• 제목/요약/키워드: mTERT

검색결과 213건 처리시간 0.021초

Cancer Cell Targeting with Mouse TERT-Specific Group I Intron of Tetrahymena thermophila

  • Ban, Gu-Yee;Song, Min-Sun;Lee, Seong-Wook
    • Journal of Microbiology and Biotechnology
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    • 제19권9호
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    • pp.1070-1076
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    • 2009
  • Telomerase reverse transcriptase (TERT), which prolongs the replicative life span of cells, is highly upregulated in 85-90% of human cancers, whereas most normal somatic tissues in humans express limited levels of the telomerase activity. Therefore, TERT has been a potential target for anticancer therapy. Recently, we described a new approach to human cancer gene therapy, which is based on the group I intron of Tetrahymena thermophila. This ribozyme can specifically mediate RNA replacement of human TERT (hTERT) transcript with a new transcript harboring anticancer activity through a trans-splicing reaction, resulting in selective regression of hTERT-positive cancer cells. However, to validate the therapeutic potential of the ribozyme in animal models, ribozymes targeting inherent transcripts of the animal should be developed. In this study, we developed a Tetrahymena-based trans-splicing ribozyme that can specifically target and replace the mouse TERT (mTERT) RNA. This ribozyme can trigger transgene activity not only also in mTERT-expressing cells but hTERT-positive cancer cells. Importantly, the ribozyme could selectively induce activity of the suicide gene, a herpes simplex virus thymidine kinase gene, in cancer cells expressing the TERT RNA and thereby specifically hamper the survival of these cells when treated with ganciclovir. The mTERT-targeting ribozyme will be useful for evaluation of the RNA replacement approach as a cancer gene therapeutic tool in the mouse model with syngeneic tumors.

酸性溶煤 속에서의 $\beta$-Mercaptan에 대한 親核性 添加反應에 관한 硏究 (III) n-Propylmercaptan 및 tert-Butylmercaptan 과의 반응 (The Kinetics and Mechanism of Nucleophilic Addition of Mercaptan to a ${\beta}$-Nitrostyrene in Acidic Media(III) n-Propylmercaptan and tert-Butylmercaptan)

  • 박옥현;김태린
    • 대한화학회지
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    • 제12권4호
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    • pp.177-183
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    • 1968
  • 親核性 添加反應性에 있어서의 mucleophile의 反應性을 정량적으로 연구하고자 前報에 이어 여러 pH에서 3,4-methylenedioxy-$\beta$-nitrostyrene에 n-propyl- 과 tert-butylmercaptan을 첨가시켜 그의 添加反應速度常數를 측정한 결과 n-propylmercaptide ion과 tert-butylmercaptide ion에 대해 각각 $1.26{\times}10^8$$3.98{\times}10^6\;M^{-2},\;sec^{-1}$를 얻었으며, 또 n-propyl 및 tert-butylmercaptan 분자의 添加反應速度常數로서 $7.07{\times}10^{-3}$$1.5{\times}10^3\;M^{-1},\;sec^{-1}$을 각각 얻었다. 한편 염기성 뿐만 아니라 산성용매 속에서도 그의 應速 메카니즘을 잘 설명할 수 있는 全體應速度式을 구하였다.

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An RNA Mapping Strategy to Identify Ribozyme-Accessible Sites on the Catalytic Subunit of Mouse Telomerase

  • Song, Min-Sun;Lee, Seong-Wook
    • Genomics & Informatics
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    • 제5권1호
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    • pp.32-35
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    • 2007
  • Telomerase reverse transcriptase (TERT) is an enzymatic ribonucleoprotein that prolongs the replicative life span of cells by maintaining protective structures at the ends of eukaryotic chromosomes. Telomerase activity is highly up-regulated in 85-90% of human cancers, and is predominately regulated by hTERT expression. In contrast, most normal somatic tissues in humans express low or undetectable levels of telomerase activity. This expression profile identifies TERT as a potential anticancer target. By using an RNA mapping strategy based on a trans-splicing ribozyme library, we identified the regions of mouse TERT (mTERT) RNA that were accessible to ribozymes. We found that particularly accessible sites were present downstream of the AUG start codon. This mTERTspecific ribozyme will be useful for validation of the RNA replacement as cancer gene therapy approach in mouse model with syngeneic tumors.

Sodium Borohydride 하에서 산소에 의한 포화- 및 불포화-질소주게 거대고리 착물 $(M=Co^{3+},\;Fe^{3+}$$Mn^{3+})$을 촉매로 한 Hindered Phenols의 산화반응 (Saturated- and Unsaturated-Azamacrocyclic Complexes $(M = Co^{3+}, Fe^{3+}$ or $Mn^{3+})$ Catalyzed Oxidation of Hindered Phenols by Molecular Oxygen under Sodium Borohydride)

  • 박유철;김성수;나훈길
    • 대한화학회지
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    • 제37권7호
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    • pp.648-654
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    • 1993
  • $[M(cyclam)X_2]Y(M=Co^{3+},\;Fe^{3+},\;Mn^{3+}\;:\;X=Cl-^,\;Br^-,\;NCS^-\;:\;Y=Cl^-,\;Br^-,\;NCS^-),\;[Co(trans-14-diene)X_2]Y(X=Cl^-,\;Br^-\;:\;Y= ClO_4^-)$$[Co(trans-14-diene)](ClO_4)_2$ 착이온은 sodium borohydride 하에서 산소를 활성화시킬 수 있었다. 활성화된 산소에 의한 2,4-di-tert-butylphenol 과 2,6-di-tert-butylphenol 산화반응의 생성물질을 각각 2,4-tert-butyl-1,6-benzoquinone(BQ) 와 3,5,3',5'-tetra-tert-butyldiphenoquinone(DPQ) 이었다. BQ와 DPQ 생성반응에서 포화 거대고리 리간드 착물인 $[Co(cyclam)X_2]Y$은 불포화 거대고리착물 $[Co(trans-14-diene)X_2]Y$에 비하여 더 효과적인 촉매제이었다. 촉매로 작용한 Co(III)-거대고리착물과 산소간의 몰 결합비$(O_2/M)$는 1/1이었고, $[M(cyclam)Cl_2]Cl(M=Fe(III)$, Mn(III))에서는 이들 비가 1/2이었다. 반응(10)과 (2)에서 산소분자의 활성종은 Co(III) 거대고리착물이온과 $[M(cyclam)Cl_2]Cl(M=Fe(III)$, Mn(III))에서 각각 superoxolike$({O_2}^-)$와 peroxolike$({O_2}^{2-})$로 가정하였다.

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Enzymatic Synthesis of L-tert-Leucine with Branched Chain Aminotransferase

  • Seo, Young-Man;Yun, Hyung-Don
    • Journal of Microbiology and Biotechnology
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    • 제21권10호
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    • pp.1049-1052
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    • 2011
  • In this study, we demonstrated the asymmetric synthesis of L-tert-leucine from trimethylpyruvate using branched-chain aminotransferase (BCAT) from Escherichia coli in the presence of L-glutamate as an amino donor. Since BCAT was severely inhibited by 2-ketoglutarate, in order to overcome this here, we developed a BCAT/aspartate aminotransferase (AspAT) and BCAT/AspAT/pyruvate decarboxylase (PDC) coupling reaction. In the BCAT/AspAT/PDC coupling reaction, 89.2 mM L-tert-leucine (ee>99%) was asymmetrically synthesized from 100 mM trimethylpyruvate.

Standardization and Method Selection for the Trenchless Repair Technology of Sewer using Cured-in-place Pipe

  • Kim, Taeeung
    • International Journal of Internet, Broadcasting and Communication
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    • 제14권2호
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    • pp.70-78
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    • 2022
  • The trenchless entire repair technology (TERT) have many different names depending on the companies, and they have the same or similar methods as well as materials. In addition, there was quiet difficulty in application of field working and even confuse to classify for new TERT, while application criteria of TERT is not listed systematically. This study proposed standardization and method for TERT affecting by pipe condition, working materials, working method, specification/quantity per unit according to field condition, strange affairs and others. Determination criteria of defective sewer pipe has proposed to effective method which modify a criteria between Ministry of Environment and Seoul Metropolitan City. A Cured-in-place pipe (CIPP) is suitable for TERT, and the design criteria for the entire broken pipe are proposed when the pipe itself deforms more than 10%. A check lists are specimen preparing, hardening site made by clamped mold, numbers, flexural and tensile property, water leak and desquamation test, and have to use material property of minimum CIPP value depend on ISO 11296-4, ISO 11297-4, KS M3550-7 and KS M3550-9.

Prognostic Relevance of Human Telomerase Reverse Transcriptase (hTERT) Expression in Patients with Gall Bladder Disease and Carcinoma

  • Deblakshmi, Raj Kumari;Deka, Manab;Saikia, Anjan Kumar;Sharma, Bir Kumar;Singh, Nidhi;Das, NN;Bose, Sujoy
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권7호
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    • pp.2923-2928
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    • 2015
  • Background: Gallbladder carcinoma (GBC) has been stated as an Indian disease, with the highest number of cases being reported from certain districts of northeast India, which has an ethnically distinct population. Unfortunately there are no scientific reports on the underlying molecular mechanisms associated with the pathogenesis of the disease from this region. Aim: The present study evaluated the role of differential expression of human telomerase reverse transcriptase (hTERT) in the development of gall bladder anomalies. Materials and Methods: Blood and tissue samples were collected from patients undergoing routine surgical resection for clinically proven cases of gallbladder disease {cholelithiasis (CL, n=50), cholecystitis (CS, n=40) and GBC (n=30) along with adjacent histopathologically proved non-neoplastic controls (n=15)} with informed consent. Whole blood was also collected from age and sex matched healthy controls (n=25) for comparative analysis. Differential hTERT mRNA expression was evaluated by semi-quantitative rt-PCR and real-time PCR based analysis using ${\beta}$-actin as an internal control. Evaluation of differential hTERT protein expression was studied by Western blot analysis and immunoflourescence. Statistical analysis for differential expression and co-relation was performed by SPSSv13.0 software. Results: Gallbladder anomalies were mostly prevalent in females. The hTERT mRNA and protein expression increased gradiently from normal

Cytotoxicity of Impregnated Dental Gingival Retraction Cord Extracts in Immortalized Human Oral Fibroblasts and Keratinocytes in vitro

  • Myung-Jin Lee;Song-Yi Yang
    • 한국재료학회지
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    • 제33권4호
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    • pp.130-134
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    • 2023
  • This study evaluated cell viability and cytokine release in immortalized human oral fibroblasts (hTERT-hNOFs) and keratinocytes (IHOK) exposed to a dental-impregnated gingival retraction cord. To prepare the extracts, dental gingival retraction cords impregnated with aluminum chloride hexahydrate were immersed in a cell culture medium for 24 h at 37 ℃. hTERT-hNOFs and IHOK were cultured for 24 h. The cell culture medium was removed and extracts of the dental gingival retraction cords were added. After incubation with the extract solution, cell viability was evaluated using an MTT assay. The levels of the cytokines IL-1α and IL-8 were measured in the supernatants of each cell type. The cell viability after exposure to the extract solution for 10 min exceeded 70 % in both cell types. The ET50 values for hTERT-hNOF and IHOK were 35.75 and 28.98 min, respectively. For IHOK, the IL-1α level was (5.35 ± 5.22) pg/mL at 10 min, (3.58 ± 5.38) pg/mL at 20 min, and (2.85 ± 4.28) pg/mL at 60 min of exposure (p > 0.05). The IL-8 level in IHOK was (67.16 ± 18.70) pg/mL at 10 min, (78.36 ± 7.50) pg/mL at 20 min, and (111.9 ± 26.10) pg/mL at 60 min of exposure (p > 0.05). Cytokine release was not observed from hTERT-hNOFs. Based on these results, cell viability and cytokine release were confirmed in cells exposed to the impregnated gingival retraction cord. In addition, the application of the extracts to hTERT-hNOF and IHOK during the actual contact time and determination of ET50 may be beneficial for evaluating the biocompatibility of dental-impregnated gingival retraction cords.

Diosgenin Inhibits hTERT Gene Expression in the A549 Lung Cancer Cell Line

  • Mohammad, Rahmati Yamchi;Somayyeh, Ghareghomi;Gholamreza, Haddadchi;Majid, Mobasseri;Yousef, Rasmi
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권11호
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    • pp.6945-6948
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    • 2013
  • Background: Diosgenin, a steroidal saponin from a therapeutic herb, fenugreek (Trigonellafoenum-graceum L.), has been recognized to have anticancer properties. Telomerase activity is not detected in typical healthy cells, while in cancer cell telomerase expression is reactivated, therefore providing a promising cancer therapeutic target. Materials and Methods: We studied the inhibitory effect of diosgenin on human telomerase reverse transcriptase gene (hTERT) expression which is critical for telomerase activity. MTT- assays and qRT-PCR analysis were conducted to assess cytotoxicity and hTERT gene expression inhibition effects, respectively. Results: MTT results showed that $IC_{50}$ values for 24, 48 and 72h after treatment were 47, 44 and $43{\mu}M$, respectively. Culturing cells with diosgenin treatment caused down-regulation of hTERT expression. Discussion: These results show that diosgenin inhibits telomerase activity by down-regulation of hTERT gene expression in the A549 lung cancer cell line.

Synthesis of New 4-(tert-Octyl)phenol Derivatives and Their Anticancer Activity against Human Prostate and Lung Cancer Cell Lines

  • Che, Haiyan;Fang, Yuanying;Gurung, Santosh K.;Luo, Jun;Yoon, Deok Hyo;Sung, Gi-Ho;Kim, Tae Woong;Park, Haeil
    • Bulletin of the Korean Chemical Society
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    • 제35권7호
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    • pp.2038-2042
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    • 2014
  • 4-(tert-Octyl)phenol derivatives bearing the D-mannitol substructure (6a, 6b, 7) were prepared from $\small{D}$-mannitol and evaluated their anticancer activity against human lung (A549) and prostate (Lncap, Du145, PC3) cancer cell lines. Among derivatives tested, the bis(tert-octyl)phenoxy compound 7 exhibited strongest proliferation inhibitory activities against human cancer cell lines tested, especially high sensitivity to human Du145 prostate cancer cells ($IC_{50}=7.3{\mu}M$).