Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 9 de 9
Filter
Add more filters










Database
Language
Publication year range
1.
Cancer Genomics Proteomics ; 16(6): 569-576, 2019.
Article in English | MEDLINE | ID: mdl-31659110

ABSTRACT

BACKGROUND/AIM: The outcome of patients with advanced hepatocellular carcinoma (HCC) remains poor and therapeutic options, including sorafenib, the first anti-cancer drug proved to prolong survival in patients with advanced HCC, are limited. However, no clinically useful predictive biomarker for sorafenib has been reported. MATERIALS AND METHODS: We exploited two-dimensional gel electrophoresis coupled with mass spectrometry to find de-regulated proteins by using conditioning of a sorafenib-resistant HCC cell line, Huh7. Tumor samples from 60 patients with HCC treated with sorafenib were analyzed and correlated with survival outcome. RESULTS: Comparative proteomics indicated three proteins including, 78 kDa glucose related protein (GRP78), 14-3-3ε, and heat shock protein 90ß (HSP90ß). The three proteins were over-expressed in sorafenib-resistant Huh7 cells. In HCC tumor samples from patients treated with sorafenib, 73% of tumor samples had a high expression of GRP78, 18% had high 14-3-3ε expression and 85% had high HSP90ß expression. Among these, GRP78 was associated with the shortest progression-free survival of HCC patients treated with sorafenib. CONCLUSION: GRP78 can be a predictive biomarker in HCC patients treated with sorafenib. Strategies designed to inhibit the GRP78-related pathway may overcome sorafenib resistance.


Subject(s)
Drug Resistance, Neoplasm/drug effects , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Heat-Shock Proteins/biosynthesis , Hematoma/metabolism , Liver Neoplasms/metabolism , Neoplasm Proteins/biosynthesis , Proteomics , Sorafenib/pharmacology , Cell Line, Tumor , Drug Resistance, Neoplasm/genetics , Endoplasmic Reticulum Chaperone BiP , Heat-Shock Proteins/genetics , Hematoma/drug therapy , Hematoma/genetics , Hematoma/pathology , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Neoplasm Proteins/genetics
2.
BMC Cancer ; 19(1): 791, 2019 Aug 09.
Article in English | MEDLINE | ID: mdl-31399076

ABSTRACT

BACKGROUND: Roles of cancer stem cells and early growth response gene 1 (Egr1) in carcinogenesis have been extensively studied in lung cancer. However, the role of Egr1 in the metastasis of lung cancer remains undetermined, especially in regard to stem cell-related pathways. METHODS: Egr1, osteopontin (OPN) and Oct4 expression in human lung cancer was determined by performing immunohistochemistry. Immunoblotting, ELISA, luciferase reporter assay, chromatin immunoprecipitation assay and RT-PCR were performed to validate the regulation of Oct4-Egr1-OPN axis. Moreover, the effect of Oct4-Egr1-OPN axis on lung cancer progression was evaluated by cell migration assay and mice study. RESULTS: We detected Oct4, Egr1, and OPN expression in clinical specimens from 79 lung cancer patients, including 72 adenocarcinomas and 7 squamous cell carcinomas. High expression of Oct4, Egr1, and OPN accounted for 53, 51, and 57% of the patients, respectively. All of the three biomarkers were positively correlated in clinical human lung cancer. Patients with high expression of OPN were significantly associated with shorter disease-free survivals than those with low expression of OPN (p < 0.05). In lung cancer cells, Oct4 transactivated the Egr1 promoter and upregulated Egr1 expression. In a human lung cancer xenograft model, Oct4-overexpressing tumors expressed elevated levels of Egr1. Furthermore, overexpression of Oct4 in lung cancer cells increased the metastatic potential. CONCLUSIONS: Egr1 exerts a promoting effect on cancer metastasis in Oct4-overexpressing lung cancer. Thus, therapeutic strategies targeting the Oct4/Egr1/OPN axis may be further explored for the treatment of lung cancer, especially when lung cancer is refractory to conventional treatment due to cancer stem cells.


Subject(s)
Early Growth Response Protein 1/metabolism , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Octamer Transcription Factor-3/metabolism , Osteopontin/genetics , Animals , Biomarkers, Tumor , Cell Line, Tumor , Gene Expression , Gene Knockdown Techniques , Humans , Immunohistochemistry , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Mice , Neoplasm Metastasis , Neoplasm Staging , Prognosis , Promoter Regions, Genetic
3.
Oncol Lett ; 17(6): 5740-5746, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31105795

ABSTRACT

Prothymosin α (ProTα) is a nuclear protein that serves a role in oncogenesis, by promoting proliferation and inhibiting apoptosis in various malignancies. The present study was designed to investigate ProTα expression in resected human non-small cell lung cancer to define the clinicopathological associations of ProTα-positive lung cancer. Immunohistochemical staining of ProTα was performed using tumor sample slides from 149 patients with non-small cell lung cancer, who underwent surgical resection. Association between the expression of ProTα and the following clinicopathological parameters was accessed: Age, sex, stage, lymph node involvement, pathological subtype, recurrence and cigarette smoking. A total of 85 tumors (57%) were classified as ProTα-positive lung cancer by staining intensity and 73 tumors (49%) were regarded as ProTα-positive by scoring index. The majority of patients with ProTα-positive tumors were younger (P=0.05) and had squamous cell carcinoma (P<0.01) compared with older and adenocarcinoma. Positive expression of ProTα by staining intensity was associated with a higher incidence rate of cancer recurrence (P=0.05) compared with negative ProTα expression. ProTα was also associated with cigarette smoking, particularly in the group with squamous cell carcinoma. Therefore, the present data suggested that ProTα-positive non-small cell lung cancer was associated with younger patients, squamous cell carcinoma, cigarette smoking and a higher incidence recurrence rate, subsequently indicating a subtype consisting of patients with smoking-associated inferior outcomes.

4.
Sci Rep ; 8(1): 6586, 2018 04 26.
Article in English | MEDLINE | ID: mdl-29700319

ABSTRACT

The elongation of long-chain fatty acids family member 6 (Elovl6) is a key enzyme in lipogenesis that catalyzes the elongation of saturated and monounsaturated fatty acids. Insulin resistance involves upregulation of Elovl6, which has been linked to obesity-related malignancies, including hepatocellular carcinoma (HCC). However, the role of Elovl6 in cancer progression remains unknown. In this study, we analyzed the expression of Elovl6 in 61 clinical HCC specimens. Patients with Elovl6 high-expressing tumors were associated with shorter disease-free survival and overall survival compared to those with Elovl6 low-expressing tumors. Knockdown of Elovl6 in HCC cells reduced cell proliferation and Akt activation, as well as sensitivity to fatty acids. Inhibition of Elovl6 reduced tumor growth and prolonged survival in mice bearing tumors. Taken together, our results indicate that Elovl6 enhances oncogenic activity in liver cancer and is associated with poor prognosis in patients with HCC. Elovl6 may be a therapeutic target for HCC; thus, further studies to confirm this strategy are warranted.


Subject(s)
Acetyltransferases/genetics , Biomarkers, Tumor , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Aged , Animals , Cell Cycle/genetics , Cell Proliferation , Disease Models, Animal , Disease Progression , Fatty Acid Elongases , Female , Gene Expression , Gene Knockdown Techniques , Heterografts , Humans , Immunohistochemistry , Liver Neoplasms/mortality , Male , Mice , Middle Aged , Prognosis
5.
Oncol Lett ; 12(1): 207-212, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27347126

ABSTRACT

Elongation of long chain fatty acids family member 6 (Elovl6) has been demonstrated to be involved in insulin resistance, obesity and lipogenesis. In addition, it has been reported that the protein is upregulated in human hepatocellular carcinoma and is implicated in nonalcoholic steatohepatitis-associated liver carcinogenesis. Excess body weight has been associated with an increased risk of postmenopausal breast cancer and poor prognosis. However, the connection between Elovl6 expression and outcome of breast cancer remains uncertain. Therefore, the present study used immunohistochemical analysis to investigate the expression of Elovl6 in breast cancer tissues from patients who had undergone curative mastectomy. Out of a total of 70 patients, 37.1% of patients exhibited positive Elovl6 expression in breast cancer tissue, whilst 62.9% were considered as negative. Positive Elov16 expression correlated with positive lymph node involvement and shorter recurrence-free survival. However, Elovl6 expression had no association with primary tumor size, lymph node metastasis, stage, grade, estrogen receptor, progesterone receptor, HER2 and age. Therefore, positive Elovl6 expression is a poor prognostic factor in patients with breast cancer that have previously undergone surgery, and may function as a potential therapeutic approach in the future, particularly in the scope of obesity related disease.

6.
Int J Hematol ; 102(3): 312-7, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26115877

ABSTRACT

Adipokines play a role in carcinogenesis in a variety of malignancies. These findings were established with regard to serum adipokines and malignancies. However, the expression of adipokines in bone marrow fluid remains unclear, and an investigation of the correlation between bone marrow adipokines and hematological malignancy is needed. The present study was designed to detect adipokine concentrations, including adiponectin, leptin and resistin, in bone marrow interstitial fluid from patients with hematological malignancy and controlled counterparts. The correlations between adipokines, body mass index, clinical parameters, and hematological malignancy were assessed. A total of 80 bone marrow samples were assessed for values of adipokines, adiponectin, leptin and resistin. Patients with hematological malignancy had lower levels of adiponectin. Adiponectin from leukemia bone marrow expressed significantly low values. The adiponectin levels were inversely correlated with body mass index. In conclusion, adiponectin was decreased in bone marrow from patients with leukemia and negatively correlated with body mass index.


Subject(s)
Adiponectin/biosynthesis , Bone Marrow/metabolism , Down-Regulation , Extracellular Fluid/metabolism , Gene Expression Regulation, Neoplastic , Hematologic Neoplasms/metabolism , Neoplasm Proteins/biosynthesis , Adult , Aged , Aged, 80 and over , Body Mass Index , Female , Humans , Male , Middle Aged
7.
Mol Med Rep ; 11(1): 547-54, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25333206

ABSTRACT

Sprouty2 is known for its tumor-suppressing effect in various human malignant diseases. In head and neck squamous cell carcinoma (HNSCC), the role of sprouty2 in tumorigenesis and clinical implication remains elusive. The aim of the present study was to investigate the expression of sprouty2 in patients with HNSCC and its function in vitro. Quantitative analysis of mRNA expression of sprouty2 was performed on frozen tumor samples from 42 patients with HNSCC and 19 with oral verrucous hyperplasia (OVH) with paired counterparts of normal mucosa. Downregulation of sprouty2 expression was demonstrated in 79% of HNSCC samples and in 58% of OVH samples compared with paired samples of normal mucosa. Enhanced expression of sprouty2 protein suppressed the growth of HNSCC cells and signaling of the phosphorylated AKT pathway. Following transfection of the sprouty2 plasmid, HNSCC cells were more sensitive to sorafenib, a tyrosine kinase inhibitor of Raf and vascular endothelial growth factor receptor. The present study suggested that sprouty2 expression was downregulated and behaved as a tumor suppressor in HNSCC. Sprouty2 expression in tumor cells enhanced sensitivity to sorafenib. Further studies are required to define the clinical impact of sprouty2 in patients with HNSCC.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Drug Resistance, Neoplasm/genetics , Gene Expression , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Hyperplasia , Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Neoplasm Grading , Neoplasm Metastasis , Neoplasm Recurrence, Local , Niacinamide/analogs & derivatives , Niacinamide/pharmacology , PTEN Phosphohydrolase/metabolism , Phenylurea Compounds/pharmacology , Phosphorylation , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Sorafenib , Squamous Cell Carcinoma of Head and Neck , Tumor Burden
8.
Int J Mol Med ; 29(5): 920-6, 2012 May.
Article in English | MEDLINE | ID: mdl-22322462

ABSTRACT

Sprouty2 (Spry2) was identified recently as a tumor suppressor gene in cancer cells which inhibits the activation of receptor tyrosine kinases (RTKs). The present study explored the effect of Spry2 in colon cancer cells in order to assess its potential use in the treatment of colon cancer. Expression of Spry2 inhibited the growth of a colon cancer cell line, HCT116, and induced sensitization to fluorouracil (5-FU) and metformin. Spry2 promoted apoptosis of cancer cells in association with activation of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) pathway and the blockade of Ras-Raf-Erk signaling. Treatment of Spry2-HCT116 cells with metformin resulted in a more prominent effect on the inhibition of cell migration. Inhibition of microRNA-21 (mir­21) induced upregulation of Spry2 and PTEN which underscores the importance of mir-21 in Spry2-associated tumorigenesis of the colon. These results point toward a potential strategy for colon cancer treatment worthy of further investigation.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Colonic Neoplasms/drug therapy , Fluorouracil/pharmacology , Hypoglycemic Agents/pharmacology , Intracellular Signaling Peptides and Proteins/genetics , Metformin/pharmacology , MicroRNAs/genetics , Cell Movement , Cell Proliferation , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , HCT116 Cells , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins , MicroRNAs/metabolism , PTEN Phosphohydrolase/genetics , PTEN Phosphohydrolase/metabolism , Up-Regulation
9.
Genomics ; 97(4): 205-13, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21195163

ABSTRACT

EBV infects more than 90% of the human population and persists in most individuals as a latent infection where the viral genome is silenced by host-driven methylation. The lytic cycle is initiated when the viral protein Zta binds to methylated BRLF1 and BRRF1 promoters. Although studies reveal the role of Zta and methylation changes in the viral genome upon EBV infection to reactivation, whether Zta plays any role in alteration of methylation in the host genome remains unknown. Using an inducible model, we demonstrate that global DNA methylation, based on whole-genome 5-methylcytosine content, and regional DNA methylation in repetitive elements, imprinting genes and the X chromosome, remains unchanged in response to Zta expression. Expression of DNA methyltransferases was also unaffected by ectopically expressed Zta. Our data imply that alteration of host gene expression following EBV reactivation may reflect methylation-independent Zta-mediated gene activation and not epigenetic modification of the host genome.


Subject(s)
DNA Methylation/genetics , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Infections/virology , Herpesvirus 4, Human/metabolism , Trans-Activators/metabolism , 5-Methylcytosine/metabolism , Base Sequence , Cell Line, Tumor , Early Growth Response Protein 1/genetics , Early Growth Response Protein 1/metabolism , Genome, Viral/genetics , Genomic Imprinting , Herpesvirus 4, Human/genetics , Humans , Immediate-Early Proteins/genetics , Immediate-Early Proteins/metabolism , Insulin-Like Growth Factor II/genetics , Insulin-Like Growth Factor II/metabolism , Molecular Sequence Data , Promoter Regions, Genetic , Sequence Analysis, DNA , Trans-Activators/genetics , X Chromosome Inactivation/genetics
SELECTION OF CITATIONS
SEARCH DETAIL
...