Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 204
Filtrar
1.
Aging (Albany NY) ; 12(7): 6340-6351, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32289750

RESUMO

Leptin signaling influences osteoblastogenesis and modulates the fate of mesenchymal stem cells (MSCs) during bone and cartilage regeneration. Although MSCs abound in the osteosarcoma (OS) microenvironment, and leptin exhibits pro-tumorigenic properties, leptin's influence on OS progression and chemoresistant signaling in MSCs remains unclear. Using cell viability and apoptosis assays, we showed that medium conditioned by leptin-treated human MSCs promotes cisplatin resistance in cultured human OS cells. Moreover, GFP-LC3 expression and chloroquine treatment experiments showed that this effect is mediated by stimulation of autophagy in OS cells. TGF-ß expression in MSCs was upregulated by leptin and suppressed by leptin receptor knockdown. Silencing TGF-ß in MSCs also abolished OS cell chemoresistance induced by leptin-conditioned medium. Cisplatin resistance was also induced when leptin-conditioned MSCs were co-injected with MG-63 OS cells to generate subcutaneous xenografts in nude mice. Finally, we observed a significant correlation between autophagy-associated gene expression in OS clinical samples and patient prognosis. We conclude that leptin upregulates TGF-ß in MSCs, which promotes autophagy-mediated chemoresistance in OS cells.

2.
Pathol Res Pract ; 216(2): 152794, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31902551

RESUMO

OBJECTIVE: To evaluate the correlation between expression of p53, Livin, Excision repair cross-complementation group 1 (ERCC1), BRCA1 and Poly (ADP-ribose) polymerase 1 (PARP 1) in epithelial ovarian cancer (EOC) tissues with platinum-based chemotherapy and prognosis in patients who received either comprehensive surgical staging or cytoreductive surgery. METHODS: The protein expressions level of five potential regulators involved in chemo-resistance, including p53, Livin, ERCC1, BRCA1 and PARP1 in EOC tissues from 66 patients were evaluated using immunohistochemistry method. We also measured preoperative CA125 level measured by an electrochemiluminescence immunoassay (ECLIA) in all patients. Cox proportional hazard regression model was established to identify whether these proteins are associated with overall survival. RESULTS: Chemo-resistance and poor overall survival were shown to be significantly related with positive expressions of p53, Livin, ERCC1, BRCA1 and PARP1. The evaluation of risk factors on the chemo-resistance showed that ERCC1 and BRCA1 are strong risk factors (OR: 21.12 and 21.61, all P < 0.01), while the positive expression of ERCC1, BRCA1 and PARP1 was significantly highly associated with the overall survival (HR: 3.9, 3.7 and 2.6, all P < 0.05, respectively). CA125 levels were significantly higher in patients with positive expression of P53, BRCA1, ERCC1 or Livin compared with those with negative expression (471:146, 667:260, 494:261 and 4589:89 U/ml, respectively, all P < 0.05). CONCLUSIONS: The elevated expression levels of ERCC1 and BRCA1 were identified as significant risk factors for chemo-resistance in EOC. Reduced expression levels of ERCC1, BRCA1 and PARP1 were significantly associated with better overall survival. The CA125 levels were significantly higher in patients with EOC specimens that were positive of p53, BRCA1, ERCC1 and Livin.

3.
Biomed Pharmacother ; 121: 109611, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731196

RESUMO

BACKGROUND: Our previous studies have showed that p-Hydroxylcinnamaldehyde (CMSP) could induce the differentiation of ESCC cells via the cAMP-RhoA-MAPK signalling pathway, which suggests a new potential strategy for ESCC treatment. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in several tumour cells by binding to the death receptors DR4 and DR5. However, TRAIL has little effect on oesophageal squamous cell carcinoma (ESCC) cells due to the loss of the receptors. The present study determined the effect of CMSP, the firstly found chemical constituent of Cochinchinamomordica seed (CMS), on TRAIL-induced apoptosis and its mechanism in ESCC cells. METHODS: MTS assays were performed to examine the CMSP- and TRAIL-mediated inhibition of ESCC cell growth. Flow cytometry and Hoechst 33258 staining assays were used to detect apoptosis in ESCC cells treated with CMSP combined with TRAIL. Western blotting was used to determine the effect of CMSP on the expression of p38, p-p38, DR4, DR5, Bid and caspase-3/8 in ESCC cells treated with CMSP combined with TRAIL. Additionally, immunodeficient Balb-c/null mouse model was used to determine the chemotherapeutic efficacy of CMSP and TRAIL against ESCC tumour xenograft growth in vivo. RESULTS: We found that the combination of CMSP and TRAIL had a greater inhibitory effect on ESCC cell viability in vitro than CMSP or TRAIL alone. CMSP enhanced the TRAIL-induced apoptosis in ESCC cells by upregulating the expression of DR4 and DR5 via the p38 MAPK signalling pathway. Furthermore, the increased expression of DR4 and DR5 upon TRAIL-induced apoptosis in ESCC cells was mediated at least in part by subsequent caspase-3 and caspase-8 activation. Moreover, the in vivo model showed that tumour growth was significantly slower in CMSP and TRAIL combination-treated mice than in mice treated with CMSP or TRAIL alone. CONCLUSION: Taken together, our findings indicate that CMSP as an extract from TCM, might be as a potential sensitizer of TRAIL and thus provide a novel strategy for the clinical treatment of ESCC.

4.
Am J Otolaryngol ; 41(1): 102318, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31732299

RESUMO

PURPOSE: Abnormal DNA methylation plays an important role in clinical diagnosis and prognosis of various tumors. DNA methylation is catalyzed by DNA methyltransferase (DNMT). However, the methylation status of MAGE-A1 and MAGE-A3 promoter regions in LSCC is unclear. To investigate the methylation levels of MAGE-A1, -A3 in LSCC and corresponding normal tissues. The expression of DNMTs (DNMT1, DNMT3a and DNMT3b) in LSCC and the relationship between the methylation status of MAGE-A1, -A3 were analyzed. MATERIALS AND METHODS: We examined methylation status of MAGE-A1, -A3 in LSCC by using MSP. Meanwhile, the expression level of DNMTs in LSCC was detected by immunohistochemistry. And further analysis the correlation between DNMTs expression level and methylation status of MAGE-A1 and MAGE-A3. RESULTS: The unmethylation rate of MAGE-A1, -A3 were 39.62% and 46.23%. The expression of DNMTs was 33.02% to 37.74%. The level of demethylation of MAGE-A1 and MAGE-A3 were negative related to DNMTs protein. MAGE-A1 and MAGE-A3 unmethylation status and DNMT3a expression were independent prognostic factors for LSCC. CONCLUSIONS: The DNMTs may participate in the methylation process of MAGE-A1 and MAGE-A3, which may play an important role in the occurrence and development of LSCC.


Assuntos
Antígenos de Neoplasias/metabolismo , Carcinoma de Células Escamosas/enzimologia , DNA (Citosina-5-)-Metiltransferases/metabolismo , Neoplasias Laríngeas/enzimologia , Proteínas de Neoplasias/metabolismo , Fragmentos de Peptídeos/metabolismo , Idoso , Carcinoma de Células Escamosas/patologia , Metilação de DNA , Feminino , Humanos , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Regiões Promotoras Genéticas
5.
J Exp Clin Cancer Res ; 38(1): 501, 2019 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-31864387

RESUMO

BACKGROUND: Esophageal cancer is one of the most common malignant tumors in the world. With currently available therapies, only 20% ~ 30% patients can survive this disease for more than 5 years. TRAIL, a natural ligand for death receptors that can induce the apoptosis of cancer cells, has been explored as a therapeutic agent for cancers, but it has been reported that many cancer cells are resistant to TRAIL, limiting the potential clinical use of TRAIL as a cancer therapy. Meanwhile, Periplocin (CPP), a natural compound from dry root of Periploca sepium Bge, has been studied for its anti-cancer activity in a variety of cancers. It is not clear whether CPP and TRAIL can have activity on esophageal squamous cell carcinoma (ESCC) cells, or whether the combination of these two agents can have synergistic activity. METHODS: We used MTS assay, flow cytometry and TUNEL assay to detect the effects of CPP alone or in combination with TRAIL on ESCC cells. The mechanism of CPP enhances the activity of TRAIL was analyzed by western blot, dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. The anti-tumor effects and the potential toxic side effects of CPP alone or in combination with TRAIL were also evaluated in vivo. RESULTS: In our studies, we found that CPP alone or in combination with TRAIL could inhibit the proliferation of ESCC cells and induce apoptosis, and we certificated that combination of two agents exert synergized functions. For the first time, we identified FoxP3 as a key transcriptional repressor for both DR4 and DR5. By down-regulating FoxP3, CPP increases the expression of DR4/DR5 and renders ESCC cells much more sensitive to TRAIL. We also showed that CPP reduced the expression of Survivin by inhibiting the activity of Wnt/ß-catenin pathway. All these contributed to synergistic activity of CPP and TRAIL on ESCC cells in vitro and in vivo. CONCLUSION: Our data suggest that CPP and TRAIL could be further explored as potential therapeutic approach for esophageal cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Saponinas/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Animais , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Carcinoma de Células Escamosas do Esôfago , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Expressão Gênica , Humanos , Masculino , Camundongos , Regiões Promotoras Genéticas , Ligação Proteica , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Via de Sinalização Wnt , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Cell Biochem ; 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31886586

RESUMO

Breast cancer is a malignant tumor that seriously threatens women's health, and luminal-like cancer subtypes account for the majority of the cases. The purpose of this study was to investigate the relationships among DNA methylation, gene expression profile, and the tumor-immune microenvironment of luminal-like breast cancer, and to identify the potential key genes that regulate immune cell infiltration in luminal-like breast cancer. The ESTIMATE algorithm was applied to calculate immune scores and stromal scores of patients with breast cancer. Kaplan-Meier curves were generated for survival analysis. The clusterProfile package was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Correlations between ADCY6 expression and immune cell infiltration-related pathways were analyzed by gene set variation analysis. R software was used for the statistical analysis and figure generation. Disease-free survival was higher in the immune score-high group than it was in the immune score-low group, while the stromal score had no correlation with prognosis. There were 515 genes that differed in both gene expression and DNA methylation levels, and these genes were mainly enriched in immune process-related pathways. ADCY6 was enriched in module A of the PPI network. Patients with downregulation and hypermethylation of ADCY6 associated with a better prognosis. ADCY6 expression was negatively correlated with the activation of immune process-related signaling pathways, immune checkpoint receptors, and ligands, except for CLEC4G. DNA methylation was found to be involved in the regulation of the key cellular pathways of luminal-like breast cancer immune cell infiltration. Additionally, ADCY6 was identified as a prognostic factor involved in the DNA methylation-regulated immune processes in luminal-like breast cancer.

7.
J Oncol ; 2019: 6340567, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772581

RESUMO

Aim: Analyze the gender difference of esophageal cancer patients in response to drug treatment. Methods: All publications on clinical trials were collected from PubMed, Scopus, and PMC. Each publication was examined to determine whether the publication is a clinical trial and whether data on gender difference were reported. Results: Selected from a total of 191 publications, data from 7 trials with a total of 2041 patients were evaluated for gender differences. These clinical trials involve different drugs and disease phenotype. A significant difference was obtained between male and female groups from Student's t-test. There is no conclusive result on age, ethnicity, tumor size, and drug influence. Conclusions: Gender difference in response to treatment potentially most likely exists in esophageal cancer patients, regardless of age, race, and drugs.

8.
J Exp Clin Cancer Res ; 38(1): 477, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775815

RESUMO

BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) are of great importance in development of different types of tumors, while the function of lncRNA ZFAS1 is rarely discussed in esophageal squamous cell carcinoma (ESCC). Therefore, we performed this study to explore the expression of exosomal lncRNA ZFAS1 and its molecular mechanism on ESCC progression. METHODS: Expression of ZFAS1 and miR-124 in ESCC tissues was detected. LncRNA ZFAS1 was silenced to detect its function in the biological functions of ESCC cells. A stable donor and recipient culture model was established. Eca109 cells transfected with overexpressed and low expressed ZFAS1 plasmid and miR-124 inhibitor labeled by Cy3 were the donor cells, and then co-cultured with recipient cells to observe the transmission of Cy3-ZFAS1 between donor cells and recipient cells. The changes of cell proliferation, apoptosis, invasion, and migration in recipient cells were detected. The in vivo experiment was conducted for verifying the in vitro results. RESULTS: LncRNA ZFAS1 was upregulated and miR-124 was down-regulated in ESCC tissues. Silencing of ZFAS1 contributed to suppressed proliferation, migration, invasion and tumor growth in vitro and induced apoptosis of ESCC cells. LncRNA ZFAS1 was considered to be a competing endogenous RNA to regulate miR-124, thereby elevating STAT3 expression. Exosomes shuttled ZFAS1 stimulated proliferation, migration and invasion of ESCC cells and restricted their apoptosis with increased STAT3 and declined miR-124. Furthermore, in vivo experiment suggested that elevated ZFAS1-exo promoted tumor growth in nude mice. CONCLUSION: This study highlights that exosomal ZFAS1 promotes the proliferation, migration and invasion of ESCC cells and inhibits their apoptosis by upregulating STAT3 and downregulating miR-124, thereby resulting in the development of tumorigenesis of ESCC.

9.
Oncol Lett ; 18(5): 4429-4440, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31611952

RESUMO

Lung cancer is one of the most widespread neoplasms worldwide. To identify the key biomarkers in its carcinogenesis and development, the mRNA microarray datasets GSE102287, GSE89047, GSE67061 and GSE74706 were obtained from the Gene Expression Omnibus database. GEO2R was used to identify the differentially expressed genes (DEGs) in lung cancer. The Database for Annotation, Visualization and Integrated Discovery was used to analyze the functions and pathways of the DEGs, while the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape were used to obtain the protein-protein interaction (PPI) network. Kaplan Meier curves were used to analyze the effect of the hub genes on overall survival (OS). Module analysis was completed using Molecular Complex Detection in Cytoscape, and one co-expression network of these significant genes was obtained with cBioPortal. A total of 552 DEGs were identified among the four microarray datasets, which were mainly enriched in 'cell proliferation', 'cell growth', 'cell division', 'angiogenesis' and 'mitotic nuclear division'. A PPI network, composed of 44 nodes and 886 edges, was constructed, and its significant module had 16 hub genes in the whole network: Opa interacting protein 5, exonuclease 1, PCNA clamp-associated factor, checkpoint kinase 1, hyaluronan-mediated motility receptor, maternal embryonic leucine zipper kinase, non-SMC condensin I complex subunit G, centromere protein F, BUB1 mitotic checkpoint serine/threonine kinase, cyclin A2, thyroid hormone receptor interactor 13, TPX2 microtubule nucleation factor, nucleolar and spindle associated protein 1, kinesin family member 20A, aurora kinase A and centrosomal protein 55. Survival analysis of these hub genes revealed that they were markedly associated with poor OS in patients with lung cancer. In summary, the hub genes and DEGs delineated in the research may aid the identification of potential targets for diagnostic and therapeutic strategies in lung cancer.

10.
Chem Res Toxicol ; 32(8): 1515-1527, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31286759

RESUMO

Esophageal cancer is prevalent in Cixian, China, but the etiology of this disease remains largely unknown. Therefore, we explored this by conducting a DNA adductome analysis. Both tumorous and nontumorous tissues were collected from patients who underwent surgical procedures at Cixian Cancer Hospital and the Fourth Hospital of Hebei Medical University, which is in a low-incidence area. N2-(3,4,5,6-Tetrahydro-2H-pyran-2-yl)deoxyguanosine (THP-dG) was the major adduct detected in samples from esophageal cancer patients in Cixian. The precursor of THP-dG, N-nitrosopiperidine (NPIP), exhibited a strong mutagenic activity under metabolic activation in the Ames test and a significant dose-dependent increase in mutation frequency during an in vivo mutagenicity test with guanine phosphoribosyltransferase (gpt) delta rats. The NPIP-induced mutation was dominated by A:T to C:G transversions, followed by G:C to A:T and A:T to G:C transitions, in the liver and esophagus of animal samples. A similar mutational pattern was observed in the mutational signature of esophageal cancer patients that demonstrated weak correlation with THP-dG levels. These findings suggested that NPIP exposure is partly involved in the development of esophageal cancer in Cixian residents.

11.
Cell Death Dis ; 10(7): 513, 2019 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-31273188

RESUMO

Long noncoding RNAs (lncRNAs) play important roles in the development and progression of human cancers. The lncRNA prostate cancer-associated transcript 1 (PCAT1) has been reported to be involved in multiple human cancers, including oesophageal squamous cell carcinoma (ESCC). However, the detailed biological functions, underlying mechanisms and clinical relevance of PCAT1 in ESCC remain unclear. Here, we confirmed that PCAT1 was highly expressed in ESCC tissues and cell lines. Knockdown of PCAT1 inhibited the growth of ESCC cells, whereas overexpression of PCAT1 showed the opposite effect both in vitro and in vivo. Moreover, knockdown of PCAT1 arrested the cell cycle at G2/M phase, reduced the expression of cyclin B1 and CDC2, and caused cells to be more sensitive to paclitaxel. Furthermore, PCAT1 could bind to miR-326, a tumour suppressor in diverse human cancers. Rescue experiments revealed that enforced expression of miR-326 attenuated the promotive effect of PCAT1 on ESCC cell growth. In addition, we discovered that PCAT1 was present in ESCC cell-derived exosomes, was higher in the serum of ESCC patients than those of healthy volunteer donors, and promoted cell growth through exosomes. Thus, our data indicate that PCAT1 promotes ESCC cell proliferation by sponging miR-326 and may serve as a non-invasive biomarker for ESCC.

12.
Chin J Cancer Res ; 31(3): 426-434, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31354211

RESUMO

Objective: To analyze the incidence and mortality rates of esophagus cancer in China from 2008 to 2012. Methods: Incident and mortality cases of esophagus cancer were retrieved from the National Central Cancer Registry (NCCR) database collecting from 135 cancer registries in China during 2008-2012. The incidence and mortality rates of esophagus cancer were calculated by area (urban/rural), region (eastern, middle, western), gender and age group (0, 1-4, 5-84 by 5 years and 85+ years). China census in 2000 and Segi's world population were applied for age-standardized rates. Joinpoint model was used for time-trend analysis. Results: The crude incidence rate of esophagus cancer was 22.57/100,000. The age-standardized incidence rates by China standard population (ASIRC) and by world standard population (ASIRW) were 14.58/100,000 and 14.80/100,000, respectively. The crude mortality rate of esophagus cancer was 17.19/100,000. The age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 10.80/100,000 and 10.86/100,000 respectively. Incidence and mortality rates of esophagus cancer were higher in males than in females and higher in rural areas than in urban areas. The crude incidence rate in middle areas was the highest among all areas, followed by western areas and eastern areas. The age-specific incidence rate of esophagus cancer was relatively low in age groups before 40 years old and then increased after 45 years old. It peaked in the age group of 80-84 years. The patterns of age-specific mortality rates of esophagus cancer were close to those of age-specific incidence rates. The ASIRC of esophagus cancer decreased dramatically by 29.87% between 2003 and 2012, from 14.33/100,000 to 10.05/100,000. The esophagus cancer incidence rate decreased by 3.76% per year (P>0.05). The mortality rate of esophagus cancer decreased annually over the decades from 2003 to 2012 in China (P>0.05). In females, the annual percentage change (APC) of mortality rate was -5.43% [95% confidence intervals (95% CI): -6.50%, -4.30%] (P<0.05) and the mortality rate of esophagus cancer in rural females was statistically significant (APC: -3.20%, 95% CI: -4.20%, -2.20%) (P<0.05). Conclusions: The focus of prevention and treatment for esophagus cancer is strengthening primary prevention of esophageal cancer, and promoting esophagus cancer secondary prevention to reduce incidence and mortality rates of esophagus cancer, prolong survival rate of patients and decline the burden of esophagus cancer in China.

13.
Mutagenesis ; 34(4): 307-313, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31165868

RESUMO

Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is an inhibitor of apoptosis proteins and plays a key role in apoptosis or programmed cell death. In the present study, we evaluated the effect of BIRC5 gene polymorphisms on the risk of developing oesophageal squamous cell carcinoma (ESCC) and patients' outcomes in a high-incidence population from northern China. A population-based case-control study was performed in 597 ESCC patients and 597 control subjects.Survival data were available for 211 patients who received platinum-based chemotherapy after surgery. Five polymorphisms (-31 C>G, -241 C>T, -625 G>C, -644 T>C and -1547 A>G) in the promoter of the BIRC5 gene were genotyped by the polymerase chain reaction-ligase detection reaction (PCR-LDR) method. Compared with the -31 CC genotype, the -31 CG/GG genotype of -31 C>G single nucleotide polymorphism (SNP) was associated with a significant elevated risk of ESCC [adjusted odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.07-1.84]. Interestingly, this association was stronger among females, younger patients and non-smokers in stratified analyses (adjusted OR = 1.72, 95% CI = 1.07-2.75; adjusted OR = 1.61, 95% CI = 1.10-2.36; adjusted OR = 1.80, 95% CI = 1.26-2.58, respectively]. Survival analyses showed that the T allele of -241 C>T SNP was associated with poor prognosis [hazard ratio (HR) = 2.99, 95% CI = 1.09-8.19) and that the C allele of -625 G>C SNP was associated with good prognosis (HR = 0.62, 95% CI = 0.38-0.99) in ESCC patients. The -31 C>G polymorphism may be involved in the development of ESCC, and the -241 C>T and -625 G>C polymorphisms may be useful prognostic markers for ESCC.

14.
Dig Liver Dis ; 51(10): 1475-1482, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31155488

RESUMO

BACKGROUND: The expression and methylation status of oncogenes are closely related to the onset and progression of cancer. AIMS: To explore the role and methylation status of melanoma-associated antigen-A11 in the pathogenesis of esophageal squamous cell carcinoma. METHODS: 116 esophageal squamous cell carcinoma patients with tumor tissues and corresponding adjacent normal tissues were obtained. The expression level and methylation status of melanoma-associated antigen-A11 in esophageal cancer cell lines and esophageal squamous cell carcinoma tissues were determined respectively. RESULTS: Significant up-regulation of melanoma-associated antigen-A11 was detected in esophageal cancer cell lines and esophageal squamous cell carcinoma tissues. Up-regulation of melanoma-associated antigen-A11 contributed to proliferation and invasion in cancer cells. Hypomethylation of the CpG site was associated with pathological differentiation, clinical stage, tumor size, lymph node metastasis and distant metastasis. Esophageal squamous cell carcinoma patients in stage III and IV, with high expression of melanoma-associated antigen-A11 or hypomethylation of the CpG site within the promoter demonstrated poor survival. CONCLUSION: Melanoma-associated antigen-A11 is up-regulated in esophageal squamous cell carcinoma at least partly by hypomethylation of the CpG site within the promoter and this hypomethylation may affect the prognosis of esophageal squamous cell carcinoma patients.

15.
Pathol Res Pract ; 215(7): 152446, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31126819

RESUMO

OBJECTIVE: To evaluate the clinical characteristics and prognostic significance of MAGE-A11 and transcription factors (SP1, TFCP2 and ZEB1) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: To assess the expression of MAGE-A11 and transcription factors (SP1, TFCP2 and ZEB1) in 121 ESCC samples were respectively detected by immunohistochemical method. RESULTS: The results showed MAGE-A11 and transcription factors (SP1,TFCP2 and ZEB1) expression were associated with some clinical features in patients, such as pathological differentiation, tumor size, clinical stage, lymph node metastasis and distant metastasis. Kaplan-Meier analysis showed that patients with ESCC having high MAGE-A11 and transcription factors (SP1,TFCP2 and ZEB1) expression had a worse prognosis compared to the patients with low expression. Multivariate Cox proportional hazards regression model revealed that MAGE-A11 expression, TFCP2 expression, lymph node metastasis and distant metastasis were independently associated with ESCC patients' survival. CONCLUSIONS: High expression of MAGE-A11 and transcription factors (SP1,TFCP2 and ZEB1) in ESCC tissues suggests promoting ESCC progression and poor prognosis, co-expression of MAGE-A11 and transcription factors even worse.


Assuntos
Antígenos de Neoplasias/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas de Neoplasias/metabolismo , Fator de Transcrição Sp1/metabolismo , Fatores de Transcrição/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida
16.
Future Oncol ; 15(14): 1617-1627, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31038363

RESUMO

Aim: To compare the performance of first-line paclitaxel liposome + oxaliplatin and SOX (tegafur/gimeracil/oteracil + oxaliplatin) in advanced gastric cancer patients. Materials & methods: Stage IIb-IV gastric cancer patients underwent either first-line paclitaxel liposome + oxaliplatin (n = 52) or SOX (n = 69) between 2010-2013, and followed up until 2015 or death. Results: Both groups had similar objective response rate (p = 0.48) and disease control rate (p = 0.992) after two chemotherapy cycles, median progression-free survival (p = 0.495) and median overall survival (p = 0.208). Liposome group had significantly lower rate of grade I-II platelet decline and liver function damage (p = 0.04 and 0.019). Multivariate COX regression identified pre-treatment neutrophil-to-lymphocyte ratio as an independent prognostic factor. Conclusion: First-line paclitaxel liposome + oxaliplatin has comparable efficacy, but causes reduced adverse reactions in advanced gastric cancer as compared with SOX.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Lipossomos , Paclitaxel/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Resultado do Tratamento
17.
J Ovarian Res ; 12(1): 29, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30917846

RESUMO

OBJECTIVE: To identify the plasma protein biomarkers related to the chemoresistance of postoperative recurrence of epithelial ovarian cancers. METHODS: Forty plasma samples from patients in chemotherapy-sensitive and chemotherapy-resistant groups (20 for each group) were collected at Gynecology Department in the Fourth Hospital of Hebei Medical University from September 2013 to September 2014. The differentially expressed proteins between two groups were screened with two-dimensional gel electrophoresis (2-DE) and further analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). RESULTS: Thirty-four differentially expressed spots were identified between the two groups. Compared with the chemo-sensitive group, 21 protein spots were up-regulated and 13 were down-regulated in the chemoresistant group, in which 14 differentially expressed proteins were identified by the Mass spectrometry and Mascot search. Among the 14 proteins, complement C4-A, IgJ chain, clusterin, α-1-antitrypsin and carbonic anhydrase 1 were up-regulated, and transthyretin, haptoglobin, ß-2-glycoprotein, Ig γ-2 chain C region, Ig γ-1 chain C region, complement factor I light chain, Igκ chain C region, complement C3 and apolipoprotein E were down-regulated in the chemoresistant group when compared with the chemosensitive group. CONCLUSION: The up-regulated proteins including transthyretin, apolipoprotein E and haptoglobin proteins and the down-regulated proteins such as clusterin, carbonic anhydrase 1, alpha-1-antitrypsin were differentially expressed in the plasma between the chemo-sensitive group and the chemoresistant group, which may be potential biomarkers for predicting the chemotresistance of epithelial ovarian cancer patients.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Epitelial do Ovário/sangue , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/sangue , Neoplasias Ovarianas/sangue , Adulto , Idoso , Carcinoma Epitelial do Ovário/tratamento farmacológico , Regulação para Baixo , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Proteoma/metabolismo , Proteômica , Regulação para Cima
18.
Mol Carcinog ; 58(6): 1033-1045, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30737960

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor family, induces apoptosis in a variety of cancer cells. However, gastric cancer (GC) cells are insensitive to TRAIL usually. In the previous study, we showed that Periplocin could induce apoptosis in GC cells via the activation of ERK1/2-EGR1 pathway. In the present study, we have shown that the combination of Periplocin and TRAIL had a greater inhibitory effect on gastric cancer cell viability in vitro and in vivo than Periplocin or TRAIL alone. Through upregulating the expression of DR4 and DR5 at transcriptional and protein levels, Periplocin enhanced the sensitivity of gastric cancer cells to TRAIL. Furthermore, enhanced activity of ERK1/2-EGR1 pathway was responsible for upregulating of DR4 and DR5 uponPeriplocin treatment, subsequently reducing the expression of Mcl-1 and Bcl2 and activating Bid and caspase-3/8. Collectively, these data implied that Periplocin might act as a sensitizer of TRAIL and could be a potential strategy for the treatment of GC.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Saponinas/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Ligante Indutor de Apoptose Relacionado a TNF/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Saponinas/farmacologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Oncol Lett ; 17(1): 332-338, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30655771

RESUMO

Correlation between RAS gene mutation and microsatellite instability (MSI) status in cancer tissues and clinicopathological parameters of patients with stage III colorectal cancer (CRC) were investigated. Tissues were collected from 180 patients diagnosed with stage III CRC in the Department of Gastrointestinal Surgery of the Fourth Hospital of Hebei Medical University from 2012 to 2016. RAS gene mutations in paraffin sections were detected by PCR and Sanger sequencing. Expression of mismatch repair proteins MLH1, MSH2, MSH6 and PMS2 was detected by immunohistochemistry, and MSI status was determined based on the positive and negative expression combinations of the above proteins, and the correlation with clinicopathological parameters of CRC was analyzed. Mutation rates of KRAS and NRAS were 48.33% (87/180) and 2.78% (5/180), respectively. Mutation rate of p.G12D in codon 12 of exon 2 in KRAS gene was the highest (31/87, 35.63%). Mutation rate of p.G12D in codon 12 of exon 2 in NRAS gene was the highest (2/5, 40%). Mutation rate of KRAS gene in right colon was higher than that in left colon and rectum (p<0.05), and mutation rate in N2b phase was higher than that in N2a and N1 phases (p<0.01). In low degree of microsatellite instability (MSI-L) and high degree of microsatellite instability (MSI-H) status, negative MKH1 protein expression was dominant (18/32, 56.25%). MSI-H in CRC patients aged ≥50 years was higher than that of CRC patients <50 years. Rates of MSI-H in N1, N2a, and N2b were 1.75, 12.82, and 1.11% (p<0.05). Mutation rate of KRAS gene in MSI-H status of stage III CRC patients was significantly higher than that in MSI-L/microsatellite stability (MSS) (p<0.05). Mutation of RAS gene and the status of MSI are involved in the occurrence and development of stage III CRC. Detection of RAS gene has important significance for the individual treatment of CRC in clinic.

20.
Medicine (Baltimore) ; 98(1): e13907, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30608415

RESUMO

According to GLOBOCAN 2012, age-standardized incidence rate (ASIR) of cervical cancer in developed and less developed countries is 9.9 vs. 15.7 per 100,000 population per year. This disparity is related to inequity in access to screening. Urban rural disparity in access to cervical cancer screening is similar in China. We aim to assess urban rural disparity in ASIR.Using population-based tumor registration data collected by us in urban Shijiazhuang city (with incidence data available for 1,217,437 women in 2012) and in Shexian County (with incidence data available for 197,416 women since 2000), we compared ASIR of cervical cancer between the two populations in 2012. We also analyzed the trend of biennial ASIR and averaged age at diagnosis of cervical cancer for 2000-2015 in Shexian County during which China was undergoing rapid changes in sexual mores. Finally, using previously published national death survey data, we compared age-standardized mortality rate (ASMR) of cervical cancer between Shijiazhuang city and Shexian County over the periods of 1973-1975 and 1990-1992.It was found that the ASIR of cervical cancer in rural Shexian County is 3 times higher than in Shijiazhuang city in 2012 (25.0 vs. 8.4 per 100,000 per year, P < .01); and the corresponding ASMR was 2 times higher over the period of 1973-1975 (25.0 vs. 13.0 per 100,000 per year, P < .01) and 8 times higher over the period of 1990-1992 (9.8 vs. 1.2 per 100,000 per year, P < .01). From 2000 to 2015 along with rapid changes in sexual behavior, the biennial ASIR of cervical cancer increased by +3.2% on average, from 19.3 to 28.5 per 100,000 per year (P < .01), and the biennial averaged age at diagnosis decreased from 55.8 to 52.1 (P < .01).Urban-rural disparity in ASIR of cervical cancer in present study is larger than that reported between developed and less developed countries in GLOBOCAN 2012, in which the disparity is considered "due to differences in access to screening." As in China, cytologists and infrastructure required for cervical cancer screening are similarly lacking in rural areas, we suggest cytological screening for cervical cancer be strengthened in disadvantaged rural settings.


Assuntos
População Rural/estatística & dados numéricos , População Urbana/estatística & dados numéricos , Neoplasias do Colo do Útero/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Fatores Socioeconômicos , Neoplasias do Colo do Útero/mortalidade , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA