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1.
Ann Surg Oncol ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898102

RESUMO

BACKGROUND: Currently, the number of negative lymph nodes (NLNs) has been paid increasing attention and is considered a prognostic indicator in diverse cancers. Therefore, it is necessary to explore the association between number of NLNs and prognosis in esophageal cancer (EC) patients. METHODS: Our data were obtained from the Surveillance, Epidemiology, and End Results 18 database. The X-tile plot was used to determine the optimal cut-off value of the number of NLNs, and propensity score matching (PSM) was performed according to the results of the X-tile plot. RESULTS: A total of 4777 patients were eligible, and 882 pairs of patients were included after PSM. The result of the X-tile plot revealed an optimal cut-off value of three NLNs. Multivariate Cox regression analysis revealed better EC-specific survival (ECSS) in patients with more than three NLNs (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.59-0.77; p < 0.001) compared with patients with three or fewer NLNs. A subgroup analysis revealed better ECSS in patients with more than three NLNs with one to two (HR 0.57, 95% CI 0.46-0.71; p < 0.001) or three to six (HR 0.68, 95% CI 0.50-0.92; p = 0.012) positive lymph nodes (PLNs). CONCLUSIONS: More than three NLNs is associated with better survival in EC patients, especially when the number of PLNs is one to two or three to six. We confirm that the combination of the number of NLNs and number of PLNs can provide better prognostic guidance for EC.

2.
J Hematol Oncol ; 12(1): 140, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864424

RESUMO

BACKGROUND: Statistical data on the incidence, mortality, and burden of breast cancer and the relevant risk factors are valuable for policy-making. We aimed to estimate breast cancer incidence, deaths, and disability-adjusted life years (DALYs) by country, gender, age group, and social-demographic status between 1990 and 2017. METHODS: We extracted breast cancer data from the 2017 Global Burden of Disease (GBD) study from 1990 through 2017 in 195 countries and territories. Data about the number of breast cancer incident cases, deaths, DALYs, and the age-standardized rates were collected. We also estimated the risk factors attributable to breast cancer deaths and DALYs using the comparative risk assessment framework of the GBD study. RESULTS: In 2017, the global incidence of breast cancer increased to 1,960,681 cases. The high social-development index (SDI) quintile included the highest number of breast cancer death cases. Between 2007 and 2017, the ASDR of breast cancer declined globally, especially in high SDI and high middle SDI countries. The related DALYs were 17,708,600 in 2017 with high middle SDI quintile as the highest contributor. Of the deaths and DALYs, alcohol use was the greatest contributor in most GBD regions and other contributors included high body mass index (BMI) and high fasting plasma glucose. CONCLUSION: The increasing global breast cancer burden is mainly observed in lower SDI countries; in higher SDI countries, the breast cancer burden tends to be relieving. Therefore, steps against attributable risk factors should be taken to reduce breast cancer burden in lower SDI countries.

3.
Oncoimmunology ; 8(12): e1659094, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741756

RESUMO

Cervical cancer (CC) is a leading cause of cancer-related death in women. Limited studies have investigated whether immune-related genes (IRGs) or tumor immune microenvironment (TIME) could be indicators for CC prognoses. The aim of this study was to develop an improved prognostic signature for CC based on IRGs or TIME to predict survival and response to immune checkpoint inhibitors (ICIs). A prognostic signature was constructed using bioinformatics method and its predictive capability was validated. The mechanisms underlying the signature's predictive capability were explored with CIBERSORT algorithm and mutation analysis. Immunophenoscore (IPS) is validated for ICIs response, and was therefore explored in relation to the signature. A prognostic signature based on 11 IRGs was developed. A multivariate analysis revealed that the 11-IRG signature was an independent prognostic factor for overall survival (OS) and progression-free interval in CC patients. In the 11-IRG signature high-risk group, CD8 T cells and resting mast cells, which are found to associate with better OS in our study, were lower; activated mast cells, associated with poorer OS, were higher, compared with the low-risk group. An IPS analysis suggested that the 11-IRG signature low-risk group, which possessed a higher IPS, represented a more immunogenic phenotype that was more inclined to respond to ICIs. In short, an 11-IRG prognostic signature for predicting CC patients' survival and response to ICIs was firmly established. The predictive capability of this model in CC requires further testing with the goal of better prognostic stratification and treatment management.

4.
Mol Ther Nucleic Acids ; 18: 56-65, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31525662

RESUMO

MicroRNAs bind to the 3' untranslated regions of mRNAs, affecting translation, tumorigenesis, and apoptosis. This study evaluated the role of TYMS (rs1059394, C > T, and rs2847153, G > A), RYR3 (rs1044129, G > A), KIAA0423 (rs1053667, T > C), and GOLGA7 (rs11337, G > T) polymorphisms for assessment of glioma risk and prognosis among the Chinese Han population. Five single-nucleotide polymorphisms were assessed in 605 glioma patients and 1,300 controls. We found a significant correlation between rs1059394 and glioma susceptibility in the homozygote and dominant genetic models (TT versus CC, odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.52-0.97, p = 0.03; CT+TT versus CC, OR = 0.74, 95% CI = 0.55-0.99, p = 0.04). The results of the Kaplan-Meier and log rank tests revealed that the rs11337 GG genotype correlated with better overall survival of glioma patients (p = 0.017) than the GT genotype. Multivariate Cox regression analysis results also showed that the rs11337 GT genotype correlated with worse overall survival (p = 0.017, hazard ratio [HR] = 1.25, 95% CI = 1.04-1.5) than the GG genotype. These results suggest that GOLGA7 (rs11337) polymorphism may play a role in the prognosis of glioma patients and that TYMS (rs1059394) is associated with glioma risk.

5.
Mol Carcinog ; 58(12): 2218-2229, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31489712

RESUMO

Long noncoding RNA (lncRNA) polymorphisms are reportedly in connection with tumor susceptibility and prognosis. Glioma is one of the most aggressive and common cancers of the central nervous system. This study aimed to investigate the relationship between four lncRNA variants and glioma susceptibility and prognosis in a Chinese Han population. Sequenom Mass-ARRAY was used to genotype 605 patients with glioma and 1300 cancer-free individuals. Odds ratios or hazard ratios and related 95% confidence intervals were calculated to estimate the correlations. Logistic and Cox regression models, log-rank tests, and Kaplan-Meier curves were used for the statistical analysis. Six inheritance models showed that ANRIL rs2151280 variant genotype (A>G) was related to the susceptibility of glioma, while the other three lncRNAs showed no association. Patients treated with temozolomide or nimustine had better progression-free survival (PFS) and overall survival (OS) than those treated with platinum. Besides, patients aged older than 40 years showed a poorer OS. The Cox multivariate analysis revealed that the rs1136410 GG genotype (A>G) was beneficial for OS and PFS. The Kaplan-Meier analyses indicated that rs1136410 A>G and the rs7763881 A>C were associated with longer OS. ANRIL rs2151280 variant genotype might increase susceptibility of glioma. In addition, PARP1 rs1136410 variant genotype could be beneficial for the overall survival of patients with glioma. More research data are needed to further validate our results.

6.
Breast Cancer Res Treat ; 176(1): 109-117, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30989461

RESUMO

PURPOSE: Targeting DNA repair mechanisms to induce apoptosis may be a promising strategy for breast cancer treatment. Olaparib is proved to have anticancer effect by inhibiting DNA repairing protein poly (ADP-ribose) polymerase (PARP). However, the cytotoxicity of olaparib is very limited to homologous recombination-proficient cells. This study aims to examine the effect and mechanism of olaparib treatment in breast cancer cell lines. METHODS: We investigated the cytotoxic effect of various doses of olaparib treatment to MCF-7 and ZR-75-1 cells in vitro. mRNA and protein levels of PARP and APE1 were examined by real-time PCR and western blot, respectively. APE1-deficient cell lines were created by RNA interference and used for in vitro cytotoxicity study as well as in vivo study. RESULTS: 2 µM or higher concentrations of olaparib lead to significant cell death and ROS production. Moreover, olaparib treatment not only inhibits PARP1, but also reduces the expression of APE1 in both mRNA and protein levels. Deficiency of APE1 resulted in increased sensitivity of MCF-7 and ZR-75-1 cells to olaparib treatment. In vivo study showed that reduction of APE1 significantly reduced the volume and weight of MCF-7 xenografted tumors when treated with olaparib, which suggests the synergistic function of inhibition of APE1 in promoting antitumor effects of olaparib treatment. CONCLUSION: To acquire better benefits for HR-proficient breast cancer patients, developing chemotherapeutic drugs antagonize APE1 would be an effective strategy to improve the clinical outcome of PARP inhibitors.


Assuntos
Neoplasias da Mama/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Ftalazinas/farmacologia , Piperazinas/farmacologia , Poli(ADP-Ribose) Polimerase-1/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Biochem Biophys Res Commun ; 505(4): 1077-1083, 2018 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-30314698

RESUMO

Perineural invasion (PNI) potentially increases the risk of relapse and abdominal pain in patients with pancreatic ductal adenocarcinoma (PDAC). However, the underlying mechanisms of PNI of PDAC is incompletely revealed. Our study aimed to investigate roles of miR-429 in modulating PNI in PDAC. We found that miR-429 was downregulated in PDAC cancer tissues and was profoundly decreased in tissues with PNI. It was reduced in nine of the ten examined pancreatic cancer cell lines. MiR-429 mimics restored its cellular expressions in MIA PaCa-2 and BxCP3 cells and significantly suppressed cell viability and invasion of the cancer cells. The online bioinformatic software predicted that neurotrophin-3 (NT-3) was a potential target gene of miR-429. It was showed that NT-3 mRNA elevated in PC cancer tissues, especially in patients presenting PNI. MiR-429 upregulation substantially suppressed the NT-3 mRNA and secretion in cancer cells. Also, the dual luciferase reporter assays confirmed the interaction between miR-429 and NT-3. When co-culturing the two PDAC cells with PC-12 cells, the invaded cell counts significantly increased comparing with the sole culture of cancer cells. However, miR-429 mimic transfection or NT-3 blocking retarded the cancer invasion in the co-culture system. Besides, we found that cancer cells conditioned medium (CM) treatment significantly increased the neurite outgrowth percentage in PC-12 cells, which was suppressed by culturing with CM from miR-429 mimics-transfected cells. In the CM cultured PC-12 cells, NT-3 receptor TrkC as well as pain-related proteins TRPV1 and TRPV2 significantly elevated. Collectively, miR-429 potentially suppressed neurotrophin-3 to alleviate PNI of PDAC.


Assuntos
MicroRNAs/farmacologia , Fatores de Crescimento Neural/antagonistas & inibidores , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Humanos , MicroRNAs/genética , Fatores de Crescimento Neural/metabolismo , Células PC12 , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ratos , Células Tumorais Cultivadas
8.
Gene ; 670: 136-147, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-29842912

RESUMO

Many molecular epidemiologic studies have shown that interleukin-6 (IL-6) polymorphisms are significantly associated with susceptibility for various cancers. However, the conclusions of these studies are inconsistent. The purpose of the present study was to explore the association between three common IL-6 loci (rs1800795, rs1800796, and rs1800797) and the risk for various cancers. We systematically searched the PubMed, Web of Science, Wanfang and China national knowledge infrastructure (CNKI) databases for relevant publications and obtained 108 eligible studies, involving 49,408 cancer patients and 61,790 cancer-free controls. Odds ratio (OR), 95% confidence interval (CI), and false positive reporting probability (FPRP) were used to evaluate cancer risk. All statistical analyses were performed using the R software meta package. We observed a non-significant association between rs1800795 and overall cancer risk, while rs1800797 was found to have a false positive association with overall risk of cancer. Subgroup analyses of rs1800797 also suggested non-significant association and rs1800795 played a protective role in liver cancer. Rs1800796 was found to be associated with overall cancer risk, particularly in Asian patients and those with prostate cancer. These findings provide evidence that IL-6 polymorphisms may affect cancer risk.


Assuntos
Interleucina-6/genética , Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Razão de Chances , Neoplasias da Próstata/genética
9.
Aging (Albany NY) ; 10(2): 266-277, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29466248

RESUMO

Previous studies have showed the associations between various BRCA1-interacting protein 1 (BRIP1) polymorphisms and cancer risk. But, these results were inconsistent. This meta-analysis based on 18 studies involving 13,716 cancer patients and 15,590 cancer-free controls is aimed at to evaluate the relationship between the four common SNPs of BRIP1 (rs2048718, rs4988344, rs4986764, and rs6504074) and cancer risk. The results showed a decreased risk of rs2048718 or rs4986764 for cervical cancer rather than breast cancer in the overall population (P < 0.05). However, rs6504074 was associated with gynecologic cancer risk among overall population (P < 0.05). Further stratification analyses by ethnicity indicated that all 4 polymorphisms (rs2048718, rs4988344, rs4986764, and rs6504074) were strongly related to cancer susceptibility in Chinese people (P < 0.05). This meta-analysis showed that rs6504074 may play a decreased risk of gynecologic cancer in the overall population. Rs4988344, rs4986764, and rs6504074 were significantly related to decreasing cancer risk in Chinese population.


Assuntos
Neoplasias da Mama/genética , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , RNA Helicases/metabolismo , Neoplasias do Colo do Útero/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Medição de Risco
10.
Cancer Manag Res ; 10: 143-151, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29403312

RESUMO

Introduction: Breast cancer is the most common cancer in women worldwide. The association between body mass index (BMI) and breast cancer risk has been paid more attention in the past few years, but the findings are still controversial. To obtain a more reliable conclusion, we performed a dose-response meta-analysis on 12 prospective cohort studies comprising 22,728,674 participants. Methods: Linear and nonlinear trend analyses were conducted to explore the dose-response relationship between BMI and breast cancer risk. The summary relative risk (SRR) and 95% confidence intervals (CIs) were used to evaluate the cancer risk. Results: The overall results showed a weak positive association between a 5-unit increase in BMI and breast cancer risk, indicating that a 5 kg/m2 increase in BMI corresponded to a 2% increase in breast cancer risk (SRR: 1.02, 95% CI: 1.01-1.04, p<0.001). Notably, further subgroup meta-analysis found that higher BMI could be a protective factor of breast cancer risk for premenopausal women (SRR: 0.98, 95% CI: 0.96-0.99, p<0.001). In addition, the dose-response result demonstrated that there was a linear association between BMI and breast cancer risk (Pnonlinearity=0.754). Conclusion: In summary, this dose-response meta-analysis of prospective cohort studies showed that every 5 kg/m2 increase in BMI corresponded to a 2% increase in breast cancer risk in women. However, higher BMI could be a protective factor in breast cancer risk for premenopausal women. Further studies are necessary to verify these findings and elucidate the pathogenic mechanisms.

11.
Biomed Pharmacother ; 98: 687-693, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29304494

RESUMO

In this study, the suppressive effect of sinomenine on the activation of SHh and the progression of breast cancer metastasis in vitro and in vivo was investigated. MDA-MB-231 breast cancer cells were treated with sinomenine and/or cyclopamine a proven SHh inhibitor. Sinomenine and cyclopamine both suppressed cell proliferation and migration, but sinomenine had a stronger suppressive effect in MDA-MB-231. In addition, sinomenine could suppress the activation of NF-κB and SHh signaling pathways, but cyclopamine could not suppress the activation of NF-κB. Subsequently, a mouse breast cancer-lung metastasis model was established. Our data on tissue examination and gene detection showed that SHh signaling was markedly activated in the metastatic model mice. The progression of lung metastasis was suppressed when mice were fed sinomenine and/or cyclopamine, while sinomenine had a stronger suppressive effect than cyclopamine in the model mice. In conclusion, sinomenine has a better effect than cyclopamine on the inhibition of breast cancer metastasis to lung in vivo and vitro, and inhibits NF-κB activation and NF-κB-mediated activation of SHh signaling pathway.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Morfinanos/farmacologia , Metástase Neoplásica/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , NF-kappa B/metabolismo , Metástase Neoplásica/patologia , Alcaloides de Veratrum/farmacologia
12.
Cell Tissue Res ; 370(3): 365-377, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28803422

RESUMO

Vessel disease is a kind of severe complication in diabetic patients. However, few pharmacologic agents can directly recover diabetic vascular function. Salidroside (SAL), a major ingredient from Rhodiola rosea, has been found to have an obvious hypoglycemic effect and a beneficial protection on vascular function in diabetes. However, whether SAL is a suitable treatment for diabetes has not so far been evaluated and the underlying mechanisms remain unknown. The present work aims to (1) investigate the potential effects of SAL on cerebrovascular relaxation in streptozotocin-induced diabetic rats or when exposed to acute hyperglycemia condition and (2) examine whether function of the BKCa channel is involved in SAL treatment for diabetic vascular relaxation. Our results indicate that chronic administration of 100 mg/kg/day SAL not only improves cerebrovascular relaxation but also increases BKCa ß1-subunit expressions at both protein and mRNA levels and enhances BKCa whole-cell and single-channel activities in cerebral VSMCs of diabetic rats. Correspondingly, acute application of 100 µM SAL induces cerebrovascular relaxation by activation of the BKCa channel. Furthermore, SAL activated the BKCa channel mainly through acting on the ß1-subunit in HEK293 cells transfected with hSloα+ß1 constructs. We concluded that SAL improved vasodilation in diabetic rats through restoring the function of the BKCa-ß1 subunit in cerebrovascular smooth muscle cells, which may be the underlying mechanism responsible for the vascular protection of SAL in diabetes.


Assuntos
Glucosídeos/farmacologia , Hipoglicemiantes/farmacologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Fenóis/farmacologia , Vasodilatação/efeitos dos fármacos , Animais , Linhagem Celular , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Células HEK293 , Humanos , Masculino , Miócitos de Músculo Liso/metabolismo , Ratos , Ratos Wistar , Estreptozocina
13.
Toxicol Mech Methods ; 27(5): 327-334, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28399782

RESUMO

Chrysophanol (CH), extracted from plants of Rheum genus, possesses various pharmacological effects including anti-inflammatory activity. The purpose of the present study was to evaluate the protective effects and the underlying mechanisms of CH on ovalbumin (OVA)-induced asthma in mice. Fifty mice were randomly assigned to five experimental groups: control group, model group, dexamethasone (2 mg/kg) group and CH (5 and 10 mg/kg) groups. The number of eosinophil cells and the production of interleukin-6 (IL-6), IL-1ß, IL-17 A and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) were measured. In addition, pulmonary histopathology, airway resistance (Raw), T-helper17 (Th17) cells frequency and RORγt expression were evaluated. Our study demonstrated that CH effectively decreased eosinophil count and inflammatory cytokines production in BALF. In addition, treatment with CH significantly inhibited the Raw, Th17 percentage and RORγt expression in OVA-induced animals compared with those in model group. Histological studies also demonstrated that CH significantly suppressed OVA-induced eosinophilia in lung tissue compared with model group. Our findings supported that CH can prevent allergic asthma in the mouse model.


Assuntos
Antraquinonas/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Ovalbumina/imunologia , Células Th17/efeitos dos fármacos , Resistência das Vias Respiratórias/efeitos dos fármacos , Resistência das Vias Respiratórias/imunologia , Animais , Antraquinonas/administração & dosagem , Antraquinonas/isolamento & purificação , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Asma/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Citometria de Fluxo , Camundongos Endogâmicos BALB C , Rheum/química , Células Th17/imunologia
14.
Cancer Med ; 6(4): 788-797, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28247570

RESUMO

c-Myc overexpression has been implicated in several malignancies including gastric cancer. Here, we report that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer via c-Myc activation both in vivo and in vitro. c-Myc mRNA and protein levels were assessed in ten primary and five local recurrent gastric cancer samples by quantitative real-time polymerase chain reaction and western blotting analysis. The gastric cancer cell line MGC803 was exposed to bile salts (100 µmol/L glycochenodeoxycholic acid and deoxycholic acid) in an acid medium (pH 5.5) for 10 min daily for 60 weeks to develop an MGC803-resistant cell line. Control MGC803 cells were grown without acids or bile salts for 60 weeks as a control. Cell morphology, proliferation, colony formation and apoptosis of MGC803-resistant cells were analyzed after 60 weeks. To determine the involvement of c-Myc in tumor progression and telomere aging in MGC803-resistant cells, we generated xenografts in nude mice and measured xenograft volume and in vivo telomerase activity. The c-Myc and hTERT protein and mRNA levels were significantly higher in local recurrent gastric cancer samples than in primary gastric cancer samples. MGC803-resistant cells showed a marked phenotypic change under normal growth conditions with more clusters and acini, and exhibited increased cell viability and colony formation and decreased apoptosis in vitro. These phenotypic changes were found to be dependent on c-Myc activation using the c-Myc inhibitor 10058-F4. MGC803-resistant cells also showed a c-Myc-dependent increase in xenograft growth and telomerase activity in vivo. In conclusion, these observations support the hypothesis that acidified bile acids enhance tumor progression and telomerase activity in gastric cancer and that these effects are dependent on c-Myc activity. These findings suggest that acidified bile acids play an important role in the malignant progression of local recurrent gastric cancer.


Assuntos
Ácidos e Sais Biliares/farmacologia , Recidiva Local de Neoplasia/genética , Proteínas Proto-Oncogênicas c-myc/genética , Neoplasias Gástricas/genética , Telomerase/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Humanos , Camundongos , Camundongos Nus , Recidiva Local de Neoplasia/metabolismo , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias Gástricas/metabolismo , Telomerase/metabolismo
15.
Aging (Albany NY) ; 9(2): 547-555, 2017 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-28228606

RESUMO

Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.


Assuntos
Neoplasias da Mama/genética , Metalotioneína/genética , Adulto , Alelos , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas
16.
Oncotarget ; 7(52): 86573-86583, 2016 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-27888808

RESUMO

The prognostic nutritional index (PNI) has been reported to correlate with the prognosis in patients with various malignancies. We performed a meta-analysis to determine the predictive potential of PNI in digestive system cancers. Twenty-three studies with a total of 7,384 patients suffering from digestive system carcinomas were involved in this meta-analysis. A lower PNI was significantly associated with the shorter overall survival (OS) [Hazard Ratio (HR) 1.83, 95% Confidence Interval (CI) 1.62-2.07], the poorer disease-free survival (DFS) (HR 1.85, 95% CI 1.19-2.89), and the higher rate of post-operative complications (HR 2.31, 95% CI 1.63-3.28). In conclusion, PNI was allowed to function as an efficient indicator for the prognosis of patients with digestive system carcinomas.


Assuntos
Neoplasias do Sistema Digestório/mortalidade , Avaliação Nutricional , Neoplasias do Sistema Digestório/cirurgia , Intervalo Livre de Doença , Humanos , Complicações Pós-Operatórias/etiologia , Prognóstico
17.
Oncotarget ; 7(47): 77175-77182, 2016 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-27738320

RESUMO

Genetic variations in transcription factor 7-like 2 (TCF7L2) are associated with cancer risk. This study was conducted to establish the relationship between TCF7L2 polymorphisms (rs1225404, rs7003146, and rs7903146) and clinical features and risk of breast cancer in Northwest Chinese Han women. In this study, three polymorphisms of TCF7L2 (rs1225404, rs7003146, and rs7903146) were genotyped in 458 patients with breast cancer and 500 healthy controls using the Sequenom MassARRAY-iPLEX system. We evaluated the associations between the polymorphisms and breast cancer using odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). The C allele of rs1225404 was associated with increased breast cancer risk (OR = 1.58, P = 0.0004, PC= 0.0012), whereas the G allele of rs7003146 was associated with decreased breast cancer risk (OR = 0.71, P = 0.01, PC= 0.03). Furthermore, the rs1225404 polymorphism positively correlated with negative progesterone receptor status. A positive correlation with positive estrogen receptor (ER) status was observed for the rs7003146 polymorphism. Our results suggest that TCF7L2 polymorphisms rs1225404 and rs7003146, but not rs7903146, may affect breast cancer risk in Northwest Chinese women. Additionally, the tag polymorphisms in TCF7L2 are associated with the clinical features of breast cancer, which may provide us novel insight into the pathogenesis of breast cancer.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Estudos de Associação Genética/métodos , Polimorfismo de Nucleotídeo Único , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Neoplasias da Mama/etnologia , Neoplasias da Mama/metabolismo , China/etnologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
18.
Oncotarget ; 7(36): 58174-58180, 2016 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-27533457

RESUMO

Mammalian target of rapamycin (mTOR) gene polymorphisms exert the major effects on the regulation of transcriptional activity and miRNA binding or splicing, which may be associated with cancer risk by affecting mTOR gene expression. However, inconsistent results have been previously reported. The present study evaluated the correlation between mTOR rs2536/rs2295080 polymorphisms and breast cancer risk. This case-control study was performed with 560 breast cancer patients and 583 healthy controls from the northwest of China. mTOR polymorphisms (rs2536 and rs2295080) were genotyped by Sequenom MassARRAY. We assessed the associations with odds ratios (ORs) and 95% confidence intervals (95% CIs). The association between mTOR rs2536 polymorphism and breast cancer risk was undetectable in our study (P > 0.05). In parallel, the significant effects were observed between mTOR rs2295080 polymorphism and breast cancer risk in the allele, codominant, and recessive models (P < 0.05). We detected no significant correlations between rs2536 polymorphism and the clinical parameters of breast cancer patients, while rs2295080 polymorphism was associated with lymph node (LN) metastasis. The Crs2536Grs2295080 haplotype was correlated with a significantly decreased risk of breast cancer (P < 0.05). In sum, the findings suggested that mTOR rs2295080 had a protective role on breast cancer susceptibility among Chinese population, while rs2536 polymorphism had no association with breast cancer risk.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Serina-Treonina Quinases TOR/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Mama/patologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Técnicas de Genotipagem , Haplótipos/genética , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único
19.
Drug Des Devel Ther ; 10: 2359-67, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27524883

RESUMO

BACKGROUND: In recent years, studies have demonstrated that polymorphisms in the promoters of Fas and FasL are significantly associated with breast cancer risk. However, the results of these studies were inconsistent. This case-control study was performed to explore the associations between Fas rs1800682 and FasL rs763110 polymorphisms and breast cancer. MATERIALS AND METHODS: A hospital-based case-control study of 560 Han Chinese females with breast cancer (583 controls) was conducted. The MassARRAY system was used to search for a possible association between the disease risk and the two single nucleotide polymorphisms, Fas rs1800682 and FasL rs763110. Statistical analyses were performed using SNPStats software to conduct Pearson's chi-square tests in five different genetic models. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after adjustment to age and body mass index. PHASE v2.1 software was used to reconstruct all common haplotypes. RESULTS: A statistically significant association was found between Fas rs1800682 and increased breast cancer risk (AG vs AA: OR =1.37, 95% CI =1.06-1.78; AA+AG vs GG: OR =1.32, 95% CI =1.04-1.66), and also it was found that the FasL rs763110 polymorphism may decrease the risk. Stratified analyses demonstrated that the rs763110 polymorphism was associated with lower breast cancer risk among postmenopausal females (heterozygote model: OR =0.69, 95% CI =0.49-0.97; dominant model: OR =0.70, 95% CI =0.51-0.96). The T allele of rs763110 was also associated with a decreased risk of lymph node metastasis (allele model: OR =0.75, 95% CI =0.57-0.97) and an increased risk of the breast cancer being human epidermal growth factor receptor 2 positive (allele model: OR =1.37, 95% CI =1.03-1.18). Moreover, haplotype analysis showed that Ars1800682Trs763110 was associated to a statistically significant degree with lower risk of breast cancer (OR =0.70, 95% CI =0.53-0.91). CONCLUSION: These data suggest that the presence of Fas rs1800683 is an important risk factor for breast cancer, whereas FasL rs763110 may exert a protective effect against the onset of breast cancer.


Assuntos
Neoplasias da Mama/genética , Proteína Ligante Fas/química , Proteína Ligante Fas/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Neoplasias da Mama/química , Estudos de Casos e Controles , Feminino , Heterozigoto , Humanos , Fatores de Risco
20.
Oncotarget ; 7(39): 62966-62975, 2016 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-27542234

RESUMO

Metastasis-associated in colon cancer-1 (MACC1) has been reported to be overexpressed in diverse human malignancies, and the increasing amount of evidences suggest that its overexpression is associated with the development and progression of many human tumors. However, the prognostic and clinicopathological value of MACC1 in colorectal cancer remains inconclusive. Therefore, we conducted this meta-analysis to investigate the effect of MACC1 overexpression on clinicopathological features and survival outcomes in colorectal cancer. PubMed, CNKI, and Wanfang databases were searched for relevant articles published update to December 2015. Correlation of MACC1 expression level with overall survival (OS), disease-free survival (DFS), and clinicopathological features were analyzed. In this meta-analysis, fifteen studies with a total of 2,161 colorectal cancer patients were included. Our results showed that MACC1 overexpression was significantly associated with poorer OS and DFS. Moreover, MACC1 overexpression was significantly associated with gender, localization, TNM stage, T stage, and N stage. Together, our meta-analysis showed that MACC1 overexpression was significantly associated with poor survival rates, regional invasion and lymph-node metastasis. MACC1 expression level can serve as a novel prognostic factor in colorectal cancer patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/metabolismo , Progressão da Doença , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Invasividade Neoplásica , Metástase Neoplásica , Prognóstico , Fatores de Transcrição/metabolismo , Resultado do Tratamento
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