• Title/Summary/Keyword: R21

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MiR-21 Upregulation Induced by Promoter Zone Histone Acetylation is Associated with Chemoresistance to Gemcitabine and Enhanced Malignancy of Pancreatic Cancer Cells

  • Song, Wei-Feng;Wang, Lei;Huang, Wei-Yi;Cai, Xun;Cui, Jiu-Jie;Wang, Li-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7529-7536
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    • 2013
  • Background and Aims: MicroRNA-21 (miR-21) is reported to be overexpressed and to contribute to proliferation, apoptosis and gemcitabine resistance in pancreatic ductal adenocarcinomas (PDACs). The aims of this study were to explore regulation of miR-21 expression by epigenetic change and its impact on chemoresistance and malignant properties of of pancreatic cancer. Materials and methods: We retrospectively collected 41 cases of advanced pancreatic cancer patients who were sensitive or resistant to gemcitabine and assessed levels of serum circulating miR-21 for correlation with cytotoxic activity. Histone acetylation in the miR-21 promoter was also studied in gemcitabine-sensitive and gemcitabine-resistant PDAC cells. Gemcitabine-resistant HPAC and PANC-1 cells were transfected with pre-miR-21 precursors (pre-miR-21) and antisense oligonucleotides (anti-miR-21), and were treated with TSA. Finally, invasion and metastasis assays were performed and alteration in mir-21, PTEN, AKT and pAKT level was evaluated in these cells. Results: Serum miR-21 levels were increased in gemcitabine-resistant PDAC patients compared with gemcitabine-sensitive subjects. The miR-21 levels were increased in 6 PDAC cells treated with gemcitabine significantly, associated with 50% inhibitory concentrations ($IC_{50}s$). Histone acetylation levels at miR-21 promoter were increased in PDAC cells after treatment with gemcitabine. Enhanced invasion and metastasis, increased miR-21 expression, decreased PTEN, elevated pAKT level were demonstrated in gemcitabine-resistant HPAC and PANC-1 cells. Pre-miR-21 transfection or TSA treatment further increased invasion and metastasis ability, decreased PTEN, and elevated pAKT levels in these two lines. In contrast, anti-miR-21 transfection could reverse invasion and metastasis, and PTEN and pAKT expressions induced by gemcitabine. Conclusions: MiR-21 upregulation induced by histone acetylation in the promoter zone is associated with chemoresistance to gemcitabine and enhanced malignant potential in pancreatic cancer cells.

MicroRNAs as Promising Biomarkers for Tumor-staging: Evaluation of MiR21 MiR155 MiR29a and MiR92a in Predicting Tumor Stage of Rectal Cancer

  • Yang, Yun;Peng, Wei;Tang, Tian;Xia, Lin;Wang, Xiao-Dong;Duan, Bao-Feng;Shu, Ye
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5175-5180
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    • 2014
  • Objective: In this study, tumor-stage predictive abilities of miR21, miR155, miR29a and miR92a were evaluated in rectal cancer (RC). Methods: Expression of miR21, miR155, miR29a and miR92a was detected and quantitated in tumor tissue and in adjacent normal tissue from 40 patients by TaqMan MicroRNA assay. Results: Significant overexpression of miR21, miR155, miR29a and miR92a was observed in RC tissues. While high expression of miR21, miR155 and miR29a in N1-2 and C-D stages presented a potential correlation with N and Duke stages, partial correlation analysis suggested that only miR155 rather than miR21 and miR29a played a greater influencing role. Receiver operating characteristics (ROC) curve analysis showed that miR155 could discriminate N0 from N1-2 with 85.0% sensitivity and 85.0% specificity, N2 from N0-1 with 90.0% sensitivity and 96.7% specificity, and C-D stage from A-B stage with 81.0% sensitivity and 84.2% specificity. Conclusions: Increase in expression of miR155 might represent a novel predictor for RC N and Dukes staging.

The MSW Pyrolysis & Melting Plant DONGBU R21 (생활폐기물 열분해용융시설 동부 R21)

  • Choi, Sang-Sim;Kim, Seok-Hwan;Kim, Kyong-Lae
    • 한국연소학회:학술대회논문집
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    • 2004.06a
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    • pp.314-328
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    • 2004
  • Mitsui Engineering and Shipbuilding Co., Ltd. (MES) has completed Recycling 21 (R21) pyrolysis and melting technology for municipal solid wastes. The basic technology is licensed from Siemens, but MES has made major improvements to the design and operation of the R21 system Consequently, up to now, MES has been completed six (6) R21 plants in Japan. The following text will provide a brief overview of the design & operating features of R21 technology, focused on the reliability of system and low emission of hazardous material, which have been proved by the successful construction & operation experience of the plants.

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Phase III of Study of R-CHOP-21 vs R-CHOP-14 for Untreated Stage III and IV B-cell Non-Hodgkin's Lymphoma: a Report from Iran

  • Payandeh, Mehrdad;Najafi, Safa;Shojaiyan, Fateme-Zahra;Sadeghi, Masoud
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1513-1517
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    • 2016
  • Background: A combination of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is one of the most effective front-line therapies to treat B-cell non-Hodgkin's lymphoma (NHL). The aim of this trial was to evaluate overall survival (OS), progression free survival (PFS) and toxicity of R-CHOP-14 compared to R-CHOP-21 in untreated stage III and IV B-cell NHL patients with Iranian ethnicity. Materials and Methods: In phase III trial, patients with previously untreated stage III and IV indolent and aggressive B-cell NHL were randomly assigned by using a minimization method to receive six to eight cycles of either R-CHOP-21 (administered every 21 days) or R-CHOP-14 (administered every 14 days with granulocyte colony-stimulating factor). Results: A total of 143 patients were randomly enrolled in our study (66 patients in R-CHOP-14 group and 77 patients in R-CHOP-21), between 2011 and 2014. The mean follow-up was 45 months at the time of treatment analysis. The 2-year and 5-year PFS rates for the R-CHOP-14 group were 83.6% vs 73.6% and for R-CHOP-21 group were 75% vs 54%. The 2-year and 5-year OS rates for R-CHOP-14 group were 98% vs 89% and for R-CHOP-21 group were 84.4% vs 67.5%. There was a significant correlation for PFS and OS in the two arms. There was no significant difference between adverse events with the two regimens. Conclusions: In our research improved survival was found with CHOP-14 as compared to CHOP-21. It is possible that drug metabolism in different races/ethnicities may be one important factor.

Identification of Serum MicroRNA-21 as a Biomarker for Early Detection and Prognosis in Human Epithelial Ovarian Cancer

  • Xu, Yun-Zhao;Xi, Qing-Hua;Ge, Wen-Liang;Zhang, Xiao-Qian
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.1057-1060
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    • 2013
  • Recent investigations have confirmed up-regulation of serum miR-21 and its diagnostic and prognostic value in several human malignancies. In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC.

The Study of CYFRA 21-1 and Epidermal Growth Factor Receptor Levels in Cancer Tissue of Bronchogenic Carcinoma Patients (폐암환자의 암조직내 CYFRA 21-1과 Epidermal Growth Factor Receptor의 측정치에 대한 연구)

  • 김대연;김송명
    • Journal of Chest Surgery
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    • v.30 no.9
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    • pp.854-861
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    • 1997
  • CYPRA 21-1 is known to be a cytokeratin 19 fragment, and it can be detected by using two specific monoclonal antibodies (KS 19-1 and BM 19-21) and can be clinically applied as a useful circulating tumor marker The epidermal growth factor receptor (EGF-R) expression was evaluated and characterized by its tyrosine protein kinase activity and by its ligand-stimulated autophosphorylation, a property shared with other peptide growth factor receptors. Autocrine or para'urine action was initiated by a growth factor, or by a transforming growth factor o, which had an extensive homology with EGP and which also stimulated tyrosine kinase activity on the EGF-R. The CYFRA 21-1 and the EGF-R levels in 30 patients with primary lung tumors were investigated. There were 24 patients with squamous cell carcinomas and 6 patients with adenocarcinomas. Specimen 5 mm3 in size were sampled at three different locations ; the main lesion, the boundary between the lesion and the unaffected tissue, and the unaffected tissue of the patients. The results were as follows 1. The CYPRA 21-1 concentration in the cancer boundary, the most malignant region,(348.6 : 89.9 ng/ml) was the lowest value. The CYFRA 21-1 concentration in unaffected tissue,(718.4$\pm$77.8 ng/ml) was higher than that in the main lesion. which had intact cellularity. 2. The EGF-R concentration in the main lesion was higher than that in the unaffected tissue, and the EGF-R concentration in a squamous cell cacinoma was higher than that in an adenocarcinoma. also, the EGF-R concentration in the cancer b undary was highest at stage 1, ll. The EGF-R concentration was higher in the main cancer lesion that in the unaffected tissue at stage 111, IV. 3. The CYFRA 21-1 was a cytoplasmic skeleton and the EGF-R was a cell-wall component; there was no correlation. In conclusion, CYFRA 21-1 was abundant in the cytoplasm but had a higher concentration in the unaffected tissue than in the main cancer lesion. The CYFRA 21-1 concentration of the tissue did not reflect the amount of cancer activity, the EGP-R was located in the cell membrane, the level of tissue that reflects cancer activity, so the main cancer lesion had a higher concentration than the unaffected tissue. CYFRA 21-1 is not a useful tumor maker at the tissue level. Because the EGF-R concentration re(looted the cancer activity, its a useful tumor marker for lung cancer.

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Genomic Analysis of miR-21-3p and Expression Pattern with Target Gene in Olive Flounder

  • Jo, Ara;Lee, Hee-Eun;Kim, Heui-Soo
    • Genomics & Informatics
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    • v.15 no.3
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    • pp.98-107
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    • 2017
  • MicroRNAs (miRNAs) act as regulators of gene expression by binding to the 3' untranslated region (UTR) of target genes. They perform important biological functions in the various species. Among many miRNAs, miR-21-3p is known to serve vital functions in development and apoptosis in olive flounder. Using genomic and bioinformatic tools, evolutionary conservation of miR-21-3p was examined in various species, and expression pattern was analyzed in olive flounder. Conserved sequences (5'-CAGUCG-3') in numerous species were detected through the stem-loop structure of miR-21-3p. Thus, we analyzed target genes of miR-21-3p. Among them, 3' UTR region of PPIL2 gene indicated the highest binding affinity with miR-21-3p based on the minimum free energy value. The PPIL2 gene showed high expression levels in testis tissue of the olive flounder, whereas miR-21-3p showed rather ubiquitous expression patterns except in testis tissue, indicating that miR-21-3p seems to control the PPIL2 gene expression in a complementary repression manner in various tissues of olive flounder. Taken together, this current study contributes to infer the target gene candidates for the miR-21-3p using bioinformatics tools. Furthermore, our data offers important information on the relationship between miR-21-3p and target gene for further functional study.

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

  • Wang, Jian-Jun;Wang, Ze-You;Chen, Rui;Xiong, Jing;Yao, Yong-Liang;Wu, Jian-Hong;Li, Guang-Xin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4203-4209
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    • 2015
  • Exosomes, membranous nanovesicles, naturally carry bio-macromolecules or miRNA and play impoetant roles in tumor pathogenesis. Here, we showed that macrophages cell-derived exosomes can function as vehicles to deliver exogenous miR-21 inhibitor into BGC-823 gastric cancer cells. Exosomes loaded with miR-21inhibitor significantly increased miR-21 levels in BGC-823, but miR-21inhibitor loaded in exosomes exerted an opposite effect. miRNA transfected with exosomes had less cellular toxicity to host cells compared to conventional transfection methods. The miR-21inhibitor loaded exosomes promoted the migration ability and reduced apoptosis of BGC-823 gastric cancer cells. These observations indicate that miR-21 acts as a tumor promoter by targeting the PDCD4 gene and preventing apoptosis of gastric cancer cells through inhibition of PDCD4 expression. Furthermore, exosome -mediated miR-21 inhibitor delivery resulted in functionally more efficient inhibition and less cellular toxicity compared to conventional transfection methods. Similar approaches could be useful in modification of target biomolecules in vitro and in vivo. These findings contribute to our understanding of the functions of miR-21 and exosomes as a carrier for therapy of gastric cancer.