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1.
Chem Biodivers ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32141193

RESUMO

Fifteen constituents, include one new lignan (schisandroside E, 1) and one new terpenoid (schisandenoid A, 2) as well as nine known lignans and four known terpenoids, were isolated from Schisandra chinensis leaves. The structures of compounds 1-2 were established by entirely meticulous spectroscopic analysis (NMR, MS, CD, IR and UV). All compounds were tested for cytotoxicity against MGC-803, Caco-2 and Ishikawa cell lines. Some compounds showed strong cytotoxicity against these three cancer cell lines with IC50﹤1 µM.

2.
Fitoterapia ; 142: 104517, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32070772

RESUMO

Eight new sesquiterpenoids named melongenaterpenes M-T (1-8), together with nine known compounds (9-17), were isolated from the 70% ethanol extract of the sepals of Solanum melongena L. The structures of all isolated compounds were elucidated based on 1D and 2D NMR spectra and a comprehensive comparison of their spectroscopic and physical data with values from the published literatures. Meanwhile, the cytotoxicity of all the isolated compounds was evaluated on the three human cancer lines of Hela, Ishikawa and MGC-803 by CCK8 assay, respectively.

3.
Nat Prod Res ; : 1-9, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951465

RESUMO

Two new alkaloids named Melongenamides H-I (1-2), together with twenty-one known compounds (3-23), were isolated from the 70% ethanol extract of the sepals of Solanum melongena L. The structures of all isolated compounds were determined by 1D and 2D NMR spectra and by comparing their spectroscopic and physical data with values from the published literatures. All the isolated compounds were evaluated the cytotoxicity against three human canner lines (Hela, Ishikawa and MGC-803) by CCK8 assay.

4.
Molecules ; 23(4)2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29642617

RESUMO

Oxidative stress, which is caused by Amyloid-ß deposition in brain, plays an important role in Alzheimer's disease. In this study, we found that lignans from Schisandra chinensis rattan stems (rsSCH-L) could reduce the escape latency and the distance travelled by the Aß1-42 injected rats while the crossing platform time was enhanced in the Morris water maze test. Further research demonstrated that lignans from rsSCH-L attenuated Aß1-42-induced neuronal cell injury by increasing the content of SOD and GSH-Px and decreasing the levels of LDH, ROS, and MDA. Moreover, rsSCH-L also inhibited the apoptosis of primary neuronal cells. The mechanisms of the apoptosis were related with the downregulation of caspase-3, caspase-8, Bax, and upregulation of Bcl-2. Taken together, the results show that rsSCH-L can improve cognitive ability in vivo. Meanwhile rsSCH-L exhibit a neuroprotective environment against oxidative stress and apoptosis in vitro. Therefore, rsSCH-L may be a potential therapeutic agent for this neurodegenerative disease.


Assuntos
Precursor de Proteína beta-Amiloide/efeitos adversos , Lignanas/administração & dosagem , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Schisandra/química , Precursor de Proteína beta-Amiloide/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Lignanas/química , Lignanas/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Caules de Planta/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
5.
Nat Prod Res ; 31(22): 2634-2640, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28278667

RESUMO

Twenty-one phenylpropanoids, including 1 new (1) and 20 known phenylpropanoids (2-21), were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra referring to the literatures, together with mass spectrometry. It was found that the isolated compounds, except for 7, 18 and 19, showed the different levels of inhibitions on NO production by LPS-induced RAW 264.7 cells at IC50 values from 27.0 to 97.3 µM.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Propanóis/química , Solanaceae/química , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Frutas/química , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Propanóis/farmacologia , Células RAW 264.7
6.
Polymers (Basel) ; 8(9)2016 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30974609

RESUMO

Using the dynamic Monte Carlo method, we investigate dynamics of semiflexible polymer translocation through a nanopore into laterally unbounded region between two parallel flat membranes with separation R in presence of an electric field inside the pore. The average translocation time τ initially decreases rapidly with increase of R in the range of R < 10 and then almost keeps constant for R ≥ 10, and the decline range increases with increase of dimensionless bending stiffness κ. We mainly study the effect of chain length N, κ and electric field strength E on the translocation process for R = 5. The translocation dynamics is significantly altered in comparison to an unconfined environment. We find τ ~ Nα, where the exponent α increases with increase of E for small κ. α initially increases slowly with increase of E and then keeps constant for moderate κ. α decreases with increase of E for large κ. However, α decreases with increase of κ under various E. In addition, we find τ ~ κß. ß decreases with increase of N under various E. These behaviors are interpreted in terms of the probability distribution of translocation time and the waiting time of an individual monomer segment passing through the pore during translocation.

7.
Asian Pac J Cancer Prev ; 16(1): 221-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25640355

RESUMO

As metformin can inhibit endometrial carcinoma (EC) cell growth and the insulin growth factor (IGF) system is active in EC, the question of whether t can regulate endometrial carcinoma cell secretion of IGF-1 or expression of IGF-1 receptor (IGF-1R) is of interest. In this study, serum IGF-1 levels in EC patients were found to be comparable with that in the non EC patients (p>0.05). However, the IGF-1 level in the medium of cultured cells after treatment with metformin was decreased (p<0.05). IGF-1R was highly expressed in human endometrial carcinoma paraffin sections, but IGF-1R and phosphor-protein kinase B/protein kinase B (p-Akt/ Akt) expression was down-regulated after metformin treatment (p<0.05). In summary, metformin can reduce the secretion of IGF-1 by Ishikawa and JEC EC cell lines and their expression of IGF-1R to deactivate downstream signaling involving the PI-3K/Akt pathway to inhibit endometrial carcinoma cell growth.


Assuntos
Carcinoma/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Fator de Crescimento Insulin-Like I/genética , Metformina/farmacologia , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/farmacologia , Carcinoma/genética , Linhagem Celular Tumoral , Regulação para Baixo/genética , Neoplasias do Endométrio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/genética , Fosforilação/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
8.
Asian Pac J Cancer Prev ; 15(8): 3741-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24870786

RESUMO

BACKGROUND: Emerging evidence implicates the platelet-derived growth factor-D (PDGF-D) in many types of human solid tumors. We investigated whether PDGF-D plays an important role in endometrial cancer (EC) in relation to clinicopathologic phenotype, angiogenesis, and patient prognosis. MATERIALS AND METHODS: We analyzed PDGF-D protein expression by Western blotting in twenty-seven human endometrial cancer tissues, and matched normal endometrial controls collected at the third Affiliated hospital of Sun Yat-sen University during 2012-2013 (n=27). Immunohistochemical staining was performed using a human PDGF-D antibody on the endometrial cancer patients collected in the same facility during January 2001 and October 2013 (n=152). Patients were followed from the time of primary surgery in 2001-2013 until death or last follow-up. We correlated the PDGF-D expression levels with clinicopathologic parameters and prognosis in human endometrial cancer patients. RESULTS: Compared with matched normal endometrial cases, PDGF-D was up-regulated in endometrial cancer. Expression of PDGF-D protein, found in 78% of the cases, was associated with nonendometrioid histologic type (p=0.028), FIGO stage III/IV (p=0.039), >50% solid tumor growth (p=0.048), pelvic LN metastasis (p=0.035) and ER and PR negativity (p=0.04 and 0.002). PDGF-D expression was also significantly associated with expression of VEGF-A (p=0.021). In multivariate analysis, PDGF-D expression proved to be an independent prognostic factor in addition to histologic grade and FIGO stage. Patients with high expression levels of PDGF-D had a significantly poorer overall survival rate compared with patients with no expression. CONCLUSIONS: PDGF-D expression is frequently up-regulated in endometrial cancer, and is associated with aggressive features and poor prognosis.


Assuntos
Carcinoma Endometrioide/metabolismo , Carcinoma/metabolismo , Linfocinas/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Idoso , Western Blotting , Carcinoma/patologia , Carcinoma Endometrioide/patologia , Estudos de Casos e Controles , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Prognóstico , Estudos Retrospectivos , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Contemp Nurse ; 44(1): 11-20, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23721383

RESUMO

BACKGROUND: The Iowa Infant Feeding Attitude Scale (IIFAS) is used to evaluate maternal infant feeding attitude. The breastfeeding rate has declined but no validated instruments to assess infant feeding attitudes or related studies have been available in mainland China. AIMS: The purpose of this study was to assess the reliability and validity of a mainland Chinese version of the IIFAS among postpartum women. METHODS: Postpartum women (N = 660) were recruited from three university hospitals in Guangzhou in mainland China. The participants completed an IIFAS questionnaire before being discharged and accepted telephone follow-up sessions at 6 weeks and 3 months postpartum. The reliability of the scale was evaluated using intra-class correlations (ICC) for test-retest reliability, correlated item-total correlations and Cronbach's a. The validity of the scale was evaluated using the content validity index (CVI), construct validity using exploratory factor analysis and predictive validity using independent t-tests. RESULTS: The ICC was 0.861. The correlated item-total correlations ranged from 0.262-0.691. Cronbach's a was 0.623. The CVI was 0.996. Four factors were extracted using exploratory factor analysis and they contributed to 48.69% of the total variance. CONCLUSIONS: The mainland Chinese version of the IIFAS scale can be considered a reliable, valid and predictive scale for assessing infant feeding attitudes among women in mainland China. In-hospital scores on the scale were significant predictors of the infant feeding method and breastfeeding duration at 3 days, 6 weeks and 3 months postpartum. Construct validity was confirmed and showed four factors. However, future studies are required to improve the lower level internal consistency of the IIFAS.


Assuntos
Comportamento Alimentar , Comportamento do Lactente , Período Pós-Parto , Psicometria , China , Feminino , Humanos , Recém-Nascido
10.
J Minim Invasive Gynecol ; 19(4): 498-502, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22621994

RESUMO

STUDY OBJECTIVE: To estimate the usefulness of hysteroscopy in the diagnosis and treatment of postcesarean scar defect. DESIGN: Retrospective study (Canadian Task Force classification III). SETTING: Two university-affiliated hospitals. PATIENTS: Sixty-two patients with postcesarean scar defects were retrospectively analyzed. INTERVENTIONS: All patients with postcesarean scar defects diagnosed using ultrasonography and hysteroscopy underwent hysteroscopic surgery, and were followed up for longer than 1 year. MEASUREMENTS AND MAIN RESULTS: Hysteroscopy revealed that 38 patients had valve-like motions at the incision sites, 22 had dome-like defects, and 2 with a history of 2 previous deliveries via cesarean section had umbilications of 2 different shades. Fifty-seven of 62 patients underwent corrective surgery via hysteroscopy. In another 3 patients, because the left wall of the fundus of the uterus was too thin (<2 mm at ultrasonography) to undergo corrective surgery, only clearance of residual blood and/or suture materials was performed. Of these 57 patients, 5 underwent removal of residual suture materials and endometrial fulguration. No complications were observed in these patients. Furthermore, after surgery, abnormal vaginal bleeding stopped in 38 patients, and its duration was shortened in 20 patients. In addition, dysmenorrhea was alleviated in 15 patients, and resolved in 7 patients. CONCLUSION: Hysteroscopy is an accurate means of diagnosis apart from surgical correction.


Assuntos
Cicatriz/patologia , Cicatriz/cirurgia , Histeroscopia , Metrorragia/patologia , Metrorragia/cirurgia , Adulto , Cesárea/efeitos adversos , Cicatriz/complicações , Feminino , Humanos , Metrorragia/etiologia , Estudos Retrospectivos
11.
Gynecol Obstet Invest ; 73(3): 252-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22414876

RESUMO

AIMS: To screen the preeclampsia-related protein by proteomics. METHODS: Proteomics was performed to identify differential protein expression profiles between normal full-term pregnancy, early-onset severe preeclampsia (ES-PE) or late-onset severe preeclampsia (LS-PE; n = 10 per group). Real-time quantitative PCR and immunohistochemistry were conducted to confirm the expression of α(1)-antitrypsin (α(1)-AT) in the decidual tissues of different subjects. ELISA was employed to detect the α(1)-AT content in the peripheral blood of 90 women (n = 30 per group). RESULTS: We successfully constructed two-dimensional electrophoresis maps of decidual tissues, and a total of 20 differentially expressed proteins were identified. The α(1)-AT expression was different among the three groups. The normal full-term pregnancy women expressed the most α(1)-AT, and the LS-PE women expressed the least amount of α(1)-AT. The difference in the α(1)-AT expression was consistent with the proteomics data. The peripheral α(1)-AT content was the highest in the normal full-term pregnancy group (1.85 ± 0.15 g/l), moderate in the ES-PE group (0.77 ± 0.14 g/l) and lowest in the LS-PE group (0.42 ± 0.07 g/l; p < 0.05). CONCLUSION: Using 2D PAGE, we identified twenty proteins with significantly altered expression in PE. These differentially expressed proteins include prevention protein, in which α(1)-AT is downregulated in PE.


Assuntos
Pré-Eclâmpsia/sangue , Proteômica/métodos , Inibidores de Serino Proteinase/sangue , alfa 1-Antitripsina/sangue , Estudos de Casos e Controles , Primers do DNA/química , Decídua/metabolismo , Eletroforese em Gel Bidimensional , Ensaio de Imunoadsorção Enzimática , Feminino , Idade Gestacional , Humanos , Imuno-Histoquímica , Pré-Eclâmpsia/genética , Gravidez , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Inibidores de Serino Proteinase/genética , alfa 1-Antitripsina/genética
12.
PLoS One ; 7(12): e52483, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23285061

RESUMO

ABT-737 is a BH3 mimetic small molecule inhibitor that can effectively inhibit the activity of antiapoptotic Bcl-2 family proteins including Bcl2, Bcl-xL and Bcl-w, and further enhances the effect of apoptosis by activating the proapoptotic proteins (t-Bid, Bad, Bim). In this study, we demonstrate that ABT-737 improved the radiation sensitivity of cervical cancer HeLa cells and thereby provoked cell apoptosis. Our results show that ABT-737 inhibited HeLa cell proliferation and activated JNK and its downstream target c-Jun, which caused the up-regulation of Bim expression. Blockade of JNK/c-Jun signaling pathway resulted in significant down-regulation of ABT-737-induced Bim mRNA and protein expression level. Also, ABT-737 could evoke the Bim promoter activity, and enhance the radiation sensitivity of HeLa cells via JNK/c-Jun and Bim signaling pathway. Our data imply that combination of ABT-737 and conventional radiation therapy might represent a highly effective therapeutic approach for future treatment of cervical cancer.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Compostos de Bifenilo/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Nitrofenóis/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Tolerância a Radiação/efeitos dos fármacos , Sulfonamidas/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Apoptose/efeitos da radiação , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2 , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Ensaios de Seleção de Medicamentos Antitumorais , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HeLa , Humanos , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Proteínas de Membrana/genética , Piperazinas/farmacologia , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-jun/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Radiação , Tolerância a Radiação/genética , Tolerância a Radiação/efeitos da radiação
13.
Int J Nanomedicine ; 5: 437-44, 2010 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-20957165

RESUMO

In many instances, multidrug resistance (MDR) is mediated by increasing the expression at the cell surface of the MDR1 gene product, P-glycoprotein (P-gp), a 170-kD energy-dependent efflux pump. The aim of this study was to investigate the potential benefit of combination therapy with magnetic Fe(3)O(4) nanoparticle [MNP (Fe(3)O(4))] and MDR1 shRNA expression vector in K562/A02 cells. For stable reversal of "classical" MDR by short hairpin RNA (shRNA) aiming directly at the target sequence (3491-3509, 1539-1557, and 3103-3121 nucleotide) of MDR1 mRNA. PGC silencer-U6-neo-GFP-shRNA/MDR1 called PGY1-1, PGY1-2, and PGY1-3 were constructed and transfected into K562/A02 cells by lipofectamine 2000. After transfected and incubated with or without MNP (Fe(3)O(4)) for 48 hours, the transcription of MDR1 mRNA and the expression of P-gp were detected by quantitative real-time PCR and Western-blot assay respectively. Meanwhile intracellular concentration of DNR in K562/A02 cells was detected by flow cytometry (FCM). PGC silencer-U6-neo-GFP-shRNA/MDR1 was successfully constructed, which was confirmed by sequencing and PGY1-2 had the greatest MDR1 gene inhibitory ratio. Analysis of the reversal ratio of MDR, the concentration of daunorubicin (DNR) and the transcription of MDR1 gene and expression of P-gp in K562/A02 showed that combination of DNR with either MNP (Fe(3)O(4)) or PGY1-2 exerted a potent cytotoxic effect on K562/A02 cells, while combination of MNP (Fe(3)O(4)) and PGY1-2 could synergistically reverse multidrug resistance. Thus our in vitro data strongly suggested that a combination of MNP (Fe(3)O(4)) and shRNA expression vector might be a more sufficient and less toxic anti-MDR method on leukemia.


Assuntos
Daunorrubicina/administração & dosagem , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Genes MDR , Nanopartículas de Magnetita/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antibióticos Antineoplásicos/administração & dosagem , Sequência de Bases , Primers do DNA/genética , Doxorrubicina/administração & dosagem , Vetores Genéticos , Humanos , Células K562 , Dados de Sequência Molecular , Nanomedicina , Transfecção
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 18(1): 67-73, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20137121

RESUMO

This study was aimed to explore the potential therapy of Gambogic acid (GA) combined with magnetic nanoparticle of Fe3O4 (Fe3O4-MNP) on leukemia. The proliferation of U937 cells and the cytotoxicity were evaluated by MTT assay. Cell apoptosis was observed and analyzed by microscopy and flow cytometry respectively. The expressions of gene and protein were detected by quantitative real-time polymerase chain reaction and Western blot respectively. The results showed that GA enhanced the cytotoxicity for U937 cells in dose- and time-dependent manners. The Fe3O4-MNP itself had not cytotoxicity, but could enhance the inhibitory effect of GA on proliferation of U937 cells. The apoptotic rate of U937 cells induced by combination of GA with Fe3O4-MNP was higher than that by GA alone. The typical apoptotic features of cells treated with GA and Fe3O4-MNP were observed. The expression levels of caspase-3 and bax after co-treatment of GA and Fe3O4-MNP were higher than that exposed to GA or Fe3O4-MNP alone, but the expressions of bcl-2, NF-kappaB and survivin were down-regulated. It is concluded that Fe3O4-MNP can promote GA-induced apoptosis in U937 cells, and the combination of GA with Fe3O4-MNP may be a safer and less toxic new therapy for leukemia.


Assuntos
Apoptose/efeitos dos fármacos , Compostos de Ferro/administração & dosagem , Compostos de Ferro/farmacologia , Xantonas/farmacologia , Humanos , Magnetismo , Nanopartículas , Células U937
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 18(1): 136-9, 2010 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-20137134

RESUMO

This study was purposed to investigate the effects of magnetic nanoparticle of Fe3O4 (Fe3O4-MNPs) on murine immune system. ICR mice were assigned randomly into four groups which were treated with normal saline, low, middle and high dose of MNP-Fe3O4 respectively. The mice were killed after being exposed by intragastric administration for 2 weeks. The ratios of spleen weight to body weight, lymphocyte transformation rate in spleen suspension and phagocytic index of macrophage in abdominal cavity were detected. The results showed that the ratios of spleen weight to body weight in Fe3O4-MNP groups were not significantly different in comparison with the control (p > 0.05). The lymphocyte transformation rate in spleen suspension in Fe3O4-MNP groups were all higher than that in control group (-0.1775 +/- 0.0246), especially in the middle dose group (0.1833 +/- 0.0593) (p < 0.05), and the phagocytic index of macrophages in abdominal cavity of middle dose group (0.2051 +/- 0.0213) was higher than that of control group and other two Fe3O4-MNP group (low dose 0.1538 +/- 0.0100, high dose 0.1511 +/- 0.0184) (p < 0.05). It is concluded that suitable dose of Fe3O4-MNP can enhance the cellular immune activity and phagocytic function of macrophages of mice.


Assuntos
Linfócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Nanopartículas de Magnetita/administração & dosagem , Animais , Imunidade Celular , Camundongos , Camundongos Endogâmicos ICR , Fagocitose
16.
J Cancer Res Clin Oncol ; 136(7): 1089-99, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20087603

RESUMO

PURPOSE: Prior studies in different tumor models have shown that, under conditions of PTEN deficiency, the mitogen-activated protein kinase (MAPK) signaling pathway appear to play a major role in the tumor cell's proliferative and survival pathway, and that pharmacological inhibition of this pathway results in tumor growth inhibition. This study aimed to explore whether sensitivity to p38MAPK inhibitors are specifically due to status of PTEN in endometrial cancer cells. METHODS: We developed a series of endometrial cancer cell lines with different PTEN expressions (Ishikawa, RL-952, HEC-1B and HEC-1A cells) or introduced the wild-type PTEN and PTEN-siRNA in four endometrial cancer cells to change its PTEN expression with a p38MAPK inhibitor, SB203580 for 2 days. Cell proliferation, cell apoptosis, and cell cycle distribution were studied, and activation of AKT, ATF-2, and p38MAPK was examined by Western blotting. RESULTS: In cultivated PTEN-deficient endometrial cancer cells, in addition to an activation of AKT, a phosphorylation of p38MAPK and ATF-2 was evident, while PTEN-positive endometrial cancer cells lacked AKT activation but revealed a reduced expression of p-p38MAPK and p-ATF-2. These PTEN-deficient endometrial cancer cells demonstrated an increased sensitivity to the anti-proliferative effects induced by SB203580 compared with the PTEN-positive endometrial cancer cells, which corresponded to alterations in cell cycle response and cell apoptosis. CONCLUSIONS: PTEN-deficient endometrial cancer cells exhibit higher p38MAPK activity, and genetic studies demonstrate that p38MAPK functions dependently of AKT. Furthermore, PTEN loss sensitizes cells to p38MAPK inhibition in endometrial carcinoma cells. These findings indicate that inhibitors of p38MAPK have the potential to be effective in the treatment of endometrial cancer patients with PTEN-deficient tumors and should be evaluated in this setting.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Fator 2 Ativador da Transcrição/metabolismo , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imidazóis/farmacologia , PTEN Fosfo-Hidrolase/deficiência , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/farmacologia , Sensibilidade e Especificidade , Células Tumorais Cultivadas , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
17.
Zhonghua Fu Chan Ke Za Zhi ; 44(7): 496-9, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19957547

RESUMO

OBJECTIVE: To find out the bacterial species in the vagina of postpartum women and the possible influencing factors on colonization. METHODS: From Jun. 2007 to Oct. 2007, 560 postpartum women from 7 hospitals in China were enrolled. Questionnaire survey, gynecological examination and Nugent score of vaginal smear and microbial spectrum study of the vaginal flora were completed. RESULTS: (1) According to the Nugent score, 48 out of the 560 women were normal (8.6%), 337 at the borderline (60.2%) and 175 (31.2%) were complicated with bacterial vaginosis (BV). Among the 560 women, Bacterium lacticum were identified in 74 cases (13.2%), but not in the rest 486 cases (86.8%). Gardnerella and bacteroids were detected in 322 women (57.5%) and small flectobacillus in 214 women (38.2%) out of the 560 subjects. (2) Influencing factors on vaginal microflora: among the 266 women who had normal vaginal delivery, 25 (9.4%) showed normal vaginal microflora, 148 (55.6%) at borderline and BV was diagnosed in 93 women (35.0%). The corresponding figures among the 294 women who underwent cesarean section were 23 (7.8%), 189 (64.3%) and 82 (27.9%), respectively. However, the incidence of BV had no statistical difference between these two groups (P = 0.204). In the 233 women who received episiotomy, 22 (9.4%) showed normal vaginal microflora, 135 (57.9%) at borderline and 76 presented with BV (32.6%), the corresponding figures among the 327 women without episiotomy were 26 (8.0%), 202 (61.8%) and 99 (30.2%), respectively. The incidence of BV did not show any statistical difference between the above two groups (P = 0.790). (3) Prenatal vaginitis were reported in 46 women, among which 5 (10.9%) with normal vaginal flora, 26 (56.5%) at borderline and 15 (32.6%) with BV, and again in the 514 women without prenatal vaginits, the above figures changed to 43 (8.4%), 311 (60.5%) and 160 (31.1%). No significant difference was found in the incidence of BV between the two groups (P = 0.962). The rate of BV in women without sex, with sex occasionally and with sex frequently during pregnancy was 27.5% (78/284), 35.6% (96/270) and 1/6, respectively (P = 0.185), and the numbers in women who had breast-feeding, bottle feeding and mixed feeding were 31.0% (67/216), 39.3% (35/89) and 28.6% (73/255), respectively (P = 0.573). CONCLUSIONS: The amount of Lactobacillus in vagina of postpartum women is greatly reduced leading to dysbacteria. The incidence of BV is not affected by vaginal delivery, episiotomy, vaginitis, prenatal intercourse and the way of feeding, but is higher in postpartum women.


Assuntos
Lactobacillus/isolamento & purificação , Período Pós-Parto , Vagina/microbiologia , Vaginose Bacteriana/microbiologia , Adulto , Cesárea , Feminino , Gardnerella/isolamento & purificação , Gardnerella/fisiologia , Humanos , Lactobacillus/fisiologia , Parto Normal , Gravidez , Comportamento Sexual , Esfregaço Vaginal , Vaginite/microbiologia , Vaginose Bacteriana/epidemiologia , Wolinella/isolamento & purificação , Wolinella/fisiologia , Adulto Jovem
18.
Int J Nanomedicine ; 4: 201-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19918366

RESUMO

Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy. We evaluated the effect of daunorubicin (DNR)-loaded magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) on K562-n/VCR cells in vivo. K562-n and its MDR counterpart K562-n/VCR cell were inoculated into nude mice subcutaneously. The mice were randomly divided into four groups: group A received normal saline, group B received DNR, group C received MNPs-Fe3O4, and group D received DNR-loaded MNPs-Fe3O4. For K562-n/VCR tumor, the weight was markedly lower in group D than that in groups A, B, and C. The transcriptions of Mdr-1 and Bcl-2 gene were significantly lower in group D than those in groups A, B, and C. The expression of Bcl-2 was lower in group D than those in groups A, B, and C, but there was no difference in the expression of P-glycoprotein. The transcriptions and expressions of Bax and caspase-3 in group D were increased significantly when compared with groups A, B, and C. In conclusion, DNR-loaded MNPs-Fe3O4 can overcome MDR in vivo.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Daunorrubicina/administração & dosagem , Óxido Ferroso-Férrico/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Animais , Sequência de Bases , Primers do DNA/genética , Sistemas de Liberação de Medicamentos , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Células K562 , Leucemia Experimental/tratamento farmacológico , Leucemia Experimental/genética , Leucemia Experimental/patologia , Magnetismo , Camundongos , Camundongos Nus , Nanomedicina , Transplante de Neoplasias , RNA Neoplásico/genética , Transplante Heterólogo
19.
Ai Zheng ; 28(11): 1158-62, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19895735

RESUMO

BACKGROUND AND OBJECTIVE: Resistance to cisplatin (DDP) remains a major obstacle for the successful treatment of ovarian cancer. This study was to determine the reversal effect of Fe3O4-magnetic nanoparticles (MNPs) on DDP-resistance of ovarian carcinoma cell line SKOV3/DDP, and to explore its correlation with apoptosis-associated genes. METHODS: SKOV3/DDP cells were divided into the DDP group, the Fe3O4-MNPs group, the combination (DDP plus Fe3O4-MNPs) group, and the control group. Cell proliferation was determined by MTT assay. Cell apoptosis was analyzed by flow cytometry (FCM). Intracellular DDP level was detected by inductively coupled plasma atomic emission spectrometry (ICP-AES). The expressions of apoptosis-associated genes, bcl-2, and survivin were detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fe3O4-MNPs reversed DDP-resistance of SKOV3/DDP cells by 2.259 folds. The cell apotosis rate and the intracellular DDP level were significantly higher in the combination group than in the DDP group (P<0.05). Moreover, the mRNA levels of bcl-2 and survivin were significantly lower in the combination group than in the DDP group(P<0.05). CONCLUSIONS: Fe3O4-MNPs can reverse the DDP resistance of ovarian carcinoma SKOV3/DDP cells, and the effect may be ascribed to the down-regulation of bcl-2 and survivin expression.


Assuntos
Cisplatino/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Compostos Férricos/farmacologia , Proteínas Inibidoras de Apoptose/metabolismo , Neoplasias Ovarianas/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Proteínas Inibidoras de Apoptose/genética , Magnetismo , Nanopartículas , Neoplasias Ovarianas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Survivina
20.
Int J Nanomedicine ; 4: 107-14, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19516889

RESUMO

To explore whether the magnetic nanoparticles of Fe3O4 (MNPs-Fe3O4) loaded with cisplatin can reverse the diaminedichloro platinum (DDP) resistance to multidrug resistance of ovarian carcinoma cells and to investigate its mechanisms. The SKOV3/DDP cells were divided into DDP treatment (DDP group), MNPs-Fe3O4 treatment (MNPs-Fe3O4 group), DDP + MNPs-Fe3O4 treatment (DDP + MNPs-Fe3O4 group), and control group. After incubation with those conjugates for 48 h, the cytotoxic effects were measured by MTT assay. Apoptosis and the intracellular DDP concentration were investigated by flow cytometry and inductively coupled plasma atomic emission spectroscopy, respectively. The expression of apoptosis associated gene Bcl-2 mRNA was detected by reverse transcription polymerase chain reaction and the expressions of MDR1, lung resistance-related protein (LRP), and P-glycoprotein (P-gp) genes were studied by Western blot. Our results indicated that the 50% inhibition concentration (IC50) of the MNPs-Fe3O4 loaded with DDP was 17.4 micromol/l, while the IC50 was 39.31 micromol/l in DDP groups (p < 0.05); Apoptosis rates of SKOV3/DDP cells increased more than those of DDP groups. Accumulation of intracellular cisplatin in DDP + MNPs-Fe3O4 groups was higher than those in DDP groups (p < 0.05). Moreover, the expression of Bcl-2 mRNA and the protein expressions of MDR1, LRP, and P-gp were decreased when compared with those of DDP groups, respectively. Our results suggest that MNPs-Fe3O4 can reverse the DDP resistance to the ovarian carcinoma cell. The effects may be associated with over-expression of MDR1, LRP, P-gp, and Bcl-2, which can increase the intracellular platinum accumulation and induce the cell apoptosis.


Assuntos
Cisplatino/administração & dosagem , Portadores de Fármacos/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Compostos Férricos/química , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Magnetismo , Nanopartículas/ultraestrutura , Resultado do Tratamento
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