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1.
Medicine (Baltimore) ; 99(2): e18514, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914023

RESUMO

BACKGROUND: This study will assess the effects of the project-based learning (PBL) for participants undergoing clinical oncology teaching (COT). METHODS: A systematic and comprehensive literature records will be identified from the electronic databases of PUBMED, EMBASE, Cochrane Library, Web of Science, Springer, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All electronic databases will be searched from their inceptions up to the present. Any relevant randomized controlled trials on the effects of PBL in participants receiving COT will be considered for inclusion. Study quality will be assessed using the Cochrane risk of bias tool. RevMan 5.3 software will be utilized for statistical analysis. RESULTS: This study will assess the effects of PBL in participants receiving COT through assessing the primary outcomes of psychological disorders, student satisfaction, and student feedback, and secondary outcomes of examination scores, excellence rates, course examination pass rates, and clinical knowledge or skills. CONCLUSION: The findings of this study will summarize the latest evidence on the effects of PBL in participants receiving in COT. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019150433.


Assuntos
Educação de Graduação em Medicina/métodos , Oncologia/educação , Estudantes/psicologia , China/epidemiologia , Bases de Dados Factuais , Humanos , Satisfação Pessoal , Pesquisa Qualitativa , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Estudantes/estatística & dados numéricos , Ensino/normas
2.
Cancer Chemother Pharmacol ; 84(2): 427-439, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31087138

RESUMO

OBJECTIVE: Although DNA-mismatch-repair-deficient (dMMR) status and aberrant expression of miRNAs are both critically implicated in the pathogenesis of resistance to 5-fluorouracil (5-FU) in colorectal cancer (CRC), whether these two factors regulate tumor response to 5-FU in a coordinated manner remains unknown. This study is designed to elucidate whether changes in miR-552 expression levels correlate to 5-FU-based chemoresistance in CRC, and to further identify the putative targets of miR-552 using multiple approaches. METHODS: miR-552 expression was assessed in 5-FU-resistant CRC tissues and cells using real-time PCR. Effects of miR-552 dysregulation on 5-FU resistance in CRC cells were determined by measuring cell viability, apoptosis and in vivo oncogenic capacity. Finally, we studied the posttranscriptional regulation of SMAD2 by miR-552 using multiple approaches including luciferase reporter assay, site-directed mutagenesis and transient/stable transfection, at molecular and functional levels. RESULTS: Expression of miR-552 was significantly downregulated in 5-FU-resistant CRC tissues and cells, and this downregulation, regulated by dMMR, was associated with poor postchemotherapy prognosis. Functionally, forced expression of miR-552 exhibited a proapoptotic effect and attenuated 5-FU resistance, whereas inhibition of miR-552 expression potentiated 5-FU resistance in CRC cells. Mechanically, miR-552 directly targeted the 3'-UTR of SMAD2, and stable ablation of SMAD2 neutralized the promoting effects of miR-552 deficiency-induced 5-FU resistance. CONCLUSIONS: Overall, our findings have revealed a critical role of miR-552/SMAD2 cascade in modulating cellular response to 5-FU chemotherapy. miR-552 may act as an efficient mechanistic link synchronizing dMMR and 5-FU resistance in CRC.

3.
J Proteomics ; 192: 366-373, 2019 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-30287406

RESUMO

The domestic silkworm Bombyx mori was domesticated from wild silkworm B. mandarina about 5000 years ago. Long-term domestication and breeding selection have led to the weight of domestic silkworm cocoon being ten times greater than that of wild silkworm cocoon. However, we found that wild silkworm cocoon has significantly much more abundance of sericin proteins than domestic silkworm cocoon. Strikingly, we found that many protease inhibitors have been significantly down-regulated in domestic silkworm cocoon compared with its wild progenitor by using isobaric tag for relative and absolute quantitation (iTraq) approach. Both real-time qPCR experiment and transcriptome data in silk gland also verified these results. In addition, our data indicated that protease inhibitor activity of wild silkworm cocoon was stronger than that of domestic silkworm cocoon, implying that relatively up-regulated protease inhibitors in wild silkworm cocoon may play protection roles against microorganisms. Thus, these protease inhibitors up-regulated in wild silkworm cocoon may have potential values in sericulture and medical practice. SIGNIFICANCE: This study revealed that there is a big difference in abundance of sericin proteins in cocoon between domestic and wild silkworms. Strikingly, many protease inhibitors have been significantly down-regulated in domestic silkworm cocoon compared with its wild progenitor. This may be due to different environments where the two silkworms live. In addition, the results also implied that relatively up-regulated protease inhibitors in wild silkworm cocoon may play protection roles against microorganisms. Thus, these protease inhibitors may have potential values in sericulture and medical practice.


Assuntos
Bombyx/metabolismo , Inibidores de Proteases/metabolismo , Proteoma/metabolismo , Sericinas/metabolismo , Animais , Especificidade da Espécie
4.
Mol Ther Nucleic Acids ; 13: 399-406, 2018 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-30368216

RESUMO

Motor neuron and pancreas homeobox 1 (MNX1) is a key developmental gene. Previous studies found that it was upregulated in several tumors, but its role in breast cancer (BC) remains unclear. In order to have a better understanding of this gene in BC, we examined the expression of MNX1 in BC tissues and normal breast tissues by qRT-PCR and by analyzing data from The Cancer Genome Atlas (TCGA) database. We also assessed the association of MNX1 expression with BC clinicopathological features and investigated the impact of MNX1 on BC survival. Potential molecular function of MNX1 was predicted through protein-protein interactions and functional enrichment. The results showed that the expression of MNX1 was significantly increased in BC tissues, especially in the HER2-positive subtype, and MNX1 expression was associated with several clinical characteristics, including menopause status, receptor status, subtypes, tumor size, lymph node metastasis, and race. In addition, patients with higher MNX1 expression had poorer survival. Enrichment analysis suggested that MNX1 is probably involved in biological processes and pathways related to nuclear division, cell cycle, and p53 signaling. In conclusion, our study suggests that MNX1 may act as a tumor promoter in BC. We hope these findings will draw more attention to MNX1 in future cancer studies.

5.
Aging (Albany NY) ; 10(6): 1402-1414, 2018 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-29909406

RESUMO

The role of rs4919510 polymorphism in microRNA-608 (miR-608) and cancer susceptibility and prognosis remain controversial and debatable. We conducted a meta-analysis of twenty-four eligible publications on the association of rs4919510 polymorphism with cancer risk and/or prognosis. Odds ratios, hazard ratios, and 95% confidence interval were used to investigate the association between this polymorphism and susceptibility, overall survival, and recurrence-free survival of cancer. Overall, eighteen case-control studies and nine cohort studies evaluated the susceptibility and prognostic value of rs4919510 polymorphism in cancer, respectively. Pooled analysis showed that rs4919510 polymorphism was not associated with cancer risk in all five genetic models. When stratifying by different cancer sites, rs4919510 polymorphism was detected to have a significant association with a decreased risk of colorectal cancer in homozygous model (P = 0.006) and recessive model (P = 0.001), subgroup analysis also emerged a weakened correlation between rs4919510 polymorphism and an increased risk of papillary thyroid cancer in heterozygote model (P = 0.04). Furthermore, the prognosis of rs4919510 variant in cancer patients showed that rs4919510 GG genotype was significant association with poor recurrence-free survival in homozygous models (P = 0.04). The meta-analysis suggested that the microRNA-608 rs4919510 polymorphism maybe associate with a significantly decreased risk for colorectal cancer. Further investigations on larger populations are required to evaluate and confirm this relationship.


Assuntos
Predisposição Genética para Doença , MicroRNAs/genética , Neoplasias/genética , Neoplasias/mortalidade , Polimorfismo Genético , Humanos , Neoplasias/patologia , Razão de Chances
6.
Oncotarget ; 8(53): 91654-91661, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29207674

RESUMO

Caveolin-1(CAV-1) was demonstrated to be a tumor suppressor gene and be implicated in the development of breast cancer (BC). Numerous potentially functional polymorphisms in CAV-1 have been identified, but their effects on BC were not clear. This case-control study aims to evaluate the relationship between CAV-1 polymorphisms and BC risk. 560 BC patients and 583 healthy controls were enrolled in the present study, all from Chinese Han population. We detected 3 single nucleotide polymorphisms (rs3807987, rs1997623, and rs7804372) in CAV-1 using the Sequenom MassARRAY method. The association between CAV-1genotypes and BC risk was assessed in six genetic models by calculating the odds ratio (OR) and 95% confidence intervals (95% CIs) with χ2-test. The CAV-1 rs3807987 polymorphism was observed to increase the risk of BC And the A allele of rs3807987 relates to a larger tumor size (≥2cm) and lower incidence of PR-positive BC while the AA genotype of rs7804372 associates with a higher ER and Her-2 positive rate among BC patients. In addition, Ars1997623Grs3807987Trs7804372 haplotype was linked to a decreased risk of BC (OR =0.64, 95%CI=0.44-0.93), whereas Crs1997623Ars3807987Trs7804372 haplotype was related to an increased BC risk (OR =1.74, 95%CI=1.04-2.92). Our study suggests that CAV-1 rs3807987 can increase the BC risk among Chinese Han women. And the rs3807987 and rs7804372 in CAV-1 may serve as predictors for prognosis of BC.

7.
Oncotarget ; 8(46): 81350-81360, 2017 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-29113394

RESUMO

IL-18 polymorphisms influence the transcriptional activity of the IL-18 gene and associated with various diseases. However, their relationships with hepatitis B virus-related liver diseases had not reached a consensus. So we conducted this case-control study with a view to clarifying the association. We included four groups: healthy controls, chronic hepatitis B virus (CHB) carriers, liver cirrhosis (LC) and hepatocellular carcinoma (HCC) groups with each group of 250 persons. Odd ratios (ORs) and 95% confidence intervals (95%CIs) with or without adjustment were calculated. Haplotype analysis was also performed. The results showed people carrying rs187238 CG genotype had a lower risk of LC (CG vs. CC: OR = 0.59, 95%CI = 0.38-0.91, P = 0.02), while GG genotype carriers had a higher risk of HCC (GG vs. CC+CG: OR = 4.73, 95%CI = 1.01-22.1, P = 0.03) than those with CC and CG genotypes in healthy group. Rs187238 GG genotype increased the risk from CHB to LC status (GG vs. CC: OR = 4.81, 95%CI = 1.03-22.6; GG vs. CC+CG: OR = 4.73, 95%CI = 1.01-22.1), meanwhile the trend also existed by controlling confounding factors (GG vs. CC: OR = 6.25, 95%CI = 1.09-35.8; GG vs. CC+CG: OR = 5.91, 95%CI = 1.04-33.7). Haplotype Crs187238Trs1946518 moderately decreased the risk of CHB carriers developing into HCC (OR = 0.69, 95%CI = 0.50-0.96, P = 0.03) after adjustment. In conclusion, IL-18 rs187238 GG genotype may increase the risk of HCC in healthy population and the risk of LC in CHB carriers.

8.
Adv Clin Exp Med ; 26(3): 421-426, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28791816

RESUMO

BACKGROUND: Breast cancer is the most common cancer in Chinese women. Inflammation contributes to tumor progression and can be induced by excessive production of pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α). However, how their levels relate to the expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) by the tumor has not been investigated. OBJECTIVES: The aim of the study is to more fully understand the significance of serum IL-6, IL-8 and TNF-α in breast cancers with different ER, PR and HER2 status. MATERIAL AND METHODS: Preoperative serum samples were collected from 110 patients diagnosed with ductal carcinoma and 30 healthy control subjects. IL-6, IL-8 and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA). Associations of cytokine levels with clinical tumor stage were evaluated, and correlations of serum cytokine levels with ER, PR and HER2 expression were determined using the Pearson correlation coefficient. RESULTS: Serum levels of IL-6 and IL-8 were significantly higher in the subjects with ductal carcinoma than in the controls, and strongly correlated with clinical tumor stage, lymph node metastasis, and ER and HER2 antigen expression (p < 0.05). TNF-α levels in stage III carcinoma patients were significantly higher than in the controls (p < 0.01) and were associated with lymph node metastasis (p < 0.01). A strong positive correlation was found between IL-8 and TNF-α levels in the cancer patients (p < 0.0001). CONCLUSIONS: The study showed that IL-6, IL-8 and TNF-α levels correlated with clinical disease stage and lymph node metastasis as well as with ER and HER2 antigen expression. Specifically, IL-6 and IL-8 seem to have significant potential as prognostic cancer biomarkers. Analyzing serum cytokine levels might help identify patients with a poor prognosis who may benefit from more aggressive disease management.


Assuntos
Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Interleucina-6/sangue , Interleucina-8/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/metabolismo , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo
9.
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
10.
J Mol Endocrinol ; 59(3): 191-204, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28515053

RESUMO

Hyperglycemia and hypertension are considered to be the two leading risk factors for vascular disease in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and hypertension at the same time in diabetes. The objectives of this study are to investigate whether berberine treatment could directly reduce blood pressure and identify the molecular mechanism underlying the vascular protection of berberine in diabetic rats. Berberine was intragastrically administered with different dosages of 50, 100 and 200 mg/kg/day to diabetic rats for 8 weeks since the injection of streptozotocin. The endothelium-dependent/-independent relaxation in middle cerebral arteries was investigated. The activity of large-conductance Ca2+-activated K+ channel (BKCa) was investigated by recording whole-cell currents, analyzing single-channel activities and assessing the expressions of α- and ß1-subunit at protein or mRNA levels. Results of the study suggest that chronic administration of 100 mg/kg/day berberine not only lowered blood glucose but also reduced blood pressure and improved vasodilation in diabetic rats. Furthermore, berberine markedly increased the function and expression of BKCa ß1-subunit in cerebral vascular smooth muscle cells (VSMCs) isolated from diabetic rats or when exposed to hyperglycemia condition. The present study provided initial evidences that berberine reduced blood pressure and improved vasodilation in diabetic rats by activation of BKCa channel in VSMCs, which suggested that berberine might provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetes. Furthermore, our work indicated that activation of BKCa channel might be the underlying mechanism responsible for the vascular protection of berberine in diabetes.


Assuntos
Berberina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Animais , Berberina/administração & dosagem , Pressão Sanguínea/genética , Diabetes Mellitus Experimental , Relação Dose-Resposta a Droga , Expressão Gênica , Hiperglicemia/metabolismo , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Masculino , Artéria Cerebral Média/efeitos dos fármacos , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Ratos , Fatores de Tempo , Vasodilatação/genética
11.
BMC Pharmacol Toxicol ; 18(1): 30, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28441970

RESUMO

BACKGROUND: Vascular disease is a common and often severe complication in diabetes mellitus. Hyperglycemia and hypertension are considered to be two of the leading risk factors for vascular complications in diabetic patients. However, few pharmacologic agents could provide a combinational therapy for controlling hyperglycemia and blood pressure in diabetic patients at the same time. Salidroside (SAL) is the major active ingredient derived from Rhodiola. Recently, it has been reported that SAL have an obvious hypoglycemic effect in diabetes and show a beneficial activity in diabetic vascular dysfunction. However, it remains unknown whether or not SAL treatment could directly reduce blood pressure in diabetes. Furthermore, it is not clear what is the molecular mechanism underlying the vascular protection of SAL treatment in diabetes. METHODS: Male diabetic Goto-Kakizaki (GK) and non-diabetic control Wistar-Kyoto (WKY) rats were administrated with different dosages of SAL (50, 100 and 200 mg/kg/day) for 4 weeks. Contractile responsiveness of cerebral artery to KCl or 5-HT was investigated by Pressure Myograph System. The activity of CaL channel was investigated by recording whole-cell currents, assessing the expressions of CaL channel α1C-subunit and its downstream kinase, MLCK, at protein or mRNA levels. RESULTS: We showed that administration of 100 mg/kg/day SAL for 4 weeks not only lowered blood glucose, but also reduced blood pressure and alleviated cerebrovascular contractile activity in diabetic GK rats, which suggested that SAL treatment may provide a combinational therapy for lowering blood glucose and reducing blood pressure in diabetes at the same time. Furthermore, SAL treatment markedly inhibited the function and expression of CaL channel in cerebral VSMCs isolated from diabetic GK rats or when exposed to hyperglycemia condition, which may be the underlying mechanism responsible for the vascular protection of SAL in diabetes. CONCLUSIONS: The present study provided evidences that SAL contributes to reducing blood pressure and alleviating cerebrovascular contractile activity in diabetic GK rats by inhibition of CaL channel in smooth muscle cells, which may provide a novel approach to treat vascular complications in diabetic patients.


Assuntos
Canais de Cálcio Tipo L/efeitos dos fármacos , Artérias Cerebrais/efeitos dos fármacos , Cardiomiopatias Diabéticas/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Músculo Liso Vascular/efeitos dos fármacos , Fenóis/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Canais de Cálcio Tipo L/genética , Células Cultivadas , Diabetes Mellitus Experimental , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , RNA Mensageiro/metabolismo , Ratos Endogâmicos WKY , Vasodilatação/efeitos dos fármacos
12.
J Cancer ; 8(4): 691-703, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28367249

RESUMO

The UGT1A1*28 polymorphism was suggested to be significantly connected with irinotecan-induced toxicity and response to chemotherapy. However, the results of previous studies are controversial. Hence we carried out a meta-analysis to investigate the effect of UGT1A1*28 polymorphism on severe diarrhea, neutropenia, and response of patients who had undergone irinotecan-based chemotherapy. The PubMed, Web of Science, Wanfang, and CNKI databases were searched for clinical trials assessing the association of UGT1A1*28 polymorphism with severe diarrhea, neutropenia, and response to irinotecan-based chemotherapy. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship under a fixed- or random-effects model. Fifty-eight studies including 6087 patients with cancer were included. Our results showed that patients carrying the TA6/7 and TA7/7 genotypes had a greater prevalence of diarrhea and neutropenia than those with the TA6/6 genotype (TA6/7+TA7/7 vs. TA6/6: diarrhea, OR = 2.18, 95%CI = 1.68-2.83; neutropenia, OR = 2.15, 95%CI = 1.71-2.70), particularly patients with metastatic colorectal cancer. Stratified analysis showed that Asians with the TA6/7 and TA7/7 genotypes were more likely to have diarrhea and neutropenia, and Caucasians with the TA6/7 and TA7/7 genotypes were more likely to have neutropenia than other groups. However, patients with the TA6/7+TA7/7 genotypes showed a higher response than patients with TA6/6 genotype (OR = 1.20, 95%CI = 1.07-1.34), particularly Caucasians (OR = 1.23, 95%CI = 1.06-1.42) and patients with metastatic colorectal cancer (OR = 1.24, 95%CI = 1.05-1.48). Our data showed that the UGT1A1*28 polymorphism had a significant relationship with toxicity and response to irinotecan-based chemotherapy. This polymorphism may be useful as a monitoring index for cancer patients receiving irinotecan-based chemotherapy.

13.
Oncotarget ; 8(22): 36885-36897, 2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28415570

RESUMO

The association of polymorphisms in programmed cell death 1 (PDCD1) gene with systemic lupus erythematosus (SLE) risk is inconsistent across different studies. This meta-analysis is aimed to provide reliable evidence to the association of five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were included in this meta-analysis. PD1.3 polymorphism was significantly associated with SLE in the overall population (A vs. G: OR = 1.35, 95% CI = 1.12-1.63; GA vs.GG: OR = 1.41, 95% CI = 1.12-1.76; AA+GA vs. GG: OR = 1.41, 95% CI = 1.13-1.7). In the stratified analyses based on ethnicity, we found a significant association in Caucasians and in Mexicans. In the subgroup analyses by gender, a significant association was found between PD1.3 polymorphism and SLE risk in males. The results also suggested an association between the PD1.6 polymorphism and decreased SLE risk (A vs. G: OR = 0.84, 95% CI = 0.73-0.96). Our meta-analysis revealed that PD1.3 polymorphism may increase the susceptibility to SLE, particularly in Caucasians, while PD1.6 may be a protective factor to SLE.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Receptor de Morte Celular Programada 1/genética , Alelos , Genótipo , Humanos , Razão de Chances , Viés de Publicação , Risco
14.
Aging (Albany NY) ; 9(2): 381-392, 2017 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-28148887

RESUMO

Previous studies have investigated the role of miR-146a rs2910164 and miR-196a-2 rs11614913 polymorphisms in hepatocellular carcinoma (HCC) susceptibility, but the results are contradictory and few specifically studied hepatitis virus-related HCC. Therefore, we conducted a meta-analysis to evaluate the association between these two polymorphisms and hepatitis virus-related HCC risk. We performed a systematical search in EMBASE, PubMed, Web of Science, CNKI and Wanfang databases as of 25th November, 2016. Finally, we assessed 14 studies involving 3852 cases and 5275 controls. Our results suggest that rs2910164 has a significant association with increased hepatitis virus-related HCC risk in allelic, homozygous, heterozygous, and dominant models (CG+GG vs. CC: OR=1.22, 95% CI=1.06-1.39, P=0.004), particularly in Chinese and HBV-related HCC subgroups. Conversely, rs11614913 was associated with lower hepatitis virus-related HCC risk in the overall analysis under allelic (T vs. C: OR=0.85, 95% CI=0.74-0.98, P=0.02), homozygous, dominant and recessive models. Subgroup analyses showed decreased risk in Chinese, HBV- and HCV-related HCC. In conclusion, miR-146a C>G (rs2910164) can increase HBV-related HCC risk while miR-196a-2 C>T (rs11614913) may decrease the risk of HBV- and HCV-related HCC, especially in the Chinese population. Further, large-scale studies including other races are required to confirm these findings.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite/complicações , Neoplasias Hepáticas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Carcinoma Hepatocelular/virologia , Predisposição Genética para Doença , Vírus de Hepatite , Humanos , Neoplasias Hepáticas/virologia , Fatores de Risco
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.
Oncol Res ; 25(1): 115-122, 2017 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-28081740

RESUMO

Tripartite motif-containing protein 37 (TRIM37), a new member of the RING-B-box-coiled-coil (RBCC) subfamily of zinc finger proteins, was found to be involved in the development and progression of several cancers. However, the expression pattern and biological functions of TRIM37 in colorectal cancer (CRC) remain unknown. Therefore, in the present study, we examined the expression pattern of TRIM37 in CRC and investigated the function of TRIM37 in the progression of CRC. Our results showed that TRIM37 expression was upregulated in CRC cell lines. Knockdown of TRIM37 inhibited CRC cell proliferation and tumor growth in vivo. Furthermore, knockdown of TRIM37 inhibited the migration and invasion in CRC cells. Last, knockdown of TRIM37 inhibited the protein level expression of ß-catenin, cyclin D1, and c-Myc in CRC cells. In conclusion, these results demonstrate that TRIM37 may play an important role in the proliferation, invasion, and tumorigenesis of CRC cells. Thus, TRIM37 may be a potential therapeutic target for the treatment of CRC.


Assuntos
Transformação Celular Neoplásica/genética , Neoplasias Colorretais/genética , Proteínas Nucleares/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Via de Sinalização Wnt
17.
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
18.
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
19.
Cancer Lett ; 379(1): 12-23, 2016 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-27195913

RESUMO

Cisplatin and paclitaxel are considered to be the backbone of chemotherapy in lung adenocarcinoma. These agents show pleiotropic effects on cell death. However, the precise mechanisms remain unclear. The present study reported that phosphorylated caspase-8 at tyrosine 380 (p-Casp8) was characterized as a biomarker of chemoresistance to TP regimen (cisplatin and paclitaxel) in patients with resectable lung adenocarcinoma with significantly poorer 5-year disease-free survival (DFS) and overall survival (OS). Cisplatin killed lung adenocarcinoma cells regardless of c-Src-induced caspase-8 phosphorylation at tyrosine 380. Subsequently, we identified a novel mechanism by which paclitaxel induced necroptosis in lung adenocarcinoma cells that was dependent upon p-Casp8, receptor-interacting protein kinase 1 (RIPK1), and RIPK3. Moreover, dasatinib, a c-Src inhibitor, dephosphorylated caspase-8 to facilitate necroptosis, rather than apoptosis, in paclitaxel-treated p-Casp8-expressing lung adenocarcinoma cells. The data from our study revealed previously unrecognized roles of p-Casp8 as a positive effector in the initiation of necroptosis and as a negative effector in the repression of the interaction between RIPK1 and RIPK3. Moreover, these outcomes supported the need for further clinical studies with the goal of evaluating the efficacy of dasatinib plus paclitaxel in the treatment of lung adenocarcinoma.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Caspase 8/metabolismo , Dasatinibe/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas pp60(c-src)/antagonistas & inibidores , Células A549 , Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Caspase 8/genética , Cisplatino/farmacologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Necrose , Paclitaxel/uso terapêutico , Fosforilação , Gravidez , Proteínas Proto-Oncogênicas pp60(c-src)/genética , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Interferência de RNA , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo , Transfecção , Resultado do Tratamento , Tirosina , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Medicine (Baltimore) ; 95(21): e3760, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27227944

RESUMO

Programmed death-1 (PD-1) is crucial in cancer and is well characterized as a negative T-cell regulator that functions by delivering inhibitory signals. We aimed to evaluate the relationship between PD-1 polymorphisms (rs10204525, rs2227982, and rs7421861) and breast cancer risk.We selected 560 breast cancer patients and 583 age-, sex-, and ethnicity-matched healthy controls from Northwest China. The PD-1 polymorphisms were genotyped by using Sequenom MassARRAY. Associations were estimated with odds ratios (ORs) and 95% confidence intervals (95% CIs).For the rs10204525 and rs7421861 polymorphisms, no differences in breast cancer risk were found in any of the genetic models. For the rs2227982 polymorphism, the variant genotypes were significantly associated with decreased breast cancer risk (CT vs CC: OR = 0.68, 95% CI = 0.52-0.91; CT + TT vs CC: OR = 0.69, 95% CI = 0.53-0.90). In analyses stratified by age, the decreased risk was observed among the younger subjects (OR = 0.68, 95% CI = 0.47-0.97). We found that the decreased risk observed for the variant genotypes of rs2227982 was associated with the Her-2 status (CT vs CC: OR = 0.55, 95% CI = 0.37-0.84; CT + TT vs CC: OR = 0.56, 95% CI = 0.38-0.82). The haplotype analysis showed that the Ars10204525 Trs2227982 Crs7421861 haplotype was associated with a significantly decreased risk of breast cancer (OR = 0.50, 95% CI = 0.34-0.75).Our findings support an association between the PD-1 rs2227982 polymorphism and decreased breast cancer risk, especially in Her-2 positive breast cancer patients in the Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Receptor de Morte Celular Programada 1/genética , Adulto , Fatores Etários , Alelos , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético , Receptor ErbB-2/genética , Risco
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