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[This retracts the article DOI: 10.1186/s12935-014-0154-0.].
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OBJECTIVE: Psoriasin (S100A7) plays a role in the malignant potential of several epithelial cancers, and could candidate diagnostic marker or therapeutic target. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. In the present study, we first evaluate the involvement of S100A7 in lung squamous cell carcinoma and its clinical usefulness for diagnosis. We then study whether knockdown of S100A7 in lung squamous cell carcinoma cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo. METHODS: We examined S100A7 expression in lung squamous cell carcinoma tissues by immunohistology. The human lung squamous cell carcinoma cell line NCI-H520 were transduced with short hairpin RNA targeting S100A7. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of S100A7 messenger RNA and protein, respectively. Cell proliferation was evaluated by the MTT assay. NF-κB phosphorylation was assayed by western blot. 1 × 10(6) of NCI-H520/S100A7 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 35 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for S100A7 protein expression. RESULTS: S100A7 protein levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. S100A7 might be a useful marker for diagnosis of lung squamous cell carcinoma. In vitro data showed that inhibition of S100A7 decreased proliferation of NCI-H520 cells. S100A7 knockdown reduced NF-κB phosphorylation and tumor growth in vivo and vivo. Explanted knockdown tumors maintained lower S100A7 levels compared with wild-type, confirmed by immunohistology. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors. CONCLUSIONS: Our present results suggest that S100A7 level is a promising tool for diagnosis of lung squamous cell carcinoma. Knockdown of S100A7 suppresses lung cancer growth in part by attenuating NF-κB activity. S100A7 may be a promising therapeutic target for lung squamous cell carcinoma.
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OBJECTIVE: To study the relationship between loss of sex chromosomes and prognosis in children with acute myeloid leukemia (AML) M2 subtype. METHODS: According to cytogenetic characteristics, 106 children with AML were divided into three groups: patients with normal karyotype (Group A, n=26), patients with abnormal karyotype who had no loss of sex chromosomes (Group B, n=52), and patients with abnormal karyotype who had loss of sex chromosomes (Group C, n=28). Prognosis was compared between the three groups. RESULTS: The 5-year event-free survival (EFS) rates of Groups A, B, and C were (38.9±11.2)%, (59.3±7.3)%, and (66.5±10.5)%, respectively; the EFS of Group C was significantly higher than that of Group A (P=0.035). The 5-year overall survival (OS) rates of Groups A, B, and C were (54.3±13.5)%, (68.1±7.7)%, and (77.9±9.8)%, respectively (P>0.05). The 5-year EFS of 58 patients with t(8;21) was (63.3±7.3)%, significantly higher than that of patients with normal karyotype (P=0.015). All the 28 cases in Group C had t(8;21), and their 5-year EFS was not significantly different from that of patients with t(8;21) in Group B (P>0.05). CONCLUSIONS: Loss of sex chromosomes is a favorable karyotype in children with AML M2 subtype and the patients in this group mostly have t(8;21). Why loss of sex chromosomes indicates a favorable prognosis is probably because it is accompanied by t(8;21) in the patients.
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Leucemia Mieloide Aguda/genética , Aberrações dos Cromossomos Sexuais , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Feminino , Humanos , Cariótipo , Leucemia Mieloide Aguda/mortalidade , Masculino , Prognóstico , Translocação GenéticaRESUMO
OBJECTIVE: To study the changes of minimal residual disease (MRD) in children with B cell acute lymphoblastic leukemia (B-ALL) of different genetic abnormalities. METHODS: Between February 2004 and April 2013, 271 newly diagnosed B-ALL pediatric patients who had finished the induction chemotherapy were enrolled in the study. The characteristics of changes in MRD in patients with different genetic abnormalities on the 15th day and at the end of the induction therapy were analyzed. RESULTS: On the 15th day of the induction chemotherapy, the MRD positive proportion in patients with hyperdiploid was higher on all the three cut-off levels of MRD≥0.1%, 1% and 10% compared to patients without hyperdiploid (P<0.05), but there was no significant difference in the MRD positive proportion on the three levels of MRD between the TEL-AML1-positive and TEL-AML1-negative groups (P>0.05). On the end of induction chemotherapy, there was no significant difference in the MRD positive proportion on the three levels of MRD between the patients with and without hyperdiploid (P>0.05), neither between the BCR-ABL-positive and negative groups. The MRD positive proportion in TEL-AML1-negative patients was significantly higher than in TEL-AML1-positive patients on all three levels of MRD (P<0.05). The MRD positive proportion on two levels of MRD≥0.01% and 0.1% in E2A-PBX1-negative patients was significantly higher than in E2A-PBX1-positive patients (P<0.05). CONCLUSIONS: Children with B-ALL of different genetic abnormalities have different MRD levels during, and at the end of, induction therapy. The prognostic significance of MRD may be related to the genetic abnormalities.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Quimioterapia de Indução , Lactente , Recém-Nascido , Masculino , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
OBJECTIVES: The efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (As2 O3 ) as induction therapy for adult acute promyelocytic leukaemia (APL) has been documented in several clinical trials. However, the role of ATRA/As2 O3 combination in induction and consolidation therapy in children remains unclear. Here, we report the efficacy of combined treatment with As2 O3 and ATRA as induction and consolidation chemotherapy to treat newly diagnosed childhood APL. METHODS: From 1998 to 2011, 43 children with newly diagnosed APL received induction and consolidation chemotherapy with ATRA and As2 O3 (Protocol B). Rates of complete remission (CR), event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) and drug toxicity were compared between children treated with Protocol B and 25 others treated previously with ATRA alone as induction chemotherapy (Protocol A). RESULTS: Of 43 patients treated with Protocol B, 41 (95.4%) achieved CR (two died of intracranial haemorrhage on day 10 and 14). In contrast, only 20 (80%) of 25 patients treated with Protocol A achieved CR. Thus, the CR rate was significantly lower in patients receiving induction chemotherapy with Protocol A than in those treated with Protocol B (P = 0.045, χ(2) = 6.508). Of the 41 patients who achieved CR on induction therapy with Protocol B, 40 also received consolidation therapy. Molecular relapse, but no overt morphological relapse, occurred in one patient at 25 months after diagnosis; this patient regained CR status with As2 O3 treatment. With a median follow-up period of 75 months, estimated EFS, DFS and OS rates were 92.5 ± 4.2%, 97.1 ± 2.9% and 95.3 ± 3.2%, respectively, for Protocol B. In contrast, with a median follow-up of 127 months, the EFS, DFS and OS rates at 75 months were 70.4 ± 9.4%, 76.4 ± 9.2% and 70.4 ± 9.4%, respectively, for Protocol A. Thus, patients treated with Protocol A showed significantly lower EFS (P = 0.021) and OS (P = 0.007) rates than those treated with Protocol B. CONCLUSIONS: Application of As2 O3 and ATRA as induction and consolidation chemotherapy resulted in excellent outcomes and improved long-term prognosis in children with newly diagnosed APL.
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Antineoplásicos/uso terapêutico , Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Óxidos/uso terapêutico , Adolescente , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/efeitos adversos , Criança , Pré-Escolar , Quimioterapia de Consolidação , Feminino , Humanos , Quimioterapia de Indução , Leucemia Promielocítica Aguda/patologia , Masculino , Neoplasia Residual , Óxidos/administração & dosagem , Óxidos/efeitos adversos , Prognóstico , Resultado do Tratamento , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos , Tretinoína/uso terapêuticoRESUMO
OBJECTIVE: To explore the efficacy and adverse effects of clofarabine for relapsed/refractory acute lymphoblastic leukemia in children. METHODS: Twenty-six pediatric patients with relapsed/refractory acute lymphoblastic leukemia were treated with clofarabine. There were 22 males and 4 females, with a mean age of 9.5 years (ranging from 4 to 17 years). They received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days. Thirteen patients received two cycles and one patient received three cycles. RESULTS: In the first cycle of clofarabine, complete remission was obtained in 11 children (42%) and partial remission was obtained in 7 children (27%). Eight children (31%) were considered unresponsive. In the second cycle, 11 (85%) of the 13 children obtained complete remission, 1 (8%) partial remission and 1 (8%) was unresponsive. One child received three cycles and obtained complete remission in each cycle. The common adverse events were myelosuppression, infection, liver dysfunction and gastrointestinal adverse reactions. There were no chemotherapy-related deaths. CONCLUSIONS: Clofarabine is effective in the treatment of children with relapsed/refractory acute lymphoblastic leukemia and its adverse effects can be tolerated. Clofarabine could be a promising new treatment for relapsed/refractory acute lymphoblastic leukemia.
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Nucleotídeos de Adenina/uso terapêutico , Antineoplásicos/uso terapêutico , Arabinonucleosídeos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Nucleotídeos de Adenina/efeitos adversos , Adolescente , Antineoplásicos/efeitos adversos , Arabinonucleosídeos/efeitos adversos , Criança , Pré-Escolar , Clofarabina , Feminino , Seguimentos , Humanos , Lactente , Masculino , RecidivaRESUMO
OBJECTIVE: To study the clinical features and etiological spectrum of pancytopenia in children. METHODS: The clinical data of 174 children with pancytopenia between September 2003 and January 2010 were retrospectively reviewed. RESULTS: Pale face was the most common clinical manifestation (147 cases, 84.5%), followed by bleeding (87 cases, 50.0%) and fever (41 cases, 23.6%). Mild to moderate anemia, severe thrombocytopenia and mild leucopenia were common in complete blood count. Of the 174 children, pancytopenia was attributed to hematopoietic system diseases in 155 cases (89.1%) and non-hematopoietic system diseases (virus infections, systemic lupus erythematosus, hypersplenism and neuroblastoma) in 6 cases (3.4%). Aplastic anemia (91 cases, 52.3%) was the most common cause of pancytopenia, followed by myelodysplastic syndrome (37 cases, 21.3%), acute leukemia and other hematological tumours (11 cases, 6.3%) and hemophagocytic syndrome (6 cases, 3.4%). The cause of pancytopenia was not identified in 13 cases (7.5%). CONCLUSIONS: Anemia, bleeding and fever are the main clinical manifestations of pancytopenia in children. Pancytopenia is mostly caused by aplastic anemia in children. Myelodysplastic syndrome, hematological tumours and hemophagocytic syndrome are also the common causes.
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Pancitopenia/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pancitopenia/sangue , Pancitopenia/diagnósticoRESUMO
UNLABELLED: OBJECTIVE To study the clinical and biological characteristics and prognosis of t(8;21)/AML1-ETO-positive childhood acute myeloid leukemia (AML). METHODS: The clinical data of 55 children who were diagnosed as t (8; 21)/AML1-ETO-positive AML were retrospectively studied. Event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) rates were estimated by the Kaplan-Meier method. Prognostic factors were evaluated by COX regression analysis software. RESULTS: Of the 55 patients, 4 patients gave up treatment after the diagnosis was confirmed and 4 patients were lost to follow-up after the first chemotherapy course. The remaining 47 patients received a double-induction therapy. The total complete remission (CR) rate was 71% and 94% after the first and second chemotherapy course, respectively. The disease was relapsed in 10 patients (21%). The 5-year EFS, DFS and OS rates were (56.1 ± 7.9)%, (59.8 ± 8.1)%, and (72.0 ± 8.1)%, respectively. Multivariate analysis showed that age was an independent risk factor for the long-term prognosis. The older children had a greater risk of experiencing an accident or death (P<0.05). The 5-year OS rate in 27 patients with regular consolidation chemotherapy was significantly higher than 13 patients with irregular chemotherapy after CRz [(47.5 ± 17.1)% vs (38.9 ± 17.3)%; P<0.01]. CONCLUSIONS: Childhood t(8;21)/AML1-ETO-positive AML is a highly heterogeneous disease, with a high CR rate and a good long-term prognosis. Age is one of the important factors affecting the long-term therapeutic effect. Regular consolidation chemotherapy applied after CR usually is helpful.
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Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Subunidade alfa 2 de Fator de Ligação ao Core/análise , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Proteínas de Fusão Oncogênica/análise , Translocação Genética , Adolescente , Exame de Medula Óssea , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prognóstico , Proteína 1 Parceira de Translocação de RUNX1RESUMO
OBJECTIVE: To investigate whether there were differences in the clinical characteristics, cytogenetic characteristics, immunophenotype and prognosis in children with B cell type acute lymphoblastic leukemia (B-ALL) carrying different fusion genes. METHODS: The research included 80 children with B-ALL from Peking University People's Hospital between March 2006 and December 2008. Eighteen children were positive for TEL/AML1, 14 for E2A/PBX1, 11 for BCR/ABL,and 2 cases for MLL/AF4, and 35 cases were negative for all of the 4 fusion genes. Data including clinical characteristics, morphology, immunophenotype and cytogenetic characteristics were collected, and the disease-free survival (DFS) was evaluated. The children were followed up until April 2009. RESULTS: In the 18 children with TEL/AML1+B-ALL, 66.7% were younger than 5 years old. They had low tumor load. FAB-L2 morphology was commonly observed, but t(12;21) was often absence in these children. Up to now,17 children who survived were disease-free. In the 14 children with E2A/PBX1+B-ALL, the majority were female. Thirteen children showed FAB-L1 morphology. Twelve children showed pre-B-ALL immunophenotype. The EFS was close to 80%. In the 11 children with BCR/ABL+B-ALL, 10 children showed common B type immunophenotype. FAB-L1 and FAB-L2 morphology was found in 4 children respectively. The DFS was less than 20%. Two children with MLL/AF4 positive B-ALL had high tumor load. Their morphologic diagnosis was FAB-L1. Both showed the Pro-B-ALL immunophenotype. One child discontinued treatment at the early stage of chemotherapy, and the other child survived disease-free until now. CONCLUSIONS: The B-ALL children with different fusion genes have different clinical characteristics, immunophenotypes and prognosis.
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Fusão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Feminino , Proteínas de Homeodomínio/genética , Humanos , Imunofenotipagem , Lactente , Masculino , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologiaRESUMO
OBJECTIVE: To compare the ettect and side-ettect of fluoxetine and combination of fluoxetine and Chinese or Tibetan medicine in treating senile depression in plateau district. Methods Ninety patients with diagnosis of senile depression conformed to CCMD-3 standard, in plateau district of 2260 - 3200 m altitude were randomly divided into three groups and treated with fluoxetine (group A), fluoxetine plus Sanpu Xinnao Xin granule (group B) and fluoxetine plus Xiaoyao pill (group C), respectively, 30 cases in each group. Therapeutic effects were evaluated with Hamilton' s depressive scale (HAMD) and treatment emergent symptom scale (TESS) after 6 weeks treatment. RESULTS: There was no significant difference in the therapeutic effects between the three groups. The adverse reaction in Group B and C was less than that in Group A (P<0.01). Conclusion Sanpu Xinnao Xin granule and Xiaoyao pill can raise the tolerance of patients with senile depression in plateau area against the adverse reaction of fluoxetine.
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Transtorno Depressivo/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fluoxetina/uso terapêutico , Fitoterapia , Idoso , Altitude , Antidepressivos de Segunda Geração/uso terapêutico , Quimioterapia Combinada , Humanos , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/uso terapêuticoRESUMO
Melanocortin-4 Receptor (MC4R) plays an important role in the regulation of human obesity. It can cooperate with leptin, neuropeptide Y(NPY) and melanocyte-stimulating hormone (MSH) to regulate body weight and feeding. Inactivation of this receptor by gene targeting in mice results in a maturity onset obesity syndrome associated with hyperphagic, hyperinsulinemia, hyperglycemia, as well as decreased linear growth and adult obesity. Multiple alignments of the sequences from individuals of several pig lines identified a single nucleotide substitution(G-->A) at position 298 of the seventh transmembrane domain. In present study, polymorphism distribution of MC4R gene fragment in resource population was studied using PCR-RFLP method based on the enzyme Taq I. The genotype was analyzed with the phenotype of the slaughtered individuals. The results showed that the frequencies of MC4R genotype varied in different breeds. The correlation analysis demonstrated the genotype of MC4R was in significant relation with back-fat thickness on thorax-waist, buttock and the average back-fat thickness, as well as with the width and area of longissmus dorsi (LD), and the percentage of skin. MC4R gene plays a role mainly in the pattern of dominant effect, and all the additive effects were not significant.
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Gorduras/metabolismo , Receptores de Peptídeos/genética , Suínos/genética , Animais , Frequência do Gene , Testes Genéticos , Genótipo , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Receptor Tipo 4 de Melanocortina , Suínos/classificação , Suínos/metabolismo , Suínos/fisiologiaRESUMO
Insulin-like growth factor 2(IGF2) play an important role in fetal growth and development, tumour cell proliferation and muscle growth. IGF2 is the major candidate gene for affecting muscle mass in pig. Here we found a Nci I PCR-RFLP within intron 8 of the porcine IGF2 gene, and studied on effect of IGF2 gene on fat deposition. A fragment of 575 bp within intron 8 was obtained and digested with enzyme Nci I. PCR-RFLP analysis in a resource family of 173 pigs showed that there were two Nci I restriction loci, which are locus A and B respectively in the fragment. To locus A, single marker analysis showed that pigs with the IGF2A2A2 genotype were 9.51% for shoulder fat thickness (P < 0.01), 10.49% for 6th-7th rib fat thickness(P < 0.01), 11.46% for thorax-waist fat thickness(P < 0.05), 19.32% for buttock fat thickness (P < 0.01) and 12.59% for average backfat thickness(P < 0.01) less thick than pigs with the IGF2A1A2 genotype. Significant differences for fat percentage and lean meat percentage between the IGF2 genotypes were also seen. Individuals of homozygote of restriction alleles had a significantly higher meat color for BF than individuals of heterozygote (4.23%, P < 0.01). To locus B, single marker analysis showed the same trend as on locus A. Individuals of homozygote of restriction alleles had a significantly less average fat thickness (18.82%, P < 0.01), fat percentage (22.43%, P < 0.01) and had more lean meat percentage (8.71%, P < 0.01), meat color for BF (4.62%, P < 0.05), water moisture (0.64%, P < 0.01) than individuals of homozygote of mutation restriction allele in locus B. IGF2 gene showed mainly in the pattern of additive effect and all the dominant effect were not significant. The value of additive effect of average fat thickness, fat percentage and lean meat percentage was -0.20 +/- 0.05(P < 0.01), -2.75 +/- 0.55 (P < 0.01), 1.79 +/- 0.46(P < 0.01), respectively. Significant correlation was found between IGF2 genotype and lean meat percentage. The result suggests that the IGF2 as a candidate gene can explain significant difference for fat deposit related traits in pig.
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Tecido Adiposo/metabolismo , Fator de Crescimento Insulin-Like II/genética , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Suínos/genética , Animais , Frequência do Gene , Suínos/metabolismoRESUMO
The study constructed the genetic linkage map of porcine chromosome 2 and further analysis of quantitative trait loci was conducted. The results of the study demonstrated that all 7 microsatellite loci we chose were with relatively high polymorphism, and its polymorphic information content was from 0.40182 to 0.58477. The genetic map we constructed for resource family was 152.9 cM in length, with the order of all loci highly consistent with the USDA map. All marker intervals were longer than USDA map with the interval between marker Sw2516 and Sw1201 as an exception. Furthermore, we conducted QTLs locating analysis by combining the genetic map with the phenotypic data. QTLs affecting lively estimated traits such as lean meat percentage, were located at 60-65 cM on chromosome 2, while QTLs for the height and marbling of Longissmus dorsi muscle were located at 20 cM and 55 cM, respectively Among them, QTL for estimated lean meat percentage was significant at chromosome-wise level (P < 0.01) and was responsible for 21.55% of the phenotypic variance. QTLs for the height and marbling of Longissmus dorsi muscle were responsible for 10.12% and 10.97% of the phenotypic variance, respectively. The additive and dominance effect of lively estimated traits were in the inverse tendency, while the QTL for the height of Longissmus dorsi muscle had its additive and dominance effect in the same tendency and was with advantageous allele in Large White. The QTLs we detected had relatively large effect on phenotype and built a basis for molecular marker assisted selection and breeding.
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Mapeamento Cromossômico/métodos , Cromossomos de Mamíferos/genética , Locos de Características Quantitativas/genética , Suínos/genética , Animais , Cruzamentos Genéticos , Feminino , Frequência do Gene , Genótipo , Masculino , Repetições de Microssatélites/genética , Polimorfismo GenéticoRESUMO
Insulin-like growth factor (IGF) is multiple proliferation controlling factor of cells, and it gets this name according to its similarity to insulin. IGF2 is a single chain protein of 67 amino acids, which is probably required for normal fetal growth and development. In this article, we discussed the gene structure, ways of its heredity, and biological effects concerning imprinting, tumor development,muscle forming and individual growing of IGF2.
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As a molecular marker,microsatellite has many advantages such as high polymorphism and good conservativeness in animal genetic research. The study chose 8 microsatellite markers that evenly distributed on chromosome 1 with a distance about 20 cM to build the genetic map of porcine chromosome 1. The results of our experiment are as follows:the number of alleles for 8 markers is 2 to 5,their gene frequency is from 0.015 to 0.75,the heterozygosity is from 0.39705 to 0.67675 and the polymorphic information content is from 0.32925 to 0.59316. The map we built is basically in consistent with the result of USDA and can be used in searching quantitative traits loci in pigs.
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In order to study the effects of low-level lead exposure on neurobehaviour development, the neurobehaviour functions in eighty-five 1-3 year-old children were assessed by Neurobehaviour Psychological Test (recommended by the Institute of Psychology, Chinese Academy of Sciences). The results showed that the increase of blood lead (BPb) level in each 100 micrograms/L was associated with an average loss of 3-4 points of Development Quotient (DQ) in these subjects. Age, hand-mouth habits and environmental lead pollution are the main risk factors. It is concluded that even in a low-level lead exposure, DQ in young children may be affected. Certain intervention steps based on the levels of lead exposure were recommended.
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Desenvolvimento Infantil , Exposição Ambiental , Chumbo/efeitos adversos , Pré-Escolar , Feminino , Humanos , Lactente , Testes de Inteligência , Chumbo/sangue , Intoxicação do Sistema Nervoso por Chumbo na Infância/diagnóstico , MasculinoRESUMO
OBJECTIVE: S100A7 plays a role in the malignant potential of several epithelial cancers, and could candidate diagnostic marker or therapeutic target. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. In the present study, we first evaluate the involvement of S100A7 in lung squamous cell carcinoma and its clinical usefulness for diagnosis. We then study whether knockdown of S100A7 in lung squamous cell carcinoma cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo. METHODS: We examined S100A7 expression in lung squamous cell carcinoma tissues by immunohistology .The human lung squamous cell carcinoma cell line NCI-H520 were transduced with short hairpin RNA targeting S100A7. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of S100A7 messenger RNA and protein, respectively. Cell proliferation was evaluated by the MTT assay. NF-κB phosphorylation was assayed by western blot. 1×10(6) of NCI-H520/S100A7 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 35 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for S100A7 protein expression. RESULTS: S100A7 protein levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. S100A7 might be a useful marker for diagnosis of lung squamous cell carcinoma. In vitro data showed that inhibition of S100A7 decreased proliferation of NCI-H520 cells. S100A7 knockdown reduced NF-κB phosphorylation and tumor growth in vivo and vivo. Explanted knockdown tumors maintained lower S100A7 levels compared with wild-type, confirmed by immunohistology. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors. CONCLUSIONS: Our present results suggest that S100A7 level is a promising tool for diagnosis of lung squamous cell carcinoma. Knockdown of S100A7 suppresses lung cancer growth in part by attenuating NF-κB activity. S100A7 may be a promising therapeutic target for lung squamous cell carcinoma.
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Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Proteínas S100/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/análise , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , NF-kappa B , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína A7 Ligante de Cálcio S100RESUMO
Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's disease (AD), but the underlying mechanisms remain to be fully elucidated. In this study, living-cell image, immunocytochemistry, and electrophysiology were used to examine the effects of soluble amyloid-ß protein (Aß) oligomers and rosiglitazone on the synapse formation, plasticity, and mitochondrial distribution in cultured neurons. Incubation of hippocampal cultures with amyloid-ß (Aß)42 oligomers (0.5 µM) for 3 h significantly decreased dendritic filopodium and synapse density. Pretreatment with rosiglitazone (0.5-5 µM) for 24 h prevented the Aß42-induced loss of dendritic filopodium and synapse in a dose-dependent manner. However, neither Aß42 oligomer nor rosiglitazone has a significant effect on the velocity and length of dendritic filopodia. Electrophysiological recording showed that acute exposure of slices with 0.5 µM Aß42 oligomers impaired hippocampal long-term potentiation (LTP). Pre-incubation of hippocampal slices with rosiglitazone significantly attenuated the Aß42-induced LTP deficit, which depended on rosiglitazone concentrations (1-5 µM) and pretreatment period (1-5 h). The beneficial effects of rosiglitazone were abolished by the peroxisome proliferator-activated receptor gamma (PPARγ) specific antagonist, GW9662. Moreover, the mitochondrial numbers in the dendrite and spine were decreased by Aß42 oligomers, which can be prevented by rosiglitazone. In conclusion, our data suggested that rosiglitazone prevents Aß42 oligomers-induced impairment via increasing mitochondrial numbers in the dendrite and spine, improving synapse formation and plasticity. This process is most likely through the PPARγ-dependent pathway and in concentration and time dependent manners. The study provides novel insights into the mechanisms for the protective effects of rosiglitzone on AD.
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Peptídeos beta-Amiloides/toxicidade , Mitocôndrias/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Nootrópicos/farmacologia , Fragmentos de Peptídeos/toxicidade , Tiazolidinedionas/farmacologia , Anilidas/farmacologia , Animais , Células Cultivadas , Fármacos do Sistema Nervoso Central/farmacologia , Dendritos/efeitos dos fármacos , Dendritos/patologia , Dendritos/fisiologia , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Espinhas Dendríticas/fisiologia , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Técnicas In Vitro , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Mitocôndrias/patologia , Mitocôndrias/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/patologia , Neurônios/fisiologia , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Ratos , Ratos Wistar , Rosiglitazona , Sinapses/efeitos dos fármacos , Sinapses/patologia , Sinapses/fisiologia , Fatores de TempoRESUMO
OBJECTIVE: To investigate the expression of the Wilms' tumor 1 (WT1) mRNA in childhood myelodysplastic syndrome (MDS), and to evaluate WT1 as a tool to differentiate MDS from aplastic anemia(AA). METHODS: The quantitative expression of WT1 transcript by using real-time quantitative polymerase chain reaction (RQ-PCR) was performed in the bone marrow samples of 36 childhood MDS and 49 childhood AA, the samples were collected from September 2008 to December 2011. RESULTS: (1) The positive rate of WT1 in severe AA (SAA) was 0, 14.3% in chronic AA (CAA), 58.6% in refractory cytopenia (RC), 100% in refractory anemia with excessive blast (RAEB) and 97.5% in acute myeloid leukemia (AML). The mean level of WT1 in SAA, CAA, RC, RAEB and AML was 0.041%, 0.357%, 7.037%, 12.680% and 24.210%, respectively. The positive rate of WT1 in RC patients was higher than that of SAA (P = 0.000) and CAA (P = 0.001). (2) The positive rate of WT1 in patients with hypoplastic MDS was 66.7% and was higher than that of SAA (P = 0.000) and CAA (P = 0.001). The mean level of WT1 in patients with hypoplastic MDS was (3.022 ± 5.040)% and higher than that of SAA \[(0.041 ± 0.047)%, P = 0.000\] and CAA\[(0.351 ± 0.479)%, P = 0.002\]. CONCLUSIONS: The level of WT1 in childhood MDS was higher than that of childhood AA. The degree of WT1 expression in MDS increased during disease progression. WT1 is a useful tool for differentiating the childhood hypoplastic MDS from AA.
Assuntos
Síndromes Mielodisplásicas/metabolismo , Proteínas WT1/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Proteínas WT1/genéticaRESUMO
Niemann-Pick disease type C (NPC) is a progressive neurodegenerative disorder characterized by accumulation of free cholesterol in late endosomes/lysosomes. The pathological basis for the disease has been poorly understood yet. In our previous study, we have demonstrated that synaptic function is impaired in this disease. In the current study, electrophysiological and fluorescent dyes studies were used to determine whether the synaptic defects result from presynaptic or postsynaptic contributions. Furthermore, we would like to ascertain whether such defects are caused by direct effect of NPC1 deficiency in neurons or indirect effect of NPC1 deficiency in glial cells. Both mean inter-event interval of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were significantly larger in NPC1(-/-) neurons than those in the wild-type neurons, while the amplitudes and the receptor kinetics were not different compared with those in wild-type controls. Synaptic vesicle exocytosis was also slower in the NPC1(-/-) neurons. The mean time constant of destaining was larger in NPC1(-/-) neurons than in wild-type controls both in the presence and absence of glial cells. All these results indicated a general presynaptic functional impairment in the NPC1(-/-) neurons and such defects were not dependent of glial cells. Therefore, neuropathology characteristics of NPC diseases may be a more possible consequence of neuronal presynaptic dysfunction than indirect defects in glial cells.