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1.
Cancer Manag Res ; 12: 5385-5394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32753956

RESUMO

PURPOSE: N6-methyladenosine (m6A) is reported to play a critical role in cancer through various mechanisms. We aimed to construct and validate an m6A RNA methylation regulators-based prognostic signature for Esophageal cancer (ESCA). MATERIALS AND METHODS: The RNA sequencing transcriptome data of 13 m6A RNA methylation regulators as well as clinical data were obtained from The Cancer Genome Atlas (TCGA) ESCA database. The differential expression of the regulators between ESCA tissues and normal tissues was assessed. Consensus clustering was conducted to explore the different ESCA clusters based on the expression of these regulators. LASSO Cox regression analysis was used to generate a prognostic signature based on m6A RNA methylation regulators expression. RESULTS: Eight regulators (KIAA1429, HNRNPC, RBM15, METTL3, WTAP, YTHDF1, YTHDC1, and YTHDF2) were found to be significantly upregulated in ESCA tissues. Significant differences of survival rate and clinicopathological features were found between the two clusters. A prognostic signature, which consists of HNRNPC and ALKBH5, was constructed based on the TCGA ESCA cohort, which can serve as an independent prognostic predictor. The results of bioinformatics analysis were further successfully validated in the clinical ESCA cohort by qRT-PCR and immunohistochemistry staining. CONCLUSION: Our study constructed and validated an m6A RNA methylation regulators-based prognostic signature. This might provide important information for developing diagnostic and therapeutic strategies.

2.
IEEE Trans Neural Netw Learn Syst ; 30(4): 1104-1118, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30137016

RESUMO

To simulate the concept acquisition and binding of different senses in the brain, a biologically inspired neural network model named perception coordination network (PCN) is proposed. It is a hierarchical structure, which is functionally divided into the primary sensory area (PSA), the primary sensory association area (SAA), and the higher order association area (HAA). The PSA contains feature neurons which respond to many elementary features, e.g., colors, shapes, syllables, and basic flavors. The SAA contains primary concept neurons which combine the elementary features in the PSA to represent unimodal concept of objects, e.g., the image of an apple, the Chinese word "[píng guǒ]" which names the apple, and the taste of the apple. The HAA contains associated neurons which connect the primary concept neurons of several PSA, e.g., connects the image, the taste, and the name of an apple. It means that the associated neurons have a multimodal response mode. Therefore, this area executes multisensory integration. PCN is an online incremental learning system, it is able to continuously acquire and bind multimodality concepts in an online way. The experimental results suggest that PCN is able to handle the multimodal concept acquisition and binding effectively.

3.
Infect Agent Cancer ; 13: 40, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30559832

RESUMO

OBJECTIVE: To determine the clinical features and survival difference of HBV related and Non-HBV related diffuse large B-cell lymphoma (DLBCL) and to evaluate the occurrence of HBV reactivation in DLBCL patients and related risk factors for HBV reactivation after R-CHOP therapy. METHODS: A total of 246 patients diagnosed with CD20+ DLBCL were enrolled from June 2010 to June 2015. The medical records and survival data were analysed. Multivariate logistic regression analysis was used to identify predictors of HBV reactivation. Survival curves were performed by the Kaplan-Meier method. RESULTS: Among patients enrolled, 80 patients were HBsAg sero-positive and 166 patients were HBsAg sero-negative. Findings showed that HBsAg sero-negative patients were significantly older than that of patients with HBsAg sero-positive (P <  0.001). Proportion of B symptom positive patients in HBsAg sero-positive were higher (p = 0.002). Higher LDH level (P = 0.019) and late Ann Arbor stage (P = 0.010) were more often observed in patients with HBsAg sero-positive. The rate of complete response, partial response, stable disease and progress disease in HBsAg sero-negative group were 63.9, 16.9, 1.1 and 18.1%, respective, which is significantly higher than that in HBsAg sero-positive group (36.2, 18.8, 1.2 and 43.8%). Kaplan-Meier analysis showed that DLBCL patients with HBsAg sero-negative had better prognosis. In total, 17 patients showed HBV reactivation among 166 patients (10.2%) with HBsAg sero-negative after R-CHOP treatment, while a significant higher HBV reactivation 18.75% (9/48) in HBsAb negative group were observed, with 8.25% (8/97) patients in HBsAb level 10-100 U/mL group, and 0% patients in HBsAb level higher than 100 U/mL group. Multivariable analysis showed that serum HBsAb and serum HBcAb were independent risk factors for HBV reactivation in DLBCL patients. CONCLUSION: Our data revealed that characteristics and prognosis were significantly different between HBV related DLBCL than non-HBV related DLBCL patients. DLBCL patients with resolved hepatitis B are at a higher risk of developing HBV reactivation after R-CHOP chemotherapy compared with HBsAg-negative/HBcAb negative patients.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(5): 1360-1365, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30295251

RESUMO

OBJECTIVE: To study whether chlorambucil has apoptotic effect on the B cell lymphoma A20 cells and its exact mechanisms in apoptotic signaling pathway. METHODS: The experimental cells were treated with 20 µmol/L chlorambucil, the control cells were treated with PBS. Annexin V-FITC Cell Apoptosis Detection Kit was used to examine cell apoptosis. Western blot was used to detect the expressions of active caspase-3, Survivin, NF-κB and pAKT. Real-time fluorescent quantitative PCR was performed to examine the mRNA expression of Survivin. RESULTS: Compared with the control group, the proportion of FITC+/PI+ apoptotic cells and the expression of active caspase-3 (t=7.384, P=0.000) in the chlorambucil treatment group was significantly elevated. However, the expression of Survivin mRNA (t=4.384, P=0.000), protein expressions of survivin (t=12.360, P=0.000), NF-κB (t=5.462, P=0.000) and pAKT (t=7.183, P=0.000) in the chlorambucil-treated group all significantly decreased. CONCLUSION: The chlorambucil can induce the apoptosis of lymphoma cells, its mechanism may related with inhibition of PI3K/AKT signaling pathway, and expression of NF-κB and survivin.


Assuntos
Apoptose , Linfoma , Linhagem Celular Tumoral , Clorambucila , Humanos , Fosfatidilinositol 3-Quinases , Transdução de Sinais
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(4): 1056-1061, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30111407

RESUMO

OBJECTIVE: To study the clinical characteristics and prognosis of patients with variant Ph chromosome-positive leukemia. METHODS: The defection of morphology, cytogenetics, immunology and molecular biology was performed in 4 cares of variant Ph chromosome-positive leukemia, and the therepeuitics outcome of 4 patients was evaluated. RESULTS: Among 4 cases of variant Ph+ leukemia, 3 cases were patients with CML, including 1 case in chronic phase and 2 cases in accelerated phase; and 1 cases was patient with adult B acute lymphoblasric leukemia(B-ALL).The defecfion of cytogenetics in 4 cases showed that 2 cases of CML displayed t(9; 22; 14) abnormality, 1 case of CML displayed t(5; 9; 22) abnormality, moreover, the BCR/ABL fution gane in 3 cases of CML all was e14a2 type, 1 cases of adult B-ALL disylayed t(9; 22; 17) abnormatlity, BCR/ABL fution gene of this case was e13a3 type, 4 patients all received treatment wire chemotherapeptic regimen contaiming methanesulfanate imatinib. As a result, 1 cases of adult B-ALL with e13a3 type BCR/ABL fusion gene positive relapsed after molecular biology remission for 4 months and died in the 10th month; and yet 3 cases of CML are still in molecular biology remission, the disease-free survival time of these 3 cases was 10, 19 and 27 months respectively. CONCLUSION: The patients with variant Ph chromosome-positive leukemia will response to the first generation tyrosine kinase inhibitors, but the prognosis of patients with e13a3 type of BCR/ABL fusion gene remains to be further explored.


Assuntos
Cromossomo Filadélfia , Proteínas de Fusão bcr-abl , Humanos , Mesilato de Imatinib , Leucemia , Prognóstico
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(4): 1072-1078, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30111410

RESUMO

OBJECTIVE: To investigate the clinical characteristics and outcome of parhents with EBV infection conbined with hemophagocytic syndrome and Hodgkin's lymphoma. METHODS: The morphotogy of bone marrow cells was observed by bone marrow smear and light microscopy, the pathologic changes of bone marrow ware analyzed by bone marrow biopsy and immunohistochemistry methord, the pathologic changes of lymphonudes ware detected by immunohistochemical methord, the paticnts were treated with ABVD (epirubicin, bleomycin, vincristine and dacarbazine) chemotherapeutic regimen. RESULTS: Fever complicatid with pancytopenia, obvious increase of ferritin and sCD25, hypofibrinogenemia, hemophogocytic phenomen of bone marrow, increase of EBV-DNA copy number ware observed, which all accorded with the criteria EBV righted hemophagocytic syndrome. The curative efficacy of amtiinfective treatmatnt was poor, After treatment with HLH-2004 regimen, the fever symptome and the laboratory indicaters such as whole blood cells, ferritin and fibrinogen all were recovered to normal levels. Left mandibular lymphadenctasis was confirmed as Hodgkin's lymphoma (mixed cell type) by pathological examination. The patient achieved complete molecular remission after 1 course chemotherapy with ABVD regimen. The level of EBV-DNA copy number were also decreased. As the reshlt, the patient's hemophagocytic syndrome had bean effectively controlled, and the Hodgkin's lymphoma is still in complete remission. CONCLUSION: Epstein-Barr virus-ratated hemophagocytic syndrome and Hodgkin's lymphoma are rare, and their long-term prognosis needs to be further explored.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 4 , Doença de Hodgkin , Humanos , Linfo-Histiocitose Hemofagocítica , Vincristina
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(6): 1641-1646, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29262890

RESUMO

OBJECTIVE: To investigate the curative effect and safety of decitabine combined with IAG regimen for treating senile MDS-transformed AML patients. METHODS: Two cases of senile MDS-transformed AML were treated with decitabine combined with IAG regimen (decitabine 25 mg/d,qd,ivgtt,d1-5,Idarubicin 10 mg/d,qd,ivgtt,d6,Ara-C 10 mg/m2,q12h, sc,d 6-19,G-CSF 300 µg,qd,ih,d6-19). The efficacy and adverse reactions were observed in these cases. RESULTS: 1 case for 2 courses and 1 case for 1 course obtained complete remission(CR). The myelosuppression and infections due to neutropenia were the most frequent adverse effects, the severe nonhematologic toxicity, such as liver and kidney and gastrointestinal reactions, were not observed in these patients. CONCLUSION: Decitabine combined with IAG regimen is an effective for treating senile MDS-transformed AML patients.


Assuntos
Doença de Alzheimer/complicações , Antimetabólitos Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azacitidina/análogos & derivados , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Azacitidina/uso terapêutico , Citarabina , Decitabina , Humanos , Resultado do Tratamento
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(4): 1066-70, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27531776

RESUMO

OBJECTIVE: To explore the action mechanism of chlorambucil against mantle cell lymphoma cell line Jeko-1. METHODS: The effect of chlorambucil on Jeko-1 cell proliferation was measured by MTT method. The effect of chlorambucil on the apoptosis of Jeko-1 cell was detected by Hoechst staining and Annexin V-FITC dual staining. The activation of PI3K/AKT signaling pathway and the expression of BAX, BCL-2, procaspase 3, procaspase 8 and procaspase 9 were detected by Western blot. RESULTS: 0, 5, 10, 20 µmol/L chlorambucil could inhibit Jeko-1 cell proliferation at 24, 48, 72 h in a time- and dose-dependent manner. Chlorambucil of 0, 5, 10, 20 µmol/L increased the apoptotic rate of Jeko-1 cells, upregulated the expression of BAX, procaspase 3, procaspase 8, procaspase 9 and PI3K, increased the phosphorylation of AKT and down-regulated the expression of BCL-2. CONCLUSION: The chlorambucil can induce the apoptosis of mantle cell lymphoma Jeko-1 cells via blocking PI3K/AKT signaling pathway.


Assuntos
Linfoma de Célula do Manto , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Clorambucila , Regulação para Baixo , Humanos , Fosfatidilinositol 3-Quinases , Fosforilação , Transdução de Sinais
9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(3): 331-6, 2016 May.
Artigo em Chinês | MEDLINE | ID: mdl-27468475

RESUMO

OBJECTIVE: To study the impact of high concentration insulin on the proliferation and apoptosis of K562 cell strain. METHODS: K562 cells were treated with different concentrations of insulin. The proliferation activity was tested by CCK-8 assay, cytometry, and trypan blue exclusion. The alterations in glucose concentration of the culture media were monitored while the apoptosis of K562 cells was detected by flow cytometry. The effects of high concentration insulin on the proliferation of K562 cells were inhibited by varying concentrations of insulin-like growth factor-1 (IGF-1) and Suramin. RESULTS: Under the range of concentration (0.1-1 mU/mL), insulin facilitated the proliferation of K562 cells. In contrast, insulin at high concentrations (1.6-100 mU/mL) had the opposite effect, in a dose- and time-dependent manner. Different concentrations of glucose in the culture medium had no significant influence on the inhibitory effect of high concentration insulin on the proliferation of human leukemia cell strain K562. At low concentration insulin inhibited the apoptosis of K562 cells, in a dose-dependent manner. In contrast, insulin at high concentration had the opposite effect, in a dose-dependent manner. Furthermore, IGF-1 reversed the inhibitory effect of high concentration insulin on the proliferation of K562 cell in a dose- and time-dependent manner. Suramin, which is an IGF-1 receptor non-specific blocker, had the opposite effect on K562 cells, also in a dose- and time-dependent manner. CONCLUSION: These results indicate insulin has a dual effect on K562 cells. The dual effect is probably mediated by the binding of insulin and IGF-1R. Inhibitory effect of high concentration insulin on the proliferation of K562 cells is unrelated with the glucose metabolism in the culture media.


Assuntos
Apoptose , Proliferação de Células , Meios de Cultura/química , Insulinas/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Fator de Crescimento Insulin-Like I/farmacologia , Células K562/efeitos dos fármacos , Suramina/farmacologia
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 24(2): 411-5, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-27151001

RESUMO

OBJECTIVE: To investigate the inhibitory effect of high concentration insulin on K562 cell proliferation and its underlying mechanism. METHODS: K562 cells were treated by different concentration of insulin and/or anti-IGF-1R antibody (IGF-1R-Ab), MTT assay and flow cytometry were used to detect the K562 cells proliferation and apoptosis, respectivety; Western blot was used to measure the expression and phosphorylation level of IGE-IR, Akt, Erk1/2 in K562 cells under the different concentration of insulin. RESULTS: MTT assay showed that less than 40 mU/ml insulin could promote K562 cell proliferation, while high concentration (> 40 mU/ml) insulin has been shown to inhibit K562 cell proliferation; Flow cytometry showed that 40 mU/ml insulin suppressed K562 cell apoptosis (P < 0.05), while 200 mU/ml insulin could significantly induce K562 cell apoptosis (P < 0.01); 0.01 to 1.0 µg/ml IGF-1R-Ab has significantly enhanced the inhibitory and inducing effects of high concentration (> 40 mU/ml) of insulin on K562 cell proliferation and apoptosis respectively (r = 0.962, P < 0.001); Western blot showed that after K562 cells were treated with different concentrations of insulin ERK, and the p-ERK expression did not change significantly, after K562 cells were treated with 200 mU/ml insulin, the expression of IGF-1R and AKT also not were changed obviously, while the phosphorylation level of IGF-1R and AKT increased. CONCLUSION: High concentration (>40 mU/ml) of insulin inhibits K562 cell proliferation and induces its apoptosis, and its mechanism may be related with the binding IGF-1R by insulin, competitively inhibiting the binding of IGF-1 and IGF-1R, the blocking the transduction of PI3K/AKT signal pathway.


Assuntos
Anticorpos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Insulina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Meios de Cultura/química , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Células K562 , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Somatomedina/imunologia
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(5): 1235-9, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26524015

RESUMO

OBJECTIVE: To explore the expression and promoter CpG island methylation status of miR-34b in leukemia cell lines and their clinical significance. METHODS: A total of 10 cases of non-hematologic diseases were selected as control group, and the bone marrow cells of control group and HL-60, K562 cells were selected; the relative expression of miR-34b was detected in bone marrow cells, HL-60 and K562 cell lines by fluorescence quantitative PCR, and the MiR-34b methylation status was detected by methylation-specific PCR, the HL-60 and K562 cell lines were treated with decitabine, and the expression levels and methylation status of miR-34b in the 2 cell lines were detected by the same method. Has-miR-34b was transfected into K562 cells, which were divided into non-transfection group, negative control group and Has-miR-34b transfection group; if the transfection was successful, the cell proliferation should be recorded at different time points of culture, and the proliferation inhibition rate should be calculated. RESULTS: The relative expression level of miR-34b in the control group was (5.23 ± 0.75), in HL-60 was (0.05 ± 0.01) and in K562 was (0.04 ± 0.01). The difference between 3 groups was statistically significant (F = 44.812, P < 0.01). The promoter regions of CpG island in HL-60 and K562 cell lines were methylated, while the bone marrow cells were not methylated in 10 cases of non hematologic diseases children.Through miR-34b expression levels of HL-60 and K562 cell lines significantly increased by decitabine treatment (P < 0.05), and the methylation of leukemia cell line promoter region CpG island was found before and after decitabine treatment, but after administration of decitabine the methylation significantly decreased, suggesting that decitabine has an inhibitory effect on methylation of promoter region CpG island. After being cultured for 48, 72, 96 and 120 hrs, the cell proliferation in Has-miR-34b transfection group reached to 24.8%, 46.7%, 33.6% and 4.7%, repectively, and significantly lower than that in non transfection group (P < 0.05). CONCLUSION: CpG island methylation of miR-34b promoter region in leukemia cell lines can decrease the expression levels of miR-34b, which is also the reason why miR-34b can reduce the inhibition of cell proliferation, thus miR-34b might be a tumor suppressor gene involved in the regulation of leukemia.


Assuntos
Ilhas de CpG , Metilação de DNA , Leucemia/genética , MicroRNAs/genética , Regiões Promotoras Genéticas , Azacitidina/análogos & derivados , Azacitidina/farmacologia , Proliferação de Células , Criança , Decitabina , Células HL-60 , Humanos , Células K562 , Reação em Cadeia da Polimerase em Tempo Real , Transfecção
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(2): 392-5, 2015 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-25948191

RESUMO

OBJECTIVE: To explore the effect of 2-methoxyestradiol (2-ME2) on apoptosis of human acute T lymphoblastic leukemia cells, and its underlying mechanism. METHODS: The growth inhibition of CEM cells was detected by MTT assay; apoptotic cells were detected by DNA laddering analysis; the expressions of P53 mRNA and protein were detected by RT-PCR and Western blot respectively. RESULTS: 2-ME2 remarkably inhibited the CEM cell growth and the 50% growth inhibitory concentration (IC50) at 48 h was 2 µmol/L. The DNA ladder could be detected in CEM cells after treating with 2 µmol/L 2-ME2 for 24, 48 and 72 hours; after treating with 2 µmol/L 2-ME2 for 24, 48 and 72 hours, a time-dependent reduction of P53 mRNA and protein expressions was found in CEM cells. CONCLUSION: The anti-leukemia effect of 2-ME2 is completed through the induction of cell apoptosis. Down-regulation of P53 gene expression may be an underlying mechanism.


Assuntos
Apoptose , Genes p53 , 2-Metoxiestradiol , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Estradiol/análogos & derivados , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras
13.
Yi Chuan ; 37(1): 41-47, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25608812

RESUMO

To uncover the molecular pathogenic mechanism of congenital osteogenesis imperfecta (OI) type I, all the 103 exons of the COL1A1 (Collagen, type Ⅰ, alpha 1) and COL1A2 (Collagen, type Ⅰ, alpha 2) genes in a child with OI type Ⅰ were screened using PCR-DNA direct sequencing. The results showed no pathological mutation in COL1A1 gene, but a novel mutation c.946G>T/p.G316C in the exon 19 of COL1A2 gene, which was inherited from her father. This mutation was not found in her mother and other six phenotypically normal relatives. By denaturing high performance liquid chromatography (DHPLC) screening, the abnormal double-peak was visualized in PCR products of exon 19 of COL1A2 gene in the proband and her father, while the normal single-peak was shown in those of her mother and all the healthy controls. Using allele specific amplification (ASA) screening, a specific band of 391 bp in COL1A2 exon 19 was amplified only in the proband and her father, but not in other samples. The amino acid encoded by the mutation site is evolutionarily highly conserved, and this mutation was a "damaging" or "probably damaging" factor to OI type Ⅰ, based on the predicting results using SIFT and Polyphen-2 softwares. In conclusion, the novel c.946G>T/p.G316C mutation in COL1A2 gene is a pathogenic mutation that could result in OI type Ⅰ. If the couple wants to get pregnant again, it is necessary to screen the mutation site in COL1A2 gene through the prenatal genetic diagnosis in the first trimester or through preimplantation genetic diagnosis (PGD) in the progestation.


Assuntos
Colágeno Tipo I/genética , Osteogênese Imperfeita/genética , Mutação Puntual , Adolescente , Adulto , Sequência de Aminoácidos , Sequência de Bases , Criança , Feminino , Testes Genéticos , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Gravidez , Adulto Jovem
14.
Zhonghua Er Ke Za Zhi ; 51(12): 915-9, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24495762

RESUMO

OBJECTIVE: To reveal the molecular genetic pathogenesis of the glycogen storage disease type III (GSDIII) and to provide a prerequisite for prenatal gene diagnosis in future. METHOD: All the coding regions as well as the border areas between exons and introns of the AGL gene and the parental relevant mutation sites were directly sequenced, so that to affirm the origin of the mutation. Then, detected novel heterozygous mutation was confirmed by cloning sequencing. Finally, definite diagnoses of the novel mutation were performed by a series of identification methods, including screening for the 100 normal controls by DHPLC in order to count the mutational frequency, analyze the conservative of the mutant amino acid sequence from 11 kinds of species and comprise the difference of the tertiary structure between the mutant protein and the normal one. RESULT: The patient had compound heterozygous mutations, the c.100C>T (p.R34X) nonsense mutation and c. 1176_1178 del TCA deletion mutation. The p.R34X has been reported abroad, but the 1176_1178 del TCA/p.His392fs mutation is a novel one. The proband's father is heterozygous with the p.R34X mutation while his mother carries the c.1176_1178 del TCA mutation. The result from searching the dbSNP database, HGMD database and papers published in recent years showed that the c.1176_1178 del TCA is a novel mutation, but not an SNP. Conservative analysis results in 11 species indicate that the amino acid of the mutation site is highly conserved in the stage of evolution. Comparison results between the mutant protein and the normal one demonstrate that the deletion mutation results in the obvious variation of the spatial conformation of AGL protein. CONCLUSION: The "c.1176_1178 del TCA (p.392delHis)" mutation is a novel pathogenic mutation. This mutation and the c.100C>T (p.R34X) is the cause that the proband suffer from the GSDIIIa disease. These two mutations are inherited from mother and father respectively. The methods from this paper can be used for further prenatal gene diagnosis.


Assuntos
Sistema da Enzima Desramificadora do Glicogênio/genética , Doença de Depósito de Glicogênio Tipo III/genética , Mutação , Adulto , Sequência de Aminoácidos , Sequência de Bases , Estudos de Casos e Controles , Pré-Escolar , Análise Mutacional de DNA , Éxons , Feminino , Sistema da Enzima Desramificadora do Glicogênio/química , Doença de Depósito de Glicogênio Tipo III/diagnóstico , Heterozigoto , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Conformação Proteica , Alinhamento de Sequência
15.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(2): 514-7, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22541130

RESUMO

Many reports have documented a role of insulin and insulin-like growth factor 1 (IGF-1) as growth factors in many cancers. The sequence and structure of insulin receptor (IR) and IGF receptor (IGF-1R) are highly similar. Both receptors are overexpressed in leukemia cells.Studies indicate that insulin can enhance the signal of the phosphoinositide 3-kinase/Akt pathways by activating IR or IGF-1R or hybrid IR/IGF-IR receptors, resulting in the proliferation of leukemia cells. High concentration of insulin may inhibit the growth of leukemia cells, the mechanism of which remains to be unclear. Inhibiting IR and IGF-IR can diminish the proliferation of leukemia cells. Therefore, the assumption of IR/IGF-1R as a potential therapeutic target in leukemia appears reasonable. This article summarizes the recent advancement associated with the signaling pathway of insulin effecting the proliferation of leukemia cells.


Assuntos
Proliferação de Células , Fator de Crescimento Insulin-Like I/metabolismo , Insulina , Leucemia/metabolismo , Receptor de Insulina/metabolismo , Linhagem Celular Tumoral , Humanos , Leucemia/patologia , Transdução de Sinais
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 19(1): 269-73, 2011 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-21362266

RESUMO

As a hormone with a number of biological effects, insulin not only displays the function of classic metabolic regulation, but also can regulate cell proliferation and differentiation, and ensure growth and development of embryos and young individuals. In vitro insulin can stimulate cell proliferation and differentiation. Insulin is also an important growth regulator in vivo, which has been proved in more and more studies. The role of insulin at the cellular level is triggered by the binding of insulin to its receptor located in the cell surface. However, insulin at the higher concentration can also been triggered by insulin-like growth factor-1 (IGF-1) receptor. Its role varies in different cell lines. Insulin receptor and insulin-like growth factor receptor-1 are widely expressed in human MDS and AML cell membranes. Recently, many studies related to the relationship between hyperinsulinemia and cancer have been reported. In this review the role and its possible mechanism in promoting human leukemia cell proliferation and inhibiting human leukemia cell proliferation are summarized. Furthermore, the potential application prospect of insulin analogues also will be described.


Assuntos
Proliferação de Células/efeitos dos fármacos , Insulina/farmacologia , Leucemia/patologia , Diferenciação Celular/efeitos dos fármacos , Humanos , Leucemia/metabolismo , Receptor IGF Tipo 1/metabolismo , Receptor de Insulina/metabolismo
17.
Immunopharmacol Immunotoxicol ; 33(1): 150-6, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20515294

RESUMO

Here in a co-cultivation system of natural killer (NK) cells and K562 cells, monocytes (MO) and/or interleukin (IL)-2/phytohemagglutinin (PHA) were administered. After MO were administered, reactive oxygen metabolites (ROM)/reactive nitrogen metabolites (RNM) productions increased, while tumor necrosis factor (TNF)-ß/interferon (IFN)-γ levels and NK cell cytotoxicity (NCC) decreased, the changes of which after administering tiopronin (TIP) or glutamylcysteinylglycine (GSH) were opposite. In conclusions, the activated MO could inhibit the NK cell activity to kill K562 cell by secreting ROM and RNM. And TIP and GSH could scavenge both ROM and RNM to reverse the inhibitory effect of MO.


Assuntos
Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Monócitos/imunologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Técnicas de Cocultura , Humanos , Interleucina-2/imunologia , Interleucina-2/farmacologia , Células K562 , Células Matadoras Naturais/citologia , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Monócitos/citologia , Monócitos/metabolismo , Fito-Hemaglutininas/imunologia , Fito-Hemaglutininas/farmacologia
18.
Zhonghua Zhong Liu Za Zhi ; 32(4): 267-71, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20510076

RESUMO

OBJECTIVE: To explore the effects of the exogenous and endogenous reactive nitrogen metabolites (RNM) as NK cell inhibitors on NK cell-mediated killing of K562 cells and the influence of Tiopronin (TIP), glutamylcysteinylglycine (GSH) and histamine dihydrochloride (DHT) as RNM scavengers on reversing the suppressing effect of RNM. METHODS: The exogenous ONOO(-) was administered in the NK+K562 culture system, then the RNM scavengers were added in the NK+K562+ONOO(-) culture system, respectively. The concentrations of RNM, TNF-beta and IFN-gamma, K562 cell inhibition rate (KIR) and the percentage of living NK cells were examined. IL-2+PHA were used as monocyte (MO) activators in the culture system of MO+NK+K562. Then TIP, GSH and DHT were administered and the parameters of NK cell activity were analyzed. RESULTS: After exogenous ONOO(-) was administered in NK+K562 culture system, the percentage of living NK cells was decreased from (93.17 +/- 2.57)% to (71.87 +/- 1.02)% (P < 0.01) and KIR was decreased from (67.47 +/- 2.64)% to (43.44 +/- 2.87)% (P < 0.01). When TIP, GSH and DHT were administered into the systems, the percentage of living NK cells was increased to (91.13 +/- 3.67)% (P < 0.05), (88.03 +/- 1.46)% (P < 0.05), (73.60 +/- 2.76)% (P > 0.05), respectively; KIR was increased to (61.58 +/- 1.89)% (P < 0.05), (60.68 +/- 2.07)% (P < 0.05) and (45.26 +/- 3.31)% (P > 0.05), respectively. When IL-2/PHA were administered in the NK+K562+MO culture system, RNM products was increased from (82.10 +/- 6.60) micromom/L to (193.65 +/- 5.95) micromom/L(P < 0.01);KIR was decreased from (90.64 +/- 3.06)% to (61.29 +/- 2.22)% (P < 0.01). When the TIP, GSH and DHT were administered in the systems, RNM products were decreased to (91.32 +/- 6.81) micromom/L (P < 0.05), (84.66 +/- 5.99) micromom/L (P < 0.05) and (188.92 +/- 5.00) micromom/L (P > 0.05), respectively; KIR was increased to (84.31 +/- 4.56)%(P < 0.05), (81.65 +/- 3.09)% (P < 0.05) and (72.20 +/- 4.10)% (P < 0.05), respectively. CONCLUSION: NK Cell-mediated killing of K562 cells can be suppressed by exogenous and endogenous RNM administration. Both of TIP and GSH can protect NK cells by scavenging RNM and enhance the antineoplasmic activity of NK cells.


Assuntos
Interferon gama/metabolismo , Células Matadoras Naturais/citologia , Linfotoxina-alfa/metabolismo , Ácido Peroxinitroso/farmacologia , Espécies Reativas de Nitrogênio/antagonistas & inibidores , Células Cultivadas , Técnicas de Cocultura , Glutationa/farmacologia , Histamina/farmacologia , Humanos , Interleucina-2/imunologia , Interleucina-2/farmacologia , Células K562 , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Monócitos/citologia , Espécies Reativas de Nitrogênio/metabolismo , Tiopronina/farmacologia
20.
J Zhejiang Univ Sci B ; 8(8): 566-9, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17657858

RESUMO

OBJECTIVE: To identify the mutations of iduronate-2-sulfatase (IDS) gene, to reveal its mutation features, and to establish a basis for genetic counseling and prenatal gene diagnosis of Hunter syndrome. METHODS: Urine glycosaminoglycans (GAGs) assay, PCR and DNA sequencing were performed to detect mutation of IDS gene of the patient and his parents. RESULTS: The result showed that the patient was: DS(++), HS(++), KS(-), CS(-), and that both of his parents were negative. A frame-shift deletion mutation (1062 del 16) was identified in exon 7 of the patient's IDS gene. His parents' genotypes were normal. CONCLUSION: The patient's mutation was not inherited by his parents but a novel one. The mutation probably altered the primary structure and tertiary structure of IDS enzyme protein remarkably and lowered the activity of IDS enzyme greatly. Therefore it is supposed to be the direct cause of the disorder.


Assuntos
Glicoproteínas/genética , Mucopolissacaridose II/enzimologia , Mucopolissacaridose II/genética , Povo Asiático/genética , Sequência de Bases , Pré-Escolar , Feminino , Glicoproteínas/urina , Humanos , Masculino , Mucopolissacaridose II/urina , Mutação/genética
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