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1.
Dent Mater J ; 39(1): 141-147, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31694994

RESUMO

The key of the root canal therapy is to eliminate the micro-organism infection, fill the root canal tightly and reduce the stimulation to the periapical tissues. However, it is quite difficult to meet all the conditions due to the defect of the material. Here we develop a novel root canal sealer (MZOE), in which zinc oxide eugenol (ZOE) were fabricated with polyhexamethylene guanidine (PHMG), and the PHMG's concentration is 0.8, 1.0, 1.2 and 1.4%. Our investigation tested its physical properties, antibacterial effect to E. faecalis, C. albicans, E. coli, S. aureus and cytotoxicity to human periodontal ligament fibroblasts (HPDLFs). The physical properties of the MZOE conformed to the ISO 6876:2001, and its antibacterial effect was stronger than ZOE (p<0.05), the RGR of HPDLFs was tested between 1 to 24%, belonging to moderate cytotoxicity. It was suggested that MZOE had good physical properties, high antibacterial effect, and moderate cytotoxicity.


Assuntos
Materiais Restauradores do Canal Radicular , Cavidade Pulpar , Escherichia coli , Guanidina , Guanidinas , Humanos , Staphylococcus aureus , Cimento de Óxido de Zinco e Eugenol
2.
Bioorg Med Chem ; 28(2): 115236, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31843459

RESUMO

Bruton's tyrosine kinase (BTK) and Janus kinase 3 (JAK3) are very promising targets for hematological malignancies and autoimmune diseases. In recent years, a few compounds have been approved as a marketed medicine, and several are undergoing clinical trials. By recombining the dominant backbone of known active compounds, constructing a foused library, and screening a broad panel of kinases, we found a class of compounds with dual activities of anti-BTK and anti-JAK3. Some of the compounds have shown 10-folds more active in the enzyme and cell-based assays than a known active compound. Furthermore, liver microsome stability experiments show that these compounds have better stability than ibrutinib. These explorations offered new clues to discover benzoxaborole fragment and pyrimidine scaffold as more effective BTK and JAK3 dual inhibitors.

3.
Dent Mater J ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694998

RESUMO

This study was to prepare and screen a novel root canal sealing agent modified by polyhexamethylene biguanide (PHMB) that was in accordance with the ISO 6876:2001 standard and to study its physical and antimicrobial properties. The modified sealers were produced by mixing a certain amount of zinc oxide with eugenol containing different concentrations of PHMB (0.05, 0.1, 0.2, 0.4, 0.6 and 0.8%) at a ratio of 1:1 (w/v). The setting time, flow, film thickness, solubility and dimensional change after solidifying were assessed to screen out the modified sealing agents that the physical properties met the mentioned standards. The modified direct contact test (DCT) was used to evaluate the antimicrobial activity against Enterococcus faecalis. The results suggested that when the concentrations of PHMB were 0.05, 0.1 and 0.2%, the modified root canal sealers showed the best performance in physical and antimicrobial properties.

4.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(1): 25-30, 2019 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-30854814

RESUMO

OBJECTIVE: This study aims to establish an effective and stable periodontal ligament cell line stably expressing human telomerase reverse transcriptase (hTERT) gene by using the adenovirus method. METHODS: Polymerase chain reaction (PCR) was used to amplify the full length of hTERT gene to construct recombinant adenovirus plasmid pAd-pshuttle-cmv-hTERT. Packaged adenovirus particles were used for infection of human periodontal ligament cells. The expression levels of hTERT and osteogenic genes, such as alkaline phosphatase, Runt-related transcription factor 2, bone sialoprotein, osteocalcin, osteopontin, and collagen Ⅰ mRNA, were detected by quantitative real-time PCR (qRT-PCR). The ability of osteogenic differentiation was observed by alizarin red staining, and the cell proliferation was determined by CCK-8. RESULTS: Adenovirus particles containing the hTERT gene were successfully constructed and infected with periodontal ligament cells. The infected cells were similar to normal periodontal ligament cells. The qRT-PCR results showed that hTERT and osteogenesis-associated genes were highly expressed in the periodontal ligament cell lines constructed by adenoviruses. Alizarin red staining showed that the periodontal ligament cell line had strong osteogenic differentiation capability. CCK-8 showed that the periodontal ligament cell line had strong proliferation capability. CONCLUSIONS: The human periodontal ligament cell line with high efficiency and stable expression of hTERT was established by the adenovirus method, thereby providing an ideal cell line for studying the mechanism of periodontal regeneration.


Assuntos
Ligamento Periodontal , Telomerase , Adenoviridae , Fosfatase Alcalina , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Humanos , Osteogênese
5.
Hum Gene Ther Methods ; 30(2): 53-59, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30704312

RESUMO

The aims of this study were to generate periodontal ligament (PDL) cells that have adenovirus- or lentivirus-mediated overexpression of human telomerase reverse transcriptase (hTERT) and to compare the osteogenic and proliferative abilities of the two cell lines to establish an efficient and stable cell model that will be more suitable for studies of PDL regeneration. After construction of the recombinant adenovirus plasmid pAd-pshuttle-cmv-hTERT, human PDL cells were infected by packaged adenovirus and lentivirus particles to establish two PDL cell lines. The expression levels of hTERT and mRNA for alkaline phosphatase, osteopontin, osteocalcin, bone sialoprotein, core-binding factor (runt-related transcription factor 2), and type I collagen were assessed for each cell line. After culture in osteoinductive culture medium for 14 days, the PDL cells were stained with alizarin red to observe formation of mineralized nodules, and proliferation activity was measured with a CCK-8 kit. A quantitative polymerase chain reaction assay indicated that the two transduced cell lines expressed hTERT levels that were significantly higher than that seen for normal PDL cells. Expression of all osteogenic genes tested, with the exception of osteopontin, was higher for both the adenovirus- and lentivirus-transduced cells relative to normal PDL cells. The expression of bone sialoprotein, osteocalcin, and runt-related transcription factor 2 in adenovirus-transduced cells was significantly higher than that for lentivirus-transduced cells. Alizarin red staining showed that the adenovirus-transduced cell line produced more mineralized nodules than the lentivirus-transduced cell line, whereas a CCK-8 test showed that the adenovirus-transduced cell line had higher proliferation activity than lentivirus-transduced cells. In conclusion, a PDL cell line established by adenovirus transduction had superior osteogenic differentiation and proliferative activity compared to the cell line produced by lentivirus transduction. The results indicate that PDL cells having adenovirus-mediated expression of hTERT would be a more suitable model for studies of PDL regeneration.

6.
Cell Death Dis ; 9(2): 168, 2018 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-29416011

RESUMO

Emerging evidence indicates that lncRNAs play important roles in cancer tumourigenesis and could be used as potential diagnostic biomarkers or therapeutic targets. However, the clinical significance and molecular mechanism of lncRNAs in gastric cancer (GC) is still unclear. The aim of this study was to explore the expression and role of lncRNAs in GC. The relative expression level of lncRNAs in GC samples was examined by an lncRNA microarray analysis, northern blot analysis and qRT-PCR analysis. A Kaplan-Meier survival analysis and univariate and multivariate Cox proportional hazards models were performed to evaluate the clinical and prognostic significance of PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) in GC patients. The binding activity of PANDAR with the p53 protein was analysed by an RNA immunoprecipitation analysis and RNA pull-down analysis. The depletion of PANDAR was conducted using the CRISPR/Cas9 system for PANDAR. The biological functions of PANDAR in GC cells were determined both in vitro and in vivo. Upregulated PANDAR in GC patients was positively correlated with increased tumour size, advanced TNM classification and a poor survival rate in GC patients. The ROC curves identified that the PANDAR level was a marker for discriminating the early-stage tumour group from the healthy group, the metastasis group from the non-metastasis group and the chemoresistance group from the chemosensitive group in GC patients. As a target, the CDKN1A gene was successfully downregulated by PANDAR. PANDAR controlled the transcription of the CDKN1A gene by competitively binding with p53 protein. In combination with a p53 activator (nutlin3), the knockout of PANDAR by CRISPR/Cas9 technology synergistically inhibited GC tumour growth in vivo. Our results suggest that the PANDAR is a powerful diagnostic and therapeutic marker for patients with GC and, combined with other chemotherapeutics, may have distinct antitumour effects.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Transcrição Genética , Proteína Supressora de Tumor p53/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Piperazinas/farmacologia , Prognóstico , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , RNA Longo não Codificante/genética , Transcrição Genética/efeitos dos fármacos
7.
Oncotarget ; 8(43): 74299-74311, 2017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-29088786

RESUMO

Pancreatic ductal adenocarcinoma (PanCa) is an extremely lethal disease characterized by mutations of p53 in up to 70% of cases. Our previous studies have confirmed that hyperglycemia may be the first clinical manifestation for the early diagnosis of PanCa. In this article, we showed that targeted knockdown of TG2 or p53 in tumor cells led to decreased cell survival in response to glucose deprivation, while this phenomenon was abolished by combined inhibition of TG2 and p53. We observed that inhibition of TG2 or p53 sensitized glucose deprivation resistance through an intracellular reactive oxygen species (ROS) pathway and the induction of Bcl-2. Moreover, to understand whether pancreatic cancer cells with TG2 and p53 combined interference had possible effects on pancreatic ß cells, we performed studies comparing pancreatic cancer cells with TG2 and p53 combined interference and pancreatic ß cells. We discovered that the supernatant of pancreatic cancer cells withTG2 and p53 combined interference decreased cell survival in pancreatic ß cells. Following the creation of an orthotopic pancreatic cancer mouse model, we revealed glucose tolerance abnormalities in the pancreatic cancer mouse model with TG2 and p53 combined interference, indicating a possible mechanism for damage of ßcells in pancreatic cancer. Taken together, our findings establish roles for TG2 and p53 in response to glucose deprivation in pancreatic cancer cells. The relationship between TG2 and p53 suggests a possible mechanism for glucose tolerance abnormalities-associated pancreatic cancer and could have therapeutic potential for cancer treatment and diagnosis.

8.
Oncotarget ; 8(17): 29116-29124, 2017 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28418859

RESUMO

To establish a screening strategy for pancreatic cancer (PC) based on new-onset diabetic mellitus (NO-DM), serum metabolomics analysis and a search for the metabolic pathways associated with PC related DM were performed. Serum samples from patients with NO-DM (n = 30) and patients with pancreatic cancer and NO-DM were examined by liquid chromatography-mass spectrometry. Data were analyzed using principal components analysis (PCA) and orthogonal projection to latent structures (OPLS) of the most significant metabolites. The diagnostic model was constructed using logistic regression analysis. Metabolic pathways were analyzed using the web-based tool MetPA. PC patients with NO-DM were older and had a lower BMI and shorter duration of DM than those with NO-DM. The metabolomic profiles of patients with PC and NO-DM were significantly different from those of patients with NO-DM in the PCA and OPLS models. Sixty two differential metabolites were identified by the OPLS model. The logistic regression model using a panel of two metabolites including N_Succinyl_L_diaminopimelic_acid and PE (18:2) had high sensitivity (93.3%) and specificity (93.1%) for PC. The top three metabolic pathways associated with PC related DM were valine, leucine and isoleucine biosynthesis and degradation, primary bile acid biosynthesis, and sphingolipid metabolism. In conclusion, screening for PC based on NO-DM using serum metabolomics in combination with clinic characteristics and CA19-9 is a potential useful strategy. Several metabolic pathways differed between PC related DM and type 2 DM.


Assuntos
Adenocarcinoma/sangue , Carcinoma Ductal Pancreático/sangue , Diabetes Mellitus Tipo 2/sangue , Redes e Vias Metabólicas , Metabolômica/métodos , Neoplasias Pancreáticas/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Fatores Etários , Idoso , Biomarcadores Tumorais/sangue , Índice de Massa Corporal , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Cromatografia Líquida , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Diferencial , Detecção Precoce de Câncer/métodos , Estudos de Viabilidade , Feminino , Humanos , Isoleucina/metabolismo , Leucina/metabolismo , Metabolismo dos Lipídeos , Masculino , Espectrometria de Massas , Metaboloma , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Análise de Componente Principal , Sensibilidade e Especificidade , Testes Sorológicos/métodos , Valina/metabolismo
9.
Surg Radiol Anat ; 38(9): 1099-1104, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26861010

RESUMO

PURPOSE: Based on a case of supernumerary cusp on the bucca of left maxillary second molar diagnosed by cone beam computed tomography (CBCT), its genesis, diagnosis and antidiastole are to be analysed. The clinic implication of CBCT is correspondingly discussed. METHODS: The supernumerary cusp was diagnosed by oral general examination, intra-oral radiograph and CBCT. The features of supernumerary cusp, fused tooth, geminated tooth and concrescence tooth, especially differentiate points among them were discussed. RESULTS: The case of supernumerary cusp on the bucca of left maxillary second molar was diagnosed definitely by the combined application of oral general examination, periapical radiograph and CBCT. CONCLUSION: Supernumerary cusp on the bucca of left maxillary second molar is a rare phenomenon, which is difficult to be differentiated from other tooth deformities. CBCT can improve accuracy of diagnosis.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Anormalidades Dentárias/diagnóstico por imagem , Adulto , Humanos , Masculino , Radiografia Dentária
10.
Exp Ther Med ; 11(2): 535-539, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26893642

RESUMO

Ectodysplasin (EDA) gene mutation is associated with hypohidrotic ectodermal dysplasia (HED). The aim of this study was to investigate the effect of ectodysplasin, transcript variant 1 (EDA-A1) on the proliferation and cell cycle of ECV304 human umbilical vein endothelial cells (HUVECs). Recombinant eukaryotic expression vectors containing mutant (M) and wild-type (W) EDA-A1 coding sequences, pcDNA3.1 (-)-EDA-A1-M and pcDNA3.1 (-)-EDA-A1-W, respectively, were transfected into ECV304 cells. The EDA-A1 gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), and the protein was detected by western blotting. The EDA-A1 gene and protein were detected in ECV304 cells transfected with pcDNA3.1 (-)-EDA-A1-M and pcDNA3.1 (-)-EDA-A1-W, but not in ECV304 cells transfected with empty plasmid or cells that had not undergone transfection. Compared with the control group, the EDA-A1 gene mutant significantly decreased the proliferation of ECV304 cells and its inhibition rate was 45.70% (P<0.01), whereas the wild-type EDA-A1 gene did not cause such growth inhibition (P>0.05). A significant increase of the fraction of cells in the G0/G1 phase of the cell cycle was observed in the ECV304 cells of the mutant group compared with wild type group, with an increase in the S phase population and a concomitant reduction in the G2/M phase population (P<0.05). These results indicate that compared with the wild-type gene, transfection with a mutant EDA-A1 gene inhibited the proliferation and cell cycle of cultured HUVECs.

11.
PLoS One ; 11(1): e0147039, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26784334

RESUMO

Recently, high-throughput sequencing has improved the understanding of the microbiological etiology of caries, but the characteristics of the microbial community structure in the human oral cavity with and without caries are not completely clear. To better understand these characteristics, Illumina MiSeq high-throughput sequencing was utilized to analyze 20 salivary samples (10 caries-free and 10 caries) from subjects from the same town in Dongxiang, Gansu, China. A total of 5,113 OTUs (Operational Taxonomic Units, 97% cutoff) were characterized in all of the salivary samples obtained from the 20 subjects. A comparison of the two groups revealed that (i) the predominant phyla were constant between the two groups; (ii) the relative abundance of the genera Veillonella, Bifidobacterium, Selenomonas, Olsenella, Parascardovia, Scardovia, Chryseobacterium, Terrimonas, Burkholderia and Sporobacter was significantly higher in the group with caries (P < 0.05); and (iii) four genera with low relative abundance (< 0.01% on average), including two characteristic genera in caries (Chryseobacterium and Scardovia), significantly influenced the microbial community structure at the genus and OTU levels. Moreover, via co-occurrence and principal component analyses, the co-prevalence of the pathogenic genera was detected in the caries samples, but in the caries-free samples, the function of clustered genera was more random. This result suggests that a synergistic effect may be influencing the assembly of the caries microbial community, whereas competition may play a more dominant role in governing the microbial community in the caries-free group. Our findings regarding the characteristics of the microbial communities of the groups with and without caries might improve the understanding of the microbiological etiology of caries and might improve the prevention and cure of caries in the future.


Assuntos
Bactérias/classificação , Cárie Dentária/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Saliva/microbiologia , Análise de Sequência de DNA/métodos , Adulto , Bactérias/genética , Bactérias/isolamento & purificação , China , DNA Bacteriano/análise , Feminino , Humanos , Masculino , Microbiota , Pessoa de Meia-Idade , Filogenia , Análise de Componente Principal
12.
J Dent Sci ; 11(1): 17-22, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30894940

RESUMO

Background/purpose: The aim of this study was to explore the presence and variability of oral Candida in adolescents before and during treatment with fixed orthodontic appliances. Materials and methods: A total of 50 patients aged 10-18 years old were randomly selected for this study. Microorganism samples were obtained prior to and after orthodontic treatment and identified by culture methods. Molecular biology techniques were used to investigate the samples further and the effect of the orthodontic appliance on oral pathogenic yeasts was studied longitudinally. Results: The percentage of patients with candidiasis and the total number of colony-forming units significantly increased 2 months after orthodontic treatment. Changes in the type of oral candidiasis prior to and after treatment were significant. Conclusion: Fixed orthodontic appliances can influence the growth of oral pathogenic yeasts among adolescents.

13.
J Hepatol ; 62(3): 563-72, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25450716

RESUMO

BACKGROUND & AIMS: By binding to T cell immunoglobulin mucin-3 (TIM-3) on activated Th1 cells, galectin-9 (Gal-9) negatively regulates Th1-type alloimmunity. Although T cells contribute to hepatic ischemia-reperfusion injury (IRI), it is unknown whether negative T cell-dependent TIM-3 co-stimulation may rescue IR-stressed orthotopic liver transplants from innate immunity-driven inflammation. METHODS: We used wild type (WT) and TIM-3 transgenic (Tg) mice (C57BL/6) as liver donors and recipients in a clinically-relevant model of hepatic cold storage (20 h at 4°C in UW solution) and syngeneic orthotopic liver transplantation (OLT). RESULTS: Orthotopic liver transplants in WT or TIM-3Tg→TIM-3Tg groups were resistant against IR-stress, evidenced by preserved hepatocellular function (serum ALT levels) and liver architecture (Suzuki's score). In contrast, orthotopic liver transplants in WT or TIM-3Tg→WT groups were susceptible to IRI. TIM-3 induction in circulating CD4+ T cells of the recipient: (1) depressed T-bet/IFN-γ, while amplifying GATA3 and IL-4/IL-10 expression in orthotopic liver transplants; (2) promoted T cell exhaustion (PD-1, LAG-3) phenotype; and (3) depressed neutrophil and macrophage infiltration/function in orthotopic liver transplants. In parallel studies, we documented for the first time that Gal-9, a natural TIM-3 ligand, was produced primarily by and released from IR-stressed hepatocytes, both in vivo and in vitro. Moreover, exogenous recombinant Gal-9 (rGal-9) potentiated liver resistance against IRI by depressing T cell activation and promoting apoptosis of CD4+ T cells. CONCLUSIONS: Harnessing TIM-3/Gal-9 signalling at the T cell-hepatocyte interface facilitates homeostasis in IR-stressed orthotopic liver transplants. Enhancing anti-oxidant hepatocyte Gal-9 potentiates liver IR-resistance. Negative regulation by recipient TIM-3+CD4+ cells provides evidence for cytoprotective functions of a discrete T cell subset, which should be spared when applying T cell-targeted immunosuppression in transplant recipients.


Assuntos
Galectinas/imunologia , Hepatócitos/imunologia , Transplante de Fígado , Receptores Virais/imunologia , Traumatismo por Reperfusão/prevenção & controle , Linfócitos T/imunologia , Adenosina , Alopurinol , Animais , Apoptose , Diferenciação Celular , Modelos Animais de Doenças , Glutationa , Receptor Celular 2 do Vírus da Hepatite A , Hepatócitos/patologia , Imunidade Inata , Técnicas In Vitro , Insulina , Transplante de Fígado/efeitos adversos , Ativação Linfocitária , Macrófagos/imunologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Neutrófilos/imunologia , Preservação de Órgãos , Soluções para Preservação de Órgãos , Rafinose , Receptores Virais/genética , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais/imunologia , Linfócitos T/patologia
14.
Oncotarget ; 5(23): 12304-16, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25365190

RESUMO

A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC). The aim of this study was to examine the role of cytosolic phospholipase A2α (cPLA2α) on AKT phosphorylation at Ser473 and cell proliferation in CRC cells with mutation in phosphoinositide 3-kinase (PI3K). AKT phosphorylation at Ser473 was resistant to EGF stimulation in CRC cell lines of DLD-1 (PIK3CAE545K mutation) and HT-29 (PIK3CAP499T mutation). Over-expression of cPLA2α by stable transfection increased basal and EGF-stimulated AKT phosphorylation and proliferation in DLD-1 cells. In contrast, silencing of cPLA2α with siRNA or inhibition with Efipladib decreased basal and EGF-stimulated AKT phosphorylation and proliferation in HT-29. Treating animals transplanted with DLD-1 with Efipladib (10 mg/kg, i.p. daily) over 14 days reduced xenograft growth by >90% with a concomitant decrease in AKT phosphorylation. In human CRC tissue, cPLA2α expression and phosphorylation were increased in 63% (77/120) compared with adjacent normal mucosa determined by immunohistochemistry. We conclude that cPLA2α is required for sustaining AKT phosphorylation at Ser473 and cell proliferation in CRC cells with PI3K mutation, and may serve as a potential therapeutic target for treatment of CRC resistant to anti-EGFR therapy.


Assuntos
Proliferação de Células/fisiologia , Neoplasias Colorretais/metabolismo , Fosfolipases A2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Elafina/genética , Xenoenxertos , Humanos , Immunoblotting , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Nus , Mutação , Fosforilação , Transfecção
15.
Oncol Lett ; 8(5): 2096-2102, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25295097

RESUMO

Pancreatic cancer (PC) is the fourth leading cause of cancer-related mortality in the United States. There is no effective serum biomarker for the early diagnosis of PC at present. Although serum UL16-binding protein 2 (ULBP2) and macrophage inhibitory cytokine-1 (MIC-1) levels are reported to be elevated in PC patients, the diagnostic and prognostic value of ULBP2 and MIC-1 alone or in combination remains unknown. The aim of the present case-control study was to compare the diagnostic value of ULBP2, MIC-1 and carbohydrate antigen 19-9 (CA19-9) in 359 serum samples, consisting of 152 cases of PC, 20 cases of pre-pancreatic cancer, 91 cases of chronic pancreatitis (CP) and 96 normal controls (NC). All patients were followed up for a median of 2 years. It was found that the serum levels of ULBP2, MIC-1 and CA19-9 were significantly higher in the PC patients compared with those in the NC group. In distinguishing PC from the CP, the highest sensitivity and specificity were ULBP2 (0.878) and CA19-9 (0.816), respectively. The area under the receiver operating characteristic curve of ULBP2 was 0.923, which was the highest of the three biomarkers. MIC-1 was the optimal choice for the diagnosis of early-stage PC (area under the curve, 0.831). Overall, MIC-1 in combination with ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC. In addition, a higher level of MIC-1 was correlated with a poorer prognosis, as calculated by the Kaplan-Meier test (P=0.039). Patients with serum MIC-1 levels of ≥1,932 ng/ml had a median survival time of 15.62±2.44 months (mean ± standard deviation) vs. 18.66±2.43 months in patients with a lower level of MIC-1. Overall, combined detection of serum MIC-1 and ULBP2 improved the diagnostic accuracy in differentiating PC from CP and NC, and serum MIC-1 level alone was a predictor of survival in the patients with PC.

16.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 32(4): 358-62, 2014 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-25241537

RESUMO

OBJECTIVE: To determine the prevalence of saliva Helicobacter pylori in Lanzhou and investigate Helicobacter pylori-related diseases. METHODS: Helicobacter pylori was detected through bacterial culture, Gram stain microscopy, and urease test from saliva samples collected from 941 residents of Lanzhou. The infection rate and growth of Helicobacter pylori among the residents were analyzed in terms of different oral health conditions, oral disease, gender, urban and rural status, and age. RESULTS: The rate of Helicobacter pylori-positive saliva in Lanzhou was 42.72%. The status of Helicobacter pylori infection showed significant difference among subjects with different oral hygiene and oral diseases. The rate of Helicobacter pylori-positive saliva among females was 47.89%, which was greater compared with the rate among males (38.45%, P = 0.004, chi2 = 8.492). The rate of Helicobacter pylori-positive saliva in the town was 33.99%, which was less than the rate for the villages (50.93%, P = 0.000, chi2 = 27.551). The rate of Helicobacter pylori-positive saliva among residents aged 10 to 59 showed a flat trend with no significant differences. However, the rate of Helicobacter pylori-positive saliva among residents over 60 years old showed a significant increase. No significant difference was found in the growth of saliva Helicobacter pylori (P = 0.086). CONCLUSION: The rate of Helicobacter pylori-positive saliva is related to the subjects' oral hygiene, oral disease, gender, age, and living conditions.


Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Saliva , Adolescente , Adulto , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
17.
World J Gastroenterol ; 20(32): 11241-8, 2014 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-25170208

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.


Assuntos
Carcinoma Ductal Pancreático/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Pancreáticas/diagnóstico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Diabetes Mellitus/epidemiologia , Testes Genéticos , Humanos , Estadiamento de Neoplasias , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Fatores de Risco
18.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 31(2): 186-90, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23662564

RESUMO

OBJECTIVE: To evaluate the effects of non-Saccharomyces albicans metabolic products on the cell cycle distribution and proliferation of human umbilical vein endothelial cell ECV304 cells in vitro. METHODS: The parallel dilution supernatant of Saccharomyces tropicalis, Saccharomyces krusei and Saccharomyces glabrata were prepared, and 1, 4, 16-fold(s) diluted concentration and control group were set up. The line of human umbilical vein endothelial cell ECV304 was cultured in vitro and treated by non-Saccharomyces albicans supernatant. The proliferous effect of ECV304 induced by non-Saccharomyces albicans supernatant after 24, 48, 72 h was detected by the methods of MTT, and the changes of cell density and cycle after 48 h were investigated by inverted microscope and flow cytometry. RESULTS: At the 24th hour, all of the higher concentration (1-fold) of non-Saccharomyces albicans supernatant and the 4-folds diluted Saccharomyces krusei could promote ECV304 proliferation(P < 0.05). After adding various non-Saccharomyces albicans supernatant at 48h and 72th hour, Saccharomyces krusei supernatant and Saccharomyces glabrata supernatant significantly increased proliferation rate of ECV304, while Saccharomyces tropicalis supernatant group showed no significant change no matter which concentration was tested. At 48th hour after adding the non-Saccharomyces albicans supernatant, the ECV304 cells density treated by Saccharomyces krusei supernatant and Saccharomyces glabrata supernatant were significantly higher under the inverted microscope. The G0/G1 population of ECV304 cells decreased while cell proliferation index (PI) increased after incubated with Saccharomyces krusei supernatant and Saccharomyces glabrata supernatant for 48 hours (P < 0.05). Saccharomyces tropicalis group showed no significant change (P > 0.05). CONCLUSION: The metabolic products of Sacharoymces krusei and Saccharomyces glabrata could induce proliferation of ECV304 cell, which suggests non-Saccharomyces albicans should be undergone more attention clinically in detection and treatment.


Assuntos
Células Endoteliais da Veia Umbilical Humana , Saccharomyces , Ciclo Celular , Divisão Celular , Proliferação de Células , Humanos , Veias Umbilicais
19.
Oncol Lett ; 5(1): 255-260, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23255931

RESUMO

Resistance to 5-fluorouracil (5-FU) in patients with gastric cancer is a serious therapeutic problem and major efforts are underway to understand the underlying mechanisms. We have previously identified RhoGDI2 as a contributor to 5-FU resistance in colon cancer cells using 2D electrophoresis and mass spectrometry and the current study aimed to further investigate this role. The expression of RhoGDI2 in seven gastric cancer cell lines was positively correlated with resistance to 5-FU. Lower 5-FU sensitivity of isolated tumor cells from patients with gastric cancer was also associated with higher RhoGDI2 expression. Ectopic expression of RhoGDI2 in gastric cancer cells increased the resistance to 5-FU and reverted low dose 5-FU-induced G2/M phase arrest without affecting the population of sub-G1 cells. Overall, these findings suggest that RhoGDI2 is associated with 5-FU resistance and is a potential therapeutic target for enhancing chemotherapy efficacy in gastric cancer.

20.
Front Biosci (Landmark Ed) ; 17: 2541-9, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22652796

RESUMO

The emerging roles of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers have drawn great attention in cancer research. We hypothesized that BMP2 promotes cancer metastasis by modulating MMP-2 secretion and activity through intracellular ROS regulation and ERK activation in human pancreatic cancer. Our data show that stimulation of PANC-1 cells with BMP2 induced MMP-2 secretion and activation, associated with decreased E-cadherin expression, resulting in epithelial-to-mesenchymal transformation (EMT) and cell invasion. Blockade of ROS by the ROS scavenger, 2-MPG, abolished cell invasion, inhibited the EMT process and decreased MMP-2 expression, suggesting ROS accumulation caused an increase in MMP-2 expression in BMP2-stimulated PANC-1 cell invasion. Furthermore, treatment of PANC-1 cells with 2-MPG or ERK inhibitor PD98059 reduced the phosphorylation of ERK, resulting in attenuation of BMP2-induced cell invasion and MMP-2 activation. Taken together, these results suggest that BMP2 induces the cell invasion of PANC-1 cells by enhancing MMP-2 secretion and acting through ROS accumulation and ERK activation.


Assuntos
Proteína Morfogenética Óssea 2/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteína Morfogenética Óssea 2/farmacologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/fisiologia , Humanos , Sistema de Sinalização das MAP Quinases , Invasividade Neoplásica/patologia , Invasividade Neoplásica/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais
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