Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Genes Dis ; 6(4): 407-418, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31832521

RESUMO

Mantle cell lymphoma (MCL) is a B-cell malignancy with poor clinical outcome and undefined pathogenesis. Development of clinically relevant cellular models for MCL research is an urgent need. Our preliminary observations lead the development of two novel hypotheses that we tested in this study: 1. multicellular spheroid might be a unique growth mode of early-stage cells in MCL; 2. MCL might be a polyclonal tumor. We made the following original observations that have not been reported: First, we have provided a new experiment method for enriching MCL early-stage cells and characterized the spheroid mode of growth as a unique feature of early-stage MCL cells in cell line as well as in clinical samples. Second, we have established a clinically relevant cellular model of MCL, the JeKo-1-spheroid cell line, that was highly enriched in early-stage sub-clones. JeKo-1-spheroid cells and the spheroid growing cells enriched from MCL patients exhibited comparably enhanced tumorigenic abilities and similar biological features. Third, Immunophenotypic analysis has revealed that MCL may be derived from precursor-B(pre-B), immature-B and mature-B cells, not only the mature-B cells as WHO classified in 2016. Fourth, MCL may be a polyclonal disease composed of CD19-/IgM-, CD19-/IgM+, CD19+/IgM+ three sub-clones, of which the CD19-/IgM+ sub-clone might be the dominant sub-clone with the strongest tumorigenic ability. Fifth, CD19+/IgM- that differentiates MCL and normal B cells may represent a new marker for MCL early detection, minor residual disease monitoring after therapies and prognosis.

3.
J Cell Biochem ; 118(9): 2645-2653, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28012196

RESUMO

Central nervous system lymphoma (CNSL) remains a diagnostical and therapeutical challenge. MiRNAs post-transcriptionally regulate expression of targeted mRNAs through binding to their 3' UTR to inhibit their translation or promote their degradation. Oncoprotein inhibitory member of the ASPP family (iASPP), a key inhibitor of tumor suppressor p53, has been reported to play oncogenic role in cancers. Our present study was aimed to determine whether the miR-184/iASPP axis is involved in the proliferation and invasion of CNSL. A reduced level of miR-184 was observed in CNSL tissues. Exogenous miR-184 inhibited cell survival and invasion, as well as the tumor volumes, while miR-184 inhibition could reverse this process. The RNA and protein levels of iASPP were significantly inhibited by miR-184, and the 3' UTR of iASPP was shown to be a target of miR-184. The expression of iASPP was up-regulated in CNSL tissues, compared to that of the normal brain tissues. The inhibition of iASPP by shRNA iASPP significantly repressed CNSL cells' proliferation and invasion, and reduced the volume of the tumor. Besides, iASPP overexpression could partly restore the suppressive effect of miR-184 on CNSL cell proliferation and invasive capability. We also revealed that miR-184/iASPP axis regulated the proliferation and invasion via PI3K/Akt signaling pathway, which presents a novel potential therapy for intervention of CNSL. Taken together, our findings revealed the detailed role of the miR-184/iASPP axis in CNSL and this axis might modulate the proliferation and invasion of CNSL via regulating the PI3K/Akt signaling pathway. J. Cell. Biochem. 118: 2645-2653, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Regiões 3' não Traduzidas , Proliferação de Células , Neoplasias do Sistema Nervoso Central/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linfoma/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Neoplásico/metabolismo , Proteínas Repressoras/metabolismo , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Linfoma/genética , Linfoma/patologia , Masculino , MicroRNAs/genética , Invasividade Neoplásica , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Proteínas Repressoras/genética , Transdução de Sinais/genética , Células Tumorais Cultivadas
4.
Blood Cells Mol Dis ; 56(1): 46-52, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26603724

RESUMO

Tanshinone IIA (TanIIA) is a traditional Chinese agent and has been widely used for treatment of cardiovascular diseases. Our previous study has shown that TanIIA can induce the differentiation of acute promyelocytic leukemia (APL) cells by increasing C/EBPß expression and induce APL cell apoptosis in vitro. In this study, we evaluated the activity of TanIIA against APL in vivo. We found that treatment with TanIIA prevented APL-mediated reduction in body weights. Treatment with TanIIA inhibited the proliferation of APL cells and triggered APL cell apoptosis and differentiation in vivo. Treatment with TanIIA significantly prolonged the survival of APL-bearing mice. Our data indicate that TanIIA has potent anti-APL activity with little adverse effect.


Assuntos
Abietanos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Leucemia Promielocítica Aguda/tratamento farmacológico , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Leucemia Promielocítica Aguda/patologia , Camundongos SCID
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 43(5): 657-60, 665, 2012 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-23230732

RESUMO

OBJECTIVE: To investigate the contribution of multidrug-resistant gene MDR1 to development of imatinib-resistance in Ph(+) acute lymphoblastic leukemia cell line SUP-B15/RI. METHODS: RT-PCR was used to examine MDR1 mRNA levels, cytotoxic effects of imatinib (IM), daunorubicin (DNR), vincristine (VCR), etoposide (VP-16) and the synergetic antiproliferation with P-gp inhibitor verapamil on sensitive SUP-B15 and SUP-B15/RI cell lines were detected by the MTT assay. The P-gp function was measured by flow cytometry. RESULTS: Increased expression of MDR1 gene in SUP-B15/RI than that of SUP-B15 cell line (P < 0.05) was observed when detected with RT-PCR. The IC50 values of SUP-B15/RI cell line inhibited by IM, DNR, VCR, VP-16 for 72 hours was higher than that of SUP-B15 (P < 0.05) and the resistant factor (RF) was (20.52 +/- 2.34), (10.33 +/- 1.88), (9.78 +/- 1.27), (3.84 +/- 0.69) respectively. The IC50 values of IM, DNR, VCR, VP-16 combined with P-gp inhibitor verapamil were decreased in SUP-B15/RI cells (P < 0.05), reversal of drug resistance was (1.44 +/- 0.43), (3.20 +/- 0.17), (1.44 +/- 0.12), (1.33 +/- 0.14) respectively. The activity of P-gp in SUP-B15/RI measured by flow cytometry was higher than that of P-gp in SUP-B15/RI cell line. CONCLUSION: The overexpression of MDR1 mRNA and higher activity of P-gp is partially responsible for acquiring of imatinib resistance in SUP-B15/RI cell line. P-gp inhibitor verapamail can partially restored the sensitivity of the SUP-B15/RI cell line to anticancer agents.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Piperazinas/farmacologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pirimidinas/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos/genética , Humanos , Mesilato de Imatinib , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
6.
Leuk Res ; 36(4): 509-13, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22285507

RESUMO

In this study, we established an imatinib resistant Ph+ acute lymphoblastic leukemia (ALL) cell line SUP-B15/RI in vitro and studied the mechanism of imatinib resistance. Our results showed that the BCR-ABL1 fusion gene and the mdr1 gene were 6.1 times and 1.7 times, respectively, as high as that of parental SUP-B15 cell line. We found no mutation in the Abl kinase domain of SUP-B15/RI. Furthermore, the detection of cell signaling pathway of PI3K/AKT/mTOR, RAS/RAF, NF-κB, JNK and STAT showed the up-regulation of phosphorylation of AKT, mTOR, P70S6K, and RAF, ERK, and MEK, down-regulation of PTEN and 4EBP-1, and no change in other cell signaling pathways in SUP-B15/RI. However, dasatinib and nilotinib showed partial resistance. Interestingly, bortezomib had no resistance. Imatinib combination with rapamycin had synergistic effect on overcoming the resistance. Altogether, over-expression of BCR-ABL1 and mdr1 gene were involved in the resistance mechanisms, and up-regulation of the cell signaling pathways of PI3K/AKT/mTOR, RAS/RAF in SUP-B15/RI cell line may be correlated with them. The SUP-B15/RI cell line was also resistant to the second generation tyrosine kinase, dasatinib, and nilotinib, not bortezomib. The combination of imatinib with rapamycin can partially overcome the resistance and blockade of the ubiquitin-proteasome can be also a promising pathway to overcome imatinib resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Transdução de Sinais/fisiologia , Antineoplásicos/farmacologia , Benzamidas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas de Fusão bcr-abl/genética , Genes MDR , Humanos , Mesilato de Imatinib , Immunoblotting , Mutação , Piperazinas/farmacologia , Pirimidinas/farmacologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
8.
Int J Hematol ; 92(4): 571-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20981511

RESUMO

Our studies indicated that Tanshinone IIA (TanIIA), which is widely applied in the treatment of cardiovascular diseases with a rare occurrence of side effects, could promote APL cell differentiation and apoptosis. We found TanIIA induced the differentiation of NB4 and MR2 cells with elevated C/EBPß and CHOP. When C/EBPß was overexpressed in NB4 cells, the level of CD11b in the transfected cells was significantly elevated. When we used CHOP siRNA to suppress CHOP expression in NB4 cells and then treated these cells with a high concentration of TanIIA, the differentiation and apoptosis of these cells were both significantly increased. These data demonstrate that C/EBPß is critical for APL cell differentiation and apoptosis induced by TanIIA, and that CHOP acts as a negative regulator of C/EBPß activity. Our study suggested that TanIIA is a promising drug for treating newly diagnosed and ATRA-resistant APL, and a high concentration of TanIIA associated with inhibition of CHOP, maybe a potentially promising therapy strategy.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Diferenciação Celular/efeitos dos fármacos , Leucemia Promielocítica Aguda/tratamento farmacológico , Fenantrenos/farmacologia , Fator de Transcrição CHOP/metabolismo , Abietanos , Proteína beta Intensificadora de Ligação a CCAAT/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patologia , Fator de Transcrição CHOP/genética
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 23(6): 622-6, 2006 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-17160939

RESUMO

OBJECTIVE: To analyze the frequency of FGB gene -1420G/A, -993C/T and -854G/A polymorphisms, and their association with plasma fibrinogen levels in patients with coronary heart disease and in health adults. METHODS: The FGB gene -1420G/A, -993C/T and -854G/A polymorphisms were analyzed with restriction fragment length polymorphisms, polymerase chain reaction with allele-specific primer and nucleotide sequencing methods. Plasma fibrinogen levels were determined by turbidimetry. RESULTS: The frequencies of -1420A were 0.33 in patients with coronary heart disease and 0.26 in health adults. The frequencies of -1420A in coronary heart disease were apparently higher than that in health adults. There were no difference in frequencies of other two alleles. The logistic study suggested -1420G/A polymorphism was associated with coronary heart disease. There are significantly difference in plasma fibrinogen levels in two groups. Plasma fibrinogen levels were significantly increased in patients with coronary heart disease. CONCLUSION: This study suggests -1420G/A polymorphism may be associated with occurrence of coronary heart disease.


Assuntos
Doença das Coronárias/genética , Fibrinogênio/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Sequência de Bases , Doença das Coronárias/metabolismo , DNA/química , DNA/genética , Feminino , Fibrinogênio/metabolismo , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...