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Herein, we report a visible light-enabled radical trihalomethylation/cyano-migration/carbonylation cascade reaction of 2-hydroxy-2-hex-5-enenitrile with CX3SO2Cl as the CX3-source (X = F, Cl) to obtain 5-oxo-2-(2,2,2-trihaloethyl)pentanenitrile compounds in the absence of a photocatalyst, transition metal and base. This reaction system is also effective to convert (benzo[d]thiazol-2-yl)-pent-4-enol to the corresponding 4-(benzo[d]thiazol-2-yl)-6,6,6-trihalo-hexanone products. These reactions occur under mild conditions, tolerate a wide range of functional groups, and provide alternative approaches for the 1,2-bifunctionalization reaction of unactivated olefins.
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A KOH-promoted cascade C-Cl bond activation and amidation of trichloromethyl aromatic compounds with formamides using water as a solvent has been developed. This methodology suggested an alternative synthetic approach for the synthesis of aryl amide compounds in the absence of catalysts, additives and organic solvents. In addition, the yields of gram-scale reactions are good and provide a basis for synthetic application.
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We report the visible-light-induced Ph3P/LiI-promoted intermolecular cascade trifluoromethyl radical addition/5-exo-dig cyclization/iodination of 1,6-enynes with Togni's reagent using LiI as the iodine source without the need of the transition metal, oxidant, and base. This reaction promises to be a useful method for the preparation of trifluoromethyl-substituted and vinyl C-I bond-containing pyrrolidines and benzofuran products with good regioselectivity and functional-group tolerance under ambient conditions.
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The first Ir(I)-catalyzed thioamide-assisted C-H arylation of ferrocenes with aryl boronic acids under base-free mild reaction conditions in the presence of Ag2CO3 as an oxidant with eco-friendly 2-MeTHF as a solvent was developed. This reaction has a wide range of substrates (37 examples) and functional group tolerance (18-94% yields), and provides promising access to aryl thioamide-ferrocene compounds with good yields and regioselectivity.
Assuntos
Ácidos Borônicos , Irídio , Ácidos Borônicos/química , Catálise , Irídio/química , Metalocenos , Estrutura Molecular , TioamidasRESUMO
Dendritic organic molecular gels are a promising class of three-dimensional network compounds. Here, we have synthesized a new type of dendritic organic molecular gel stationary phase (SiO2-G3) by using benzyl alcohol as raw material and dimethyl 5-hydroxyisophthalate as growth unit to synthesize a third-generation organic molecular gel G3, which grafted onto the silica surface by cyanogen chloride (CC). The developed stationary phase not only exhibits high molecular shape selectivity but also has a RPLC/HILIC/IEC mixed-mode characteristic for HPLC due to the ordered structure, the multiple strong π-π stacking interactions and the introduction of a hydrophilic triazine fraction during the grafting process. Compared with a commercial C18 column, the developed column exhibited flexible selectivity, enhanced separation performance and excellent separation of monosubstituted benzene, polycyclic aromatic hydrocarbons (PAHs), positional isomers, nucleosides and nucleobases, benzoic acid and aniline compounds. In addition, the new column provided baseline separation of polycyclic aromatic hydrocarbon contaminants in Yellow River water, verifying its potential for application in the analysis of real samples.
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Hidrocarbonetos Policíclicos Aromáticos , Dióxido de Silício , Dióxido de Silício/química , Cromatografia Líquida , Interações Hidrofóbicas e Hidrofílicas , Cromatografia Líquida de Alta Pressão/métodos , Géis , Hidrocarbonetos Policíclicos Aromáticos/análiseRESUMO
BACKGROUND: Platinum-based chemotherapy is emerging as the first line of treatment for castration resistant prostate cancer. Among the family of platinum (IV)-based compounds, a member known as CPA-7 inhibits the growth of multiple cancer cell lines. However, how and to what extent CPA-7 elicits its anti-prostate cancer effects in vivo is largely unknown. METHODS: In this study, we firstly assessed the potential toxicity of the synthesized CPA-7 in a prostate cancer model as well as in normal mice. Next, we evaluated the in vitro effects of CPA-7 on the growth of prostate cancer cells using cell counting assay, and calculated the tumor sizes and cumulative survival rate of the tumor bearing mice by Kaplan-Meier method during CPA-7 treatment. Then we measured the expression level of the activated form of STAT3 (one targets of CPA-7) and its transcriptive activity post CPA-7 treatment by synergistically using western blot, IHC, and firefly luciferase reporter assays. Finally, effects of CPA-7 on immune cell trafficking in the tumor draining lymph nodes and in the spleens are evaluated with flow cytometry. RESULTS: Treatment with CPA-7 significantly inhibited growth of prostate cancer cells in vitro, and also in mice resulting in a prolonged survival and a decreased recurrence rate. These therapeutic effects are due, at least in part, to functional depletion of STAT3 in prostate tumor tissue as well as in the surrounding areas of tumor cell invasion. CPA-7 treatment also resulted in a reduced level of regulatory T cells and increased levels of cytotoxic T and T helper cells in the spleen and in tumor infiltrating lymph nodes. This favorable effect on immune cell trafficking may account for the amnestic immune response against recurrent prostate cancer. CONCLUSIONS: CPA-7 is a promising new therapeutic agent for prostate cancer that both inhibits tumor cell proliferation and stimulates anti-tumor immunity. It has potential as first line treatment and/or as an adjuvant for refractory prostate cancer.
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Compostos Clorados/farmacologia , Compostos de Platina/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Western Blotting , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HEK293 , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Masculino , Camundongos Endogâmicos C57BL , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/metabolismo , Fator de Transcrição STAT3/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Transplante Homólogo , Carga Tumoral/efeitos dos fármacosRESUMO
OBJECTIVE: The inhibition of the neovascularization in tumors is a potential therapeutic target of cancer. Vascular endothelial growth inhibitor (VEGI) is a member of the TNF superfamily which has the ability to suppress the formation of new vessels in tumors. In order to study the association between VEGI gene polymorphisms and breast cancer risk, a case-control study was conducted in Chinese Han women in Northeast China. METHODS: Our study involved 708 female breast cancer patients and 685 healthy volunteers. Four SNPs of VEGI gene were analyzed through the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The association between VEGI gene polymorphisms and breast cancer risk was analyzed in our study. The relation between VEGI gene variants and clinical features of breast cancer including lymph node (LN) metastasis, estrogen receptor (ER), progestrogen receptor (PR), tumor protein 53 (p53), human epidermal growth factor receptor 2 (Her-2) and triple negative (ER-/PR-/Her-2-) status was analyzed as well. RESULTS: We found that the CT genotype and T allele of rs6478106 were more frequent in patients than in controls. There was also a statistical difference in the distribution of Crs6478106Grs4263839 haplotype between patients and controls. In addition, SNP rs6478106 and rs4979462 were related with the Her-2 status. CONCLUSIONS: Our results suggest that VEGI gene variants may be related to the breast cancer risk and the clinical features of breast cancer in Chinese Han women in Northeast China.
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A suicide gene can convert nontoxic prodrugs into toxic products to kill tumor cells. In this study, our aim was to transfect lentivirus-mediated CD/TK fusion gene into Wistar rat's neural stem cells (NSC) and then implant the NSC into a C6 glioma model to observe a C6 glioma growth inhibition effect. Primary NSC and stable transfection CD/TK fusion gene cell lines were established. To observe the tumor size and rat survival period in different groups, C6 glioma cell apoptosis and cell viability rate were applied to analyze the tumor inhibition effect of the neural stem cells' transfected CD/TK fusion gene. C6 cell viability showed that CDglyTK-NSC + GCV/5-Fc (group 1) was lower than CDglyTK-NSC (group 2), NSC + GCV/5-Fc (group 3), and control (group 4) from day 2 (p < 0.05), and the apoptosis rate was higher in group 1 compared with that of other groups (50.6%, p < 0.05) either in vitro or in vivo (35.47%, p < 0.05); both cell viability and apoptosis had no significance in the other three groups. In vivo, tumor size in group 1 was 7.76 ± 1.37 mm(3), which is smaller than the others (group2 27.28 ± 4.11 mm(3), group3 27.94 ± 2.08 and 28.61 ± 2.97 mm(3); p < 0.05). The other groups' tumor size was not significant (p > 0.05). Survival time of rats treated with CDglyTK-NSC + GCV/5-Fc (group 1) was significantly longer than that of the other groups (p < 0.05; group 1 48.86 ± 1.97, group 2 28.67 ± 3.75, group 3 31.5 ± 1.27, group 4 29.3 ± 1.33). We also showed that the transfected C6 cells had a migratory capacity toward gliomas in vivo. Transfected CD/TK fusion gene neural stem cells combined with propyl-guanosine and 5-flucytosine double prodrug significantly inhibit the development of glioma.
Assuntos
Neoplasias Encefálicas/terapia , Citosina Desaminase/metabolismo , Glioblastoma/terapia , Células-Tronco Neurais/transplante , Timidina Quinase/metabolismo , Animais , Antimetabólitos/administração & dosagem , Antimetabólitos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/administração & dosagem , Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Células Cultivadas , Terapia Combinada , Citosina Desaminase/genética , Feminino , Flucitosina/administração & dosagem , Flucitosina/farmacologia , Ganciclovir/administração & dosagem , Ganciclovir/farmacologia , Vetores Genéticos/genética , Glioblastoma/genética , Glioblastoma/patologia , Lentivirus/genética , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Gravidez , Ratos , Ratos Wistar , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Timidina Quinase/genética , Transfecção , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genéticaRESUMO
In a previous study, we noticed that some ascitic cells isolated from melanoma patients survive, proliferate, and differentiate into giant phagocytes after the other cells died. Similar phenomena were observed in the primary cultures of mouse lung and liver cells. In the present study, the effects of dying cells on abdominal exudate cells, and the biological characteristics of the differentiated cells were studied. The results indicate that necrotic cells induce CD14(-)/CD68(+) fraction of abdominal exudate cells to proliferate and differentiate into giant phagocytes; however, apoptotic cells had no such effect. Morphologic studies revealed that the large phagocytes possess characteristics of macrophages. Moreover, necrotic cells enhance the expression of CD14, CD68, CD80, and CD86, and the differentiated cells expressed high levels of CD68 and CD86. Our results indicate that necrotic cells induce CD14(-)/CD68(+) fraction of abdominal exudate cells to proliferate and differentiate, and the differentiated cells possess characteristics similar to macrophages.
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Diferenciação Celular/imunologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/fisiologia , Animais , Antígenos CD/metabolismo , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/imunologia , Exsudatos e Transudatos/imunologia , Humanos , Imunofenotipagem , Camundongos , Necrose/imunologia , FenótipoRESUMO
A direct protocol for Rh-catalyzed C-H amidation of ferrocenes in a ball mill using dioxazolones as the amide source under solvent-free conditions was developed. The corresponding ortho-aminated products were formed in 3â hours and the yields were up to 99% in the absence of base. This method could be a typically sustainable and environmental-friendly alternative method to traditional methodologies, with the advantages of wide substrate range, good functional group tolerance and gram-scale synthesis.
RESUMO
We developed a Cp*Rh(III)-catalyzed C-H arylation of ferrocenethionamides with arylboronic acids for the synthesis of aryl-ferrocenes under mild and base-free conditions, using Ag2 CO3 as oxidant. The reaction results in high yields and excellent regioselectivity accommodating a broad scope of substrate range and functional group compatibility, and provides an alternative protocol for the generation of highly functionalized aryl-ferrocene compounds.
Assuntos
Ácidos Borônicos , Metalocenos , Ácidos Borônicos/química , CatáliseRESUMO
CD27 and its ligand, CD70, are major costimulatory molecules whose interaction can regulate the expansion and differentiation of effector and memory T-cell populations. Their abnormal expression can disturb the immune response and lead to an increased risk of cancer. This study aims to evaluate the associations between single nucleotide polymorphisms (SNPs) in CD27/CD70 gene and breast cancer susceptibility. Five tagSNPs and one coding polymorphism in CD27, as well as three tagSNPs in CD70, were genotyped in a case-control study of 610 breast cancer patients and 617 healthy controls. In CD27, rs3136550 CT and rs2267966 AT genotypes were associated with a decreased risk of breast cancer (P = 0.03, OR = 0.76; P = 0.02, OR = 0.75, respectively). In CD70, AG and GG genotypes in rs1862511 and CC genotype in rs2059154 also showed significant associations with a decreased risk of breast cancer (P = 2.00 × 10(-3), OR = 0.69; P = 0.03, OR = 0.62; P = 2.00 × 10(-3), OR = 0.53; respectively). Significant associations were also found in the dominant and recessive models for rs2059154 and dominant model for rs1862511. In haplotype analysis, CCGAG haplotype in CD27 and TAA haplotype in CD70 conferred an increased risk of breast cancer (P = 5.60 × 10(-3); P = 7.75 × 10(-5), respectively), but TGC, TAC and TGA haplotypes in CD70 were associated with a decreased risk of breast cancer (P = 0.01; P = 5.2 × 10(-3); P = 2.00 × 10(-3), respectively). The associations of CCGAG, TAA, TAC and TGA haplotypes remained significant after correcting P value for multiple testing. Significant associations were shown between the SNPs of CD27 and lymph node metastasis, and ER and PR statuses. These results indicate that CD27 and CD70 gene polymorphisms may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in a northern Chinese population.
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Povo Asiático/genética , Neoplasias da Mama/genética , Ligante CD27/genética , Polimorfismo de Nucleotídeo Único , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , RiscoRESUMO
Computer simulation and experimental study of a pulsed electrical-discharge DF laser pumped by the SF(6)-D(2) non-chain reaction are presented. The computer model encompassing 28 reactions is based on laser rate equations theory, and applied to approximately describe the chemical processes of non-chain DF laser. A comprehensive study of the dependence of number density on time for all particles in the gain area is conducted by numerical calculation adopting Runge-Kutta method. The output performance of non-chain pulsed DF laser as a function of the output mirror reflectivity and the mixture ratio are analyzed. The calculation results are compared with experimental data, showing good agreement with each other. Both the theoretical analysis and experimental results present that the laser output performance can be improved by optimizing the mixture ratio and output mirror reflectivity. The optimum values of mixture ratio and output mirror reflectivity are respectively 10:1 and 30%. The single pulse energy of 4.95J, pulse duration of 148.8ns and peak power of 33.27 MW are achieved under the optimum conditions.
Assuntos
Lasers , Simulação por Computador , Campos Eletromagnéticos , Desenho de Equipamento , Análise de Falha de Equipamento , Modelos TeóricosRESUMO
Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that plays a pivotal role in downregulating T-cell mediated immune responses. To determine the role of CTLA-4 in tumor immunity, and to validate previous results as well, we investigated four tag single nucleotide polymorphisms (SNPs) of CTLA-4 in a relatively large Chinese Han cohort from northeastern China. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 581 patients and 566 age-matched controls. Our data indicated that compared with the common genotype and allele of each SNP, the -1722 CC genotype and C allele showed an increased risk of breast cancer (P = 0.030, odds ratio (OR) = 1.457, 95% confidence internal (CI) 1.036-2.051; P = 0.024, OR = 1.214, 95% CI 1.026-1.436, respectively). The -1661 GG genotype and G allele were also associated with an increased risk of breast cancer (P = 0.018, OR = 1.396, 95% CI 1.058-1.843; P = 0.013, OR = 1.353, 95% CI 1.066-1.717, respectively). In the haplotype analysis, the CAAA haplotype showed a higher frequency in cases (P = 0.004), and this association remained significant after correcting the P value for multiple testing. Associations were shown between the SNPs of CTLA-4 and lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR) and P53 statuses. These results indicate that some SNPs in the CTLA-4 gene may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in Han women in northeastern China.
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Neoplasias da Mama/genética , Antígeno CTLA-4/genética , Estudos de Associação Genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Neoplasias da Mama/patologia , China , Feminino , Genótipo , Haplótipos , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Risco , Proteína Supressora de Tumor p53/metabolismoRESUMO
Several molecular epidemiological studies were conducted in recent years to evaluate the association between NQO1 Pro187Ser polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 3177 cases with breast cancer and 4038 controls from seven published case-control studies showed that the 187Ser allele was not associated with a significantly increased risk of breast cancer (Ser versus Pro: P = 0.33, OR = 1.08, 95% CI = 0.92-1.28; Ser/Ser versus Pro/Pro: P = 0.58, OR = 1.16, 95% CI = 0.68-2.00; Ser/Ser versus Pro/Ser + Pro/Pro: P = 0.62, OR = 1.14, 95% CI = 0.68-1.90; Ser/Ser + Pro/Ser versus Pro/Pro: P = 0.30, OR = 1.07, 95% CI = 0.94-1.22). In the stratified analysis by ethnicity, we found that the Pro187Ser polymorphism was associated with increased breast cancer risk in Caucasians in the additive genetic model and dominant genetic model (P = 0.03, OR = 1.13, 95% CI = 1.01-1.26; P = 0.03, OR = 1.15, 95% CI = 1.01-1.30, respectively), whereas no significant in Asians (P = 0.44, OR = 0.94, 95% CI = 0.80-1.10) and postmenopausal women (P = 0.99, OR = 1.00, 95% CI = 0.84-1.19). The results suggest that NQO1 Pro187Ser polymorphism may contribute to breast cancer development in Caucasians.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , NAD(P)H Desidrogenase (Quinona)/genética , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Humanos , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
The infiltrative duct carcinoma (IDC) is the most common malignant breast cancer in females and genetic factors appear to play a significant role in the susceptibility of IDC. The LFA-1 is a crucial co-stimulatory molecule in immune system and may affect the development of breast IDC. In order to clarify the association of LFA-1 polymorphisms with IDC, a case-control study was conducted in women from Heilongjiang Province, Northeast of China. We scrutinized four genetic polymorphisms in LFA-1 gene, which may influence the activity and function of LFA-1. Our research subjects consist of 537 cases with IDC and 577 age-matched healthy controls. Genotypes were determined by PCR-RFLP. Data were analyzed using the χ(2) test by SPSS 13.0 and Haploview 4.1 softwares. The association between LFA-1 polymorphisms and the clinical features of IDC was analyzed. In rs2230433, the frequency of GG genotype and G allele was lower in cases than in controls (P = 0.0316 and 0.0480). And rs2230433, CG genotype was higher in cases (P = 0.0397). In rs8058823, the frequency of AA genotype and A allele was lower in cases than in controls (P = 0.00000418 and 0.00000267). And rs8058823, AG genotype was higher in cases (P = 0.00000747). The frequency of haplotype CCGA was lower in patients. Significant association was shown between the four SNPs of LFA-1 gene and estrogen receptor (ER), progesterone receptor (PR), C-erbB-2, and P53 statuses. In addition, no association was found between LFA-1 gene polymorphisms and tumor size, and neither was it between LFA-1 gene polymorphisms and lymph node metastasis. Our results primarily suggested that LFA-1 gene polymorphisms may predict the sporadic breast IDC risk and prognosis factors in Chinese Han women in Heilongjiang Province.
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Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/patologia , Predisposição Genética para Doença , Antígeno-1 Associado à Função Linfocitária/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , China , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/genética , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Proteína Supressora de Tumor p53/genética , Adulto JovemRESUMO
The programmed death-1 (PD-1) is a potent immunoregulatory molecule which is responsible for the negative regulation of T-cell activation and peripheral tolerance. In order to investigate the association between polymorphisms of PD-1 and breast cancer, a case-control study was conducted in Chinese female population consisting of 490 cases with breast cancer and 512 age-matched healthy individuals from Heilongjiang Province of China. Four polymorphisms of the PD-1 gene, including rs36084323 (PD-1.1), rs7421861, rs2227982 (PD-1.9), and rs2227981 (PD-1.5), were selected and genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The frequencies of PD-1.1 GG genotype and PD-1.5 CT genotype were significantly lower in cases compared with controls (P = 0.020 and 0.004, respectively), and PD-1.5 CC genotype and C allele had higher frequencies in cases (P = 0.003 and 0.010). In haplotype analysis, we observed that the frequencies of ATTC and GTCT haplotypes were lower in cases than those of in controls (P = 0.0055 and 0.0012, respectively), whereas the GTCC and ATCC haplotypes had higher frequencies in cases (P = 0.0040 and 0.00008037, respectively). Additionally, strong association was showed between PD-1.1 and P53, and haplotype CCTA was associated with ER status. These results primarily suggest that PD-1 gene polymorphisms may affect the breast cancer risk and prognosis in Chinese Han females of Heilongjiang Province in Northeast China.
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Povo Asiático/genética , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor de Morte Celular Programada 1/genética , Adulto , Alelos , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , China/etnologia , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , RiscoRESUMO
BACKGROUND: Inducible costimulator (ICOS), a costimulatory molecular of the CD28 family, provides positive signal to enhance T cell proliferation. Its abnormal expression can disturb the immune response and entail an increased risk of cancer. To investigate whether single nucleotide polymorphisms (SNPs) in the ICOS gene are associated with sporadic breast cancer susceptibility and progression in Chinese women, a case-control study was conducted. METHODS: In the study cohort, we genotyped five SNPs (rs11889031, rs10932029, rs4675374, rs10183087 and rs10932037) in ICOS gene among 609 breast cancer patients and 665 age-matched healthy controls. Furthermore, the positive results were replicated in an independent validation cohort of 619 patients and 682 age-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes. RESULTS: In rs10932029, compared with TT genotype and T allele, the CT genotype and C allele showed a significantly increased risk of breast cancer (P = 0.030, OR = 1.467, 95% CI 1.037-2.077; P = 0.017, OR = 1.481, 95% CI 1.070-2.049, respectively), and the associations were also significant in the validation cohort (P = 0.002, OR = 1.693, 95% CI 1.211-2.357; P = 0.003, OR = 1.607, 95% CI 1.171-2.204, respectively). Haplotype analysis showed that CTCAC haplotype containing rs10932029 T allele had a lower frequency in cases than in controls (P = 0.015), whereas haplotype CCCAC containing rs10932029 C allele was more common in cases than in controls (P = 0.013). In the analysis of clinicopathologic features, rs11889031 CT genotype and T allele were associated with progesterone receptor (PR) status and lymph node metastasis, which were further supported by our validation cohort. Moreover, some haplotypes were associated with estrogen receptor (ER) and PR statuses. CONCLUSIONS: These results indicate that ICOS gene polymorphisms may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in a northern Chinese population.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-IdadeRESUMO
B and T lymphocyte attenuator (BTLA) is an immunoinhibitory receptor with the ability to deliver inhibitory signals for suppressing lymphocyte activation. To identify the influences of BTLA gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in women from northeast of China, Heilongjiang Province. We genotyped five SNPs (rs9288952, rs2931761, rs2633562, rs2705535 and rs1844089) in BTLA gene among exons and introns. Our research groups consist of 592 patients with breast cancer and 506 age/sex-matched healthy controls. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction with confronting two-pair primer (PCR-CTPP) methods. Data were analyzed using the chi-square test by EXCEL, SPSS and Haploview softwares. The frequencies of BTLA rs1844089 CT and rs2705535 AG were higher in patients than in controls (P = 0.0164; P = 0.0031), and rs1844089 CC, rs2705535 GG and rs9288952 CC genotypes had lower incidences in patients than in controls (P = 0.0483; P = 0.0098; P = 0.0400). The frequency of haplotype CAAAT was significantly higher in patients (P = 0.0112). Strong association was shown between five SNPs of BTLA gene and tumor size, estrogen receptor (ER), progesterone receptor (PR), C-erbB-2 and P53 statuses. Strong association was observed between tumor size, ER, PR, P53 and the CAGAT(P = 0.012), TAAGT(P = 0.0378), CAGAT(P = 0.0013), CAAGT(P = 0.0373) and CAAAT(P = 0.0306) haplotypes. These results primarily suggested that BTLA gene polymorphisms may affect the sporadic breast cancer risk and prognosis in Chinese women in northeast of Heilongjiang Province.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Receptores Imunológicos/genética , Adulto , Idoso , Povo Asiático/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Genes erbB-2 , Genótipo , Haplótipos , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Fatores de Risco , Proteína Supressora de Tumor p53/metabolismo , Adulto JovemRESUMO
It was reported that the functional polymorphism Ser326Cys in the human 8-oxoguanine DNA glycosylase gene was associated with breast cancer risk; however, the published studies have inconsistent conclusions. To elucidate the effect of hOGG1 Ser326Cys on the susceptibility to breast cancer, all available studies were collected in this meta-analysis. We extracted the data from 10 case-control studies that were published in the PubMed database from 2003 to 2008 using the search phrases "human 8-oxoguanine DNA glycosylase, hOGG1, OGG1, OGG, polymorphism, genetic variation, and breast cancer." This meta-analysis included 4,963 breast cancer cases and 4,776 control subjects. The results showed that individuals who carrying the hOGG1 326Cys allele in the additive model did not have significantly increased risk of breast cancer compared with those carrying the 326Ser allele (P = 0.47, OR = 1.02; 95% CI = 0.96-1.09); similarly, no significant association between the hOGG1 326Cys allele and breast cancer risk was found either in the recessive genetic model (P = 0.34, OR = 1.06; 95% CI = 0.94-1.18) for Cys/Cys versus Ser/Cys + Ser/Ser, or dominant genetic model (P = 0.78, OR = 1.01; 95% CI = 0.93-1.11) for Cys/Cys + Ser/Cys versus Ser/Ser. In the stratified analysis, the meta-analysis showed the association between hOGG1 326Cys allele in the additive model and breast cancer was significant in European subjects (P = 0.04, OR = 0.71; 95% CI = 0.51-0.98), and dominant genetic model (P = 0.004, OR = 0.44; 95% CI = 0.25-0.77). However, the association was not significant between this polymorphism and different menopausal status (premenopausal and postmenopausal) and the other ethnicities (Asians and Americans). The meta-analysis suggested that the hOGG1 326Cys allele plays a significant protective effect to breast cancer in European women.