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BACKGROUND: The associations of occupational activity (OA), commuting, leisure-time physical activity (LTPA), and sitting with overweight/obesity in working adults are controversial. This study explored these factors with the risk of overall and abdominal overweight/obesity in a Chinese working population and whether these associations differ by gender. METHODS: A cross-sectional study was conducted. Data analysis was done among 6739 employed participants. Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the studied associations. RESULTS: For male employees, those with heavy OA had a lower overall (OR 0.76; 95% CI, 0.62-0.93) and abdominal (OR 0.76; 95% CI, 0.62-0.93) overweight/obesity risk than those with light OA. Those with LTPA ≥150 min/week had a lower risk of overall (OR 0.73; 95% CI, 0.56-0.96) and abdominal (OR 0.70; 95% CI, 0.53-0.91) overweight/obesity than those with LTPA <150 min/week. Men with leisure-sitting time <2.5 h/day had a significantly lower risk of abdominal overweight/obesity than those sitting ≥4 h/day (OR 0.80; 95% CI, 0.65-0.99). And men who cycled to/from work had a lower risk of overall (OR 0.69; 95% CI, 0.53-0.90) and abdominal overweight/obesity (OR 0.71; 95% CI, 0.54-0.92) than passive transports. However, the above significant associations disappeared among female employees. CONCLUSIONS: Heavy OA, cycling to/from work, and LTPA were associated with lower risk of overall or abdominal overweight/obesity in male employees. Reducing leisure sitting time can also help male employees reduce the risk of abdominal overweight/obesity. More research on gender disparity in the risk of overweight and obesity should be done.
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Emprego , Exercício Físico , Disparidades nos Níveis de Saúde , Atividades de Lazer , Sobrepeso/epidemiologia , Postura , Meios de Transporte/estatística & dados numéricos , Adolescente , Adulto , Idoso , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Fatores de Risco , Comportamento Sedentário , Distribuição por Sexo , Fatores de Tempo , Adulto JovemRESUMO
Synthesis of novel HIV-1 protease inhibitors incorporating dioxatriquinane-derived P2-ligands is described. The tricyclic ligand alcohol contains five contiguous chiral centers. The ligand alcohols were prepared in optically active form by an enzymatic asymmetrization of mesodiacetate, cascade radical cyclization, and Lewis acid catalyzed reduction as the key steps. Inhibitors with dioxatriquinane-derived P2-ligands exhibited low nanomolar HIV-1 protease activity.
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BACKGROUND: Whether cigarette smoking and alcohol consumption are associated with the risk of metabolic syndrome (MetS) remains controversial. This study investigated the associations of cigarette smoking and alcohol consumption with MetS in a male population in China. METHODS: We conducted a cross-sectional study. A questionnaire was used to collect data on cigarette smoking, alcohol consumption, MetS status, and other related information from 8169 men aged 19-97 years. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between smoking and alcohol consumption and the risk of MetS. RESULTS: The prevalence of MetS was 15.2% in the study population. Proportions of current smokers and drinkers were 48.2% and 46.5%, respectively. Adjusted OR of MetS was 1.34 (95% CI, 1.01-1.79) among smokers who smoked ≥40 cigarettes/day compared with nonsmokers and 1.22 (95% CI 1.03-1.46) for those who consumed 0.1-99 grams of alcohol/day compared with nondrinkers. Adjusted OR was 2.32 (95% CI 1.45-3.73) among ex-drinkers who never smoked, 1.98 (95% CI 1.35-2.91) among ex-drinkers who were current smokers, and 1.34 (95% CI 1.08-1.68) among current drinkers who never smoked compared with those who neither smoked nor drank. There was a significant interaction between smoking and drinking alcohol on MetS (P for interaction is 0.001). CONCLUSIONS: Our study indicated that smoking and drinking is associated with higher prevalence of MetS. Interactions between smoking and drinking on the risk of MetS in men in China may also exist. Our findings need to be confirmed in future case-control or cohort studies.
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Consumo de Bebidas Alcoólicas/epidemiologia , Síndrome Metabólica/epidemiologia , Fumar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Objectives: This study aimed to explore the synergistic interaction effect between hyperuricemia and hypertension towards chronic kidney disease in patients with type 2 diabetes. Methods: This research originates from a cross-sectional study performed in Zhejiang Province, Eastern China, between March and November 2018. The correlation between serum uric acid levels and the risk of chronic kidney disease was assessed using a restricted cubic spline model. An unconditional multivariable logistic regression model, along with an interaction table, was utilized to explore the potential interaction effect of hyperuricemia and hypertension towards chronic kidney disease. Results: 1,756 patients with type 2 diabetes were included in this study, the prevalence of chronic kidney disease (CKD) was 27.62% in this population. A U-shaped non-linear pattern emerged correlating serum uric acid (SUA) levels and CKD risk, indicating that both low and high SUA levels were linked to an increased CKD risk. This risk achieved its lowest point (nadir) at SUA approximately equals to 285µmol/L (p for trend <0.05). Once adjustments for age, gender, education level, abnormal fasting plasma glucose (FPG), abnormal hemoglobin A1c (HbA1c), abnormal total cholesterol (TC), abnormal high-density lipoprotein cholesterol (HDL-C), alcohol consumption and duration of diabetes were factored in, it was found that patients with both hyperuricemia and hypertension demonstrated a 5.42-fold (95% CI: 3.72-7.90) increased CKD risk compared to the reference group. The additive interaction between hyperuricemia and hypertension was statistically significant, as manifested by the following values: a relative excess risk due to interaction (RERI) of 2.57 (95% CI: 0.71-4.71), an attributable proportion due to interaction (AP) of 0.47 (95% CI: 0.14-0.64), and a synergy index (SI) of 2.39 (95% CI: 1.24-4.58). In contrast, there was no significant interaction effect in multiplicative scale. Conclusion: Hyperuricemia and hypertension may contribute additively to CKD, beyond their isolated impacts. Evaluating the risk of CKD in type 2 diabetes patients necessitates considering this potential interaction.
Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Hiperuricemia , Insuficiência Renal Crônica , Ácido Úrico , Humanos , Hiperuricemia/epidemiologia , Hiperuricemia/sangue , Hiperuricemia/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Estudos Transversais , Masculino , Feminino , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Pessoa de Meia-Idade , Hipertensão/epidemiologia , Hipertensão/sangue , Hipertensão/complicações , China/epidemiologia , Idoso , Ácido Úrico/sangue , Fatores de Risco , Adulto , PrevalênciaRESUMO
We report that GRL-0519, a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing tris-tetrahydrofuranylurethane (tris-THF) and a sulfonamide isostere, is highly potent against laboratory HIV-1 strains and primary clinical isolates (50% effective concentration [EC50], 0.0005 to 0.0007 µM) with minimal cytotoxicity (50% cytotoxic concentration [CC50], 44.6 µM). GRL-0519 blocked the infectivity and replication of HIV-1NL4-3 variants selected by up to a 5 µM concentration of ritonavir, lopinavir, or atazanavir (EC50, 0.0028 to 0.0033 µM). GRL-0519 was also potent against multi-PI-resistant clinical HIV-1 variants isolated from patients who no longer responded to existing antiviral regimens after long-term antiretroviral therapy, highly darunavir (DRV)-resistant variants, and HIV-2ROD. The development of resistance against GRL-0519 was substantially delayed compared to other PIs, including amprenavir (APV) and DRV. The effects of nonspecific binding of human serum proteins on GRL-0519's antiviral activity were insignificant. Our analysis of the crystal structures of GRL-0519 (3OK9) and DRV (2IEN) with protease suggested that the tris-THF moiety, compared to the bis-THF moiety present in DRV, has greater water-mediated polar interactions with key active-site residues of protease and that the tris-THF moiety and paramethoxy group effectively fill the S2 and S2' binding pockets, respectively, of the protease. The present data demonstrate that GRL-0519 has highly favorable features as a potential therapeutic agent for treating patients infected with wild-type and/or multi-PI-resistant variants and that the tris-THF moiety is critical for strong binding of GRL-0519 to the HIV protease substrate binding site and appears to be responsible for its favorable antiretroviral characteristics.
Assuntos
Furanos/farmacologia , Inibidores da Protease de HIV/farmacologia , Protease de HIV/metabolismo , HIV-1/efeitos dos fármacos , Sulfonamidas/farmacologia , Replicação Viral/efeitos dos fármacos , Sequência de Aminoácidos , Sulfato de Atazanavir , Sítios de Ligação , Carbamatos/química , Carbamatos/farmacologia , Linhagem Celular Tumoral , Darunavir , Farmacorresistência Viral/efeitos dos fármacos , Furanos/química , Inibidores da Protease de HIV/química , HIV-1/enzimologia , HIV-1/isolamento & purificação , Humanos , Concentração Inibidora 50 , Lopinavir/química , Lopinavir/farmacologia , Simulação de Acoplamento Molecular , Dados de Sequência Molecular , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Ligação Proteica , Piridinas/química , Piridinas/farmacologia , Ritonavir/química , Ritonavir/farmacologia , Relação Estrutura-Atividade , Sulfonamidas/química , Linfócitos T/efeitos dos fármacos , Linfócitos T/virologiaRESUMO
Ornithine decarboxylase (ODC), the first rate-limiting enzyme of polyamine biosynthesis, was found to be associated with cell growth, proliferation and transformation. ODC gene expression in gastric cancer was increased and its level was positively correlated with the degree of malignity of gastric mucosa and development of gastric lesions. In order to evaluate the therapeutic effects of antisense RNA of ODC on gastric cancer, an antisense RNA of ODC expressing plasmid pcDNA-ODCr which delivered a 120 bp fragment complementary to the initiation codon of ODC gene was constructed and transfected to gastric cancer cells SGC7901 and MGC803. Expression of ODC in gastric cancer cells was determined by western blot. Cell proliferation was assessed by MTS assay. Cell cycle was analyzed by flow cytometry and Matrigel assay was performed to assess the ability of gastric cancer cell invasiveness. The results showed that the ODC gene expression in gastric cancer cells transfected with the pcDNA-ODCr was downregulated efficiently. Tumor cell proliferation was suppressed significantly, and cell cycle was arrested at G1 phase. Gastric cancer cells had reduced invasiveness after gene transfer. Our study suggested that antisense RNA of ODC expressing plasmid pcDNA-ODCr had antitumor activity by inhibiting the expression of ODC, and downregulation of ODC expression using a gene therapy approach might be a novel therapeutic strategy for gastric cancer.
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Regulação Neoplásica da Expressão Gênica , Ornitina Descarboxilase/biossíntese , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Colágeno/química , Combinação de Medicamentos , Citometria de Fluxo/métodos , Perfilação da Expressão Gênica , Técnicas de Transferência de Genes , Terapia Genética/métodos , Humanos , Laminina/química , Oligonucleotídeos Antissenso/genética , Plasmídeos/metabolismo , Proteoglicanas/química , RNA/metabolismoRESUMO
Peloruside B (2), a natural congener of peloruside A (1), was isolated in sub-milligram quantities from the New Zealand marine sponge Mycale hentscheli. Peloruside B promotes microtubule polymerization and arrests cells in the G(2)/M phase of mitosis similar to paclitaxel, and its bioactivity was comparable to that of peloruside A. NMR-directed isolation, structure elucidation, structure confirmation by total synthesis, and bioactivity of peloruside B are described in this article. The synthesis features Sharpless dihydroxylation, Brown's asymmetric allylboration reaction, reductive aldol coupling, Yamaguchi macrolactonization, and selective methylation.
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Antineoplásicos/síntese química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Lactonas/química , Lactonas/síntese química , Lactonas/farmacologia , Macrolídeos/síntese química , Macrolídeos/farmacologia , Poríferos/química , Animais , Ciclo Celular/efeitos dos fármacos , Lactonas/isolamento & purificação , Macrolídeos/química , Macrolídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Nova Zelândia , Paclitaxel/química , Paclitaxel/farmacologiaRESUMO
The expression of Ornithine decarboxylase (ODC) which is the first key enzyme of polyamine biosynthesis is increased in cancer cells. We had blocked the polyamine synthesis pathway using the adenoviral-mediated antisense ODC in some cancer cells such as prostate cancers and colorectal cancers. These researches demonstrated that ODC antisense expression could inhibit tumor cell growth. In order to reach the goal of applying the targeting gene therapy in clinical practice, we cloned the antisense ODC RNA which was driven by cancer specific promoter (hTERT promoter; telomerase reverse transcriptase promoter) into the adenovirus vector (rAd-CMV-GFP-hTERTp-ODC). Human cancer cell lines (HepG2, Bel-7402, A549) and normal cell lines (HELF, LO2) were infected separately with rAd-CMV-GFP-hTERTp-ODC as well as with control vector (rAd-CMV-GFP). Luciferase activity assay was performed to determine hTERT promoter activity. Cell growth curves analysis, western blot analysis, flow cytometry analysis and Matrigel invasion assays were performed to assess properties of cell growth and invasiveness. The results showed that there was significant inhibition of ODC expression and cell proliferation in cancer cells treated with rAd-CMV-GFP-hTERTp-ODC compared with cells treated with PBS or rAd-CMV-GFP, and no significant inhibition was detected in normal cells. Our research offers a powerful and safe new therapeutic strategy for cancer targeted treatment.
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Adenoviridae/genética , Ornitina Descarboxilase/metabolismo , Regiões Promotoras Genéticas , RNA Antissenso/uso terapêutico , Telomerase/genética , Western Blotting , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Colágeno/metabolismo , Combinação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Ensaios Enzimáticos , Citometria de Fluxo , Proteínas de Fluorescência Verde/metabolismo , Humanos , Laminina/metabolismo , Luciferases/metabolismo , Invasividade Neoplásica , Proteoglicanas/metabolismo , Transdução GenéticaRESUMO
Tumstatin is the 28 kDa NC1 domain of the alpha3 chain of type IV collagen that inhibits pathological angiogenesis and suppresses endothelial cell proliferation and tumor growth. In the present paper, we expressed and purified recombinant human tumstatin protein and then prepared the anti-tumstatin polyclonal antibody. To investigate the expression of tumstatin in renal carcinoma, tumstatin protein was detected by western blotting using the prepared anti-tumstatin antibody and tumstatin mRNA levels were assayed by RT-PCR. The results showed that the expression of tumstatin gene was down-regulated in renal carcinoma tissues and cells. Our study suggests that as a novel endogenous angiogenesis inhibitor, tumstatin gene expression may be a marker for diagnosis, therapy and prognosis of renal carcinoma.
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Autoantígenos/genética , Colágeno Tipo IV/genética , Regulação para Baixo/genética , Neoplasias Renais/genética , Anticorpos Antineoplásicos/biossíntese , Autoantígenos/imunologia , Autoantígenos/isolamento & purificação , Autoantígenos/metabolismo , Clonagem Molecular , Colágeno Tipo IV/imunologia , Colágeno Tipo IV/isolamento & purificação , Colágeno Tipo IV/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Rim/metabolismo , Rim/patologia , Neoplasias Renais/imunologia , Neoplasias Renais/patologiaRESUMO
Spermidine/spermine N(1)-acetyltransferase (SSAT) is the rate-limiting step in polyamine catabolism. In a previous study, we constructed a recombinant adenovirus, Ad-SSAT, which can express human SSAT. In the present study, we investigated the effect of upregulated and downregulated SSAT on gastric cancer cells. We found that upregulated SSAT could inhibit the growth of MGC803 and SGC7901 cells, whereas adverse results were found with downregulated SSAT. We further analyzed cell cycle profiles and the expression levels of the major cell cycle regulatory proteins of S phase. The results showed that the growth inhibition was caused by S phase arrest. Ad-SSAT suppressed the expression of cyclin A and nuclear factor E2F1 in MGC803 and SGC7901 cells. We observed the E2F promoter activity caused by Ad-SSAT using a reporter gene assay. We also investigated the antitumorigenicity of upregulated SSAT by Ad-SSAT using a SGC7901 xenograft model in nude mice. Our results suggest that the upregulation of SSAT by Ad-SSAT infection inhibited the growth of gastric cancer in vitro and in vivo. Ad-SSAT arrested gastric cancer cells in S phase, which was mediated through downregulation of the cyclin A-E2F signaling pathway.
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Acetiltransferases/fisiologia , Adenoviridae/genética , Neoplasias Gástricas/prevenção & controle , Acetiltransferases/genética , Animais , Poliaminas Biogênicas/análise , Linhagem Celular Tumoral , Ciclina A/antagonistas & inibidores , Fator de Transcrição E2F1/antagonistas & inibidores , Vetores Genéticos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fase S , Neoplasias Gástricas/química , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/patologia , Regulação para CimaRESUMO
An enantioselective total synthesis of (+)-peloruside A (1) is described. Peloruside A (1) is a potent microtubule stabilizer with significant clinical potential. The synthesis is convergent and involves the assembly of C1-C10 segment 2 and C11-C24 segment 3 by a novel aldol protocol followed by Yamaguchi macrolactonization of the resulting seco-acid, selective methylation of hemi-ketal and removal of the protecting groups to peloruside A.
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Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Lactonas/síntese química , Microtúbulos/efeitos dos fármacos , Animais , Compostos Bicíclicos Heterocíclicos com Pontes/química , Ciclização , Lactonas/química , Estrutura Molecular , Poríferos/química , EstereoisomerismoRESUMO
Spermidine/spermine N1-acetyltransferase (SSAT) is a key enzyme of polyamine catabolism. In a previous study, we constructed a recombinant adenovirus, Ad-SSAT, which can express human SSAT. In the present study, we investigated the effect of Ad-SSAT on the growth and cell cycle of colorectal cancer cells. We found that Ad-SSAT increased the expression of SSAT and inhibited the growth of HT-29 and Lovo cells. The growth inhibition was caused by cell cycle arrest in the S phase. Furthermore, Ad-SSAT was shown to suppress the expression of cyclin A and nuclear factor E2F-1 in HT-29 and Lovo cells. The inhibitory effect of Ad-SSAT on cyclin A promoter activity was also observed in a reporter gene assay. Our results suggest that the expression of SSAT mediated by Ad-SSAT infection inhibits the growth of colorectal cancer cells and induces cell cycle arrest at the S phase, through a mechanism involving the suppression of cyclin A and E2F-1 expression.
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Acetiltransferases/genética , Ciclo Celular/fisiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Espermidina/fisiologia , Acetiltransferases/metabolismo , Adenoviridae/genética , Western Blotting , Linhagem Celular Tumoral , Ciclina A/metabolismo , Fator de Transcrição E2F1/metabolismo , Expressão Gênica , Vetores Genéticos , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TransfecçãoRESUMO
AIM: To construct a recombinant adenovirus that can express human spermidine/ spermine N1-acetyltransferase (SSAT) and detect its inhibitory effect on colorectal cancer cell growth in vitro. METHODS: A 516 bp cDNA of SSAT was amplified and cloned into a pGL3-hTERT plasmid. The pGL3-hTERT-SSAT recombinant was digested, and the small fragment was cloned into the shuttle vector pAdTrack. The pAdTrack-hTERT-SSAT plasmids were recombined with pAdEasy-1 vectors in AdEasy-1 cells. Positive clones were selected and transfected into the HEK293 packaging cells (transformed human embryonic kidney cells) after they were linearized by PacI. The process of adenovirus packaging and amplification was monitored by green fluorescent protein (GFP) expression. The SSAT protein levels were determined by Western blotting, and the intracellular polyamine content was detected by reverse-phase high performance liquid chromatography. The MTS (3-(4, 5-dimethylthiaol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(-4- sulfophenyl)-2H-tetrazolium, inner salt) and colony-forming assays were used to analyze the gene transduction efficiency and effect on the growth of HT-29 and LoVo cells. A viable cell count was used to determine the cell growth with or without exogenous polyamines. RESULTS: The GFP expression in 293 cells during virus packing and amplification was observed by fluorescence microscopy. Western blotting results demonstrated that Ad-hTERT-SSAT could increase the expression of SSAT, and consequently, spermidine and spermine were reduced to low levels. The MTS and colony-forming assay results showed that HT-29 and LoVo cell growth were significantly inhibited, and the inhibitory effect could be partially reversed by exogenous spermidine and spermine. CONCLUSION: The successfully constructed recombinant adenovirus Ad-hTERT-SSAT could accelerate polyamine catabolism and inhibit the colorectal cell growth in vitro. It also has therapeutic potential in the treatment of colorectal cancer.
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Acetiltransferases/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Espermidina/metabolismo , Espermina/metabolismo , Acetiltransferases/metabolismo , Adenoviridae/genética , Sequência de Bases , Linhagem Celular , DNA Complementar/química , Expressão Gênica , Vetores Genéticos , Proteínas de Fluorescência Verde/metabolismo , Células HT29 , Humanos , Rim/citologia , Dados de Sequência Molecular , Plasmídeos , TransfecçãoRESUMO
BACKGROUND: Evidence on the interrelations between cigarette smoking and a cluster of lifestyle behaviors is scarce for the Chinese youth population. This study is conducted to identify the associations between cigarette smoking and multiple health-related behaviors in a Chinese sample of adolescents. METHODS: We used data from 2012 Zhejiang Youth Risk Behavior Survey, which is a school-based survey of 19,542 adolescents that assess risk behaviors using a self-reported questionnaire. The interrelations of cigarette smoking with lifestyle behaviors were investigated using logistic regression models. RESULTS: Cigarette smoking was significantly inversely associated with breakfast (AOR = 0.58), vegetables (AOR = 0.81), fruits (AOR = 0.81), milk consumption (AOR = 0.69) and attending physical education classes (AOR = 0.69), while positively associated with soft drinks (AOR = 2.05), fast food consumption (AOR = 1.21), muscle strengthening activity (AOR = 1.67), computer use (AOR = 1.93) and alcohol drinking (AOR = 5.40). CONCLUSIONS: The results suggested that cigarette smoking was associated with a cluster of health-related behaviors in adolescents, which should be considered in health promotion interventions to target multiple health behaviors.
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A novel diastereoselective synthesis of substituted pyrrolidines has been developed. Asymmetric multicomponent reactions of optically active phenyldihydrofuran, N-tosyl imino ester, and silane reagents in a one-pot operation afforded highly substituted pyrrolidine derivatives diastereoselectively. The reaction is quite efficient and constructed up to three stereogenic centers in a single operation.
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Prolina/química , Pirrolidinas/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , EstereoisomerismoRESUMO
TiCl(4)-promoted multicomponent reactions involving N-tosyl imino ester, cyclic enol ether, and silane reagents in a single one-pot operation provide functionalized alpha-amino acids with multiple stereogenic centers in good to excellent yields. Cis/trans selectivities with optically active substituted dihydrofurans have been investigated.
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Aminoácidos/química , Titânio/química , Modelos Moleculares , Ressonância Magnética Nuclear BiomolecularRESUMO
AIM: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. METHODS: PC-3m cells were treated with 0-16 mmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. RESULTS: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 mmol/L antisense HSP70 oligomer for 48 hr or 8 mmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 mmol/L antisense HSP70 oligomer treatment for 48 hr or 8 mmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. CONCLUSION: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.
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Androgênios/fisiologia , Apoptose/fisiologia , Proliferação de Células , Proteínas de Choque Térmico HSP70/biossíntese , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA de Neoplasias/biossíntese , DNA de Neoplasias/isolamento & purificação , Relação Dose-Resposta a Droga , Eletroforese em Gel de Ágar , Humanos , Cinética , Masculino , Oligonucleotídeos Antissenso/farmacologiaRESUMO
AIM: To study the characteristic pattern of the age-related growth of the human prostate gland. METHODS: The volume (weight) of the prostate in 1,601 males, aged from newborn to 92 years, was determined by B-ultrasonography. RESULTS: Prostatic volume determination by B-ultrasonography in 1601 males (1301 normal subjects and 300 BPH patients) pointed out that the age-stratified growth of human prostate could be categorized into 4 life stages: (1) the first slow growing phase (from newborn to 9 years): the prostate grows slowly at a rate of 0.14 g per year; (2) the first rapid growing phase (from 10 to 30 years): the prostate grows at a rate of 0.84 g per year; (3) the second slow growing phase (from 30 to 50 years), the prostate grows at a rate of 0.21 g per year; (4) the second rapid growing phase (from 50 to 90 years): the prostate grows at one of the following rates: in one group the growth rate is of 0.50 g per year and in the other 1.20 g per year, leading to benign prostatic hyperplasia (BPH). CONCLUSION: The volumes of the prostate are different in different age groups and it grows with age at different rates in four life phases. The prostate growth in phases can be expressed by the following equation: Y=19.36+1.36X'-0.58X'(2+0.33X'3), where Y = prostate volume, X = age (up to 70 years), X'=(X-35.5)/10.
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Próstata/crescimento & desenvolvimento , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Próstata/anatomia & histologia , Próstata/diagnóstico por imagem , UltrassonografiaRESUMO
OBJECTIVE: To study the effect of gene expression of mouse uroplakin II (UPII) promoter on human bladder cell cancer cell line. METHODS: The mRNA expression of different cell lines was quantified by RT-PCR. Green fluorescent protein (GFP) and luciferase (Luc) were used as reporter genes. The plasmids carrying UPII or GFP were constructed and transfected into human cell lines of bladder transitional cell cancer (BIU-87), kindey cancer (GRC-1), vascular endothelium (EC), lung cancer cell line (A549) and skin fibroblast cell line (Hs27). GFP activity of cells was detected by confocual microscopy and flow cytometry (FCM). Luciferase value was measured by luminometer (microplate) and luciferase to beta-galactosidase ratios (L/G values) were used for evaluating transfection efficiency. RESULTS: RT-PCR showed high expression level of UPII mRNA in bladder cancer cell line BIU-87, whereas low level or no expression in nonbladder cancer cell lines. The activity of GFP in bladder cancer (BIU-87) cell was higher than that in the other cell lines (5 - 10/HP versus 0 - 2/HP), with 4.34% positive cells in BIU-87 detected by FCM, but no positive cell was found in the other cell lines. L/G values indicated that the luciferase expression in human bladder cancer cells transfected with mouse UPII promoter was 1.8 - 8.2-fold as high as that in the nonbladder cell lines. CONCLUSION: Mouse UPII promoter gene can be expressed in a tissue-specific fashion in human urinary bladder cancer. It is capable of initiating transcription of reporter genes in human bladder cancer cell line.
Assuntos
Proteínas de Membrana/genética , Regiões Promotoras Genéticas , Neoplasias da Bexiga Urinária/genética , Animais , Linhagem Celular Tumoral , Citometria de Fluxo , Terapia Genética , Proteínas de Fluorescência Verde , Humanos , Proteínas Luminescentes/genética , Camundongos , Especificidade de Órgãos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Neoplasias da Bexiga Urinária/terapia , Uroplaquina IIRESUMO
Both diabetes mellitus and cancer are prevalent diseases worldwide. It is evident that there is a substantial increase in cancer incidence in diabetic patients. Epidemiologic studies have indicated that diabetic patients are at significantly higher risk of common cancers including pancreatic, liver, breast, colorectal, urinary tract, gastric and female reproductive cancers. Mortality due to cancer is moderately increased among patients with diabetes compared with those without. There is increasing evidence that some cancers are associated with diabetes, but the underlying mechanisms of this potential association have not been fully elucidated. Insulin is a potent growth factor that promotes cell proliferation and carcinogenesis directly and/or through insulin-like growth factor 1 (IGF-1). Hyperinsulinemia leads to an increase in the bioactivity of IGF-1 by inhibiting IGF binding protein-1. Hyperglycemia serves as a subordinate plausible explanation of carcinogenesis. High glucose may exert direct and indirect effects upon cancer cells to promote proliferation. Also chronic inflammation is considered as a hallmark of carcinogenesis. The multiple drugs involved in the treatment of diabetes seem to modify the risk of cancer. Screening to detect cancer at an early stage and appropriate treatment of diabetic patients with cancer are important to improve their prognosis. This paper summarizes the associations between diabetes and common cancers, interprets possible mechanisms involved, and addresses implications for medical practice.