Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Neural Regen Res ; 14(12): 2126-2131, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31397351

RESUMO

The specific mechanisms by which acupuncture affects the central nervous system are unclear. In the International Standard Scalp Acupuncture system, acupuncture needles are applied at the middle line of the vertex, anterior parietal-temporal oblique line, and the posterior parietal-temporal oblique line. We conducted a single-arm prospective clinical trial in which seven healthy elderly volunteers (three men and four women; 50-70 years old) received International Standard Scalp Acupuncture at MS5 (the mid-sagittal line between Baihui (DU20) and Qianding (DU21)), the left MS6 (line joining Sishencong (EX-HN1) and Xuanli (GB6)), and the left MS7 (line joining DU20 and Qubin (GB7)). After acupuncture, resting-state functional magnetic resonance imaging demonstrated changes in the fractional amplitude of low frequency fluctuations and regional homogeneity in various areas, showing remarkable enhancement of regional homogeneity in the bilateral anterior cingulate, left medial frontal gyrus, supramarginal gyrus, right middle frontal gyrus, and inferior frontal gyrus. Functional connectivity based on a seed region at the right middle frontal gyrus (42, 51, 9) decreased at the bilateral medial superior frontal gyrus. Our data preliminarily indicates that the international standard scalp acupuncture in healthy elderly participants specifcally enhances the correlation between the brain regions involved in cognition and implementation of the brain network regulation system and the surrounding adjacent brain regions. The study was approved by the Ethics Committee of the China-Japan Union Hospital at Jilin University, China, on July 18, 2016 (approval No. 2016ks043).

2.
Sci Rep ; 6: 37052, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27845389

RESUMO

Hepatocellular carcinoma (HCC) is refractory to chemotherapies, necessitating novel effective agents. The lysosome inhibitor Bafilomycin A1 (BafA1) at high concentrations displays cytotoxicity in a variety of cancers. Here we show that BafA1 at nanomolar concentrations suppresses HCC cell growth in both 2 dimensional (2D) and 3D cultures. BafA1 induced cell cycle arrest in the G1 phase and triggered Cyclin D1 turnover in HCC cells in a dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) dependent manner. Notably, BafA1 induced caspase-independent cell death in HCC cells by impairing autophagy flux as demonstrated by elevated LC3 conversion and p62/SQSTM1 levels. Moreover, genetic ablation of LC3 significantly attenuated BafA1-induced cytotoxicity of HCC cells. We further demonstrate that pharmacological down-regulation or genetic depletion of p38 MAPK decreased BafA1-induced cell death via abolishment of BafA1-induced upregulation of Puma. Notably, knockdown of Puma impaired BafA1-induced HCC cell death, and overexpression of Puma enhanced BafA1-mediated HCC cell death, suggesting a role for Puma in BafA1-mediated cytotoxicity. Interestingly, pharmacological inhibition of JNK with SP600125 enhanced BafA1-mediated cytotoxicity both in vitro and in xenografts derived from HCC cells. Taken together, our data suggest that BafA1 may offer potential as an effective therapy for HCC.


Assuntos
Autofagia/efeitos dos fármacos , Carcinoma Hepatocelular , Caspases , Neoplasias Hepáticas , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrolídeos/farmacologia , Proteínas de Neoplasias , Animais , Autofagia/genética , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Caspases/genética , Caspases/metabolismo , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Sistema de Sinalização das MAP Quinases/genética , Camundongos , Camundongos Nus , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Environ Entomol ; 45(4): 1076-80, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27330147

RESUMO

Galeruca daurica (Joannis) is a new pest on the grasslands of Inner Mongolia, China. It is univoltine and overwinters in the egg stage. Larvae and adults feed on the foliage of Allium plants. To assess the requirements to terminate egg diapause and subsequent effects on post-diapause development rate, eggs were held at different temperature regimes. Exposure to low temperatures was required to terminate egg diapause. Prolonged exposure (2 mo vs 1 mo) to 5°C and outside ambient conditions (mean temperature: 10.5°C; range: -7.1-21.6°C) enhanced the termination of egg diapause. Prolonged exposure also reduced the time to egg hatch; e.g., eggs held for 2 mo versus 1 mo at 5°C developed more quickly when subsequently placed at warmer temperatures. Egg hatch was observed at 17, 21, 25, and 29°C, but not at 15°C. Regression analysis identified 16.2°C as the minimum temperature for post-diapause development. The temperature requirement to complete embryonic development (from diapause termination to egg hatch) was calculated to be 103.1 to 140.9 degree-days.


Assuntos
Besouros/crescimento & desenvolvimento , Diapausa de Inseto , Animais , China , Temperatura Baixa , Besouros/embriologia , Óvulo/crescimento & desenvolvimento
4.
Zhonghua Fu Chan Ke Za Zhi ; 51(1): 40-5, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-26899006

RESUMO

OBJECTIVE: To detect and explore the expression and clinical significance of dual specificity tyrosine phosphorylation regulated kinase1b (Dyrk1b) in the specimens and cells of cervical lesions. METHODS: (1) All the data were collected from 75 patients with cervical cancer and 52 cases with squamous intraepithelial lesion (SIL) admitted in the First Affiliated Hospital of Dalian Medical College during Jan. 2011 to Dec. 2013 and confirmed by pathological examination, included 60 cases of stage Ⅰ and 15 cases of stage Ⅱ, 12 cases with low-grade squamous intraepithelial lesion (LSIL) and 40 cases with high-grade squamous intraepithelial lesion (HSIL). While, 28 cases with chronic cervicitis were chosen as the control group. The protein expression of Dyrk1b was detected by immunohistochemistry among the four groups. (2) The expression of Dyrk1b in HeLa and SiHa cells were detected by western blot method and the expression of Dyrk1b protein were also detected after treatment of AZ191 (5, 10 µmol/L) for 48 hours in HeLa and SiHa cells. (3) The cellular survival and proliferation of HeLa and SiHa cells treated by different concentrations of AZ191 (2.5, 5, 10, 25, 50, 100 µmol/L) for 48 hours were detected by methyl thiazolyl tetrazolium (MTT) assay. (4) The rate of apoptosis of HeLa and SiHa cells was detected by flowcytometry after treatment of AZ191 (5, 10 µmol/L) for 48 hours. RESULTS: (1) The positive rates of Dyrk1b protein in chronic cervicitis, LSIL, HSIL and cervical squamous cancer by immunohistochemistry were 11%(3/28), 1/12, 42% (17/40) and 71% (53/75), respectively. The expression of Dyrk1b in cervical squamous cancer and HISL were higher than those in LSIL and chronic cervicitis (P<0.01), there were significant difference between cervical squamous cancer and HSIL, or between HSIL and LSIL (all P<0.05), while there were not significant difference between LSIL and chronic cervicitis (P>0.05). Expression of Dyrk1b was correlated with stromal invasion depth of cervical cancer (P<0.05), but not with age, clinical stage, lymph node metastasis, and serum squamous cell carcinom antigen (SCC-Ag) levels (all P>0.05). (2) Dyrk1b protein was expressed in different levels in HeLa and SiHa cells, and the expression of Dyrk1b was decreased gradually as the increased of the concentration of AZ191 in both HeLa and SiHa cells by treatment of AZ191 for 48 hours. (3) Different concentration of AZ191 treated on cervical cancer cells could inhibit the cellular proliferation and induce cell apoptosis in a concentration-dependent manner (P<0.01), concomitant to the decreased cell survival rate. The apoptosis rate of HeLa and SiHa were increased significantly after 10 µmol/L AZ191-treatment for 48 hours, but no any difference induced by 5 µmol/L AZ191-treatment compared to control group. Also,there was no any difference between Hela and SiHa cells in either inhibitory effect or apoptosis rate induced by AZ191. CONCLUSIONS: Dyrk1b is over-expressed in either specimens or cells of cervical cancer. The expression of Dyrk1b protein in cervical lesions is increased as the progression of disease. Dyrk1b inhibitor AZ191 could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner in cervical cancer cells.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasia Intraepitelial Cervical/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia , Apoptose , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Neoplasia Intraepitelial Cervical/genética , Neoplasia Intraepitelial Cervical/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Imuno-Histoquímica , Metástase Linfática , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/metabolismo , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
5.
Cancer Cell Int ; 13(1): 2, 2013 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-23311607

RESUMO

BACKGROUND: Mirk/Dyrk1B contributes to G0 arrest by destabilization of cyclin D1 and stabilization of p27kip1 to maintain the viability of quiescent human cancer cells, and it could be negatively regulated by mitogenic-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling. This study was performed to investigate the effect of Mirk/Dyrk1B on cell cycle and survival of human cancer cells involving MAPK/ERK signaling. METHODS: The correlations between Mirk/Dyrk1B expression and active ERK1/2 detected by western blot in both ovarian cancer and non-small cell lung cancer (NSCLC) cells were analyzed by simple regression. Mirk/Dyrk1B unique phosphopeptides with sites associated with Mirk/Dyrk1B protein were isolated and quantitated by liquid chromatography coupled to tandem mass/mass spectrometry (LC-MS/MS) proteomics analysis. The human cancer cells were treated with small interfering RNAs (siRNAs) and/or U0126, an inhibitor of MEK for indicated duration, followed by investigating the alterations of cell cycle and apoptosis as well as related proteins examined by flow cytometry and Western blot, respectively. RESULTS: Our study demonstrated the widely expressed Mirk/Dyrk1B proteins in the human cancer cells were positively correlated with the levels of activated ERK1/2. Moreover, Mirk/Dyrk1B protein expressions consistent with the tyrosine autophosphorylated levels in the human cancer cells were increased by U0126 or growth factor-depleted culture. Conversely, knockdown of Mirk/Dyrk1B by siRNA led to up-regulated activation of c-Raf-MEK-ERK1/2 pathway and subsequent changes in cell cycle proteins (cyclin D1, p27kip1), accompanied by increased growth rate and cells from G0/G1 into S of cell cycle which could be blocked by U0126 in a dose-dependent manner, indicating Mirk/Dyrk1B may sequester MAPK/ERK pathway, and vice versa. Whereas, combined Mirk siRNA and U0126 induced cell apoptosis in the human cancer cells. CONCLUSIONS: These data together show that Mirk/Dyrk1B mediates cell cycle and survival via interacting with MAPK/ERK signals and simultaneous inhibition of both pathways may be a novel therapeutic target for human cancer.

6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 26(11): 1330-5, 2012 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-23230667

RESUMO

OBJECTIVE: To evaluate the effectiveness of percutaneous vertebroplasty (PVP) in the treatment of osteoporotic vertebral compression fractures with or without intravertebral clefts by unilateral approach and the impact of intravertebral clefts on the effectiveness. METHODS: The clinical data of 65 patients who met the inclusion criteria of osteoporotic vertebral compression fracture were retrospectively analyzed. According to having intravertebral clefts or not, the patients were divided into 2 groups: cleft group (group A, n=25) and non-cleft group (group B, n=40). There was no significant difference in gender, age, cause of injury, the level of fracture vertebrae, degree of damage, and interval of injury and operation between 2 groups (P > 0.05). All patients were given PVP procedure by unilateral approach. The operation time, the injected volume of bone cement, time to ambulate, complications, and adjacent vertebral re-fracture were recorded. The height of anterior and middle column and the posterior convex Cobb angle of injured spine were measured on the lateral X-ray film in standing position at preoperation and 1, 48 weeks after operation. The visual analogue scale (VAS) score and Oswestry disability index (ODI) system were used to evaluate the pain relief and improvement of daily activity function respectively at preoperation and 1, 4, and 48 weeks after operation. RESULTS: There was no significant difference in the operation time and time to ambulate between 2 groups (P > 0.05). The injected volume of bone cement in group B was significantly less than that in group A (t=1.833, P=0.034). Asymptomatic cement leakage occurred in 6 patients (4 in group A and 2 in group B), in group A including 1 case of venous leakage, 2 cases of paravertebral leakage, and 1 case of intradiscal leakage; in group B including 2 cases of venous leakage. No symptomatic pulmonary embolism was observed. The vital sign was stable during operation and postoperatively. All patients were followed up 12-30 months (mean, 18.5 months). No re-fracture of the vertebrae occurred during the follow-up. The postoperative VAS score, ODI, the height of anterior and middle column, and the posterior convex Cobb angle of injured spine were improved significantly when compared with the preoperative ones in 2 groups (P < 0.05), but no significant difference was found between 2 groups at pre- and post-operation (P > 0.05). CONCLUSION: PVP by unilateral approach is safty and efficacy in the treatment of osteoporosis vertebral compression fracture combined with intravertebral clefts. Intravertebral clefts have no significant impact on the effectiveness in the pain relief and function improvement.


Assuntos
Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/métodos , Idoso , Idoso de 80 Anos ou mais , Cimentos para Ossos/uso terapêutico , Extravasamento de Materiais Terapêuticos e Diagnósticos/epidemiologia , Feminino , Fraturas por Compressão/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/patologia , Dor/etiologia , Medição da Dor , Estudos Retrospectivos , Fraturas da Coluna Vertebral/patologia , Coluna Vertebral/patologia , Coluna Vertebral/cirurgia , Resultado do Tratamento
7.
Int J Oncol ; 40(4): 1203-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22159921

RESUMO

Minibrain-related kinase (Mirk) is a serine/threonine kinase which is also known as the dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B). It is known that Dyrk1A, the closest family member to Mirk/Dyrk1B can mediate cellular localization of mammalian forkhead subclass O (FoxO1), a transcription factor, although the effect of Mirk/Dyrk1B on FoxO factors remains to be defined. In this study, we showed that Mirk/Dyrk1B protein was overexpressed in 5 of 8 ovarian cancer cell lines and negatively correlated with the protein level of FoxO factors (FoxO1+FoxO3A). Knockdown of Mirk by small interfering RNA (siRNA) resulted in cell apoptosis and sensitized cells to cisplatin accompanied by nuclear translocation of FoxO1 and/or FoxO3A as well as increased Bim, TRADD, cleaved caspase-3 and PARP. Furthermore, combined siRNAs of Mirk with FoxO1 and/or FoxO3A led to fewer apoptotic cells and cisplatin sensitivity compared to Mirk siRNA alone, suggesting that FoxO is involved in Mirk-mediated cell survival and chemosensitivity of ovarian cancer. Taken together, Mirk/Dyrk1B plays an important role in ovarian cancer cell survival through modulating FoxO translocation and may be a novel therapeutic target for ovarian cancer.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Adulto , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Feminino , Proteína Forkhead Box O1 , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Técnicas de Silenciamento de Genes , Humanos , Microscopia Confocal , Pessoa de Meia-Idade , Neoplasias Ovarianas/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética
8.
Artigo em Chinês | MEDLINE | ID: mdl-20839437

RESUMO

OBJECTIVE: To explore the effectiveness and methods of intervention assistant operation in the treatment of phalanx closed fracture combined with artery crisis. METHODS: Between August 2002 and December 2008, 24 cases (31 toes) of phalanx closed fracture combined with artery crisis were treated. There were 17 males (22 toes) and 7 females (9 toes), aged from 16 to 62 years (mean, 38 years). The causes of injury included crush and bruise (20 cases), traffic accident (3 cases), and machine twist (1 case). The locations were the first toe (19 toes), the second toe (10 toes), and the third toe (2 toes). The period between injury and hospitalization was 1-10 hours (mean, 6.8 hours). Phalanx angiography was performed by using venous indwelling needle for dorsalis pedis artery and posterior tibial artery puncture; according to angiography results, proper treatment could be done, then the contrast medium was injected to the artery to observe the blood supply. According to different types and locations of fracture, Kirschner wire and plate were chosen to fix fracture after the blood supply were recovered. RESULTS: Two cases (2 toes) received amputation due to necrosis at 4 days and 6 days after interventional therapy, respectively. Twenty-two cases (29 toes) survived. Incision healed primarily in 21 cases. Exudation occurred at wound of 1 case and was cured at 3 weeks after dressing change. Twenty-two cases (29 toes) were followed up 1-6 years (mean, 3.5 years) postoperatively. Two cases (3 toes) felt cool or anaesthesia and could not tolerate even in cold environment. The other toes had no senses of cold pain and paresthesia. Two cases (2 toes) had nonunion and achieved fracture healing after grafting bone. The mean union time was 4.5 months (range, 3-6 months) in other cases. CONCLUSION: Intervention assistant operation is an effective measure in the treatment of phalanx closed fracture combined with artery crisis.


Assuntos
Artérias/lesões , Fraturas Fechadas/terapia , Falanges dos Dedos do Pé/lesões , Adolescente , Adulto , Cateterismo Periférico , Feminino , Fixação Interna de Fraturas/métodos , Fraturas Fechadas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
Nat Chem Biol ; 6(4): 291-9, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20190765

RESUMO

We describe a strategy for comprehending signaling pathways that are active in lung cancer cells and that are targeted by dasatinib using chemical proteomics to identify direct interacting proteins combined with immunoaffinity purification of tyrosine-phosphorylated peptides corresponding to activated tyrosine kinases. We identified nearly 40 different kinase targets of dasatinib. These include SRC-family kinase (SFK) members (LYN, SRC, FYN, LCK and YES), nonreceptor tyrosine kinases (FRK, BRK and ACK) and receptor tyrosine kinases (Ephrin receptors, DDR1 and EGFR). Using quantitative phosphoproteomics, we identified peptides corresponding to autophosphorylation sites of these tyrosine kinases that are inhibited in a concentration-dependent manner by dasatinib. Using drug-resistant gatekeeper mutants, we show that SFKs (particularly SRC and FYN), as well as EGFR, are relevant targets for dasatinib action. The combined mass spectrometry-based approach described here provides a system-level view of dasatinib action in cancer cells and suggests both functional targets and a rationale for combinatorial therapeutic strategies.


Assuntos
Neoplasias Pulmonares/tratamento farmacológico , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Proteômica/métodos , Pirimidinas/farmacologia , Tiazóis/farmacologia , Apoptose , Linhagem Celular Tumoral , Dasatinibe , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Espectrometria de Massas , Peptídeos/química , Peptídeos/metabolismo , Fenótipo , Fosforilação/efeitos dos fármacos , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Pirimidinas/metabolismo , Pirimidinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Tiazóis/metabolismo , Tiazóis/uso terapêutico
10.
Int J Oncol ; 35(2): 337-45, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19578748

RESUMO

Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in human cancer including lung cancer and has been implicated in transformation, tumorigenicity, and metastasis. One putative downstream gene regulated by Stat3 is MUC1 which also has important roles in tumorigenesis. We determined if Stat3 regulates MUC1 in lung cancer cell lines and what function MUC1 plays in lung cancer cell biology. We examined MUC1 expression in non-small cell lung cancer (NSCLC) cell lines and found high levels of MUC1 protein expression associated with higher levels of tyrosine phosphorylated STAT3. STAT3 knockdown downregulated MUC1 expression whereas constitutive STAT3 expression increased MUC1 expression at mRNA and protein levels. MUC1 knockdown induced cellular apoptosis concomitant with reduced Bcl-XL and sensitized cells to cisplatin treatment. MUC1 knockdown inhibited tumor growth and metastasis in an orthotopic mouse model of lung cancer by activating apoptosis and inhibiting cell proliferation in vivo. These results demonstrate that constitutively activated STAT3 regulates expression of MUC1, which mediates lung cancer cell survival and metastasis in vitro and in vivo. MUC1 appears to be a cooperating oncoprotein with multiple oncogenic tyrosine kinase pathways and could be an effective target for the treatment of lung cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Mucina-1/fisiologia , Fator de Transcrição STAT3/fisiologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular , Cisplatino/uso terapêutico , Proteína-Tirosina Quinases de Adesão Focal/fisiologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Mucina-1/genética , Invasividade Neoplásica , Fosforilação , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais
11.
Cancer Biol Ther ; 8(17): 1671-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19633423

RESUMO

Minibrain-related kinase (Mirk) is a member of the dual specificity tyrosine-phosphorylation-regulated kinase (Dyrk)/minibrain family of dual-specificity protein kinases and is identical to Dyrk1B. Mirk/Dyrk1B is a serine/threonine kinase that has been found to be upregulated in solid tumors and mediates cell survival in colon cancer, pancreatic ductal adenocarcinoma and rhabdomyosarcomas. There is little known about Mirk in lung cancer. In the present study, we showed that Mirk protein was widely overexpressed in 13 of 19 NSCLC cell lines. Mirk immunoprecipitation coupled with anti-phosphotyrosine western blotting confirmed tyrosine phosphorylation of Mirk in NSCLC cells. Mirk knockdown by small interfering RNA induced cell apoptosis concomitant with upregulation of Bak, a Bcl-2 family member, and downregulation of signal transducers and activators of transcription 3 (STAT3) tyrosine phosphorylation. Mirk knockdown led to decreased cell colony formation in vitro as well as delayed tumor growth in an orthotopic mouse model and sensitized cells to cisplatin-induced apoptosis. Using automated quantitative determination of the Mirk protein in tumor specimens of patients with early-stage lung cancer, overexpression of Mirk was found in nearly 90% of tumor specimens in both the cytoplasm and nucleus. These results suggest that Mirk is overexpressed in lung cancer, acts as a survival factor in lung cancer cells and may be a novel therapeutic target.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Adulto , Idoso , Animais , Apoptose , Western Blotting , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Modelos Animais de Doenças , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/biossíntese , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/biossíntese , Proteínas Tirosina Quinases/deficiência , Proteínas Tirosina Quinases/genética , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Transfecção , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo
12.
Cancer Sci ; 100(3): 389-95, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19154413

RESUMO

Hyperleptinemia is a common feature of obese women who have a higher risk of endometrial cancer than women with normal weights, and epidemiologic studies have suggested a correlation between obesity and endometrial carcinoma. Therefore, understanding of the molecular mechanism involved in leptin signaling transduction is important in endometrial cancer prevention and treatment. In this study, both isoforms of the leptin receptor (Ob-R), the long form (Ob-Rb) and short form (Ob-Ra), were detected as being expressed in six endometrial cancer cell lines with various differentiation status by western blotting, and Ob-Ra was found to be more abundant than Ob-Rb in these cells. Moreover, the expressions of both isoforms were inversely correlated with histoprognostic grading. We also showed that leptin stimulated cell proliferation and induced activations of signal transducers and activators of transcription 3 (STAT3), extracellular signal-regulated kinase (ERK1/2), AKT, and cyclooxygenase (COX)-2 in endometrial cancer cells dose-dependently by [(3)H] thymidine incorporation assay and western blotting. Leptin-stimulation resulted in increased expression of COX-2 mRNA and prostaglandin E2 (PGE2) production of endometrial cancer cells by reverse transcription-polymerase chain reaction and enzyme immunoassay, respectively, which was effectively blocked by pharmacological inhibitors of Janus tyrosine kinase 2 (JAK2), AG490; of mitogen-activated protein kinase (MAPK) kinase, U0126; of phosphatidylinositol 3-kinase (PI3K), LY294002; and of COX-2, NS398. These results suggest that leptin promotes cell proliferation of endometrial cancer cells via the aforementioned multiple signal-transduction pathways. Leptin-induced functional activation of COX-2 is JAK2/STAT3-, MAPK/ERK-, and PI3K/AKT-dependent, indicating that COX-2 may be a critical factor of endometrial carcinogenesis in obesity.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Neoplasias do Endométrio/metabolismo , Ativação Enzimática/fisiologia , Leptina/metabolismo , Transdução de Sinais/fisiologia , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imunoensaio , Janus Quinase 2/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores para Leptina/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/metabolismo
13.
Zhongguo Gu Shang ; 21(1): 7-9, 2008 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-19102258

RESUMO

OBJECTIVE: To explore the feasibility of percutaneous vertebroplasty for the treatment of acute burst thoracolumbar fracture. METHODS: Fifty-eight patients (male 38 and female 20, ranging in age from 38 to 70 years, with an average of 56.8 years) with acute burst thoracolumbar fracture were treated by percutaneous vertebroplasty. The injuried vertebrae were T11 in 3 cases, T12 18 cases, L1 29 cases, L2 5 cases and L3 3 cases. All suited cases were classified into 3 types according to injuried vertebral shapes,type I (safe type 26 cases), type II (risk type 21 cases), and type III (marginal type 11 cases). RESULTS: All the patients were followed up ranging from 1 to 2.5 years (mean 1.6 years). Fifty-three patients could walk in 1 to 3 days after operation. Among 55 patients who obtained complete recovery (CR), 39 patients could do daily works and 16 patients could do houseworks. The CR rate was 95%. Three patients who obtained partial recovery (PR), could live by themselves and felt slight lumbago after movements. The PR rate was 5%. CONCLUSION: Percutaneous vertebroplasty for the treatment of acute burst thoracolumbar fracture is a feasible and effective method even for particular risks.


Assuntos
Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Vertebroplastia/métodos , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Radiografia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/cirurgia
14.
J Asian Nat Prod Res ; 10(7-8): 673-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18636380

RESUMO

Two new xanthone O-glycosides, polyhongkongenosides A (1) and B (2), together with four known xanthone glycosides, were isolated from the herbs of Polygala hongkongensis Hemsl. Their structures were elucidated on the basis of UV, IR, NMR, and MS spectral data. The antioxidant in vitro activities of 1-6 were determined by the scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals and hydroxyl radicals and their reductive activities to Fe3+. Mangiferin, one of the four known xanthone glycosides, showed potential scavenging effect on DPPH and hydroxy radicals and reductive activity to Fe3+ with IC50 values of 4.7, 13.9, 23.7 microM, respectively.


Assuntos
Antioxidantes/química , Glicosídeos/química , Polygala/química , Xantonas/química , Compostos de Bifenilo/química , Hidrazinas/química , Estrutura Molecular , Picratos
15.
Nat Prod Res ; 21(7): 580-4, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17613814

RESUMO

A new dihydroisocoumarins, 6-methoxy-8-hydroxy-3-(4-hydroxyphenyl)isochroman-1-one, named as hongkongenin (1), and seven known flavonoids were isolated from the methanol extract whole plant of Polygala hongkongensis Hemsl. Their structures were established on the basis of UV, IR, NMR, and MS spectral data. It is the first report of the occurrence of isocoumarins in Polygala, and the known compounds 2-8 were isolated from this plant for the first time. Flavonoids showed potent antioxidant activities in vitro against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, hydroxyl radicals, and reductive activity to Fe3+.


Assuntos
Antioxidantes/isolamento & purificação , Isocumarinas/isolamento & purificação , Polygala/química , Antioxidantes/química , Compostos de Bifenilo/química , Flavonoides/química , Flavonoides/isolamento & purificação , Depuradores de Radicais Livres/química , Depuradores de Radicais Livres/isolamento & purificação , Hidrazinas/química , Radical Hidroxila/química , Concentração Inibidora 50 , Ferro/química , Isocumarinas/química , Ressonância Magnética Nuclear Biomolecular , Rotação Ocular , Picratos , Componentes Aéreos da Planta/química , Plantas Medicinais/química , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Zhongguo Zhong Yao Za Zhi ; 32(21): 2256-8, 2007 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-18309667

RESUMO

OBJECTIVE: To investigate the chemical constituents of the rhizomes of Actaea asiatica in order to obtain a more comprehensive understanding of its effective components. METHOD: Compounds were separated by silica gel chromatography, RP-C18 chromatography and semi-preparative high performance liquid chromatography, and their structures were established by spectral analysis and chemical evidence. RESULT: Six compounds were isolated from the ethyl acetate extract. Their structures were identified as 25-O-acetylcimigenol (1), 12beta-hydroxycimigenol (2), 23-epi-26-deoxyactein (3), 27-deoxyacetylacteol (4), 26-deoxycimicifugenin (5) and beta-sitosterol (6). CONCLUSION: All these compounds mentioned above were isolated from the plant for the first time.


Assuntos
Actaea/química , Plantas Medicinais/química , Rizoma/química , Saponinas/isolamento & purificação , Triterpenos/isolamento & purificação , Lanosterol/análogos & derivados , Lanosterol/química , Lanosterol/isolamento & purificação , Saponinas/química , Sitosteroides/química , Sitosteroides/isolamento & purificação , Triterpenos/química
17.
J Nat Prod ; 69(10): 1500-2, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17067171

RESUMO

Three new 9,19-cycloartane triterpene glycosides, asiaticoside A (1), asiaticoside B (2), and 25-O-ethylcimigenol-3-O-beta-D-xylopyranoside (3), together with cimiacemoside I (4), 25-O-acetylcimigenol-3-beta-O-D-xyloside (5), and 25-anhydrocimigenol-beta-O-D-xyloside (6) were isolated from the roots/rhizomes extract of Actaea asiatica, and their structures were established by spectroscopic methods (IR, HRESIMS, and NMR). Compounds 1-3, 5, and 6 had notable cytotoxicity against HepG2 and MCF-7 cancer cell lines.


Assuntos
Actaea/química , Antineoplásicos Fitogênicos , Medicamentos de Ervas Chinesas , Plantas Medicinais/química , Saponinas , Triterpenos , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Raízes de Plantas/química , Rizoma/química , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
18.
Int J Oncol ; 26(3): 737-44, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15703831

RESUMO

The extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway plays a critical role in the anticancer action in vitro. ERK1/2 activation or phosphorylation is responsible for increased cyclooxygenase-2 (COX-2) protein expression in some cancer cells treated with selective COX-2 inhibitor NS398. We determined the effect of NS398 on ERK signaling and the synergistic effect of combined treatment with NS398 and a specific MEK inhibitor U0126 on three human endometrial cancer cell lines: Ishikawa, HEC-1A and AN3CA cells. Results showed that NS398 and U0126 individually, and especially the combination of both exhibited profound anti-proliferation of all three cell lines in a time- and concentration-dependent manner by [3-(4, 5)-dimethylthiazol-z-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay. The phosphorylated ERK1/2 was up-regulated in HEC-1A and AN3CA cells, but the COX-2 protein expression was unchanged in the three cancer cell lines treated with NS398 alone. However, both phosphorylated ERK1/2 and COX-2 protein expression were concentration-dependently decreased in all three cell types by combined treatment with NS398 and U0126 assessed by western blot analysis. Simultaneously, the combination of NS398 and U0126 resulted in 2-fold increase in apoptosis of all three lines over that by the individual alone, and enhanced G0/G1 phase arrest of Ishikawa and HEC-1A cells induced by U0126 treatment determined by flow cytometry. The synergistic and complementary effects of combining NS398 and U0126 were found to be associated with activation of caspase-3, alterations of Bcl-2 family proteins and cell cycle regulatory proteins detected by western blot analysis. Taken together, these findings correlate with blocking MEK-ERK signaling cascade and down-regulating COX-2 protein expression in endometrial cancer cells with combination treatment of NS398 and U0126, suggesting that the combinatory use of NS398 and specific MEK inhibitors may be valuable for chemotherapy or chemoprevention of human endometrial cancer.


Assuntos
Butadienos/farmacologia , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase/farmacologia , Neoplasias do Endométrio/patologia , Inibidores Enzimáticos/farmacologia , Nitrilos/farmacologia , Nitrobenzenos/farmacologia , Sulfonamidas/farmacologia , Western Blotting , MAP Quinases Reguladas por Sinal Extracelular/farmacologia , Feminino , Humanos , MAP Quinase Quinase Quinases/farmacologia , Transdução de Sinais , Células Tumorais Cultivadas
19.
Cancer Sci ; 95(11): 901-7, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15546508

RESUMO

We determined the effects of several non-steroidal anti-inflammatory drugs (NSAIDs), aspirin (acetylsalicylic acid, ASA), indomethacin and a cyclooxygenase-2 (COX-2)-selective inhibitor (NS398), on cellular proliferation and regulation of COX-2 protein expression in endometrial cancer cells in vitro, and investigated their modes of action. All three NSAIDs markedly inhibited the proliferation of Ishikawa, HEC-1A and AN3CA endometrial cancer cell lines in a time- and concentration-dependent manner. ASA and indomethacin triggered apoptosis in cells of all three lines through release of cytosolic cytochrome c, activation of caspase-9 and-3, and cleavage of poly(ADP-ribose) polymerase (PARP), but NS398 induced minimal apoptosis only in Ishikawa cells. ASA altered the cell cycle distribution, with G2/M phase accumulation of cells, and induced overexpression of Ki-67 protein. Both ASA and indomethacin reduced the protein levels of Bcl-2 and Bcl-xl, but upregulated those of Bax and Bcl-xs. COX-2 protein expression and PGE(2) production were upregulated by ASA and indomethacin in all three cell lines. However, NS398 did not alter COX-2 protein expression or PGE(2) production in these cells. These results indicate that NSAIDs inhibit proliferation of endometrial cancer cells independently of the reduction of COX-2 protein expression. A cytochrome c-dependent apoptotic pathway and/or cell cycle arrest may contribute to the inhibitory effects of these NSAIDs.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Neoplasias do Endométrio/enzimologia , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Apoptose , Aspirina/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/farmacologia , Ativação Enzimática , Feminino , Humanos , Indometacina/farmacologia , Proteínas de Membrana , Células Tumorais Cultivadas
20.
Biol Pharm Bull ; 27(2): 156-61, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14758024

RESUMO

Juzen-taiho-to, a Kampo formula, originally consists of a mixture of Shimotsu-to and Shikunshi-to formulas together with two other crude ingredients. Juzen-taiho-to is reported to have a preventive effect on endometrial carcinogenesis in mice. Shimotsu-to exerts an inhibitory effect on estrogen-induced expression of c-fos, interleukin (IL)-1alpha and tumor necrosis factor (TNF)-alpha in uteri of ovarectomized mice. In the present study, short- and long-term experiments were designed to determine the effects of Juzen-taiho-to and Shimotsu-to on the estrogen-related endometrial carcinogenesis in mouse uteri, associated with the expression of cyclooxygenase (COX)-1 and -2. In the short-term experiment, exposure to Juzen-taiho-to or Shimotsu-to significantly reduced estradiol-17beta (E(2))-stimulated expressions of COX-2 mRNA (p<0.05) as well as the protein. However, no effects on the expression of COX-1 were observed. Shikunshi-to did not affect COX expression. In the long-term experiment, 90 female ICR mice were given N-methyl-N-nitrosourea (MNU) into their uterine corpora. The animals were divided into four groups as follows: group 1, a diet containing 0.07% Shimotsu-to and 5 ppm E(2); group 2, a diet containing 5 ppm E(2); group 3, a diet containing 0.07% Shimotsu-to; group 4 served as a control. Exposure of Shimotsu-to reduced the incidence of MNU- and E(2)-induced endometrial adenocarcinoma and atypical hyperplasia at the termination of the experiment (30 weeks). The above findings and our previous reports suggest that Shimotsu-to is responsible for the preventive effects of Juzen-taiho-to on estrogen-related endometrial carcinogenesis in mice, through the inhibition of estrogen-related COX-2 as well as c-fos, IL-1alpha and TNF-alpha expressions.


Assuntos
Anticarcinógenos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias do Endométrio/prevenção & controle , Animais , Anticarcinógenos/química , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Medicamentos de Ervas Chinesas/química , Neoplasias do Endométrio/induzido quimicamente , Neoplasias do Endométrio/metabolismo , Estradiol , Feminino , Isoenzimas/biossíntese , Isoenzimas/genética , Medicina Kampo , Proteínas de Membrana , Metilnitrosoureia , Camundongos , Camundongos Endogâmicos ICR , Prostaglandina-Endoperóxido Sintases/biossíntese , Prostaglandina-Endoperóxido Sintases/genética , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA