• Title/Summary/Keyword: Gene survival

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Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

  • Demir, Lutfiye;Yigit, Seyran;Sadullahoglu, Canan;Akyol, Murat;Cokmert, Suna;Kucukzeybek, Yuksel;Alacacioglu, Ahmet;Cakalagaoglu, Fulya;Tarhan, Mustafa Oktay
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9739-9745
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    • 2014
  • Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

Evaluation and Assessment of Biosafety for Bacillus thuringiensis (Bt)-transgenic Rice: Responses of Daphnia magna Fed on Bt-transgenic Rice Variety (해충저항성 Bacillus thuringiensis (Bt) 벼의 환경위해성 평가: 해충저항성 Bt벼가 물벼룩(Daphnia magna)에 미치는 영향)

  • Oh, Sung-Dug;Shin, Hye-Chul;Sohn, Soo-In;Lee, Ki-Jong;Kim, Hyo-Jin;Ryu, Tae-Hun;Lee, Jang-Yong;Park, Beom-Seok;Kweon, Soon-Jong;Suh, Seok-Cheol;Park, Jong-Sug
    • Journal of Applied Biological Chemistry
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    • v.54 no.4
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    • pp.296-302
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    • 2011
  • Insect-resistant transgenic rice was developed by inserting the mCry1Ac1 a modified gene from the soil bacterium Bacillus thuringiensis (Bt). For biosafety assessment, we studied the effects on survival of cantor Daphnia magna, a commonly used as a model organism in ecotoxicological studies. D. magna fed on Bt rice and its near non-genetically modified (GM) counterparts (Nakdong) grown in the same environment (100% ground rice suspension). The Bt rice was comfirmed to have the insertion of T-DNA and protein expression by the polymerase chain reaction and ELISA analysis. Feeding study showed similar cumulative immobility and abnormal response of D. magna between Bt rice and non-GM counterparts. 48 h-$EC_{50}$ values of Bt rice and non-GM rice showed 4,429 and 2,889 mg/L respectively. The rice no observed effect concentration (NOEC) values for D. magna was suggested 1,000 mg/L. We conclude that the tested Bt-rice and Nakdong similar cumulative immobility for D. magna the widely used model organism. We found out that there is strong possibility that the growth of Bt rice didn't affect to non-target insects.

Genetic variation in populations of the Korean endemic Eranthis byunsanensis (Ranunculaceae) (한국 특산식물 변산바람꽃(Eranthis byunsanensis)의 유전적 변이)

  • So, Soonku;Lee, Byongsoon;Park, Ki-Ryong
    • Korean Journal of Plant Taxonomy
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    • v.42 no.4
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    • pp.253-259
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    • 2012
  • The genetic variation in populations of Eranthis byunsanensis, an endemic and rare species of Korea, was studied using starch gel electrophoresis. All five known populations were sampled for allozyme electrophoresis of nine enzymes coded by 10 loci. The overall genetic variation of E. byunsanensis population was shown to be considerably high within the populations (A = 2.4, P = 90.0, $H_E$ = 0.311). A positive $F_{IS}$ value of E. byunsanensis indicated an overall deficiency of heterozygotes, and a low $F_{ST}$ value (0.131) showed little differentiation among populations. The high genetic variation, less genetic differentiation among populations, and a significant amount of heterozygote deficiency propose the hypothesis that they have an experience of recent isolation and fragmentation of their habitat. Thus, the rate of gene flow has been drastically reduced, and the rate of inbreeding in E. byunsanensis populations has increased. Current habitats in Mai-san and Naro-do are vulnerable due to their small population size and the levels of anthropogenic activity in the region constantly threatening survival of this species. Because of the high genetic variation and low levels of differentiation among populations in E. byunsanensis, it is not issue which populations have a priority for protection, but we may concern the plan to maintain population continuously and diminish the rate of inbreeding.

Molecular Target Therapy of AKT and NF-kB Signaling Pathways and Multidrug Resistance by Specific Cell Penetrating Inhibitor Peptides in HL-60 Cells

  • Davoudi, Zahra;Akbarzadeh, Abolfazl;Rahmatiyamchi, Mohammad;Movassaghpour, Ali Akbar;Alipour, Mohsen;Nejati-Koshki, Kazem;Sadeghi, Zohre;Dariushnejad, Hassan;Zarghami, Nosratollah
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4353-4358
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    • 2014
  • Background: PI3/AKT and NF-kB signaling pathways are constitutively active in acute myeloid leukemia and cross-talk between the two has been shown in various cancers. However, their role in acute myeloid leukemia has not been completely explored. We therefore used cell penetrating inhibitor peptides to define the contributions of AKT and NF-kB to survival and multi drug resistance (MDR) in HL-60 cells. Materials and Methods: Inhibition of AKT and NF-kB activity by AKT inhibitor peptide and NBD inhibitor peptide, respectively, resulted in decreased expression of mRNA for the MDR1 gene as assessed by real time PCR. In addition, treatment of HL-60 cells with AKT and NBD inhibitor peptides led to inhibition of cell viability and induction of apoptosis in a dose dependent manner as detected by flow cytometer. Results: Finally, co-treatment of HL-60 cells with sub-optimal doses of AKT and NBD inhibitor peptides led to synergistic apoptotic responses in AML cells. Conclusions: These data support a strong biological link between NF-kB and PI3-kinase/AKT pathways in the modulation of antiapoptotic and multi drug resistant effects in AML cells. Synergistic targeting of these pathways using NF-kB and PI3-kinase/AK inhibitor peptides may have a therapeutic potential for AML and possibly other malignancies with constitutive activation of these pathways.

A Case Report of the Primary Lung Lymphoma (폐 종괴로 발현한 원발성 폐림프종 치험 1예)

  • Kim, Ye-Ree;Youn, Seong-Yuk;Yoo, Kwang-Ha;Ahn, Chul-Min;Kim, Hyung-Joong;Jin, Choon-Jo
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.2
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    • pp.272-278
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    • 1999
  • The primary lymphoma in the lung is very rare. Moot of the primary pulmonary lymphomas, which represent 3-4 % of extra-nodal lymphomas, are low-grade B-cell lymphoma. The low-grade B-cell lymphomas progress slowly and the prognosis of these are more favorable than that of the nodal lymphomas. However, high-grade forms progress rapidly with more severe course. The diagnosis of primary pulmonary lymphomas generally relies on the histopathologic findings of lung specimens obtained by surgical excision of the lesions or open-lung biopsy. Recently, less aggressive biopsies(transbronchial, transthoracic) and/or immunocyto-chemical, immunochemical and gene rearrangement studies on materials obtained by bronchoalveolar lavage have been used occasionally. The treatment of the primary pulmonary lymphomas has not been precisely codified. Several clinical data suggest that limited surgery or non-aggressive chemotherapy can provide long-term survival in patients with such slowly developing neoplasm, and demonstrated the need for the development of noninvasive diagnootic methods. In this study, we report a case of high-grade B-cell lymphoma of the lung which was treated with combination chemotherapy.

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Probiotic Properties and Immunomodulator Evaluation of the Potential Feed Additive Pediococcus acidilactici SRCM102607 (잠재적 사료첨가제로서 Pediococcus acidilactici SRCM102607의 생균제 특성 및 면역활성 효과)

  • Shin, Su-Jin;Ha, Gwangsu;Jeong, Su-Ji;Ryu, Myeong Seon;Kim, Jinwon;Yang, Hee-Jong;Kwak, Mi-Sun;Sung, Moon-Hee;Jeong, Do-Youn
    • Journal of Life Science
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    • v.30 no.10
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    • pp.896-904
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    • 2020
  • The purpose of this study was to investigate the probiotic characteristics and immune activities of selected lactic acid bacterial (LAB) strains as feed additives in livestock. 301 LAB strains isolated from traditional fermented foods were first assessed for their antibacterial activity potential. Of the 301 isolates, five showed antibacterial activity against five livestock pathogens (Esherichia coli KCCM11234, Listeria monocytogens KCTC3710, Salmonella Typhimurium KCTC1926, Staphylococcus aureus KCCM11593, and Shigella flexneri KCTC2517). The probiotic characteristics of the five selected strains were also investigated by antioxidative activity, hemolysis, bile salt hydrolase, acid resistance and bile tolerance. The SRCM102607 strain was found to have superior probiotic properties and was selected for further experimentation. 16S rRNA gene sequencing showed that SRCM102607 is Pediococcus acidilactici, which was labeled as P. acidilactici SRCM102607 (KCCM 12246P). The survival characteristics of P. acidilactici SRCM102607 in artificial gastrointestinal conditions were assessed under exposed acidic (pH 2.0) and bile (0.5% and 1.0%) conditions. P. acidilactici SRCM102607 was also confirmed to have resistance to various antibiotics, including amikacin, gentamicin, vancomycin, and etc. The TNF-α production by P. acidilactici SRCM102607 was 171.86±4.00 ng/ml. These results show that P. acidilactici RCM102607 has excellent potential for use as a probiotic livestock feed additive.

Prognostic Significance of Hes-1, a Downstream Target of Notch Signaling in Hepatocellular Carcinoma

  • Zou, Jing-Huai;Xue, Tong-Chun;Sun, Chun;Li, Yan;Liu, Bin-Bin;Sun, Rui-Xia;Chen, Jie;Ren, Zheng-Gang;Ye, Sheng-Long
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3811-3816
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    • 2015
  • Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

PU.1 Is Identified as a Novel Metastasis Suppressor in Hepatocellular Carcinoma Regulating the miR-615-5p/IGF2 Axis

  • Song, Li-Jie;Zhang, Wei-Jie;Chang, Zhi-Wei;Pan, Yan-Feng;Zong, Hong;Fan, Qing-Xia;Wang, Liu-Xing
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3667-3671
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    • 2015
  • Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

Radiosensitization Effect of Overexpression of Adenovirus-mediated SIRT6 on A549 Non-small Cell Lung Cancer Cells

  • Cai, Yong;Sheng, Zhao-Ying;Liang, Shi-Xiong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7297-7301
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    • 2014
  • Objective: To explore the radiosensitization effect of overexpression of silent information regulator 6 (SIRT6) on A549 non-small cell lung cancer (NSCLC) cells. Methods: Adenovirus vector Ad-SIRT6 causing overexpression of SIRT6 was established. Western blotting and MTT assay were adopted to detect the level of SIRT6 protein and the inhibitory rate of A549 cell proliferation after different concentrations of adenovirus transduction (0, 25, 100, 200, and 400 pfu/cell) for 24 h. Control group, Ad-null group and Ad-SIRT6 group were designed in this experiment and virus concentration of the latter two groups was 200 pfu/cell. Colony formation assays were employed to test survival fraction (SF) of the 3 groups after 0, 2, 4, 6, 8, 10 X-ray irradiation. Flow cytometry was used to detect the status of cell cycle of 3 groups after 48 h of 4Gy X-ray irradiation and Western blotting was used to determine the expression of apoptosis-related genes of 3 groups after 48 h of 4GyX-ray irradiation. Results: In the range of 25~400 pfu/cell, the inhibitory rate of A549 cell proliferation increased as adenovirus concentration raised. The inhibitory rates under the concentrations of 0, 25, 100, 200, and 400 pfu/cell were 0%, $4.23{\pm}0.34%$, $12.7{\pm}2.57%$, $22.6{\pm}3.38%$, $32.2{\pm}3.22%$, $38.7{\pm}4.09%$ and $47.8{\pm}5.58%$ and there were significantly differences among groups (P<0.05). SF in Ad-SIRT6 group was lower than Ad-null and control groups after 4~10Gy X-ray irradiation (P<0.05) and the sensitization enhancement ratio (SER) was 1.35 when compared with control group. Moreover, after 48 h of 4Gy X-ray irradiation, there appeared a significant increase in G1-phase cell proportion, upregulated expression of the level of apoptosis-promoting genes (Bax and Cleaved caspase-3), but a obvious decline in S-phase and G2-phase cell proportion and a significant decrease of the level of apoptosis-inhibiting gene (Bal-2) in the Ad-SIRT6 group (P<0.05). Conclusion: The over-expression of adenovirus-mediated SIRT6, which has radiosensitization effect on A549 cells of NSCLC, can inhibit the proliferation of A549 cells and cause G0/G1 phase retardation as well as induce apoptosis of cells.

Polyethylenimine Mediated Gene Delivery with Various Liposomal Formulations (폴리에틸렌이민 및 그들의 리포좀이 중재된 Plasmid DNA의 운반)

  • Han, In Sook;Jun, Mi Sook;Lee, Kab Yong
    • Journal of the Korean Chemical Society
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    • v.43 no.2
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    • pp.193-198
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    • 1999
  • The transfection efficiency of plasmid DNA was inspected using multi-cationic polymer, 5, 10, 25 and 50KD polyethylenimine (PEI). The optimal neutralization ratio of PEI/DNA complexes by agarose assay was 1.5-2.0 (nmol/nmol) without much difference in molecular weight of PEI.In vitro transfection assay, most of PEI-mediated plasmid delivery was better compared to the naked DNA. Especially, 25KD PEI at optimal condition gave higher transfection rather than the standard assay of DEAE-dextran or Lipofectin. To enhance the cell targeting delivery, the liposome formulations were introduced using phospholipids. As a result, PC/PE liposomes increased 2-2.5 times of the transfection efficiency of PEI single or PC/PE single delivery, but not the case of 25KD PEI. Moreover, the DOTAP/PE-introduced PEI delivery reduced the transfection of DOTAP/PE single delivery. All these results proved that the PEI can be used not only good transfectants and but also good DNA condensing agents in neutral/anionic liposome for cell targeting delivery.

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