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Past reports have shown that the sensitivity of cancer cells to TRAIL-induced apoptosis is related to their expression of TRAIL-death receptors on the cell surface. However, the level of TRAIL-death receptors expression on cancer cells is always low. Our previous research showed that nasopharyngeal carcinoma (NPC) cells have a poor sensitivity to low doses of TRAIL. Here, we evaluated combined treatment with the energy inhibitor 3-bromopyruvate (3BP) and TRAIL as a method to produce an increased apoptotic response in NPC cells. The results showed that 3BP and TRAIL together produced higher cytotoxicity and increased TRAIL-R2 expression in NPC cells compared with the effects of either 3BP or TRAIL alone. These findings led us to hypothesize that 3BP may sensitize NPC cells to TRAIL. 3BP is a metabolic blocker that inhibits hexokinase II activity, suppresses ATP production, and induces endoplasmic reticulum (ER) stress. Our results showed that 3BP also activated AMP-activated protein kinase, which we found to play an important role in the induction of ER stress by 3BP. Furthermore, the induction of TRAIL-R2 expression and the sensitization of the NPC cells to TRAIL by 3BP were reduced when we inhibited the expression of CHOP. Taken together, our results showed that a low dose of 3BP sensitized NPC cells to TRAIL-induced apoptosis by the upregulation of CHOP, which was mediated by the activation of AMP-activated protein kinase and ER stress. The results showed that 3BP is a promising candidate agent for enhancing the therapeutic response to TRAIL in NPC.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Piruvatos/farmacologia , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Fator de Transcrição CHOP/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Sinergismo Farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Piruvatos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/biossíntese , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Fator de Transcrição CHOP/biossíntese , Fator de Transcrição CHOP/genética , Transfecção , Regulação para Cima/efeitos dos fármacosRESUMO
pancreatic cancer is a common malignant tumor of digestive system, with poor prognosis. About 80% of patients have lost the opportunity of surgical resection when diagnosed. In different treatment schemes, radioactive seed 125I implantation can improve the quality of life of patients with unresectable pancreatic cancer and is expected to improve their survival rate. This article reviews the clinical applications of 125I particle implantation therapy combined with chemotherapy, cryotherapy, intracavitary irradiation, stent placement, radiofrequency ablation, nanoknife, and bypass surgery, in order to better promote its clinical application. However, it is necessary to establish unified dosage standards and regulatory guidelines to make them safer and more widely serve clinical practice.
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Ectopic thyroid (ETG) is a thyroid tissue located outside the normal anatomical position, often occurring in the chest. Clinical symptoms are related to its location and its impact on adjacent structures. In ETG imaging examination, single photon emission computed tomography (SPECT) nuclide imaging of thyroid perchlorate ( 99Tc mO 4-) is the most commonly used method for localization and characterization. ETG with normal function shows high radiation uptake in the corresponding area. For difficult to distinguish tumors in the base of the tongue and the thyrohyoid region, 131I or 123I imaging with more specificity for thyroid tissue uptake is needed. ETG exhibits a variety of manifestations in computed tomography (CT) and magnetic resonance imaging (MRI), mostly irregular soft tissue density masses with clear boundaries and uneven density. There are low-density cystic changes or high-density calcifications within the masses, with uneven or uniform enhancement. In ultrasound, ETG is mainly hypoechoic, with some showing cystic solid echoes and abundant blood flow signals within the gland. Asymptomatic ETG patients usually do not require treatment, while symptomatic patients often require surgical resection and have a good prognosis. Before surgery, relevant examinations should be combined to clarify the nature of the tumor as much as possible, to avoid permanent hypothyroidism caused by misdiagnosis and misresection.
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Objective:To investigate the high resolution computed tomography (HRCT) findings, laboratory test results and clinical manifestations of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis complicated with lung interstitial lesions, and to analyze the correlation between the HRCT findings and clinical course of disease.Methods:Twenty-seven patients with anti-MDA5 antibody positive associated dermatomyositis (DM) were included and divided into two groups: acute/subacute group ( n=15) and chronic group ( n=12). HRCT images of lung were analyzed. Clinical data including gender, age, clinical manifestations and course of disease, anti-Ro52 antibody, creatine kinase (CK), antinuclear antibody (ANA), anti-Jo-1 antibody and erythrocyte sedimentation rate (ESR) were also collected. χ2 test was adopted for statistical analysis. Results:① Interstitial changes were 100%(27/27). The proportion of unilateral localized distribution was the most [48%(13/27)], followed by bilateral localized distribution [30%(8/27)], and bilateral diffuse distribution [22%(6/27)). ② Among the HRCT findings of lung interstitial changes, ground glass shadow was the most common presentations [59%(16/27)], followed by subpleural curve sign [63%(17/27)] and interlobular septal thickening [56%(15/27)], while honeycomb sign [0(0/27)] had the lowest rate of presentation. ③ Compared with the chronic progressive group, the acute/subacute progressive group presented as chest tightness (80% vs 8%, χ2=13.715, P<0.05) and dyspnea (47% vs 0, χ2=7.560, P<0.05). Acute/subacute HRCT showed ground glass opacity (87% vs 25%, χ2=10.501, P<0.05). The prominent HRCT showed interlobular septal thickening in the chronic course group (83% vs 33%, χ2=6.750, P<0.05). ④ The anti-MDA5 antibody (+++) index was significantly different (88% vs 25%, χ2=8.168, P<0.05). There was no significant difference in anti-Ro52 antibody (+), ANA(+), anti-Jo-1 antibody(+), CK elevation and ESR elevation between the two groups ( P>0.05). Conclusion:Most dermatomyositis patients with positive anti-MDA5 antibody are complicated with interstitial lung lesions, the HRCT manifestations of lung are diverse. In order to confirm the diagnosis of this disease, clinical manifestations, laboratory and pathological examinations are required.
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Objective To investigate the influence of menstrucal cycle and anatomic site on the fractional anisotropy (FA) values of diffusion tensor imaging (DTI) in normal breast. Methods Prospectively enrolled 96 volunteers, who have identified with normal menstrucal phase and without breast diseases were found via the breast examination, ultrasound and MRI scan. The cases were divided into three groups according to menstrucal phase: menstrual period group(menstrual cramps 1 to 6 d), proliferative phase group(menstrual cramps 7 to 14 d) and secretory phase group(menstrual cramps 15 d to the next), and each group consisted of 32 subjects. All subjects were performed bilateral breast cross-sectional T1WI, T2WI, DWI and DTI scaning. On the nipple level figture, the mammary gland was divided into three regions including the anterior, central and posterior parts, and the FA values of the different phases and regions were measured. The Kruskal-Wallis H test was applied to analyse the difference of FA values in different menstrual phase and anatomic site. Results The FA values of the anterior region in menstrual phase, proliferative phase and secretary phase were 0.21 ± 0.07, 0.24 ± 0.09 and 0.17 ± 0.07, and the difference had significant difference(P=0.014).The FA values of the central region were respectively 0.15±0.08, 0.18±0.09 and 0.15±0.07, and without the statistically significant difference(P=0.090). The FA values of the posterior region were 0.21 ± 0.11, 0.24 ± 0.13 and 0.16 ± 0.11, and also showed significant difference(P=0.002). In different regions, the difference of FA values between menstrual phases and proliferative phases were also had statistically significant(P=0.018, 0.045, respectively). In the same region, the FA value was lowest in the secretary phase, and the proliferative phase was slightly higher than menstrual phase. Conclusion The FA values are affected by menstrual cycle and anatomic site.
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Objective To investigate the clinicopathological features and prognosis in patients with thymoma and patients with thymoma and myasthenia gravis ( MG) . Methods A retrospective analysis was performed on the clinicopathological data of 161 patients pathologically diagnosed with thymoma alone or thymoma and MG from 2008 to 2014. In those patients, 128 had thymoma with MG and 33 had thymoma alone. The survival rates were calculated using the Kaplan?Meier method and analyzed using χ2 test or Fisher′s exact probability test. Results The mean age of onset was 45. 2 years for patients with thymoma and MG and 48. 5 years for patients with thymoma alone. In patients with thymoma and MG, 74. 2% had a tumor diameter of ≤5 cm, while 75. 8% of patients with thymoma alone had a tumor diameter of ≥5 cm. According to the Masaoka staging system, 78. 1% of patients with thymoma and MG had stage Ⅰ+Ⅱdisease, while 51. 1% of patients with thymoma alone had stage Ⅲ+Ⅳ disease. There was no significant difference in the 3?year overall survival ( OS) rate between the two groups ( 98. 1% vs. 81. 8%, P=1. 000) . The 5?year OS rate was significantly higher in patients with thymoma and MG than in patients with thymoma alone ( 91. 1% vs. 42. 9%, P= 0. 000 ) . In all patients, 140 patients with complete resection had significantly higher 3?and 5?year OS rates than 21 patients with incomplete resection ( 97. 2% vs. 58. 8%, P=0. 000;92. 7% vs. 25. 0%, P=0. 000). In patients with stage Ⅱ disease, there were no significant differences in the 3?or 5?year OS rates between patients with complete resection alone ( n=25) and patients with complete resection and postoperative radiotherapy ( n=25) ( 95% vs. 100%, P=1. 000;86% vs. 100%, P=0. 467). Conclusions Compared with patients with thymoma alone, patients with thymoma and MG have an earlier age of onset, substantially smaller tumor diameters, and earlier Masaoka stages. MG and complete resection are positive prognostic factors for patients with thymoma. Radiotherapy after complete resection can reduce the recurrence rate in patients with stage Ⅱ disease.
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OBJECTIVE@#To explore the effects of 3-methyladenine (3-MA, an autophagy inhibitor) on sensitivities of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy and the underlying mechanisms. @*METHODS@#Cell proliferation was examined by MTT and colony formation assay, while cell apoptosis was evaluated by annexin V/PI double staining and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining. Mitochondrial membrane potential was measured by commercial kit (JC-1). The expression of endoplasmic reticulum stress (ERS)-related protein, glucose-regulated protein 78 (GRP78) and autophagy-related protein beclin1, microtubule-associated protein 1 light chain 3 (LC3) were examined by Western blot. @*RESULTS@#Cisplatin (DDP), ionizing radiation (IR) or tunicamycin (TM) treatment obviously inhibited the proliferation of HONE-1 cells in a concentration-dependent and time-dependent manner. Compared with control group, pretreatment with 1 mmol/L of 3-MA significantly reduced cell viability and enhanced the apoptosis in the DDP (6.00 μmol/L), 4.00 Gy IR or TM (1.00 μmol/L) groups. There was no significant difference in the apoptosis between the DDP (5.8%) and 4Gy IR (6.7%) groups. Compared with the control group, protein levels of GRP78, beclin1 and lipid-conjugated membrane-bound form (LC3-II) were significantly increased after the treatment of DDP, 4.00 Gy IR or TM, which were inhibited by pretreatment of 3-MA. @*CONCLUSION@#3-MA can sensitize HONE-1 cells to chemotherapy and radiotherapy, which is related to prevention of endoplasmic reticulum stress-induced autophagy in nasopharyngeal carcinoma cells.
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Humanos , Adenina , Farmacologia , Apoptose , Proteínas Reguladoras de Apoptose , Metabolismo , Autofagia , Proteína Beclina-1 , Carcinoma , Linhagem Celular Tumoral , Efeitos da Radiação , Proliferação de Células , Sobrevivência Celular , Cisplatino , Farmacologia , Estresse do Retículo Endoplasmático , Proteínas de Choque Térmico , Metabolismo , Potencial da Membrana Mitocondrial , Proteínas de Membrana , Metabolismo , Proteínas Associadas aos Microtúbulos , Metabolismo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Patologia , Radiação Ionizante , Radiossensibilizantes , Farmacologia , Tunicamicina , FarmacologiaRESUMO
<p><b>OBJECTIVE</b>To investigate the effect of low-molecular-weight heparin (LMWH) combined with paclitaxel (PTX) on the invasiveness and migration of nasopharyngeal carcinoma cells and explore the molecular mechanisms.</p><p><b>METHODS</b>MTT assay was used to detect the growth inhibition induced by LMWH and PTX in CNE1 and CNE2 cells. Wound healing assay and Transwell migration assay were employed to assess the effects of the drugs on the cell migration, and Transwell invasion assay was used to evaluate the cell invasiveness. The cellular expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were analyzed by Western blotting. ELISA was used to determine the expression of heparanase (HPA) in the culture medium of the cells.</p><p><b>RESULTS</b>MTT assay showed an obvious suppression of CNE1 and CNE2 cell proliferation in response to LMWH and PTX treatments. Treatment with 200 U·ml LMWH combined with 0.1 µmol·L PTX for 24 h resulted in the inhibition rates of migration of 66.70% and 70.53% in CNE1 and CNE2 cells, respectively significantly higher than the rates in cells with PTX treatment alone. The combined treatment with LMWH and PTX for 24 h also caused a significantly higher inhibition rate of cell invasion than LMWH and PTX alone. LMWH enhanced the down-regulation of MMP-9 and HPA induced by PTX.</p><p><b>CONCLUSION</b>LMWH can enhance the inhibitory effect of PTX on the migration and invasion of nasopharyngeal carcinoma cells, the mechanism of which may involve the down-regulation of MMP-9 and HPA expressions.</p>
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Humanos , Carcinoma , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Glucuronidase , Metabolismo , Heparina Liase , Metabolismo , Heparina de Baixo Peso Molecular , Farmacologia , Metaloproteinase 9 da Matriz , Metabolismo , Neoplasias Nasofaríngeas , Patologia , Paclitaxel , Farmacologia , Inibidor Tecidual de Metaloproteinase-1 , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To study the effects of tunicamycin (a glycosylation inhibitor) combined with cisplatin on the proliferation and apoptosis of human nasopharyngeal carcinoma cells and explore the molecular mechanism.</p><p><b>METHODS</b>Nasopharyngeal carcinoma CNE-1 and CNE-2 cells cultured in vitro were treated with different concentrations of tunicamycin with or without cisplatin. The inhibition of cell proliferation was examined using MTT assay and colony formation assay, and the cell apoptosis was analyzed using flow cytometry with propidium iodide staining. The expressions of Bax, Bcl-2, and GRP78 in cells treated with 3 µmol/L tunicamycin with or without 6.00 µmol/L cisplatin were measured with Western blotting.</p><p><b>RESULTS</b>Treatment with tunicamycin or cisplatin obviously inhibited the proliferation of CNE-1 and CNE-2 cells. Treatment with 3 µmol/L tunicamycin for 24, 36 and 48 h resulted in a viability of 72.13%, 51.97%, and 37.56% in CNE-1 cells and 85.61%, 56.95%, and 43.66% in CNE-2 cells, respectively, and the combined treatment with 6 µmol/L cisplatin lowered the cell viability to 67.97%, 47.76%, and 34.68% in CNE-1 cells and 56.89%, 37.05%, and 29.30% in CNE-2 cells, respectively. Tunicamycin at 0.3 µmol/L combined with 0.6 µmol/L cisplatin showed an obviously enhanced inhibitory effect on colony formation of CNE-1 and CNE-2 cells. Tunicamycin treatment (3 µmol/L) of CNE-1 and CNE-2 cells for 48 h induced an apoptosis rate of only 8.89% and 8.67%, but when combined with 6 µmol/L cisplatin, the cell apoptosis rate increased to 37.02% and 32.25%, significantly higher than that in cells with cisplatin treatment alone (7.25% and 6.36%, respectively). Compared with tunicamycin and cisplatin alone, the combined treatment significantly increased Bax expression and decreased Bcl-2 expression in the cells; tunicamycin up-regulated the expression of GRP-78 and enhanced the activity of caspase-3.</p><p><b>CONCLUSION</b>Tunicamycin can inhibit the proliferation of CNE-1 and CNE-2 cells and enhance cisplatin-induced cell death, the mechanism of which may involve excessive endoplasmic reticulum stress response and increased activity of caspase-3.</p>