• 대한예방의학회:학술대회논문집
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• 2004.10a
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• pp.39-40
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• 2004

• Journal of Microbiology and Biotechnology
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• v.13 no.3
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• pp.422-428
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• 2003

Umbilical cord blood (UCB), a rich source of hematopoietic stem/progenitor cells, has been proposed as an alternative to bone marrow and peripheral blood for transplantation treatment. Ex vivo expansion of cord blood stem cells could make the use of cord blood transplant feasible even for adult patients. However, the optimal cytokine cocktail for expansion of stem cells is yet to be established. This study compares proliferation, apoptosis, and telomerase activities in human cord blood stem cells cultured ex vivo with FLT3 ligand (FL)/thrombopoietin (TPO) or FL/TPO/stem cell factor (SCF), with a view to determine optimal combination of cytokines. CD34+ cells were cultured in DMEM containing either FL (50 ng/ml) and TPO (10 ng/ml) (FT group) or FL (50 ng/ml), TPO (10 ng/ml) and SCF (50 ng/ml) (FTS group). The cell proliferation rate was ten times higher in the FTS group. Although cells cultured with the two different combinations of cytokines were maintained for a long term (up to 8 weeks), a large number of cells underwent differentiation during this period. Cells cultured in FTS displayed lower levels of apoptosis compared to those of the FT group during the Initial 7 days of culture. The CD34+ fraction in both groups was markedly decreased to $21-30\%$ , and only $5-6\%$ was detected at 14 days of culture. Telomerase activity detected in human CD34+ cord blood at low levels was upregulated during the early phase of culture and decreased to baseline levels in the later phase. The telomerase activity of cord blood cultured in FT was lower than that of the FTS group. Our results suggest that, on adding stem cell factors to the FT cytokines, cultured CD34+ cord blood cells display a greater degree of cell proliferation and decreased apoptosis. However, during CD34+ cord blood cell culture, a Barge number of cells undergo differentiation, indicating that more potent novel cytokines or new culture conditioning methods should be developed to maintain their ability to engraft and sustain long-term hematopoiesis.

• Herbal Formula Science
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• v.26 no.4
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• pp.319-327
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• 2018

Objectives : Astragali Radix is known as a perennial plant, and it is estimated that there may be differences in the contents and their components depending on the ages. The components of astragali radix may activate differently. Methods : The astragali radix components cultivated in Jecheon( one year ), Korea, Shanxi province( 7 years ), China, Inner Mongolia( 5 years) and Inner Mongolia ( 8 years ) were extracted with pure ethyl alcohol and identified the component molecules. The extracted components of astragali radix were measured the activity of Telomerase for confirmation of their Telomere lengths. Results : The cell activity has been shown the greatest contribution in astragali radix of Inner Mongolia(8 years). Although there is the difference in cell activity between the two products of the 5 and 7 years, the difference between the values was small and the 7 years product was slightly higher than 5 years product. Conclusions : Total Astragaloside contents were highest in the product of Inner Mongolia(8 years), followed by the 7 year product of Shanxi province. Especially, astragaloside and cycloastragenol (TA-65) among the astragali radix components have shown to be increased Telomerase activity in the DNA metabolism of the cells, and the efficacy depends on the ages of growth.

• The Korea Journal of Herbology
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• v.27 no.3
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• pp.39-55
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• 2012

Objectives : Recently there have been encouraging results, from a western perspective, in the cancer research field regarding the anticancer effects of herbal medicine. This paper was aimed to review herbal medicine playing its anticancer role in terms of apoptosis, inflammation control, differentiation and telomerase. Methods : New studies for tang, medicinal herb itself or effective ingradients of medicinal herb showing anti-cancer effectiveness were reviewed and summarized in terms of pharmacological action. Results : Ethanol extracts of $Spatholobus$ $suberectus$ greatly inhibited cancer cell growth inducing cell apoptosis and cytotoxic effects. $Scutellaria$ $baicalensis$ may be responsible for its anticancer activity showing inhibition of $PGE_2$ synthesis via suppression of COX-2 expression. Saikosaponins isolated from $Bupleurum$ induced the differentiation of C6 glioma cells, cancer cells, into astrocytes, normal cells. Acetone extract of $Bupleurum$ $scorzonerifolium$ inhibited proliferation of human lung cancer cells via inducing apoptosis and suppressing telomerase activity. Conclusions : Herbal medicine inhibited cancer cell growth inducing cell apoptosis and cytotoxic effects. Inflammation persisting for a decade eventually elevates the risk of cancer sufficiently that it is discernible in case control epidemiological studies. Differentiation therapy is defined as a therapy to treat cancers by inducing differentiation of the stem cells. Telomerase expression is a hallmark of cancer. Nearly the complete spectrum of human tumors has been shown to be telomerase positive.

• Archives of Pharmacal Research
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• v.28 no.3
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• pp.351-357
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• 2005

Endosulfan is one of the organochlorine pesticides, which are well-known endocrine disruptors (EDs), and it acts as an estrogen agonist. Estrogen is a group of hormones that play an important role in mammary gland function and are implicated in mammary carcinogenesis. In the present study, we studied the effects of endosulfan on nodule like alveolar lesion (NLAL) formation in mouse mammary gland development using a mouse mammary gland organ culture (MMOC) system. Although endosulfan-treated mammary glands did not form NLALs, more alveolar buds were formed in this group than in the negative control (vehicle-treated) group. In addition, telomerase reverse transcriptase (TERT) mRNA expression levels were increased in endosulfan-treated mammary glands in a dose-dependent manner. Telomerase can be activated by estrogen, therefore, we examined the effects of endosulfan on telomerase activity, and found that the telomerase activity in estrogen receptor-positive MCF-7 cells was up-regulated by endosulfan treatment. Moreover, this activation was accompanied by the up­regulation of the TERT mRNA expression. Also, transient expression assays using CAT reporter plasm ids containing various fragments of the TERT promoter showed that this imperfect palindromic estrogen-responsive element is almost certainly responsible for the transcriptional activation by endosulfan. These results may help elucidate the endocrine disrupting mechanism of endosulfan.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.133-140
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• 2009

Caveolin may be a molecular target for modulation of aging process in cochlear hair cells and have association with oxotoxicity. First we investigated the basal expression of caveolin-1, caveolin-2, caveolin-3, nitric oxide synthase, and superoxide dismutase in UB/OC-1 cochlear hair cell line. By using a RNA interference technique, we investigated whether down-regulation of caveolin influenced telomerase activity and reactive oxygen species (ROS) production in cochlear hair cells. In addition, cisplatin and gentamycin, known ototoxic drugs, were administered to the cochlear cells to determine their impact on caveolin expression. Further attempts at elucidating cellular aging mechanism with caveolin and ototoxic drugs were carried out. The main discoveries were the presence of caveolin-1 in UB/OC-1 cells and that down-regulation of caveolin-1 reduced protein kinase A activity. Telomerase was activated by caveolin down-regulation and caveolin down-regulation inhibited oxidative stress at the mitochondrial level. When cisplatin and gentamycin were administered to the cochlear hair cells during a caveolin expression state, a decrease in telomerase activity and increase ROS activity was observed. Caveolin-1 may modulate the senescent mechanisms in cochlear cells. An increase in caveolin-1 levels can lead to ROS production in the mitochondria which may cause ototoxicity.

• Molecules and Cells
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• v.27 no.2
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• pp.143-148
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• 2009

EBV-transformed lymphoblastoid cell lines (LCLs) are used as a resource for human genetic, immunological, and pharmacogenomic studies. We investigated the biological activity of 20 LCL strains during continuous long-term subculture up to a passage number of 160. Out of 20 LCL strains, 17 proliferated up to a passage number of 160, at which point LCLs are generally considered as "immortalized". The other three LCL strains lost the ability to proliferate at an average passage number of 41, during which these LCLs may have undergone cellular crisis. These non-immortal LCL strains exhibited no telomerase activity, decreased EBV gene expression, and a lower copy number of the EBV genome and mitochondrial DNA when compared with immortal LCLs. Thus, this study suggests that sustained EBV viral activity as well as telomerase activity may be required for complete LCL immortalization.

• 대한두경부종양학회:학술대회논문집
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• 1996.11a
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• pp.265.1-265.1
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• 1996

• Reproductive and Developmental Biology
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• v.35 no.1
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• pp.105-113
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• 2011

The present study investigated the nuclear remodeling, development potential with telomerase activity and transcription level of X-linked genes (ANT3, HPRT, MeCP2, RPS4X, XIAP, XIST and ZFX) in the bovine somatic cell nuclear transfer (SCNT) embryos using two different fusion and activation methods. Female adult fibroblasts were injected into perivitelline space of in vitro matured oocytes. The oocyte-nucleus complexes were fused and followed by immediately either activated (Group 1), or activated at 1 h post-fusion (hpf) (Group 2), respectively. The incidence of normal premature chromosome condensation (PCC) at 1 hpf was slightly increased in the Group 2, compared to those of Group 1, but there was no significant (p<0.05) difference. The incidence of normal pronucleus (PN) and chromosome spread at 5 and 18 hpf were significantly (p<0.05) higher in the Group 2 than those of Group 1. The cleavage rate to 2-cell stage, developmental rate to blastocyst stage, and the mean number of total and ICM cell numbers were significantly (p<0.05) higher in the Group 2, compared to those of Group 1. Level of telomerase activity was significantly (p<0.05) higher in the SCNT blastocysts of Group 2, compared to those of Group 1. Transcript levels of HPRT, MeCP2 and XIST were not significantly (p<0.05) different between blastocysts of Group 1 and 2. However, transcript level of ANT3, RPS4X, XIAP and ZFX were significantly (p<0.05) up-regulated in the SCNT blastocysts of Group 2, compared to those of Group 1. Taken together, it is concluded that oocyte activation at 1 hpf induces the enhanced developmental potential by efficient nuclear remodeling and subsequent facilitation of the nuclear reprogramming of bovine SCNT embryos.

• Journal of Microbiology and Biotechnology
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• v.19 no.9
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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.