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1.
Cell Cycle ; 17(8): 1014-1025, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29886802

RESUMO

The Wnt signaling pathway controls stem cell identity in the intestinal epithelium and cancer stem cells (CSCs). The transcription factor Ascl2 (Wnt target gene) is fate decider of intestinal cryptic stem cells and colon cancer stem cells. It is unclear how Wnt signaling is translated into Ascl2 expression and keeping the self-renewal of CRC progenitor cells. We showed that the exogenous Ascl2 in colorectal cancer (CRC) cells activated the endogenous Ascl2 expression via a direct autoactivatory loop, including Ascl2 binding to its own promoter and further transcriptional activation. Higher Ascl2 expression in human CRC cancerous tissues led to greater enrichment in Ascl2 immunoprecipitated DNA within the Ascl2 promoter in the CRC cancerous sample than the peri-cancerous mucosa. Ascl2 binding to its own promoter and inducing further transcriptional activation of the Ascl2 gene was predominant in the CD133+CD44+ CRC population. R-spondin1/Wnt activated Ascl2 expression dose-dependently in the CD133+CD44+ CRC population, but not in the CD133-CD44- CRC population, which was caused by differences in Ascl2 autoregulation under R-spondin1/Wnt activation. R-spondin1/Wnt treatment in the CD133+CD44+ or CRC CD133-CD44- populations exerted a different pattern of stemness maintenance, which was defined by alterations of the mRNA levels of stemness-associated genes, the protein expression levels (Bmi1, C-myc, Oct-4 and Nanog) and tumorsphere formation. The results indicated that Ascl2 autoregulation formed a transcriptional switch that was enhanced by Wnt signaling in the CD133+CD44+ CRC population, thus conferring their self-renewal.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Autorrenovação Celular , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Homeostase , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Antígenos CD/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Biológicos , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Trombospondinas/metabolismo , Transcrição Gênica , Ativação Transcricional/genética
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1493-1497, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070131

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Shengxue mixture combined with intraosseous blood infusion for treatment of aplastic anemia patients. METHODS: From 2011 to 2015, Institute of blood diseases of Shaanxi Medical University admitted 53 patients with aplastic anemia. The patients were treated with shengxue mixture 200 ml, orally, twice a day. Stanozolol tablets, Adult 2 mg, three times a day, mycophenolate mofetil 1.0 g, twice a day. Intraosseous infusion of the following medicine were administered in patients: recombinant human EPO 10000 U, recombinant human G-CSF 450 µg, recombinant human IL-11 4.5 mg, dexmethasone 20 mg, once a week, a total of four times. One month later, the blood cell counts and bone marrow biopsy were performed. Consolidation treatment continued for 3 to 6 months after discharge, and therapeutic effect was observed and followed-up for more than a year. RESULTS: After one month of treatment, 40 patients were basically cured (75.47%), 8 patients were remitted(15.09%), Hemoglobin level, white blood cell count and platelet count were significantly improved after treatment (P<0.01). The overall response rate was 90.57%(48 patients). Patients with bone marrow hyperplasia was 46 (86.79%), versus 9(16.98%) before treatment. There was a difference (P<0.05). After 3 to 6 months of treatment, 40 patients were cured (75.47%); 8 patients were remitted(15.09%); 3 patients were obviously improved(5.66%); 2 patients were ineffective(3.77%). The overall response rate was 96.23%(51 cases). No obvious side effects were observed. No patients were relapsed after one year. CONCLUSION: Shengxue mixture combined with Intraosseous infusion is a fast, efficient, safe method for the treatment of aplastic anemia.


Assuntos
Anemia Aplástica/terapia , Medicamentos de Ervas Chinesas , Infusões Intraósseas , Eritropoetina , Fator Estimulador de Colônias de Granulócitos , Humanos
3.
Exp Cell Res ; 360(2): 243-256, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28899657

RESUMO

We have reported that Achaete scute-like 2 (Ascl2) transcriptionally repressed miR-200 family members and affected the epithelial-mesenchymal transition (EMT)-mesenchymal-epithelial transition (MET) plasticity in colorectal cancer (CRC) cells. However, little is known about the regulation of the Ascl2/miR-200 axis. Here, we found that hypoxia inducible factor-1α (HIF-1α) mRNA levels were positively correlated with Ascl2 mRNA levels and inversely correlated with miR-200b in CRC samples. Mechanistically, we showed that Ascl2 was a downstream target of HIF-1α and had a critical role in the EMT phenotype induced by hypoxia or HIF-1α over-expression. Hypoxia or HIF-1α over-expression activated Ascl2 expression in CRC cells in a direct transcriptional mechanism via binding with the hypoxia-response element (HRE) at the proximal Ascl2 promoter. HIF-1α-induced Ascl2 expression repressed miR-200b expression to induce EMT occurrence. Furthermore, we found HIF-1α was a direct target of miR-200b. MiR-200b bound with the 3'-UTR of HIF-1α in CRC cells. HIF-1α/Ascl2/miR-200b regulatory feedback circuit modulated the EMT-MET plasticity of CRC cells. Our results confirmed a novel HIF-1α/Ascl2/miR-200b regulatory feedback circuit in modulating EMT-MET plasticity of CRC cells, which could serve as a possible therapeutic target.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/genética , Retroalimentação Fisiológica/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , MicroRNAs/fisiologia , Linhagem Celular Tumoral , Plasticidade Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Transdução de Sinais/genética , Hipóxia Tumoral/genética
4.
Oncotarget ; 8(65): 109301-109318, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29312609

RESUMO

Achaete scute-like 2 (Ascl2) is the Wnt signaling target, its regulation by other signaling is undefined. Now we demonstrated that CD133+/CD44+ cell population from HT-29 or Caco-2 cells exhibited cancer stem cell (CSC) properties with highly expressed Ascl2, which is related to the Hippo signaling pathway. YAP1 interference in CD133+/CD44+ HT-29 or Caco-2 cells reduced their proliferation, colony-forming ability and tumorsphere formation in vitro and inhibited the 'stemness'-associated genes and Ascl2 expression. Enforcing YAP1 expression in HT-29 or Caco-2 cells triggered the opposite changes. Ascl2 interference reversed the phenotype of YAP1-enforced expressed HT-29 or Caco-2 cells. Krüppel-like factor 5 (KLF5) protein, not KLF5 mRNA levels, were increased due to YAP1 overexpression which is reported to prevent KLF5 degradation. Co-immunoprecipitation (Co-IP) assays demonstrated that YAP1 bound with KLF5 in HT-29 and Caco-2 cells. Luciferase and chromatin immunoprecipitation (ChIP) assays indicated that both YAP1 and KLF5 bound to the first two loci with GC-boxes in Ascl2 promoter and induced Ascl2 transcription. The decreased Ascl2 transcription by YAP1 interference required an intact KLF5 binding site (GC-box) within Ascl2 promoter, KLF5 knockdown reduced YAP1 binding and Ascl2 luciferase reporter activity upon YAP1 overexpression. Positive correlation among YAP1 and Ascl2 mRNA levels was observed in colorectal cancer (CRC) samples. Thus, our study demonstrated that Ascl2, a fate decider of CRC progenitor cells can be activated by the Hippo signaling pathway in CRC progenitor cells, and ensured their self-renewability.

5.
Int J Oncol ; 40(4): 1089-96, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22134377

RESUMO

Realgar has been used in Western medicine and Chinese traditional medicine since ancient times, and its promising anticancer activity has attracted much attention in recent years, especially for acute promyelocytic leukemia (APL). However, the therapeutic action of realgar treatment for APL remains to be fully elucidated. Cellular cytotoxicity, proliferation, apoptosis and differentiation were comprehensively investigated in realgar-treated cell lines derived from PML-RARα+ APL patient, including the all-trans retinoic acid (ATRA)-sensitive NB4 and ATRA-resistant MR2 cell lines. For analysis of key regulators of apoptosis and differentiation, gene expression profiles were performed in NB4 cells. Realgar was found to induce apoptosis and differentiation in both cell lines, and these effects were exerted simultaneously. Gene expression profiles indicated that genes influenced by realgar treatment were involved in the modulation of signal transduction, translation, transcription, metabolism and the immune response. Given its low toxicity, realgar is a promising alternative reagent for the therapy of APL. Our data contribute to an understanding of the underlying mechanism responsible for the therapeutic effects of realgar in the clinical treatment of APL.


Assuntos
Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Leucemia Promielocítica Aguda/tratamento farmacológico , Sulfetos/farmacologia , Tretinoína/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , DNA de Neoplasias/análise , DNA de Neoplasias/genética , Intervalo Livre de Doença , Perfilação da Expressão Gênica , Humanos , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Análise em Microsséries , Proteínas de Fusão Oncogênica/metabolismo , Transdução de Sinais
6.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 31(7): 888-91, 2011 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-21866655

RESUMO

OBJECTIVE: To study the effect and safety of haemostatic apozem combined with haemostatic mixture on hemophilia hemorrhage. METHODS: Five hundred hemophilia patients were randomly recruited from Shaanxi Yida Hematology Institute from February 2005 to July 2010. Under the condition of using no blood products such as platelet cofactors VIII and IX, oral administration of haemostatic apozem combined with intravenous dripping of haemostatic mixture were given to 332 hemorrhagic patients and 451 patients in need of surgery for hemorrhagic prevention. The treatment was lasted for three successive weeks. The hemostatic time, hemorrhage absorption (recovery) time, and their safety were observed. RESULTS: The hemostatic time for open bleeding and closed bleeding was (0.85 +/- 0.83) h and (2.69 +/- 0.65) h respectively. The average hemostatic time was (2.00 +/- 0.69) h. The recovery time for different portions was as follows respectively: intra-cranial hemorrhage (14.13 +/- 6.01) days; muscular hemorrhage (18.18 +/- 7.34) days; hematuria (8.25 +/- 4.69) days; arthrorrhagia(3.27 +/- 1.31) days; ecchymoma (7.16 +/- 2.32) days; bleeding of oral and nasal cavities (4.26 +/- 1.35) days; intramedullary hemorrhage (19.15 +/- 1.36) days; hematoma ulceration (50.01 +/- 20.91) days. The hemorrhage recovery ratio was 99.10% (329/332). The success rate of preventing from surgery hemorrhage was 100% (451/451). No severe adverse reaction occurred during the therapeutic course. CONCLUSIONS: Haemostatic apozem combined with haemostatic mixture was effective and fast in preventing and treating hemophilia hemorrhage, with no complications or adverse reactions. It could be taken as the first choice for prevention and treatment of hemophilia hemorrhage.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemorragia/prevenção & controle , Hemostáticos/uso terapêutico , Fitoterapia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Mol Med Rep ; 3(5): 749-57, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21472309

RESUMO

Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal cells. The cancer-specific pro-apoptotic action of Par-4 is encoded in its centrally located SAC domain. In this study, to further enhance the anti-cancer effect of Par-4 in order to overcome the limitations of peptide therapy, a recombinant adeno-associated virus was constructed using the following strategies: the secretory expression of therapeutic peptide, a HA2TAT-mediated cytosolic delivery technique, and an adeno-associated virus gene transfer system. To test the hypothesis that Par-4 has an additive bystander effect as an anti-cancer therapy, we designed a secretory protein by adding a secretory signal peptide NT4(Si) to the Par-4 SAC-HA2TAT peptide gene sequence [NT4(Si)-Par-4 SAC-HA2TAT]. The results indicated that, compared to the normal NIH3T3 cell line, AAV-NT4(Si)-Par-4 SAC-HA2TAT significantly suppressed cell growth and induced rapid cell death in HepG2 cells in a time-dependent manner through successful gene transfer and secretory expression of therapeutic peptide at 48 h post-transfection. In addition, the secretory properties of Par-4 may greatly increase its effectiveness in cancer therapy when delivered in vivo.

8.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 25(10): 900-2, 2009 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-19811737

RESUMO

AIM: To explore the different effect and mechanism of arsenic sulfide on telomerase activity and hTERT-mRNA expression in CML cell lines-K562 and APL cell lines-NB4. METHODS: Telomerase activity was determined by polymerase chain reaction enzyme-linked immunoassay (PCR-ELISA). The expression of hTERT-mRNA was analyzed by semi-quantitative RT-PCR. Flow cytometry was used to analyze the cell cycle and apoptosis. RESULTS: 0.15-0.6 mg/L arsenic sulfide (72 h)can induce apoptosis and inhibit telomerase activity and hTERT-mRNA expression in NB4 cell. The concentration of arsenic sulfide with the same effect on K562 cell was 0.3-3 mg/L. 0.3 mg/L arsenic sulfide (72 h) can cause the proportion of the NB4 cell in G2/M phase increased, but for K562 cell, The concentration of arsenic sulfide was 1.5 mg/L. CONCLUSION: Telomerase system may be one of the pathway for arsenic sulfide inducing apoptosis of NB4 and K562 cell; G2/M phrase arrest may have correlation with decrease of telomerase activity; The sensitivity of NB4 and K562 cell for arsenic sulfide is different, the mechanism of it need to study more.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Leucemia/patologia , Sulfetos/farmacologia , Telomerase/genética , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Leucemia/enzimologia , Leucemia/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Telomerase/metabolismo
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 17(1): 69-73, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19236750

RESUMO

This study was aimed to investigate on effect of As(2)O(3) on expressions of COX-2, MMP-2 and MMP-9 in SGC7901 and K562 cells. SGC7901 and K562 cells were cultured in RPMI 1640 medium and were inoculated in culture medium with different concentrations of As(2)O(3) and at different times. Expressions of COX-2, MMP-2 and MMP-9 in SGC7901 and K562 cells were measured by using Western blot, while the levels of COX-2 mRNA and MMP-2 mRNA were measured with fluorescence quantitative RT-PCR. The results showed that the expression of COX-2, MMP-2 and MMP-9 decreased in dose- and time-dependent manners after treating with As(2)O(3). The levels of COX-2 mRNA and MMP-2 mRNA reduced in groups treated with As(2)O(3). In conclusion, As(2)O(3) inhibits expressions of COX-2, MMP-2 and MMP-9 in K562 and SGC7901 cells, suggesting that As(2)O(3) inhibits tumor development through its effect on angiogenesis involved in solid and hematologic malignancies.


Assuntos
Arsenicais/farmacologia , Ciclo-Oxigenase 2/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Óxidos/farmacologia , Trióxido de Arsênio , Regulação Leucêmica da Expressão Gênica , Humanos , Células K562
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 16(6): 1303-7, 2008 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-19099632

RESUMO

This study was aimed to investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 in gastric cancer in order to clarify the role of As2O3 in lymphangiogenesis and metastasis of tumor. The gastric cancer model was established in nude mice by using gastric cancer cell line SGC-7901. As2O3 was injected to the two treatment groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected to the control group. Expression of VEGF-C and VEGFR-3 were detected by immunohistochemistry and were analyzed with QWin550cW image Acquiring & Analysis System. The results showed that the expression of VEGF-C and VEGFR-3 in cancer cells significantly reduced in the arsenic -treated groups. The expression of VEGF-C and VEGFR-3 in 5 mg/kg group was significantly less than that in 2.5 mg/kg group. The gray ratio analysis confirmed that there were significant difference between control group and two treated group, as well as between 2.5 mg/kg-treated group and 5 mg/kg-treated group. It is concluded that As2O3 can inhibit expression of VEGF-C and VEGFR-3 of human gastric cancer xenografts in nude mice, which suggests that As2O3 may inhibit the lymphangiogenesis by suppressing the expression of VEGF-C and VEGFR-3.


Assuntos
Arsenicais/farmacologia , Óxidos/farmacologia , Neoplasias Gástricas/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Trióxido de Arsênio , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
11.
World J Gastroenterol ; 13(48): 6498-505, 2007 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-18161919

RESUMO

AIM: To investigate the effect of arsenic trioxide (As2O3) on expression of vascular endothelial growth factor receptor-1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR) in human gastric tumor cells and proliferation of vascular endothelial cells. METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were treated with As2O3. Microvessel density (MVD) and expression of Flt-1 and KDR were detected by immunofluorescence laser confocal microscopy. SGC-7901 cells were treated respectively by exogenous recombinant human VEGF165 or VEGF165 + As2O3. Cell viability was measured by MTT assay. Cell viability of ECV304 cells was measured by MTT assay, and cell cycle and apoptosis were analyzed using flow cytometry. RESULTS: The tumor growth inhibition was 30.33% and 50.85%, respectively, in mice treated with As2O3 2.5 and 5 mg/kg. MVD was significantly lower in arsenic-treated mice than in the control group. The fluorescence intensity levels of Flt-1 and KDR were significantly less in the arsenic-treated mice than in the control group. VEGF165 may accelerate growth of SGC7901 cells, but As2O3 may disturb the stimulating effect of VEGF165. ECV304 cell growth was suppressed by 76.51%, 71.09% and 61.49% after 48 h treatment with As2O3 at 0.5, 2.5 and 5 micromol/L, respectively. Early apoptosis in the As2O3-treated mice was 2.88-5.1 times higher than that in the controls, and late apoptosis was 1.17-1.67 times higher than that in the controls. CONCLUSION: Our results showed that As2O3 delays tumor growth, inhibits MVD, down-regulates Flt-1 and KDR expression, and disturbs the stimulating effect of VEGF165 on the growth of SGC7901 cells. These results suggest that As2O3 might delay growth of gastric tumors through inhibiting the paracrine and autocrine pathways of VEGF/VEGFRs.


Assuntos
Arsenicais/farmacologia , Proliferação de Células/efeitos dos fármacos , Cloretos/farmacologia , Endotélio Vascular/citologia , Neoplasias Gástricas/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endotélio Vascular/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microcirculação/efeitos dos fármacos , Neoplasias Gástricas/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
12.
World J Gastroenterol ; 12(36): 5780-6, 2006 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-17007042

RESUMO

AIM: To investigate the inhibitory effect of As(2)O(3) on angiogenesis of tumor and expression of vascular endothelial growth factor (VEGF) in tumor cells in vivo and in vitro. METHODS: The solid tumor model was formed in nude mice with the gastric cancer cell line SGC-7901. The animals were randomly divided into three groups. As(2)O(3) was injected into the arsenic-treated groups (2.5 mg/kg and 5 mg/kg) and the same volume of saline solution was injected into the control group. Microvessel density (MVD) and expression of VEGF were detected with immunofluorescence laser confocal technology. Further expression of VEGF protein and VEGF mRNA was measured with Western bloting and fluorescence quantitative RT- PCR in SGC-7901 cells treated with As(2)O(3). RESULTS: In nude mice, after treatment with 5 mg/kg and 2.5 mg/kg As(2)O(3) respectively, about 50% and 30% tumor growth inhibition were observed correspondingly (P<0.05, P<0.05). Decrease in MVD appeared in As(2)O(3)-treated tumors compared with control group (P<0.001, P<0.001). MVD in tumors was significantly lower in 5 mg/kg group than in 2.5 mg/kg group (P<0.01). The fluorescence intensity levels of VEGF in tumor cells were significantly lowered in the arsenic-treated groups (P<0.01, P<0.01). The fluorescence intensity level of VEGF in 5 mg/kg group was lower than that in 2.5 mg/kg group (P<0.01). In vitro, the expression of VEGF protein decreased in dose- and time-dependent manner after the treatment with As(2)O(3), but in VEGF mRNA no significant difference was found between the control group and the treated groups. CONCLUSION: As(2)O(3) can inhibit solid tumor growth by inhibiting the formation of new blood vessels. One of the mechanisms is that As(2)O(3) can inhibit VEGF protein expression.


Assuntos
Antineoplásicos/farmacologia , Arsenicais/farmacologia , Neovascularização Patológica/tratamento farmacológico , Óxidos/farmacologia , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Trióxido de Arsênio , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/genética , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
13.
Zhong Xi Yi Jie He Xue Bao ; 4(2): 160-5, 2006 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16529693

RESUMO

OBJECTIVE: To compare the changes of gene expression profiles of multiple myeloma cell line RPMI 8226 before and after 24-hour intervention of arsenic trioxide. METHODS: The responses of the RPMI 8226 cells to arsenic trioxide were determined with cDNA microarray which included 4,096 different human genes. RESULTS: Of these 4,096 genes, the expressions of 273 genes were altered significantly at mRNA level. The expressions of 121 genes were up-regulated while the expressions of 152 genes were down-regulated. CONCLUSION: The effect of arsenic trioxide on RPMI 8226 cells is related to changing the expression levels of a number of genes. ZFYVE16, ALK1 and TXNIP genes may play important roles in apoptosis and differentiation of RPMI 8226 cells.


Assuntos
Antineoplásicos/farmacologia , Arsenicais/farmacologia , Perfilação da Expressão Gênica , Mieloma Múltiplo/patologia , Óxidos/farmacologia , Apoptose/efeitos dos fármacos , Trióxido de Arsênio , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Células Tumorais Cultivadas
14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 22(2): 154-6, 160, 2006 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16507246

RESUMO

AIM: To synthesize antiangiogenic peptide fragment of betapep-25, to construct and identify the recombinant prokaryotic expression plasmid containing betapep-25 peptide. METHODS: The fragment encoding betapep-25 peptide was designed and synthesized artificially and was cloned into vector pGEM-T easy after being identified by sequencing. After being digested by Nae I and BamH I, T-betapep-25 peptide fragment was cloned into recombinant vector pBV220-NT4, which was digested by Nae I and BamH I. The constructed recombinant prokaryotic expression plasmid pBV220-NT4-betapep-25 was digested using BamH I, EcoR I and BamH I, respectively. RESULTS: The sequcence of betapep-25 synthesized artificially and analyzed by digestion was consistent with the published results. Fragments of 4,030 bp, 364 bp and 3,666 bp were obtained after digestion of recombinant prokaryotic expression plasmid pBV220-NT4-betapep-25 using BamH I, EcoR I and BamH I, respectively, which demonstrated the successful cloning and construction of recombinant prokaryotic expression plasmid. CONCLUSION: The successful construction recombinant prokaryotic expression plasmid expressing betapep-25 provides a foundation for further research on its mechanism of anti-tumor activity in vivo and in vitro.


Assuntos
Expressão Gênica , Células Procarióticas/metabolismo , Proteínas/metabolismo , Transfecção , Clonagem Molecular , Vetores Genéticos/genética , Peptídeos/genética , Peptídeos/metabolismo , Plasmídeos/genética , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase/métodos , Proteínas/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Técnicas do Sistema de Duplo-Híbrido
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 31(1): 24-7, 2006 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-16562669

RESUMO

OBJECTIVE: To explore the effect of realgar on the gene expression profiles of multiple myeloma cell line RPMI 8226 by apply cDNA microarray. METHODS: The gene expression of RPMI 8226 cells before and after 48 hours of realgar treatment was determined with a cDNA microarray representing 4096 human genes. RESULTS: At the mRNA level, 164 genes were differentially altered; 53 genes were up-regulated; and 111 genes were down-regulated. CONCLUSION: The realgar treatment to RPMI 8226 cell line may induce a number of gene changes. Many genes may be involved in the pathogenesis of multiple myeloma. BTG1, ALK1, and TXNIP genes may play an important role in the apoptosis and differentiation of RPMI 8226 cells.


Assuntos
Arsenicais/farmacologia , Perfilação da Expressão Gênica , Mieloma Múltiplo/patologia , Sulfetos/farmacologia , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Células Tumorais Cultivadas
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 13(3): 386-90, 2005 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-15972126

RESUMO

To study the effect of realgar on expression of survivin in leukemia cell lines, HL-60 and Jurket cell lines were used as in vitro models. The expression of survivin was detected by Western blot analysis and immunofluorescence, and the expressions of Fas and caspase-3 were examined by immunohistochemistry. The results showed that the expression of survivin was positive in the two cell lines. HL-60 cells did not express Fas and caspase-3, and Jurket cells were Fas-positive and caspase-3 was negative. Realgar induced a dose- and time-dependent down-regulation of survivin expression in Jurket cells, and especially in HL-60. Caspase-3 expression changed from negative to positive in HL-60 cell, but there still was no expression in Jurket cell. It is concluded that survivin expression level decreased during leukemia cell apoptosis induced by Realgar. The down-regulation of survivin expression may be an important mechanism in leukemia cell apoptosis induced by realgar through mitochondrial pathway.


Assuntos
Arsenicais/farmacologia , Proteínas Associadas aos Microtúbulos/biossíntese , Proteínas de Neoplasias/biossíntese , Sulfetos/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3/metabolismo , Relação Dose-Resposta a Droga , Imunofluorescência , Células HL-60 , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose , Células Jurkat , Leucemia/metabolismo , Leucemia/patologia , Survivina , Fatores de Tempo , Receptor fas/metabolismo
17.
Acta Haematol ; 113(4): 247-54, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15983431

RESUMO

Arsenic compounds (As(2)O(3 )or()As(4)S(4)) have been used successfully for the treatment of acute promyelocytic leukemia (APL) for quite a long time. It has been noticed that the sensitivity to apoptosis induced by As(2)O(3 )varies among various leukemia cells. It was reported by several groups that As(2)O(3) could induce apoptosis in APL-derived NB4 cells at concentrations of 0.5-1 mumol/l, whereas in other leukemia cells like K562, As(2)O(3) has no effects at the same concentration. K562 cells undergo apoptosis only when the concentration of As(2)O(3 )is greater than 2 mumol/l. Another arsenic compound, realgar (As(4)S(4)), a traditional Chinese mineral medicine, has been used to treat APL effectively and demonstrated to have lower toxicity than As(2)O(3). It would be interesting to know whether NB4 and K562 cells will show different sensitivity to realgar as well and if there is a difference, what is the cellular mechanism of it. In our present study, K562 cells were much less sensitive than NB4 cells to apoptosis induced by realgar. We confirm that the expression of bcl-x(L) is significantly higher in K562 cells than that in NB4 cells and is not downregulated upon realgar treatment. K562 cells become sensitive to realgar at clinically acceptable concentrations when bcl-x(L) expression level is downregulated by transfecting bcl-x(L) antisense RNA vector into the cells. Our results suggest that the increased bcl-x(L) expression in K562 cells contributes to its insensitivity to realgar-induced apoptosis.


Assuntos
Apoptose/fisiologia , Arsenicais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sulfetos/farmacologia , Apoptose/efeitos dos fármacos , Sequência de Bases , Primers do DNA , Humanos , Células K562 , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Proteína bcl-X
18.
Chin Med J (Engl) ; 116(7): 1074-7, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12890387

RESUMO

OBJECTIVES: To compare the gene expression profiles of acute promyelocytic leukemia cell line NB(4) before and after 12 hours of realgar treatment using cDNA microarray. METHODS: Two cDNA probes were prepared through reverse transcription from mRNA of both untreated and realgar treated NB(4) cells. The probes were labeled with Cy3 and Cy5 fluorescence dyes individually, hybridized with cDNA microarray representing 1003 different human genes, and scanned for fluorescent intensity. The genes were screened through the analysis of the difference in two gene expression profiles. RESULTS: The analysis of gene expression profiles indicates that 9 genes were up-regulated and 37 genes were down-regulated. Among the 9 up-regulated genes, 2 genes were involved in a proteasome degradation pathway. Some genes related to protein synthesis, signal transduction and cell receptors were down-regulated. CONCLUSION: PSMC2 and PSMD1 genes may play an important role in the apoptosis and partial differentiation of NB(4) cells.


Assuntos
Arsenicais/farmacologia , Expressão Gênica/efeitos dos fármacos , Leucemia Promielocítica Aguda/genética , Sulfetos/farmacologia , Regulação para Baixo , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Células Tumorais Cultivadas , Regulação para Cima
19.
Acta Pharmacol Sin ; 24(7): 646-50, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12852829

RESUMO

AIM: To investigate the gene expression profiles of acute promyelocytic leukemia (APL) cell line NB4 treated with arsenic trioxide (As2O3) using cDNA microarray. METHODS: Two cDNA probes were prepared through reverse transcription from mRNA of NB4 cells treated with or without arsenic trioxide. The probes were labeled with Cy3 and Cy5 fluorescence dyes individually, hybridized with cDNA microarray representing 1003 different human genes, and their fluorescent intensities were scanned. The genes were screened through the analysis of the difference in two gene expression profiles. RESULTS: The analysis of gene expression profiles indicated that after the treatment of arsenic trioxide (0.5 micromol/L) 3 genes were up-regulated, among which, PSMB6 gene was involved in proteasome degradation pathway, and 18 genes related to RNA processing, protein synthesis, and signal transduction were down-regulated. CONCLUSION: PSMB6 and ITGB1 genes may be related to the differentiation and/or apoptosis of NB4 cells induced by As2O3.


Assuntos
Antineoplásicos/farmacologia , Apoptose , Arsenicais/farmacologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Oncogenes , Óxidos/farmacologia , Trióxido de Arsênio , Diferenciação Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Leucemia Promielocítica Aguda/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Células Tumorais Cultivadas
20.
World J Gastroenterol ; 9(4): 665-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12679906

RESUMO

AIM: To study estrogen receptor (ER) and estrogen receptor messenger RNA (ERmRNA) expression in gastric carcinoma tissues and to investigate their association with the pathologic types of gastric carcinoma. METHODS: The expression of ER and ERmRNA in gastric carcinoma tissues (15 males and 15 females, 42-70 years old) was detected by immunohistochemistry and in situ hybridization, respectively. RESULTS: The positive rate of ER (immunohistochemistry) was 33.3 % in males and 46.7 % in females. In Borrmann IV gastric carcinoma ER positive rate was greater than that in other pathologic types, and in poorly differentiated adenocarcinoma and signet ring cell carcinoma the positive rates were greater than those in other histological types of both males and females (P<0.05). The ER was more highly expressed in diffused gastric carcinoma than in non-diffused gastric carcinoma (P<0.05). The ER positive rate was also related to regional lymph nodes metastases (P<0.05), and was significantly higher in females above 55 years old, and higher in males under 55 years old (P<0.05). The ERmRNA (in situ hybridization) positive rate was 73.3 % in males and 86.7 % in females. The ERmRNA positive rates were almost the same in Borrmann I, II, III and IV gastric carcinoma (P>0.05). ERmRNA was expressed in all tubular adenocarcinoma, poorly differentiated adenocarcinoma and signet ring cell carcinoma (P<0.05). The ERmRNA positive rate was related to both regional lymph nodes metastases and gastric carcinoma growth patterns, and was higher in both sexes above 55 years old but without statistical significance (P>0.05). The positive rate of ERmRNA expression by in situ hybridization was higher than that of ER expression by immunohistochemistry (P<0.05). CONCLUSION: ERmRNA expression is related to the pathological behaviors of gastric carcinoma, which might help to predict the prognosis and predict the effectiveness of endocrine therapy for gastric carcinoma.


Assuntos
Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , Receptores de Estrogênio/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Neoplasias Gástricas/classificação , Neoplasias Gástricas/patologia , Transcrição Gênica
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