participants), 72 (100.0%) completed the trial. The analysis sets of full analysis set, per-protocol set, and safety analysis set included 72 cases (32 cases in Center A, 16 cases in Center B, and 24 cases in Center C). The consistency, completion rate, and first success rate were 100% (P = 1.00), and the first success rates of vital signs and radiation dose rate were 91.7% (P = 1.000), 100.0% (P = 0.120), and 100.0% (P = 1.000). There was no significant difference in vital signs and radiation dose rate measurement results between the robot measurement group and the control group (P = 0.000, 0.044, and 0.023), and subjective satisfaction in the robot measurement group was 71/72 (98.6%), compared to 67/72 (93.1%) in the control group. For safety evaluation, there was no adverse event related to the mobile robot. Conclusion: The mobile robots have good effectiveness and safety in providing vital signs and radiation dose rate measurement services for patients treated with radionuclides.
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Radioisótopos de Yodo , Robótica , Humanos , Masculino , Adulto , Femenino , Radioisótopos de Yodo/uso terapéutico , China , Signos Vitales , Dosis de RadiaciónRESUMEN
OBJECTIVE: In the initial assessment of thyroid nodules, thyrotropin (TSH) has very low sensitivity for assessing functional thyroid nodules (FTNs). The false negativity in FTNs and the false positivity in non-FTNs misinterpreted by TSH will raise unnecessary assessment costs. Therefore, the aim of this study is to explore the values of the TSH and color flow Doppler sonography (CFDS) combined strategies in reducing the unnecessary assessment costs. METHODS: 2383 patients with thyroid nodules were retrospectively analyzed, including 107 FTNs and 2276 non-FTNs. Four strategies including TSH, CFDS, Combination 1 (TSH+/CFDS+, TSH+/CFDS-, and TSH-/CFDS+ defined as positive; TSH-/CFDS- defined as negative) and Combination 2 (TSH+/CFDS+ defined as positive; TSH+/CFDS-, TSH-/CFDS+, and TSH-/CFDS- defined as negative) were separately used for initial assessment. The four strategies were compared using the testing cost ratio of fine-needle aspiration (FNA) to thyroid scintigraphy (TS) (marked as CFNA/TS) as main outcome measure. RESULTS: Compared with TSH, Combination 1 prevented 15.89 % of FTNs from unnecessary FNA, but increased the number of non-FTNs subjected to unnecessary 99mTc-TS by 9.31 %. Combination 2 prevented 5.32 % of non-FTNs from unnecessary TS, but increased the number of FTNs subjected to unnecessary FNA by 18.69 %. When CFNA/TS was <6.05, the lowest total cost was found in Combination 2. The TSH and Combination 1 were optimal at 6.05 ≤ CFNA/TS ≤ 12.47 and CFNA/TS > 12.47, respectively. CONCLUSIONS: The combined strategies can be used to supplement TSH in the initial assessment of thyroid nodules in iodine-adequate areas, depending on the testing costs of FNA and TS.
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Análisis Costo-Beneficio , Yodo/metabolismo , Nódulo Tiroideo/sangre , Nódulo Tiroideo/diagnóstico , Tirotropina/sangre , Ultrasonografía Doppler en Color/economía , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Nódulo Tiroideo/metabolismo , Adulto JovenRESUMEN
Epidemiological data has demonstrated that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 µm (PM2.5) is associated with cancer incidence. However, the precise mechanisms underlying PM2.5-mediated hepatocellular carcinoma cancer (HCC) migration and invasion remain unclear. The aim of the present study was to explore the response of the HCC cell lines HepG2 and HuH-7 to PM2.5 exposure. The results revealed that PM2.5 treatment promoted the migration and invasion of HCC cells, in addition to increasing protein levels of matrix metalloproteinase (MMP)-13. Additionally, PM2.5 induced intracellular reactive oxygen species formation in HCC cells. Further investigation revealed that phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) increased in response to PM2.5 exposure in HCC cells, and the AKT antagonist LY294002 reduced PM2.5-induced migration, invasion and MMP-13 expression. In addition, the data from the present study demonstrated that high concentrations of PM2.5 decreased the proliferation of normal HL7702 hepatocyte cells and promoted apoptosis. These results indicate that the activation of AKT by PM2.5 results in MMP-13 overexpression, and stimulates HCC cell migration and invasion. In conclusion, the results from the present study demonstrate that PM2.5 promotes HCC development and elucidate a potential underlying molecular mechanism for this effect.
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To investigate the prognostic significance of TGFßR2 expression and chemotherapy in Chinese non-small cell lung cancer (NSCLC) patients, TGFßR2 expression NSCLC was analyzed in silico using the Oncomine database, and subsequently analyzed with quantitative RT-PCR in 308 NSCLC biopsies, 42 of which were paired with adjacent non-neoplastic tissues. Our results show that TGFßR2 expression was also increased in NSCLC biopsies relative to normal tissue samples and correlated with poor prognosis. TGFßR2 expression was also significantly correlated with other clinical parameters such as tumor differentiation, invasion of lung membrane, and chemotherapy. Moreover, overall survival (OS) and disease free survival (DFS) was increased in patients with low TGFßR2 expressing NSCLC and who had undergone chemotherapy. Thus, high expression of TGFßR2 is a significant risk factor for decreased OS and DFS in NSCLC patients. Thus, TGFßR2 is a potential prognostic tumor biomarker for chemotherapy.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Proteínas Serina-Treonina Quinasas/genética , Receptores de Factores de Crecimiento Transformadores beta/genética , Biomarcadores de Tumor/metabolismo , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Theranostic nanoparticles based on superparamagnetic iron oxide (SPIO) have a great promise for tumor diagnosis and gene therapy. However, the availability of theranostic nanoparticles with efficient gene transfection and minimal toxicity remains a big challenge. In this study, we construct an intelligent SPIO-based nanoparticle comprising a SPIO inner core and a disulfide-containing polyethylenimine (SSPEI) outer layer, which is referred to as a SSPEI-SPIO nanoparticle, for redox-triggered gene release in response to an intracellular reducing environment. We reveal that SSPEI-SPIO nanoparticles are capable of binding genes to form nano-complexes and mediating a facilitated gene release in the presence of dithiothreitol (5-20 mM), thereby leading to high transfection efficiency against different cancer cells. The SSPEI-SPIO nanoparticles are also able to deliver small interfering RNA (siRNA) for the silencing of human telomerase reverse transcriptase genes in HepG2 cells, causing their apoptosis and growth inhibition. Further, the nanoparticles are applicable as T2-negative contrast agents for magnetic resonance (MR) imaging of a tumor xenografted in a nude mouse. Importantly, SSPEI-SPIO nanoparticles have relatively low cytotoxicity in vitro at a high concentration of 100 µg/mL. The results of this study demonstrate the utility of a disulfide-containing cationic polymer-decorated SPIO nanoparticle as highly potent and low-toxic theranostic nano-system for specific nucleic acid delivery inside cancer cells.
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Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Polietileneimina/química , ARN Interferente Pequeño/genética , Transfección/métodos , Animales , Supervivencia Celular/efectos de los fármacos , Disulfuros , Células Hep G2 , Humanos , Ratones , Ratones Desnudos , ARN Interferente Pequeño/farmacología , Telomerasa/análisis , Telomerasa/genética , Telomerasa/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To investigate the in vivo and in vitro therapeutic effect of 188Re-MAG3-depreotide on non-small cell lung cancer (NSCLC). METHODS: MTT was done to measure the cell proliferation; flow cytometry to detect cell apoptosis; Transwell invasion assay to determine the invasiveness of NSCLC. In addition, HE staining, TUNEL staining and immunohistochemistry for CD34 were employed to investigate the influence of 188Re-MAG3-depreotide on the growth of NSCLC. RESULTS: 1) Within 2-6 days, the inhibitory effect of 188Re-MAG3-depreotide on the proliferation of A549 cells and SPC-A1 cells increased over time. 2) At 48 h after treatment with 188Re-MAG3-depreotide, the apoptosis rate of A549 cells and SPC-A1 cells was 23.1% and 22.6%, respectively. 3) After 188Re-MAG3-depreotide treatment, the number of invasive A549 cells and SPC-A1 cells was reduced by about 3 times when compared with control group. 4) The cancer in the control group presented with unlimited growth. The cancer growth continued after treatment with 188Re or MAG3-depreotide alone, while the cancer growth was markedly inhibited after 188Re-MAG3-depreotide treatment when compared with control group. CONCLUSION: 188Re-MAG3-depreotide can inhibit the proliferation and invasion of A549 cells and SPC-A1 cells. Treatment with 7.4MBq 188Re-MAG3-depreotide via tail vein can significantly suppress the in vivo cancer growth and induce the apoptosis of cancer cells. These findings demonstrate that 188Re-MAG3-depreotide can induce the apoptosis of NSCLC cells and directly kill the NSCLC cells, which provide evidence for the radiotherapy of NSCLC.
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Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Compuestos Organometálicos/farmacología , Somatostatina/análogos & derivados , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Terapia Molecular Dirigida , Invasividad Neoplásica , Somatostatina/farmacología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Glucokinase (GCK) is the key glucose phosphorylation enzyme which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) based on its enzyme function as the first rate-limiting step in the glycolysis pathway and regulates glucose-stimulated insulin secretion. In the past decade, the relationship between GCK and T2D has been reported in various ethnic groups. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis. METHODS: Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. RESULTS: A total of 24 articles involving 88,229 cases and 210,239 controls were included. An overall random-effects per-allele OR of 1.06 (95% CI: 1.03-1.09; P<10(-4)) was found for the GCK -30G>A polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians; whereas no significant associations were found among Asians. In addition, we found that the -30G>A polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. Besides, -30G>A homozygous was found to be significantly associated with increased fasting plasma glucose level with weighted mean difference (WMD) of 0.15 (95%: 0.05-0.24, Pâ=â0.001) compared with G/G genotype. CONCLUSIONS: This meta-analysis demonstrated that the -30G>A polymorphism of GCK is a risk factor associated with increased T2D susceptibility, but these associations vary in different ethnic populations.
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Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Glucoquinasa/genética , Glucosa/metabolismo , Polimorfismo Genético , Pueblo Asiatico/genética , Glucemia , Ayuno , Predisposición Genética a la Enfermedad , Glucoquinasa/metabolismo , Humanos , Sesgo de Publicación , Riesgo , Población Blanca/genéticaRESUMEN
BACKGROUND: Technetium-99m or (99m)Tc is widely used for labeling peptide in nuclear medicine. Somatostatin and its analog can inhibit tumor cell growth after binding with its receptor. This research was to study the preclinical effect of a new (99m)Tc-6-hydrazinopyridine-3-carboxylic acid (HYNIC)-depreotide, indirect (99m)Tc labeling of depreotide using HYNIC as a bifunctional chelator. METHODS: The cyclopeptide, cyclo-[(N-Me) Phe-Tyr-D-Trp-Lys-Val-Hcy], the linear peptide, and [ClCH(2)-CO×b-Dap-Lys- Cys-Lys×amide] were synthesized by Fmoc solid-phase synthesis. The cyclopeptide and the linear peptide were linked by liquid-phase synthesis. The product depreotide was isolated and purified by high performance liquid chromatography and was confirmed by mass spectrography. Depreotide was labeled with (99m)Tc through a direct labeling method, using HYNIC as a bifunctional chelator. Paper chromatography method was used to calculate the labeling rate, and through the comparative analysis selected the best mark conditions. The new (99m)Tc-HYNIC-depreotide was tested by high-performance liquid chromatography (HPLC). The internalization and externalization rates of the new (99m)Tc-HYNIC-depreotide were studied in A549 cells. Furthermore, biodistribution of the radiopeptide was studied in nude mice, bearing tumors from human lung carcinoma cells SPC-A1. RESULTS: The molecular of synthesize depreotide was 1358, and the purity of it was 95.29%. The labeling efficiency of (99m)Tc-HYNIC-depreotide was highest at pH 6.0 and 15°C, about (70.95 ± 0.84)%. The labeling rate of the new (99m)Tc-HYNIC-depreotide rose to a peak of (20.75 ± 0.48)% at 60 minutes in A549 cells at 37°C and decreased slightly later, while it elevated gradually during the time course at 4°C and 25°C. The internalization rate of the new (99m)Tc-HYNIC-depreotide at 37°C increased gradually and reached the peak of 84.4% in 120 minutes, while the externalization rate of the new (99m)Tc-HYNIC-depreotide was always less than 20%. In mice bearing the experimental SPC-A1 tumor, the new (99m)Tc-HYNIC-depreotide demonstrated a high tumor uptake of (4.05 ± 0.04)% ID/g at 1.5 hpi and remained high ((2.51 ± 0.06)% ID/g) at 4 hpi. The tumor-to-lung activity concentration ratio (T/Lu) was very high for the new (99m)Tc-HYNIC-depreotide at all time points. So did the tumor-to-muscle activity (T/Mu) and tumor-to-blood activity concentration ratios (T/Bl). CONCLUSION: The findings suggested that the new (99m)Tc-HYNIC-depreotide might be a promising candidate radiopharmaceutical for imaging somatostatin receptor positive lung cancer.
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Hidrazinas/química , Neoplasias Pulmonares/patología , Ácidos Nicotínicos/química , Tecnecio/química , Animales , Línea Celular Tumoral , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Desnudos , Receptores de Somatostatina/metabolismoRESUMEN
The (99m)Tc-labeled agent, ((99m)TcO)depreotide, has received regulatory approval in the United States and Europe for use in the detection of cancer. It is essential to establish a simple and reliable method of direct radiolabeling of (99m)Tc-depreotide and to investigate its specific receptor binding properties with human non small cell lung cancer (NSCLC) A549 cell in vitro. So we made some researches as follow: Depreotide was labeled with (99m)Tc using SnCl2 as a reductant. Labeling efficiencies at different pH values and temperatures were compared. Radioreceptor assay was used to observe the uptake kinetics, stagnation and retention half time of (99m)Tc-depreotide in A549 cells. As the results of the investigation ,many facts is shown below: The labeling rate of pH 6.0 group was higher than that of pH 5.0 and pH7.0 groups. The labeling rate decreased when temperature increased from 15 °C to 50 °C. The uptake rate increased with rising temperature, and the maximum uptake was observed at 60 min at 37 °C. The cleaning curves were similar at different temperatures, and the half cleaning time at 37 °C was 48 min. The results showed that the optimal conditions for labeling depreotide with (99m)Tc was found to be below 15 °C at a pH lower than 6.0. Furthermore, at 37 °C, (99m)Tc-depreotid may have the potential as an ideal imaging agent for somatostatin receptors.