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1.
Zhonghua Wai Ke Za Zhi ; 60(7): 666-673, 2022 Jul 01.
Artigo em Chinês | MEDLINE | ID: mdl-35775259

RESUMO

Objectives: To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer. Methods: The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ2 test. Results: Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months,P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%,P<0.05;32.9% vs. 21.9%,P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%,P>0.05). Conclusions: The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients' compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.


Assuntos
Adenocarcinoma , Pancreatopatias , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/cirurgia , Pancreatopatias/diagnóstico , Pancreatopatias/terapia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Equipe de Assistência ao Paciente , Cooperação do Paciente , Prognóstico , Estudos Retrospectivos , Adulto Jovem , Neoplasias Pancreáticas
3.
Zhonghua Yu Fang Yi Xue Za Zhi ; 51(10): 910-914, 2017 Oct 06.
Artigo em Chinês | MEDLINE | ID: mdl-29036993

RESUMO

Objective: To discuss the main causes and risk factors of disability and death among current Chinese adolescents. Methods: Subnational data of China from Global Burden of Disease Study 2015 (GBD 2015) was used to rank the causes and risk factors leading to death and disability adjusted life years (DALY) in Chinese adolescents aged between 10 and 19 years old, and thereby to analyze the main cauese and risk factors of death and DALY among Chinese adolescents in different genders. Results: In 2015, among Chinese adolescents aged 10-19 years old, the total DALY was 13 million 490 thousand years, and the total number of deaths was 63 258 cases. The top 3 causes of DALY were skin and subcutaneous diseases, iron-deficiency anemia and road injuries, resulting in DALY (constituent ratio) of 1 411 (10.5%), 1 094 (8.1%) and 1 029 (7.6%) thousand years respectively. The top 3 causes of death were road injuries, drowning and leukemia, causing 13 881 (21.9%), 9 895 (15.6%) and 4 620 (7.3%) deaths (constituent ratio) respectively. The top 3 risk factors of DALY were iron deficiency, alcohol use and drug use, causing 1 094 (8.1%), 487 (3.6%) and 220 thousand years (1.6%) DALY (constituent ratio) respectively. The top 3 risk factors of death were alcohol use, occupational injuries and drug use, causing 5 957 (9.4%), 1 523 (2.4%) and 810 (1.3%) deaths respectively. Conclusion: Unintentional injury was the top cause of DALY and death in Chinese adolescents, followed by skin and subcutaneous diseases and iron-deficiency anemia. Iron deficiency and alcohol use were the top two risk factors of DALY and death.


Assuntos
Causas de Morte/tendências , Efeitos Psicossociais da Doença , Pessoas com Deficiência/estatística & dados numéricos , Adolescente , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Anos de Vida Ajustados por Qualidade de Vida , Adulto Jovem
8.
Carcinogenesis ; 31(4): 745-50, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20118199

RESUMO

miR-34a is a transcriptional target of p53 and implicated in carcinogenesis. We studied the role of miR-34a methylation in a panel of hematological malignancies including acute leukemia [acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL)], chronic leukemia [chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML)], multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL). The methylation status of miR-34a promoter was studied in 12 cell lines and 188 diagnostic samples by methylation-specific polymerase chain reaction. miR-34a promoter was unmethylated in normal controls but methylated in 75% lymphoma and 37% myeloma cell lines. Hypomethylating treatment led to re-expression of pri-miR-34a transcript in lymphoma cells with homozygous miR-34a methylation. In primary samples at diagnosis, miR-34a methylation was detected in 4% CLL, 5.5% MM samples and 18.8% of NHL at diagnosis but none of ALL, AML and CML (P = 0.011). In MM patients with paired samples, miR-34a methylation status remained unchanged at progression. Amongst lymphoid malignancies, miR-34a was preferentially methylated in NHL (P = 0.018), in particular natural killer (NK)/T-cell lymphoma. In conclusion, amongst hematological malignancies, miR-34a methylation is preferentially hypermethylated in NHL, in particular NK/T-cell lymphoma, in a tumor-specific manner, therefore the role of miR-34a in lymphomagenesis warrants further study.


Assuntos
Metilação de DNA , Epigênese Genética , Neoplasias Hematológicas/genética , MicroRNAs/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Feminino , Genes p53 , Humanos , Perda de Heterozigosidade , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas
9.
J Exp Med ; 170(2): 571-6, 1989 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-2754392

RESUMO

Striking similarities between vaccinia virus hemagglutinin (VVHA) and proteins belonging to the Ig superfamily clearly indicate that VVHA, a 315-amino acid glycoprotein expressed on the surface of the infected cells, is a novel viral protein that can be added to the expanding list of the Ig superfamily. Its deduced amino acid sequence contains one Ig-like domain at the NH2 terminus, followed by two tandem repeating units and a hydrophobic region, suggestive of membrane spanning. The results offer an opportunity for the further study of the probable evolutionary and possible functional relationship between VVHA and other members of the Ig superfamily. Our observation, together with a recent finding that human CMV possibly encodes a protein similar to the MHC class I antigens (13), provides evidence supporting the fact that the viral capture of cellular Ig-related genes is more common than expected in vaccinia and other viruses, and that usage of an Ig-like domain as recognition signals might be extended from higher animals to animal viruses.


Assuntos
Hemaglutininas Virais/genética , Vaccinia virus/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Dados de Sequência Molecular , Família Multigênica , Conformação Proteica , Solubilidade , Proteínas Virais/genética , Proteínas Virais/ultraestrutura
10.
J Pathol ; 217(3): 353-61, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19090486

RESUMO

The NF-kappaB signalling pathway plays important roles in liver organogenesis and carcinogenesis. Mouse embryos deficient in IKKbeta die in mid-gestation, due to excessive apoptosis of hepatoblasts. Although activation of the NF-kappaB signalling pathway has been demonstrated in human hepatocellular carcinoma, the role of NF-kappaB is controversial. Here, we have generated transgenic mice in which a constitutively active form of IKKbeta was expressed in a hepatocyte-specific manner. Using electrophoretic mobility shift assay, we documented increased NF-kappaB activities and up-regulated levels of NF-kappaB downstream target genes, Bcl-xL and STAT5, in the transgenic mouse livers. These results confirmed that the NF-kappaB pathway was activated in the livers of the transgenic mice. However, there was no significant difference in tumour formation between transgenic and wild-type mice up to an age of 50 weeks. When we treated the transgenic mice with the chemical carcinogen diethylnitrosamine (DEN), we observed no significant differences in the incidence and size of liver tumours formed in these mice with and without DEN treatment at 35 weeks of age, suggesting that the activated NF-kappaB pathway in the livers of the transgenic mice did not enhance hepatocarcinogenesis. Interestingly, some of the transient transgenic embryos (E12.5) had abnormal excessive accumulation of nucleated red blood cells in their developing livers. In summary, NF-kappaB activation in hepatocytes did not significantly affect chemical hepatocarcinogenesis. In addition, the TTR/IKKCA transgenic mice may serve as a useful model for studying the role of NF-kappaB activation in hepatocarcinogenesis as well as inflammatory and metabolic diseases.


Assuntos
Carcinoma Hepatocelular/metabolismo , Hepatócitos/metabolismo , Quinase I-kappa B/genética , Neoplasias Hepáticas Experimentais/metabolismo , NF-kappa B/metabolismo , Animais , Western Blotting/métodos , Carcinoma Hepatocelular/induzido quimicamente , Linhagem Celular Tumoral , Dietilnitrosamina , Ensaio de Desvio de Mobilidade Eletroforética , Quinase I-kappa B/metabolismo , Imuno-Histoquímica , Fígado/embriologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Masculino , Camundongos , Camundongos Transgênicos , NF-kappa B/análise , Transfecção/métodos
11.
Hong Kong Med J ; 15 Suppl 2: 37-40, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19258633

RESUMO

1. Infection with SARS coronavirus (SARS-CoV) induces a cellular stress condition known as the unfolded protein response (UPR). UPR induction is mediated primarily by viral spike (S) protein. The modulation of UPR by S protein involves activation of PERK protein kinase. Other branches of the UPR pathways controlled by IRE1 and ATF6 proteins, respectively, are not involved. 2. The protease inhibitor Ben-HCl effectively suppresses SARS-CoV infection by blocking virus entry. Viral infectivity is associated with the cleavage of S protein by the cellular protease factor Xa. 3. Two new aspects of the interaction between SARS-CoV S protein and the cell have been defined. These have important implications in the pathogenesis of SARS, providing opportunities for developing vaccines and antivirals against SARS-CoV. 4. Counteracting the UPR and targeting the cleavage of S protein with small molecule pharmaceutical agents represent two new anti-SARS-CoV strategies. 5. The receptor-binding domain of S protein delivered via adeno-associated virus can efficiently induce mucosal immunity and provide long-term protection against SARS-CoV infection.


Assuntos
Glicoproteínas de Membrana/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , Proteínas do Envelope Viral/metabolismo , eIF-2 Quinase/metabolismo , Animais , Células Cultivadas , Chlorocebus aethiops , Sistemas de Liberação de Medicamentos , Fator Xa/metabolismo , Inibidores de Proteases/farmacologia , Dobramento de Proteína/efeitos dos fármacos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus , Células Vero , Internalização do Vírus/efeitos dos fármacos
12.
Oncogene ; 26(21): 3069-80, 2007 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-17099724

RESUMO

Epstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma (NPC) and can be detected in early premalignant lesions of nasopharyngeal epithelium. The latent membrane protein 1 (LMP1) is an oncoprotein encoded by the EBV and is believed to play a role in transforming premalignant nasopharyngeal epithelial cells into cancer cells. RASSF1A is a tumor-suppressor gene commonly inactivated in many types of human cancer including NPC. In this study, we report a novel function of LMP1, in down-regulating RASSF1A expression in human epithelial cells. Downregulation of RASSF1A expression by LMP1 is dependent on the activation of intracellular signaling of NF-kappaB involving the C-terminal activating regions (CTARs) of LMP1. LMP1 expression also suppresses the transcriptional activity of the RASSF1A core promoter. RASSF1A stabilizes microtubules and regulates mitotic events. Aberrant mitotic spindles and chromosome aberrations are reported phenotypes in RASSF1A inactivated cells. In this study, we observed that LMP1 expression in human epithelial cells could induce aberrant mitotic spindles, disorganized interphase microtubules and aneuploidy. LMP1 expression could also suppress microtubule dynamics as exemplified by tracking movements of the growing tips of microtubules in live cells by transfecting EGFP-tagged EB1 into cells. The aberrant mitotic spindles and interphase microtubule organization induced by LMP1 could be rescued by transfecting RASSF1A expression plasmid into cells. Downregulation of RASSF1A expression by LMP1 may facilitate its role in transformation of premalignant nasopharyngeal epithelial cells into cancer cells.


Assuntos
Aberrações Cromossômicas , Regulação para Baixo/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Microtúbulos/metabolismo , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genética , Proteínas da Matriz Viral/fisiologia , Linhagem Celular , Linhagem Celular Transformada , Linhagem Celular Tumoral , Células HeLa , Humanos , Microtúbulos/patologia , NF-kappa B/fisiologia , Proteínas Supressoras de Tumor/biossíntese
13.
Gene Ther ; 15(3): 191-202, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17972920

RESUMO

To induce RNA interference (RNAi), either small interfering RNAs (siRNAs) are directly introduced into the cell or short hairpin RNAs (shRNAs) are expressed from a DNA vector. At present, shRNAs are commonly synthesized by RNA polymerase III (Pol III) promoters of the H1 and U6 RNAs. In this study, we designed and characterized a new set of plasmid vectors driven by promoters of the Epstein-Barr virus (EBV)-encoded small RNAs (EBERs). The EBERs are the most abundant transcript in infected cells and they are transcribed by Pol III. We showed that the EBER promoters were able to drive the expression of shRNA fusion transcripts. siRNAs processed from these fusion transcripts specifically and effectively inhibited the expression of homologous reporter or endogenous genes in various types of cells. The partial EBER sequences in the fusion transcripts did not activate double-stranded RNA-dependent protein kinase or suppress RNAi. In nasopharyngeal carcinoma cells, the EBER2 promoter was stronger than the H1 and U6 promoters in shRNA synthesis, leading to more effective knockdown of the target genes. Taken together, our findings suggest that the EBER promoters fundamentally different from those of H1 and U6 can be used to drive the intracellular expression of shRNAs for effective silencing of target genes in mammalian cells and particularly, in EBV-infected cells.


Assuntos
Terapia Genética/métodos , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/terapia , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno , Linhagem Celular Tumoral , Estudos de Viabilidade , Expressão Gênica , Inativação Gênica , Engenharia Genética , Vetores Genéticos/farmacologia , Humanos , Neoplasias Nasofaríngeas/metabolismo , RNA Polimerase III/genética , RNA Mensageiro/análise , Proteínas Recombinantes de Fusão/genética
14.
Zhonghua Liu Xing Bing Xue Za Zhi ; 39(6): 852-857, 2018 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-29936760

RESUMO

Objective: To evaluate the prevalence and trend of diabetes mellitus among Chinese adults during the past thirty years. Methods: Papers, published before October 1, 2017 and related to the prevalence of diabetes mellitus among Chinese adults, were searched through PubMed, China Knowledge Resource Integrated Database, Wanfang Digital Database and VIP Citation Databases. Stata 13.0 software was used to estimate the prevalence of diabetes mellitus, with pooled prevalence calculated based on random effects. Subgroup analysis was conducted based on time, sex, areas and body mass index groups of investigation. Continuous fractional polynomial regression model on the midpoint of each survey period, weighted by the number of participants in each study, was used to estimate and illustrate the trends of prevalence of diabetes over the years. Results: In total, 15 studies were included and two of them were excluded in the primary analysis with the age limitation of participants as ≥40 years old, for recruitment. The average prevalence of diabetes among Chinese adults was 6.3% (95%CI: 4.6%-8.0%), during the past thirty years. The pooled prevalence appeared higher in urban than in rural areas and higher in men than in women. Between 1980 and 2013, the increase of Chinese diabetes prevalence did not follow the linear trend. Before 2000, the average prevalence showed as 3.5% (95%CI: 2.0%-4.9%), with an annual increase rate as 0.17%. Since 2000, the average annual prevalence of diabetes mellitus had appeared around 8.0% (95%CI: 6.0%-10.1%), with an annual growth rate of 0.72% (95%CI: 0.34%-1.10%). Conclusion: The prevalence of diabetes in Chinese adults had been rapidly increasing since the year 2000, indicating that efforts should be strengthened for diabetes prevention, in China.


Assuntos
Povo Asiático/estatística & dados numéricos , Diabetes Mellitus/epidemiologia , Adulto , Índice de Massa Corporal , China/epidemiologia , Diabetes Mellitus/etnologia , Feminino , Humanos , Masculino , Modelos Estatísticos , Prevalência , População Rural , Distribuição por Sexo , Inquéritos e Questionários , População Urbana
15.
Sci Rep ; 8(1): 2421, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402968

RESUMO

RASopathies are a group of heterogeneous conditions caused by germline mutations in RAS/MAPK signalling pathway genes. With next-generation sequencing (NGS), sequencing capacity is no longer a limitation to molecular diagnosis. Instead, the rising number of variants of unknown significance (VUSs) poses challenges to clinical interpretation and genetic counselling. We investigated the potential of an integrated pipeline combining NGS and the functional assessment of variants for the diagnosis of RASopathies. We included 63 Chinese patients with RASopathies that had previously tested negative for PTPN11 and HRAS mutations. In these patients, we performed a genetic analysis of genes associated with RASopathies using a multigene NGS panel and Sanger sequencing. For the VUSs, we evaluated evidence from genetic, bioinformatic and functional data. Twenty disease-causing mutations were identified in the 63 patients, providing a primary diagnostic yield of 31.7%. Four VUSs were identified in five patients. The functional assessment supported the pathogenicity of the RAF1 and RIT1 VUSs, while the significance of two VUSs in A2ML1 remained unclear. In summary, functional analysis improved the diagnostic yield from 31.7% to 36.5%. Although technically demanding and time-consuming, a functional genetic diagnostic analysis can ease the clinical translation of these findings to aid bedside interpretation.


Assuntos
Síndrome de Costello/genética , Displasia Ectodérmica/genética , Insuficiência de Crescimento/genética , Cardiopatias Congênitas/genética , Neurofibromatose 1/genética , Síndrome de Noonan/genética , Proteínas Proto-Oncogênicas c-raf/genética , Proteínas ras/genética , Adolescente , Animais , Bioensaio , Criança , Pré-Escolar , Biologia Computacional , Síndrome de Costello/patologia , Displasia Ectodérmica/patologia , Fácies , Insuficiência de Crescimento/patologia , Feminino , Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Mutação em Linhagem Germinativa , Cardiopatias Congênitas/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , MAP Quinase Quinase 1/genética , Masculino , Mutação de Sentido Incorreto , Neurofibromatose 1/patologia , Síndrome de Noonan/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína SOS1/genética , Peixe-Zebra , alfa-Macroglobulinas/genética
16.
Sci Rep ; 7(1): 9491, 2017 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-28842675

RESUMO

Grazing is the primary land use in the Hulunber meadow steppe. However, the quantitative effects of grazing on ecosystem carbon dioxide (CO2) fluxes in this zone remain unclear. A controlled experiment was conducted from 2010 to 2014 to study the effects of six stocking rates on CO2 flux, and the results showed that there were significant differences in CO2 fluxes by year, treatment, and month. The effects of light and intermediate grazing remained relatively constant with grazing year, whereas the effects of heavy grazing increased substantially with grazing duration. CO2 flux significantly decreased with increasing grazing intensity and duration, and it was significantly positively correlated with rainfall, soil moisture (SM), the carbon to nitrogen ratio (C/N ratio), soil available phosphorus (SAP), soil NH4+-N, soil NO3-N, aboveground biomass (AGB), coverage, height, and litter and negatively correlated with air temperature, total soil N (TN) and microbial biomass N (MBN). A correspondence analysis showed that the main factors influencing changes in CO2 emissions under grazing were AGB, height, coverage, SM, NH4+-N and NO3-N. Increased rainfall and reduced grazing resulted in greater CO2 emissions. Our study provides important information to improve our understanding of the role of livestock grazing in GHG emissions.

17.
Oncogene ; 18(29): 4182-90, 1999 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-10435631

RESUMO

A20 is a Cys2/Cys2 zinc finger protein which is induced by a variety of inflammatory stimuli and which has been characterized as an inhibitor of cell death by a yet unknown mechanism. In order to clarify its molecular mechanism of action, we used the yeast two-hybrid system to screen for proteins that interact with A20. A cDNA fragment was isolated which encoded a portion of a novel protein (TXBP151), which was recently found to be a human T-cell leukemia virus type-I (HTLV-I) Tax-binding protein. The full-length 2386 bp TXBP151 mRNA encodes a protein of 86 kDa. Like A20, overexpression of TXBP151 could inhibit apoptosis induced by tumour necrosis factor (TNF) in NIH3T3 cells. Moreover, transfection of antisense TXBP151 partially abolished the anti-apoptotic effect of A20. Furthermore, apoptosis induced by TNF or CD95 (Fas/APO-1) was associated with proteolysis of TXBP151. This degradation could be inhibited by the broad-spectrum caspase inhibitor zVAD-fmk or by expression of the cowpox virus-derived inhibitor CrmA, suggesting that TXBP151 is a novel substrate for caspase family members. TXBP151 was indeed found to be specifically cleaved in vitro by members of the caspase-3-like subfamily, viz. caspase-3, caspase-6 and caspase-7. Thus TXBP151 appears to be a novel A20-binding protein which might mediate the anti-apoptotic activity of A20, and which can be processed by specific caspases.


Assuntos
Apoptose , Proteínas de Transporte/metabolismo , Caspases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Neoplasias , Processamento de Proteína Pós-Traducional , Proteínas/metabolismo , Proteínas Virais , Dedos de Zinco , Células 3T3 , Clorometilcetonas de Aminoácidos/farmacologia , Sequência de Aminoácidos , Animais , Apoptose/efeitos dos fármacos , Sequência de Bases , Proteínas de Transporte/isolamento & purificação , Linhagem Celular , Clonagem Molecular , Cisteína Endopeptidases , Inibidores de Cisteína Proteinase/farmacologia , DNA Complementar/genética , Proteínas de Ligação a DNA , Dactinomicina/farmacologia , Genes , Células HeLa , Humanos , Camundongos , Dados de Sequência Molecular , Proteínas Nucleares , Inibidores da Síntese de Ácido Nucleico/farmacologia , Oligonucleotídeos Antissenso/farmacologia , Ligação Proteica , RNA Mensageiro/genética , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae/genética , Serpinas/fisiologia , Especificidade por Substrato , Transfecção , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Fator de Necrose Tumoral alfa/farmacologia , Receptor fas/fisiologia
18.
Oncogene ; 23(25): 4488-94, 2004 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-15064751

RESUMO

Nasopharyngeal carcinoma is closely associated with Epstein-Barr virus (EBV) infection. The EBV-encoded LMP1 has cell transformation property. It suppresses cellular senescence and enhances cell survival in various cell types. Many of the downstream events of LMP1 expression are mediated through its ability to activate NF-kappaB. In this study, we report a novel function of LMP1 to induce Id1 expression in nasopharyngeal epithelial cells (NP69) and human embryonal kidney cells (HEK293). The Id1 is a basic helix-loop-helix (bHLH) protein and a negative transcriptional regulator of p16(INK4a). Expression of Id1 facilitates cellular immortalization and stimulates cell proliferation. With the combination of both specific chemical inhibitors and genetic inhibitors of cell signaling, we showed that induction of Id1 by LMP1 was dependent on its NF-kappaB activation domain at the carboxy-terminal region, CTAR1 and CTAR2. Induction of Id1 by LMP1 may facilitate clonal expansion of premalignant nasopharyngeal epithelial cells infected with EBV and may promote their malignant transformation.


Assuntos
Células Epiteliais/metabolismo , Regulação Viral da Expressão Gênica , Herpesvirus Humano 4/fisiologia , Nasofaringe/citologia , Proteínas Repressoras , Fatores de Transcrição/fisiologia , Proteínas da Matriz Viral/fisiologia , Carcinoma/epidemiologia , Carcinoma/etiologia , Carcinoma/virologia , Células Clonais/patologia , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Células Epiteliais/virologia , Infecções por Vírus Epstein-Barr/genética , Genes p16 , Hong Kong/epidemiologia , Humanos , Proteína 1 Inibidora de Diferenciação , NF-kappa B/fisiologia , Neoplasias Nasofaríngeas/epidemiologia , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/virologia , Estrutura Terciária de Proteína , Deleção de Sequência , Transdução de Sinais , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Transcrição Gênica , Proteínas da Matriz Viral/química
19.
Biochim Biophys Acta ; 1541(3): 212-20, 2001 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-11755215

RESUMO

Chromosomal instability (CIN) is one of the common features in prostate cancer, especially in advanced stages. Recently, the involvement of p53 in CIN through the regulation of centrosome amplification has been proposed in certain tumor types. In this study, we investigated the relationship between p53 and centrosome amplification in prostate cancer cells. Increased centrosome number and size were observed in DU145 and PC3 containing nonfunctional p53 compared to LNCap which expressed wild-type p53. Transfection of p53 into PC3 cells resulted in a decreased cell growth rate, G2/M arrest and decreased centrosome abnormalities. We provide the first evidence on a correlation between loss of p53 function and centrosome amplification in prostate cancer cells. Our results indicate that p53 may play a role in the regulation of centrosome amplification and loss of p53 may be one of the mechanisms involving CIN in prostate cancer cells.


Assuntos
Centrossomo/metabolismo , Proteína Supressora de Tumor p53/biossíntese , Centrossomo/patologia , Fragilidade Cromossômica/genética , Fase G2 , Humanos , Masculino , Mitose , Neoplasias da Próstata , Coloração e Rotulagem , Transfecção , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética
20.
Leukemia ; 11 Suppl 3: 3-6, 1997 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9209279

RESUMO

The yeast one-hybrid and two-hybrid systems for the detection of protein-DNA and protein-protein interactions were used as an in vivo approach to investigate the functional characteristics of HTLV-1 Tax expressed in yeast. Tax, when targeted to the upstream activating sequence (UAS) via the DNA-binding domain of Gal4 (Gal4BD), was found to activate a minimal promoter in yeast, indicating the presence of a functionally intact activation domain. Using the two-hybrid assay in which Tax was fused to either Gal4BD or Gal4 activation domain (Gal4AD), we demonstrate that Tax self-associates in the nucleus of yeast cells. Mutational analysis was performed to delineate the functional domain(s) necessary for Tax-mediated trans-activation and self-association. Based on our results, we propose a pleiotropic mechanism in which Tax facilitates protein-protein dimerization of various cellular partners.


Assuntos
Produtos do Gene tax/metabolismo , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Proteínas de Saccharomyces cerevisiae , Fatores de Transcrição , Ativação Transcricional , Clonagem Molecular , Proteínas de Ligação a DNA , Dimerização , Proteínas Fúngicas/biossíntese , Proteínas Fúngicas/metabolismo , Produtos do Gene tax/biossíntese , Humanos , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae , beta-Galactosidase/biossíntese
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