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1.
Int Immunopharmacol ; 72: 437-444, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030100

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated acquired autoimmune hemorrhagic disease. About one-third of patients are unresponsive to first-line therapies. Thalidomide (THD) as an immunomodulatory agent is now used to treat several autoimmune disorders. Therefore, we assessed the safety and efficacy of THD in corticosteroid-resistant or relapsed ITP patients, and preliminarily explore its mechanism. METHODS: 50 newly-diagnosed ITP patients and 47 healthy volunteers were enrolled in this study. Additionally, 17 corticosteroid-resistant or relapsed ITP patients were recruited, with 7 cases in the rhTPO + THD group and 10 cases in the THD monotherapy group. Overall response rate at 6, 12, and 24 months were assessed. Levels of Neuropilin-1(NRP-1), regulatory T cells (Tregs) and regulatory B cells (Bregs) were detected. RESULTS: Expression of NRP-1, Tregs and Bregs were reduced in newly-diagnosed ITP patients. In vitro, THD treatment upregulated expression of NRP-1and Tregs only in ITP patients. As for corticosteroid-resistant or relapsed ITP patients, overall response rate at 6, 12, and 24 months was 85.7%, 57.1% and 100% in the rhTPO + THD group and 60%, 75% and 83.3% in the THD group, respectively. Additionally, rhTPO plus THD or THD therapy significantly increased the levels of NRP-1, Tregs and Bregs in responders. CONCLUSIONS: Our study shows for the first time that NRP-1 is involved in the pathogenesis of ITP, THD could induce response in ITP patients by upregulating NRP-1 expression and restoring the proportion of Tregs and Bregs. THD might be served as a novel therapeutic agent in corticosteroid-resistant or relapsed ITP patients.


Assuntos
Imunossupressores/uso terapêutico , Neuropilina-1/imunologia , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Talidomida/uso terapêutico , Adolescente , Corticosteroides/uso terapêutico , Adulto , Linfócitos B Reguladores/efeitos dos fármacos , Linfócitos B Reguladores/imunologia , Resistência a Medicamentos , Feminino , Humanos , Imunossupressores/farmacologia , Masculino , Pessoa de Meia-Idade , Neuropilina-1/genética , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Talidomida/farmacologia , Regulação para Cima/efeitos dos fármacos , Adulto Jovem
2.
Transl Oncol ; 8(3): 163-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26055173

RESUMO

High-intensity focused ultrasound (HIFU) is a rapidly developing, non-invasive technique for local treatment of solid tumors that produce coagulative tumor necrosis. This study is aimed to investigate the feasibility of proton magnetic resonance spectroscopy (MRS) on early assessing treatment of HIFU ablation in rabbit with VX2 liver tumor. HIFU ablation was performed on normal liver and VX2 tumor in rabbit, and MRS was performed on normal liver and VX2 tumor before and 2 days after 100% HIFU ablation or 80% ablation in tumor volume. Choline (Cho) and choline/lipid (Cho/Lip) ratios between complete and partial HIFU ablation of tumor were compared. Tissues were harvested and sequentially sliced to confirm the necrosis. In normal liver, the Cho value liver was not obviously changed after HIFU (P > .05), but the Cho/Lip ratio was decreased (P < .05). Cho in liver VX2 tumor was much higher than that in normal liver (P < .001). Cho and Cho/Lip ratio were significantly decreased in tumor after complete HIFU ablation and partial HIFU ablation, and the Cho value in complete HIFU tumor ablation did not show any difference from that in normal liver after HIFU (P > .05); however, the Cho value in partial ablation was still higher than that in normal liver before or in tumor after complete HIFU treatment due to the residual part of tumors, and Cho/Lip ratio is lower than that in complete HIFU treatment (P < .001). The changes in MRS parameters were consistent with histopathologic changes of the tumor tissues after treatment. MRS could differentiate the complete tumor necrosis from residual tumor tissue, when combined with magnetic resonance imaging. We conclude that MRS may be applied as an important, non-invasive biomarker for monitoring the thoroughness of HIFU ablation.

3.
Zhonghua Gan Zang Bing Za Zhi ; 19(2): 102-5, 2011 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-21492511

RESUMO

To investigate the clinical value of 1H magnetic resonance spectroscopy (1H MRS) in the evaluation of high intensity focused ultrasound (HIFU) ablation for primary liver cancer. Routine magnetic resonance sequences, contrast-enhanced magnetic resonance imaging and respiratory-triggered single voxel point resolved spectroscopy sequence (PRESS) were performed on 24 patients with primary liver cancer before and after HIFU ablation. A respiratory-triggered axial T2 weighted imaging (T2WI) was used as localizer for PRESS. Spectroscopy data was transmitted to a personal computer and was post-processed with a custom software (Saker, provided by Ning Jing, an engineer in GE Healthcare). It would be considered "technical success" if the baselines of spectra were stable and main metabolites were without overlapping and could be identified. Integral areas of choline (Cho) peak at 3.2 parts per million (ppm) and lipid (Lip) peak at 1.3 ppm were measured, and the choline to lipid (Cho/Lip) ratios were calculated. The differences of areas of Cho, Lip peak and Cho/Lip ratios before and after HIFU ablation were compared by using paired samples t test, and a P value of less than 0.05 was considered statistically significant. The technical success rate of 1H-MRS was 87.50% (42/48). Integral areas of Cho peak and Lip peak of 20 patients with satisfied spectra were measured, and the Cho/Lip ratios were calculated. The Integral area of Cho peak decreased from 34 597+/-6 802 before HIFU ablation to 6 372+/-2 466 after HIFU ablation (t = 18.02, P less than 0.01). The Integral area of Lip peak increased from 147 948+/-16 317 before HIFU ablation to 149 069+/-16 345 after HIFU ablation (t = -15.11, P less than 0.01). The Cho/Lip ratio decreased from 0.23+/-0.03 before HIFU ablation to 0.04+/-0.02 after HIFU ablation (t = 25.32, P less than 0.01). 1H-MRS could provide information of metabolites changes of primary liver cancer after HIFU ablation and could be used as a complementary sequence to other magnetic resonance sequences to evaluate all around primary liver cancer after HIFU ablation.

4.
Chin J Cancer ; 29(2): 151-7, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20109342

RESUMO

BACKGROUND AND OBJECTIVE: Epithelial-mesenchymal transition (EMT) not only initiates invasion and metastasis of tumors, but also induces multidrug resistance in tumor cells. Our experiment analyzed the dependability between breast cancer resistant protein (BCRP) and EMT in breast cancer to explore the effect of EMT on BCRP-mediated multidrug resistance. METHODS: The expressions of BCRP and transcription inhibitor Snai1 (Snail) in breast cancer were detected by immunohistochemistry. The eukaryotic expression vector pCDNA3.1-Snail was constructed and then transfected into human breast cancer cell line MCF-7. Snail, epithelial marker gene E-cadherin, interstitial marker gene Vimentin, multidrug resistance protein BCRP, and relative drug resistance were measured by immunofluorescence, Western blot, real-time polymerase chain reaction (PCR), and MTT assay. RESULTS: Immunohistochemistry showed that Snail was highly correlated with BCRP in breast cancer. Immunofluorescence, Western blot, real-time PCR revealed that compared with parent cell MCF-7, after transfected with Snail, the expression of E-cadherin in MCF-7 decreased, but Snail, Vimentin, and BCRP increased. MTT displayed that the relative drug resistance increased to 9.93. CONCLUSION: After transfected with eukaryotic expression vector pCDNA3.1-Snail, breast cancer cells MCF-7 showed EMT with BCRP-mediated multidrug resistance.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Neoplasias da Mama/metabolismo , Resistência a Múltiplos Medicamentos , Transição Epitelial-Mesenquimal , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Vetores Genéticos , Humanos , Pessoa de Meia-Idade , Mitoxantrona/farmacologia , Proteínas de Neoplasias/genética , Plasmídeos , RNA Mensageiro/metabolismo , Fatores de Transcrição da Família Snail , Fatores de Transcrição/genética , Transfecção , Vimentina/genética , Vimentina/metabolismo
5.
Zhonghua Gan Zang Bing Za Zhi ; 17(5): 350-3, 2009 May.
Artigo em Chinês | MEDLINE | ID: mdl-19497200

RESUMO

OBJECTIVE: To investigate the ideal approach in creating rabbit model of hepatic fibrosis and to evaluate the feasibility and value of dynamic whole-liver 3D magnetic resonance (MR) perfusion-weighted imaging (PWI) in the quantitative study on the staging of hepatic fibrosis. METHODS: Rabbit model of hepatic fibrosis was created by intraperitoneal injection of 5% and 100% carbon tetrachloride (0.1 ml/kg, once a week) respectively. MR perfusion weighted imaging was performed at the 6th, 8th, 10th and 12th week since injection. The time of peak (TOP), the time to peak (TTP), the maximum slope of increase(MSI) and the maximal relative signal increase (MRSI) of portal vein and hepatic parenchyma were analyzed quantitatively, and were compared with pathological results. Comparison of different concentrations of CCl4 was analyzed using chi-square test. Inter-group comparison of perfusion parameters was analyzed using one-way ANOVA P less than 0.05 was regarded as statistically significant. RESULTS: 40% of the rabbits treated with 5% carbon tetrachloride developed hepatic fibrosis, while 75% of the rabbits treated with 100% carbon tetrachloride developed hepatic fibrosis; the mortality rate is significantly different between these two groups (X2=5.013, P less than 0.05). PWI examination was successfully achieved in 31 rabbits, liver perfusion baseline was stable, and good TIC curve was obtained. With the progress of hepatic fibrosis, TOP and TTP of portal vein and hepatic parenchyma were increased, and MSI and MRSI were decreased. There were significant differences among stage of S0-S2, S3 and S4. CONCLUSIONS: The method (100% carbon tetrachloride intraperitoneal injection, 0.1 ml/kg, once a week) has high success rate of creating rabbit model of hepatic fibrosis. The stage of hepatic fibrosis could be evaluated quantitatively with dynamic whole-liver 3D MR perfusion-weighted imaging.


Assuntos
Modelos Animais de Doenças , Imagem Tridimensional , Cirrose Hepática Experimental/diagnóstico , Fígado/patologia , Angiografia por Ressonância Magnética/métodos , Animais , Tetracloreto de Carbono/administração & dosagem , Interpretação de Imagem Assistida por Computador/métodos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Circulação Hepática , Cirrose Hepática Experimental/diagnóstico por imagem , Masculino , Curva ROC , Coelhos , Radiografia , Sensibilidade e Especificidade
6.
Zhonghua Yan Ke Za Zhi ; 45(11): 987-91, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-20137416

RESUMO

OBJECTIVE: To compare the aqueous humor concentration of levofloxacin 0.5%, gatifloxacin 0.3% and levofloxacin 0.3% ophthalmic solution after topical dosing in human eyes. METHODS: A randomized, double-blind and parallel study was conducted. Senile cataract patients (150 eyes in 150 cases) receiving phacoemulsification in eye center affiliated second hospital of Zhejiang university were randomized into three groups: levofloxacin 0.5%, 50 eyes;gatifloxacin 0.3%, 50 eyes and levofloxacin 0.3%, 50 eyes. Each group was randomized into five sub-groups, with 10 eyes in each sub-group. Each group received either levofloxacin 0.5% or topical gatifloxacin 0.3% or levofloxacin 0.3% preoperatively. One drop of antibiotic was administered every 15 minutes for 4 doses. More than 100 microl aqueous samples were obtained from different sub-groups during surgery, 15.0, 30.0, 60.0, 120.0 and 180.0 min after the last drop, respectively. Then 100 microl aqueous samples were put into test tube by sample injector accurately. Concentration of the antimicrobial agents was determined by the HPLC (high pressure liquid chromatography). Variance analysis was performed to detect differences among the antibiotic treatment groups. The differences between two groups were assumed by t-test. RESULTS: Humor concentration of levofloxacin 0.5% (1.61 +/- 0.48), (2.41 +/- 0.80), (2.93 +/- 0.50), (2.56 +/- 0.63), (1.87 +/- 0.88) mg/L was significantly higher than that of gatifloxacin 0.3% (0.70 +/- 0.18), (1.29 +/- 0.54), (1.59 +/- 0.67), (1.41 +/- 0.50), (1.13 +/- 0.28) mg/L and levofloxacin 0.3% (0.55 +/- 0.39), (1.15 +/- 0.42), (1.38 +/- 0.49), (1.02 +/- 0.33), (0.55 +/- 0.31) mg/L at the same period after the last drop (F = 23.64, 12.82, 21.13, 25.00, 12.22;P < 0.05). CONCLUSION: Topically applied levofloxacin 0.5% had the higher aqueous humor drug level than gatifloxacin 0.3% and levofloxacin 0.3%.


Assuntos
Antibacterianos/administração & dosagem , Humor Aquoso/química , Fluoroquinolonas/administração & dosagem , Levofloxacino , Ofloxacino/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Feminino , Gatifloxacina , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas
7.
Zhonghua Gan Zang Bing Za Zhi ; 16(4): 294-7, 2008 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-18423154

RESUMO

OBJECTIVE: To evaluate the application of 3D liver acquisition volume acceleration (3D-LAVA) integrated with array spatial sensitivity encoding technique (ASSET) in liver dynamic-enhancement scanning. METHODS: One hundred forty-seven patients underwent conventional plain and contrast enhancement liver MR imaging. 3D-LAVA and 2D fast spoiled gradient recalled echo were used for contrast enhancement liver MR scanning in 90 and 57 patients respectively. In the 3D-LAVA group, integrated ASSET was used in 72 out of the 90 patients. Of the 57 patients who underwent examinations using 2D fast spoiled gradient recalled echo, portal vein CE-MRA was performed on 20. The ability of 3D-LAVA to detect the lesions and the advantage to shorten the acquisition time after integrating with ASSET were analyzed. Original images of 60 patients in the 3D-LAVA group were processed using MIP to illustrate the anatomy of the portal vein. They were compared with those shown by CE-MRA to evaluate the illustration abilities of the two approaches. RESULTS: 3D-LAVA is more sensitive than 2D-FSPGR in detecting metastatic hepatic carcinomas. In the 3D-LAVA group integrated with ASSET, earlier and peak arterial phase images were acquired in 34 cases; and earlier, peak and late arterial phase images were acquired in 23 cases. The illustrations of the portal vein anatomy by 3D-LAVA were similar to those shown by portal vein CE-MRA. CONCLUSION: 3D-LAVA integrated with ASSET can obtain higher quality multi-phase dynamic enhancement images of the liver in a shorter time, and in the meantime also shows the vascular anatomy.


Assuntos
Aumento da Imagem/métodos , Imagem Tridimensional/métodos , Fígado/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
8.
Zhongguo Zhen Jiu ; 27(10): 749-52, 2007 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-18257352

RESUMO

OBJECTIVE: To explore distribution of the Liver and Lung Channels in the brain so as to provide imaging basis for construction of channel theory in the brain. METHODS: Sixty healthy student volunteers were randomly divided into a Liver Channel group (I) and a Lung Channel group (II), and the each group was further divided into five subgroups with 6 volunteers in each subgroup, based on five-shu-point principles which, were Dadun (LR 1, I 1), Xingjian (LR 2, I 2), Taichong (LR 3, I 3), Zhongfeng (LR 4, I 4), Ququan (LR 8, I 5), Shaoshang (LU 11, II 1), Yuji (LU 10, II 2), Taiyuan (LU 9, II 3), Jingqu (LU 8, II 4), and Chize (LU 5, II 5), respectively. In order to observe the brain activating patterns during acupuncture at the different acupoints, functional magnetic resonance imaging (fMRI) technique was adopted. All image data were then analyzed with SPM 2 software. The statistical parameter gram was composed of the pixel P < 0.01, and anatomic location was made according to Talairach coordinate, attaining experimentally activated areas, and the commonly activated area of five-shu-point of each channel was considered as the brain distribution of the Liver and Lung Channels. RESULTS: The common areas activated by the five-shu-points of the Liver Channel were homolateral Brodmann area (BA) 34, BA 47, red nucleus, contralateral BA 19, BA 30, BA 39, the superior parietal lobule, cerebellum decline, and bilateral BA 3 and culmen. The common areas activated by the five-shu-points of the Lung Channels included homolateral BA 2, BA 18, BA 35, and contralateral BA 9 and substania nigra. CONCLUSION: There are relatively specific corresponding brain areas for the Liver and Lung Channels, indicating that there is possible relatively specific connection between channels and the brain.


Assuntos
Terapia por Acupuntura/métodos , Encéfalo/anatomia & histologia , Imagem por Ressonância Magnética/métodos , Meridianos , Pontos de Acupuntura , Adulto , Feminino , Humanos , Fígado , Pulmão , Masculino , Medicina Tradicional Chinesa
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