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1.
Am J Cancer Res ; 13(8): 3482-3499, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693144

RESUMO

Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.

2.
Food Funct ; 14(10): 4621-4631, 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37158592

RESUMO

The abnormal accumulation of fused in sarcoma (FUS) is a pathological hallmark in a proportion of patients with frontotemporal dementia and amyotrophic lateral sclerosis. Therefore, the clearance of FUS aggregates is a possible therapeutic strategy for FUS-associated neurodegenerative diseases. This study reports that curcumin can strongly suppress FUS droplet formation and stress granule aggregation of FUS. Fluorescence spectra and isothermal titration calorimetry showed that curcumin can bind FUS through hydrophobic interactions, thereby reducing the ß-sheet content of FUS. Aggregated FUS sequesters pyruvate kinase, leading to reduced ATP levels. However, results from a metabolomics study revealed that curcumin changed the metabolism pattern and differentially expressed metabolites were enriched in glycolysis. Curcumin attenuated FUS aggregation-mediated sequestration of pyruvate kinase and restored cellular metabolism, consequently increasing ATP levels. These results indicate that curcumin is a potent inhibitor of FUS liquid-liquid phase separation and provide novel insights into the effect of curcumin in ameliorating abnormal metabolism.


Assuntos
Curcumina , Demência Frontotemporal , Sarcoma , Humanos , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , Curcumina/farmacologia , Demência Frontotemporal/metabolismo , Trifosfato de Adenosina , Mutação , Proteína FUS de Ligação a RNA/química , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo
3.
Chem Biodivers ; 18(5): e2001069, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33855794

RESUMO

Breast cancer is one of the most common cancer with high morbidity and mortality in women. This study aimed to explore the potential mechanism of costunolide inducing MCF-7 cells apoptosis by multi-spectroscopy, molecular docking, and cell experiments. The results manifested that costunolide interacted with calf thymus DNA (ct-DNA) in a spontaneous manner, and the minor groove as the preferential binding mode. Furthermore, costunolide inhibited cell proliferation and colony formation. Hoechst 33258 staining showed that cell apoptosis induced by costunolide might be related to DNA damage. The apoptosis mechanism relied on regulating the protein expression of Bax, Bcl-2, p53, Caspase-3 and the activation of p38MAPK and nuclear factor κB (NF-κB) pathways. This study will provide some experimental basis and potential therapeutic strategy for breast cancer treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Simulação de Acoplamento Molecular , Sesquiterpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Bovinos , Proliferação de Células/efeitos dos fármacos , DNA/química , DNA/efeitos dos fármacos , Dano ao DNA , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Células MCF-7 , Sesquiterpenos/química , Espectrofotometria Ultravioleta
4.
Chin J Nat Med ; 17(10): 778-784, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31703758

RESUMO

Thibetanosides E-H (1-4), four new steroidal constituents including three rare sulfonates (2-4), were isolated from the roots and rhizomes of Helleborus thibetanus, together with nine known steroidal compounds (5-13). Their structures were elucidated by detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical evidence. In this study, compounds 2-13 were evaluated for their cytotoxic activities against HCT116, A549 and HepG2 tumor cell lines in vitro. Among them, compound 8 (thibetanoside C) showed cytotoxicities against A549 cells(IC50 39.6 ± 1.9 µmol·L-1) and HepG2 cells(IC50 41.5 ± 1.1 µmol·L-1), respectively. Compound 9 (23S, 24S)-24-[(O-ß-D-fucopyranosyl)oxy]-3ß, 23-dihydroxy-spirosta-5, 25(27)-diene-1ß-ylO-(4-O-acetyl- α-L-rhamnopyranosyl)-(1→2)-O-[ß-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside) showed cytotoxicity against HCT116 cells(IC50 33.6 ± 2.1 µmol·L-1).


Assuntos
Citotoxinas/química , Medicamentos de Ervas Chinesas/química , Helleborus/química , Esteroides/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citotoxinas/isolamento & purificação , Citotoxinas/toxicidade , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Estrutura Molecular , Raízes de Plantas/química , Esteroides/isolamento & purificação , Esteroides/farmacologia
5.
Chin J Nat Med ; 17(8): 624-630, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31472900

RESUMO

Five new polyhydroxylated furostanol saponins were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as tupistrosides J-N (1-5), together with four known furostanol saponins (6-9), on the basis of physico-chemical properties and spectral analysis. Among them, compounds 3 and 5 showed cytotoxicity against human cancer cell lines SW620 with IC50 values of 72.5 ± 2.4 and 77.3 ± 2.5 µmol·L-1, respectively. Compound 4 showed cytotoxicity against human cancer cell line HepG2 with IC50 value of 88.6 ± 2.1 µmol·L-1.


Assuntos
Antineoplásicos/química , Liliaceae/química , Saponinas/química , Esteróis/química , Células A549 , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Extratos Vegetais/química , Rizoma/química , Saponinas/farmacologia , Esteróis/farmacologia
6.
Molecules ; 23(5)2018 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-29724065

RESUMO

Inflammatory bowel disease (IBD) is a notable health problem and may considerably affect the quality of human life. Previously, the protective roles of tryptanthrin (TRYP) against dextran sulfate sodium (DSS) induced colitis has been proved, but the concrete mechanism remained elusive. It has been suggested that TRYP could diminish the weight loss and improve the health conditions of mice with DSS induced colitis. Hematoxylin and eosin staining revealed that TRYP could improve the histopathological structure of the colon tissue. Two signaling pathways (TNF-α/NF-κBp65 and IL-6/STAT3) were investigated using immunochemistry and western blot. The detected concentrations of the two cytokines TNF-α and IL-6 showed that their levels decreased after TRYP treatment of the colitis. The protein expression level of NF-κBp65 in cytoplasm increased after TRYP treatment of the induced colitis. However, the protein level of NF-κBp65 in the nucleus decreased after administration of TRYP. The expression level of IκBα, the inhibitory protein of NF-κBp65, was tested and the results suggested that TRYP could inhibit the degradation of IκBα. The phosphorylation level of STAT3 was inhibited by TRYP and the expression level of STAT3 and p-STAT3 decreased after administration of TRYP. We conclude that TRYP improves the health condition of mice with DSS induced colitis by regulating the TNF-α/NF-κBp65 and IL-6/STAT3 signaling pathways via inhibiting the degradation of IκBα and the phosphorylation of STAT3.


Assuntos
Colite , Sulfato de Dextrana/toxicidade , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Quinazolinas/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/patologia , Masculino , Camundongos
7.
Molecules ; 21(10)2016 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-27689974

RESUMO

Cordycepin is an active component of the traditional Chinese medicine Cordyceps sinensis and Cordyceps militaris with notable anticancer activity. Though the prominent inhibitory activity was reported in different kinds of cancer cell lines, the concrete mechanisms remain elusive. It was reported that cordycepin could be converted into tri-phosphates in vivo to confuse a number of enzymes and interfere the normal cell function. For the inhibitory mechanism of EGFR inhibitors and the structure similarity of ATP and tri-phosphated cordycepin, human lung cancer cell line H1975 was employed to investigate the inhibitory effect of cordycepin. The results showed that cordycepin could inhibit cell proliferation and induce apoptosis in a dose-dependent manner. Cell cycle analysis revealed that H1975 cells could be arrested at the G0/G1 phase after cordycepin treatment. The expression levels of apoptosis-related protein Caspase-3 and Bcl-2 and phosphorylated expression levels of EGFR, AKT and ERK1/2 were all decreased compared with the control group stimulated with EGF. However, the protein expression levels of proapoptotic protein Bax and cleaved caspase-3 were increased. These results implied that cordycepin could inhibit cell proliferation and induce apoptosis via the EGFR signaling pathway. Our results indicated that there was potential to seek a novel EGFR inhibitor from cordycepin and its chemical derivatives.

8.
Mol Med Rep ; 12(2): 2383-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25892617

RESUMO

The present study aimed to determine the antitumor effects of polysaccharides extracted from Pleurotus ostreatus mycelium on gastric cancer in vitro and in vivo. Polysaccharides were extracted from Pleurotus ostreatus mycelium and an antitumor component, known as Pleurotus ostreatus mycelium polysaccharides 2 (POMP2), with a relative molecular weight of 29 kDa, was then sequentially purified using Sephadex G200 size-exclusion chromatography and diethylaminoethyl-52 cellulose ion-exchange chromatography. The MTT method was used to determine the proliferation of BGC-823 cells treated with POMP2; cell migration assay, colony formation assay and in vivo antitumor tests were used to assess the effect of POMP2 on migration, cell survival and the in vivo tumor formation of BGH-823 cells. Results of the MTT assay indicated that POMP2 had a marked inhibitory effect on the BGC-823 human gastric cancer cell line; when administered at a concentration of 400 mg/l for 72 h, the rate of inhibition was 35.6%. In addition, the colony forming capacity of the BGC-823 cells was significantly reduced following treatment with POMP2. A migration assay indicated that the invasive capabilities of the BGC-823 cells were also significantly inhibited by POMP2. Furthermore, in vivo tests of mice engrafted with BGC-823 cancer cells demonstrated that both tumor weight and volume were markedly reduced following two weeks of treatment with POMP2. The results of the present study suggested that the polysaccharide POMP2 may have a potential application as a natural antitumor treatment for gastric cancer.


Assuntos
Antineoplásicos/farmacologia , Carcinoma/tratamento farmacológico , Polissacarídeos Fúngicos/farmacologia , Micélio/química , Pleurotus/química , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Carcinoma/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Gástricas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Yao Xue Xue Bao ; 50(12): 1613-21, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27169285

RESUMO

Thirteen of 4-anilinoquinazoline derivatives with imine groups at position 6 of quinazoline ring were synthesized and their antitumor activities were evaluated by MTT assay and Western blotting analysis. Among these compounds, 13a-131 were reported first time. The MTT assay was carried out on three human cancer cell lines (A549, HepG2 and SMMC7721) with EGFR highly expressed. Among the tested compounds, 13i and 13j exhibited notable inhibition potency and their IC50 values on three cell lines were equivalent to or less than those of gefitinib. Compound 14, without imine group substituted, displayed excellent inhibitor potency only on A549 cell line. Compounds 14 and 13j were chosen to perform Western blotting analysis on A549. The results showed that both of the compounds could inhibit the expression level of phosphorylated EGFR remarkably. It was concluded that the inhibitor potency of compound 14 was almost equivalent to that of gefitinib and the inhibitor potency of 13j was better than that of gefitinib.


Assuntos
Compostos de Anilina/farmacologia , Antineoplásicos/farmacologia , Receptores ErbB/antagonistas & inibidores , Quinazolinas/farmacologia , Linhagem Celular Tumoral , Gefitinibe , Humanos , Concentração Inibidora 50 , Fosforilação
10.
Planta Med ; 80(17): 1597-604, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25340467

RESUMO

Total steroid saponins isolated from Dioscorea zingiberensis have shown a variety of beneficial bioactivities. However, there are no reports about their neuroprotective effects, until now. Therefore, in the present study, we explored the neuroprotective effects of the total steroid saponins from D. zingiberensis on rats against transient focal cerebral ischemia-reperfusion and their underlying mechanisms. Healthy adult Sprague-Dawley rats were randomly assigned to six groups. After pretreatment with D. zingiberensis total steroid saponins intragastrically for six days, the rats were subjected to an ischemia injury by surgery on the middle cerebral artery occlusion for 90 min. Compared to the ischemia-reperfusion group, the D. zingiberensis total steroid saponin group of rats, especially those given a 30-mg/kg dose, showed not only a marked reduction in neurological deficit scores, cerebral infarct volume, and brain edema, but also an increase in neuron survival (Nissl bodies) in the hippocampal cornuammons 1 and cortex hemisphere of the ipsilateral ischemia. At the same time, the inflammatory cytokines in serum induced by the middle cerebral artery occlusion were significantly decreased by the preadministration of D. zingiberensis total steroid saponins. Furthermore, the increase of caspase-3 was evidently reduced in the hippocampal cornuammons 1 and cortex of the hemisphere injured brain. Finally, the downregulating antiapoptotic Bcl-2 and upregulating proapoptotic Bax proteins were obviously suppressed. Taken together, the current findings suggest that D. zingiberensis total steroid saponins played a potential neuroprotective role against a severe injury induced by transient focal cerebral ischemic reperfusion in a rat experimental model, and this role may be mediated by its anti-inflammatory and antiapoptotic actions.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Dioscorea/química , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Saponinas/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Masculino , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Ratos Sprague-Dawley , Saponinas/química , Saponinas/isolamento & purificação
11.
J Huazhong Univ Sci Technolog Med Sci ; 34(5): 646-651, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25318872

RESUMO

Inflammation plays an essential role in the pathophysiology of atherosclerosis. Our study was aimed to investigate whether salvianolate, a novel water-soluble phenolic compound of Danshen, alleviates atherosclerosis via regulating the inflammation in rats. High fat diet feeding plus vitamin D3 injection was used to induce atherosclerosis in rats. Salvianolate (60, 120 or 240 mg/kg) or placebo was given to atherosclerotic rats. The plasma lipids, interleukin 6 (IL-6) and C reactive protein (CRP) were measured by ELISA. CD4+CD25+Foxp3+ cells were determined by flow cytometry. Histological changes were examined by hematoxylin and eosin staining. The results showed that the levels of plasma IL-6 and CRP were elevated in the rats fed on high fat diet, and the histological analysis demonstrated the successful establishment of atherosclerosis models. Treatment with salvianolate alleviated the atherosclerotic process and decreased the levels of plasma IL-6 and CRP. Also the number of CD4+CD25+Foxp3+ cells was increased in salvianolate-treated rats. It was concluded that salvianolate could treat atherosclerosis via modulating the inflammation at cytokine and cell levels.


Assuntos
Aterosclerose/prevenção & controle , Inflamação/prevenção & controle , Extratos Vegetais/farmacologia , Salvia miltiorrhiza/química , Animais , Aterosclerose/sangue , Aterosclerose/etiologia , Proteína C-Reativa/metabolismo , Colecalciferol/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Inflamação/sangue , Interleucina-6/sangue , Lipídeos/sangue , Contagem de Linfócitos , Masculino , Fitoterapia , Ratos Wistar , Receptores de Complemento 3b/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Vitaminas/administração & dosagem
12.
Eur J Radiol ; 81(11): 3504-10, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22658867

RESUMO

OBJECTIVE: To retrospectively review the imaging features of surgically and pathologically confirmed intracranial hemangiopericytoma and anaplastic hemangiopericytoma. METHODS: Thirty-nine cases of surgically and pathologically confirmed hemangiopericytoma and anaplastic hemangiopericytoma were analyzed retrospectively. The MRI features were compared with pathological findings in all cases. RESULTS: Of the 39 cases, 21 were anaplastic hemangiopericytoma (WHO grade III) and the remaining cases were hemangiopericytoma (WHO grade II); all lesions were solitary. MRI of anaplastic hemangiopericytoma showed that 20 cases were lobulated, and nine grew cross-leaf. The lesions showed mixed iso-high-low signal (n=20) or iso-signal (n=1) on plain T1WI, and mixed high-low signal (n=20) or iso-signal (n=1) on plain T2WI. After contrast injection, marked heterogeneous enhancement was seen in 19 cases. Significant necrosis and cystic changes were seen in 16 cases, and the "dural tail sign" was found in two cases. Ten cases had bony destruction, and 16 showed significant peritumoral edema. In 18 cases of hemangiopericytoma, nine were oval-shaped and three grew cross-leaf. The lesions showed mixed iso-low signal (n=10) or iso-signal (n=8) on plain T1WI, and mixed iso-high signal (n=10) or iso-signal (n=8) on plain T2WI. After contrast injection, significant uniform enhancement was seen in 10 cases. Significant necrosis and cystic changes were seen in seven cases, and "dural tail sign" was seen in six cases. Two cases had bony destruction. No case showed significant peritumoral edema. Pathological immunohistochemical Ki67 staining showed a concentration of ∼18.4% positive cells in anaplastic hemangiopericytoma, whereas in hemangiopericytoma it was 7.12%. CONCLUSION: Imaging findings of intracranial anaplastic hemangiopericytoma had more pronounced lobulation, cross-leaf growth tendency, more and easier bleeding, more necrosis, more cystic changes giving rise to heterogeneous signals, rarer frequency of the "dural tail sign", more damage near the skull, and more significant peritumoral edema than hemangiopericytoma. These features may help differentiate these two types of malignancy.


Assuntos
Neoplasias Encefálicas/patologia , Encéfalo/patologia , Hemangiopericitoma/patologia , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
13.
Yao Xue Xue Bao ; 47(1): 72-6, 2012 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-22493808

RESUMO

A series of paeonol derivatives have been synthesized by simple acylation and etherification of the paeonol. Anti-tumor activities of the synthesized compounds were evaluated against HeLa and MCF-7 cells lines in vitro by the standard MTT assay. It was found that the derivatives were more active against HeLa than MCF-7. The results also indicated that 4-methoxy group is the synergistic group of paeonol's anti-tumor activity and ketone carbonyl side chain is essential functional group of paeonol's anti-tumor activity. Compound 2d had stronger antiproliferative activities than paeonol against HeLa and MCF-7 cell lines with IC50 values of 2.67 and 4.74 micromol x L(-1) respectively. The results showed that paeonol derivatives were worth to be intensively studied further.


Assuntos
Acetofenonas/síntese química , Antineoplásicos Fitogênicos/síntese química , Proliferação de Células/efeitos dos fármacos , Acetofenonas/química , Acetofenonas/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Concentração Inibidora 50 , Células MCF-7 , Relação Estrutura-Atividade
14.
Eur J Radiol ; 81(5): 968-73, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21354736

RESUMO

OBJECTIVE: To discuss the MRI features of the intracranial lymphoplasmacyte-rich meningioma and the correlation between the MRI features and pathology. METHODS: Review retrospectively the MRI and pathologic data of seven patients with lymphoplasmacyte-rich meningioma which were confirmed by surgery and pathology. RESULTS: The seven cases of lymphoplasmacyte-rich meningioma were solitary, six cases demonstrated flat growth along the meninges, five cases had not yet formed specific nodules, and two cases exhibited irregular lobulation. Seven cases had no clear boundary, peritumoral brain edema was obvious and adjacent brain tissues were invaded to varying degrees. After plain MRI scans, the focuses of seven cases exhibited lower-isointense signal in T1WI, five cases revealed higher-isointense signal and two cases showed lower-isointense signal in T2WI. Enhancement scans demonstrated marked enhancement in seven cases, and the meninges in six cases thicken irregularly and extensively. Pathology showed the richness and diversity of cells, an infiltration containing plasma cells and lymphocytes, as well as the unequal areas of neoplastic spindle cells and meninge epithelial cells. CONCLUSION: Lymphoplasmacyte-rich meningioma is a subtype meningioma of WHO I-grade, which is seldom seen and whose imaging appearances are varied from ordinary meningioma. Its features include growing flat along the meninges, irregular forms, unclear boundary, obvious edema, notable strengthening effect, usual invasion of adjacent brain tissues, and similar inflammation.


Assuntos
Neoplasias Encefálicas/patologia , Encéfalo/patologia , Linfócitos/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Meníngeas/patologia , Meningioma/patologia , Adolescente , Adulto , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
15.
Int J Oncol ; 39(4): 915-24, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21769424

RESUMO

Centrosome amplification can drive chromosomal instability (CIN) which is a major source of tumor initiation. The present study aimed to investigate the impact of nuclear factor kappa B (NF-κB) on centrosome amplification of Hep-2 cells. Immunofluorescence was performed to display centrosomes. BAY11-7082 was used as an inhibitor of NF-κB to assess the inhibition of centrosome amplification, and cyclin-dependent kinase 2 (CDK2), ensuring cell cycle cycle coordination with centrosome cycle was detected by Western blotting. Furthermore, a 1556-bp fragment of the CDK2 promoter was analyzed using the TRANSFAC-TESS software. Luciferase assay, including a series of truncated CDK2 promoters and site mutations, was carried out to determine NF-κB binding sites in the CDK2 promoter. Electrophoresis mobility shift and chromatin immunoprecipitation assays were applied to confirm whether NF-κB indeed binds to the 5'-promoter region of the CDK2 gene. To reveal the clinical significance of CDK2 expression in laryngeal squamous cell cancer, mRNA and protein levels were assessed by RT-PCR and Western blotting, respectively. We found that the transcription factor NF-κB plays a role in centrosome amplification in Hep-2 cells. Centrosome amplification is reduced by inhibition of the NF-κB pathway. Moreover, expression of the p65 subunit of NF-κB is sufficient to promote centrosome amplification and increase in CDK2 protein levels. We further identified a functional NF-κB binding site located in the CDK2 promoter. Single mutation of the NF-κB site III (construct mutIII) however resulted in 76±5% (p<0.01) luciferase activity reduction. Electromobility shift assays and chromatin immunoprecipitaton results suggest that NF-κB indeed binds to this responsive element associating with CDK2 expression and centrosome amplification. RT-PCR and Western blotting results revealed that both mRNA and protein levels of CDK2 were significantly higher in tumor tissues than those in paired adjacent normal laryngeal tissues.


Assuntos
Centrossomo/metabolismo , Quinase 2 Dependente de Ciclina/genética , Amplificação de Genes , Neoplasias Laríngeas/genética , NF-kappa B/metabolismo , Neoplasias de Células Escamosas/genética , Sequência de Bases , Sítios de Ligação , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Linhagem Celular Tumoral , Centrossomo/efeitos dos fármacos , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/metabolismo , Proteínas de Ligação a DNA/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Células HEK293 , Humanos , Neoplasias Laríngeas/metabolismo , Dados de Sequência Molecular , Mutação , NF-kappa B/antagonistas & inibidores , NF-kappa B/biossíntese , NF-kappa B/genética , Neoplasias de Células Escamosas/metabolismo , Nitrilas/farmacologia , Regiões Promotoras Genéticas , Subunidades Proteicas , Sulfonas/farmacologia , Ativação Transcricional , Transfecção , Regulação para Cima
16.
J Bone Miner Metab ; 28(3): 299-305, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19855926

RESUMO

The efficacy and safety of intravenous ibandronate were evaluated in postmenopausal osteoporosis women in China. In this multicenter, positive drug-controlled study, 158 postmenopausal osteoporotic women were randomized to receive 2 mg ibandronate given intravenously once every 3 months or 70 mg alendronate given orally once per week. All women also received supplemental calcium (500 mg) and vitamin D (200 IU) daily. One hundred fifty-one patients completed the 1-year study. Ibandronate produced mean increases in bone mineral density (BMD) by 4.27% at the lumbar spine, 3.48% at the femoral neck, and 2.03% at the trochanter. Mean increases in BMD by 4.24% at the lumbar spine, 2.72% at the femoral neck, and 2.99% at the trochanter were observed in the alendronate group. No significant difference was found between the two groups in BMD in all sites measured. Significant decreases in serum c-telopeptide of type I collagen (CTX) and alkaline phosphatase (ALP) were found in the two groups after 1 and 3 months of treatment, respectively; these serum CTX and ALP levels were then maintained at the decreased levels throughout the study period (12 months). No changes of stature were found in the patients of the two groups. Adverse events were similar in the two groups, except more mild muscle pain was observed in the first month after infusion of ibandronate than with oral alendronate (P < 0.001). The results observed in Chinese patients may support the observation that intravenous ibandronate significantly reduced bone resorption and increased BMD with good tolerance in Chinese postmenopausal osteoporotic women. Use of intravenous ibandronate possibly could potentially improve compliance as compared with other oral bisphosphonates because it may avoid the peptic side effects of oral bisphosphonate.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/sangue , Difosfonatos/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Idoso , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Estatura , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , China , Colágeno Tipo I/sangue , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Feminino , Fêmur/química , Colo do Fêmur/química , Humanos , Ácido Ibandrônico , Infusões Intravenosas , Vértebras Lombares/química , Pessoa de Meia-Idade , Doenças Musculares/induzido quimicamente , Osteoporose Pós-Menopausa/sangue , Dor/induzido quimicamente , Peptídeos/sangue , Fatores de Tempo
17.
Zhonghua Fu Chan Ke Za Zhi ; 44(8): 597-600, 2009 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-20003788

RESUMO

OBJECTIVE: To investigate the efficacy and safety of remifemin (isopropanolic extract of cimicifuga racemosa) treating perimenopausal symptoms in comparison of tibolone. METHODS: One hundred and eighty postmenopausal women at range of 40 - 60 years old were enrolled in a multicenter, randomized and double blind study. They were divided into remifemin and tibolone group at ratio 1:1. The therapeutic strategy was remifemin 20 mg bid po for 12 weeks in remifemin group and tibolone 2.5 mg qd po for 12 weeks in tibolone group. To evaluate therapeutic effect, total score of Kupperman menopause index (KMI) was used as the major observed index and single item score of KMI were secondary observed index. Safety warning was determined by laboratory tests and adverse events at timepoint of before, at 4 and 12 weeks treatment. RESULTS: (1) Total score of KMI: it were 24 +/- 5 in remifemin group and 25 +/- 6 in tibolone group before treatment. At timepoint of 4 weeks treatment, it were 11 +/- 6 in remifemin group and 11 +/- 7 in tibolone group. At timepoint of 12 weeks treatment, it were 7 +/- 6 in remifemin group and 6 +/- 5 in tibolone group. Total KMI score between two groups did not show statistical difference at various timepoint (P > 0.05). (2) Single item score of KMI: when compared before, at 4 and 12 weeks treatment, did show remarkable difference (P < 0.05) either in remifemin or in tibolone group. However, those single items of KMI score did not show statistical difference between 4 and 12 weeks timepoint in each treatment group (P > 0.05). (3) Adverse effect: the incidence of adverse effect in remifemin group was significantly lower than that of tibolone group. None case with vaginal bleeding was observed in remifemin group, however, 17 cases with vaginal bleeding occurred in tibolone group (19%, 17/90). The incidence of breast swelling were 16% (14/90) in remifemin group and 36% (32/90) in tibolone group; before treatment, the thickness of endometrium were (2.6 +/- 1.1) mm in remifemin group and (2.8 +/- 1.1) mm in tibolone group; at timepoint of 12 weeks treatment, the thickness of endometrium were (2.9 +/- 1.4) mm in remifemin group and (3.4 +/- 2.0) mm in tibolone group. In comparison of thickness of endometrium before and at 12 weeks treatment, no remarkable changes was observed in remifemin group, however, endometrium displayed significantly thicker in tibolone group. CONCLUSIONS: Our study suggested that remifemin was one effective and safe agent to manage women with climacteric symptom. It has similar therapeutic effect and lower incidence of adverse effect when compared with tibolone.


Assuntos
Cimicifuga/química , Norpregnenos/uso terapêutico , Perimenopausa/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Administração Oral , Adulto , Cimicifuga/efeitos adversos , Método Duplo-Cego , Endométrio/efeitos dos fármacos , Feminino , Fogachos/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/tratamento farmacológico , Norpregnenos/administração & dosagem , Norpregnenos/efeitos adversos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Hemorragia Uterina/etiologia
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 8(6): 484-6, 2005 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-16299645

RESUMO

OBJECTIVE: To investigate the clinicopathologic characteristics of colonic cancer. METHODS: All clinical data of surgical cases from hospital registry from 1982 to 2002 were analyzed using SPSS 11.0 software. RESULTS: There were 1075 patients with colonic cancer including 573 males and 502 females. The median age of the patients was 58 years. 90.8% of the patients aged over 40 years . The proportion of right colonic cancer was 64.7%. Well-differentiated and moderately differentiated adenocarcinoma accounted for 69.8%, and mucous carcinoma 13.6%. The proportions of early stage I, advanced stage II, III and IV cancer were 8.1%, 45.0%, 26.5% and 20.3% respectively. The 5-, 10-year survival rates were 61.9% and 53.0% respectively. CONCLUSIONS: The risk for colonic cancer is significantly increased in patients over 40 years. The frequency of right colonic cancer is higher than that of left colonic cancer. The overall survival rate is high.


Assuntos
Neoplasias do Colo/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
20.
Zhonghua Yi Xue Za Zhi ; 84(4): 269-73, 2004 Feb 17.
Artigo em Chinês | MEDLINE | ID: mdl-15059505

RESUMO

OBJECTIVE: To determine the effect of raloxifene hydrochloride (RLX) on the lumbar spine and total hip bone mineral density (BMD), bone metabolism and serum lipids in Chinese postmenopausal women with osteoporosis. METHODS: 204 Chinese postmenopausal women with osteoporosis from 3 hospitals in Beijing and Shanghai were randomly divided into 2 groups of 102 women: RLX group (RLX of the dosage of 60 mg/day was given for 12 months) and placebo group. In addition, 500 mg of elemental calcium and 200 units of vitamin D were given daily to all women. BMD, serum bone markers and lipids were measured before and after drug administration. The BMD of lumber spine and hip was measured by dual-energy X-ray absorptiometry (DEXA). Serum bone gamma-carboxyglutamic acid-containing protein (BGP) and C-teloppeptide were analyzed by one-step ELISA. Serum lipids were measured by enzymatic method. RESULTS: By the end of the 12-month study period, the lumbar spine BMD was increased by 3.3% +/- 4.8% in the RLX group and 1.0% +/- 4.9% in the placebo group (P < 0.001); the hip BMD was increased by 1.4% +/- 4.8%in the RLX group and decreased by 0.9% +/- 5.0% in the placebo group (P < 0.01). New vertebral fracture occurred in none of the subjects in the RLX group and in 5 subjects of the placebo group (P = 0.059). The serum BGP and CTX decreased by 41.7% and 61.5% respectively in the RLX group, both significantly more than those in the placebo group (10.6% and 35.6% respectively, both P < 0.001). Both the total cholesterol and low-density lipoprotein cholesterol were significantly lower in the RLX group than in the placebo group (both P < 0.001), however, there were no significant differences in high-density lipoprotein cholesterol and triglycerides between these two groups. One subject in the RLX group and 5 subjects in the placebo group discontinued the study due to adverse events. There were no differences in the number of subjects with hot flushes (3 in the RLX group and 1 in the placebo group) and the number of subjects with leg cramps (9 in the RLX group and 4 in the placebo group). No venous thromboembolic event was reported. CONCLUSION: RLX of the dosage of 60 mg/day for 12 months significantly increases the lumbar spine and total hip bone BMD, significantly decreases bone turnover and has favorable effects on serum lipids in Chinese postmenopausal women with osteoporosis.


Assuntos
Densidade Óssea/efeitos dos fármacos , Antagonistas de Estrogênios/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Cloridrato de Raloxifeno/uso terapêutico , Ácido 1-Carboxiglutâmico/sangue , Absorciometria de Fóton , Idoso , Colágeno/sangue , Colágeno Tipo I , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Antagonistas de Estrogênios/efeitos adversos , Feminino , Humanos , Lipídeos/sangue , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/metabolismo , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/metabolismo , Ossos Pélvicos/efeitos dos fármacos , Ossos Pélvicos/metabolismo , Peptídeos/sangue , Cloridrato de Raloxifeno/efeitos adversos , Resultado do Tratamento
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