• Title/Summary/Keyword: Human tumor cell line

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Characterization of the NF-$textsc{k}$B Activation Induced by TR8, an Osteoclastogenic Tumor Necrosis Factor Receptor Family Member

  • Kim, Hong-Hee
    • Archives of Pharmacal Research
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    • v.22 no.5
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    • pp.454-458
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    • 1999
  • TR8 is a recently identified member of the tumor necrosis factor (TNF) receptor superfamily. TR8 seems to play important roles in bone metabolism as stimulation of this receptor with its ligand, TL8 or osteoclast differentiation factor (ODF), induced the differentiation and activation of osteoclasts. Despite its important biological functions, the biochemcial events ensuing form TR8 activation have not been revealed in detail. Most of TNF receptor family proteins provoke the activation of the NF-$textsc{k}$B transcription factor. In the present study, we examined the signaling potential of TR8 to induce NF-B activation. When overexpressed in a human embryonic kidney cell line by transient transfection, TR8 caused a strong activation of NF-$textsc{k}$B, which was further increased upon stimulation with TL8. The TR8-induced NF-B activation was abrogated by the co-expression of the TRAF6 mutnat lacking the Ring and zinc finger domains and that of the kinase-inactive mutant NIK. Taken together, our study suggests that the presence of intact TRAF6 and the kiase activity of NIK may be essential for TR8 to induce NF-$textsc{k}$B activation.

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Effect of Bamboo salt-pro on carries-inducing properties of Streptococcus mutans

  • Shin, Hye-Young;You, Hyeon-Hee;Shin, Tae-Yong;Kim, Hyung-Min;You, Yong-Ouk
    • Advances in Traditional Medicine
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    • v.3 no.1
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    • pp.40-45
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    • 2003
  • We studied the effect of Bamboo salt-pro on the growth and acid production of S. mutans. The growth of S.mutans was reduced by the presence of the Bamboo salt-pro (1 mg/ml) and NaCl (1 mg/ml) significantly, and the positive control group (1 % of NaF) also exhibited antibacterial activity significantly. Bamboo salt-pro (1 mg/ml) reduced the rate of acid production by S. mutans. Bamboo salt alone did not demonstrate such a reduction in acid production at the concentration of 1 mg/ml. The inhibitory action of Bamboo salt-pro on acid production was found at a concentration of 1 mg/ml, but bamboo salt alone was not at a concentration of 1 mg/ml. In addition, we investigated the anti-inflammatory effect of Bamboo salt-pro on human mast cell line HMC-1. Bamboo salt-pro (0.1 and 0.01 mg/ml) inhibited significantly the secretion of inflammatory cytokine, tumor necrosis factor-a with $59.47{\pm}0.15%$, $51.98{\pm}0.16%$ respectively. Our results suggest that Bamboo salt-pro importantly contributes to the prevention or treatment of periodontitis and other oral diseases and inflammatory diseases.

Mutational Analysis of K-ras and p53 Genes in Human Lung and Pancreatic Carcinoma Cell Lines (사람 폐암과 췌장암 세포주에서 K-ras p53 유전자의 돌연변이에 대한 연구)

  • 정경이;정노팔
    • The Korean Journal of Zoology
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    • v.39 no.3
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    • pp.231-238
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    • 1996
  • Several types of human lung and pancreatic carcinoma cell lines were cultured and their chromosomal DNAs were extracted. These DNAs were then partially amplified by PCR (Polymerase Chain Reaction) and sequenced to analyze the types and frequency of mutations, and their possible relation in the oncogene, K-ras and suppressor gene, p53. Regardless of the cell line origin, 81% were found to possess at least one mutation. Among the cell lines analyzed, 54.5% of the mutations were found in either K-ras or p53. Except for one nonsense mutation, all mutations were missense with either base insertions or substitutions. Furthermore, besides the p53 codons Known to be mutated simultaneously with' ras to enhance tumor growth, p53 164-165 and 248 were found to be mutated simultaneously with K-ms. Regardless of the site of p53 mutation, all K-ras mutations found in these cases occurred at exon 1, codon 12.

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Effects of Hoesaeng-san Ethanol Extract on the Human Mast cell-mediated Inflammatory Responses (회생산(回生散) 에탄올 추출물이 비만세포 매개성 염증반응에 미치는 영향)

  • Park, Jee Hea;Kwon, Dong Yeol;Lee, Su Kyung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.1
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    • pp.45-52
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    • 2014
  • Hoesaeng-san is known to be effective for treating diarrhea and vomiting. However the therapeutic mechanism of Hoesaeng-san is still not well understood. The aim of the present study was to demonstrate the effects of Hoesaeng-san ethanol extract (HSSEE) on the expression of pro-inflammatory cytokines, as well as to elucidate its mechanism of action in the human mast cell line (HMC-1). Mast Cell were stimulated with phorbol 12-myristate 13-acetate (PMA) plus A23187 in the presence or absence of HSSEE. To study the possible effects of HSSEE, ELISA, RT-PCR, Western blot analysis were used in this study. HSSEE significantly inhibited the PMA plus A23187-induction of inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6 and IL-8. In activated HMC-1 cells, phosphorylation of extra-signal response kinase (ERK) 1/2 and c-jun n-terminal kinase (JNK)1/2 decreased after treatment with HSSEE. Moreover HSSEE inhibited PMA plus A23187-induced nuclear factor (NF)-${\kappa}B$ activation and $I{\kappa}B$ degradation. HSSEE suppressed the expression of TNF-${\alpha}$, IL-6, IL-8 through a decrease in the ERK 1/2 and JNK 1/2, as well as activation of NF-${\kappa}B$. These results indicated that HSSEE exerted a regulatory effect on inflammatory reactions mediated by mast cells.

Anti-proliferative Effect of Tetra-arsenic Oxide (TetraAs®) in Human Gastric Cancer Cells in Vitro

  • Chung, Won-Heui;Koo, Hye-Jin;Kuh, Hyo-Jeong
    • Journal of Pharmaceutical Investigation
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    • v.37 no.5
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    • pp.305-309
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    • 2007
  • Arsenic compounds have been used to treat various diseases including cancer in oriental medicine. Arsenic trioxide ($As_2O_3,\;Trisenox^{(R)}$) has been used for the treatment of leukemia and its anti-solid tumor activity has also been reported recently. Tetra-arsenic oxide ($As_4O_6,\;TetraAs^{(R)}$) is a newly developed arsenic compound which has shown an anticancer activity in some human cancer cell lines. The purpose of this study was to evaluate the anti-gastric cancer potential of TetraAs and to search for an agent with synergistic interaction with TetraAs against human gastric cancers. We analysed anti-proliferative effect of TetraAs when given alone and in combination with other chemotherapeutic agents such as 5-FU, paclitaxel, and cisplatin in SNU-216, a human gastric cancer cell line. The $IC_{50}$ of these 4 anti-cancer drugs ranged from 5.8 nM to $7.5\;{\mu}M$ with a potency rank of order paclitaxel>TetraAs>cisplatin>5-FU. TetraAs showed 10-fold greater potency than 5-FU and cisplatin at the same effect level of $IC_{50}$. TetraAs+5-FU and TetraAs+paclitaxel showed synergistic and additive interaction, respectively. On the other hand, TetraAs with cisplatin group appeared to be strongly antagonistic. Apoptotic population was measured and compared between single and combination treatment. The apoptotic cells for the combination of TetraAs+5-FU showed significant increase compared to single TetraAs treatment. On the contrary, TetraAs+cisplatin showed less apoptotic cells compared to TetraAs or cisplatin alone treatment. Overall, our results indicate that TetraAs can be effectively combined with 5-FU or paclitaxel, but not with cisplatin for synergistic anti-cancer effect, which warrants further evaluation using in vivo models.

Palmitic acid induces inflammatory cytokines and regulates tRNA-derived stress-induced RNAs in human trophoblasts

  • Changwon Yang;Garam An;Jisoo Song;Gwonhwa Song;Whasun Lim
    • Journal of Animal Reproduction and Biotechnology
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    • v.37 no.4
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    • pp.218-225
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    • 2022
  • High levels of proinflammatory cytokines have been observed in obese pregnancies. Obesity during pregnancy may increase the risk of various pregnancyrelated complications, with pathogenesis resulting from excessive inflammation. Palmitic acid (PA) is a saturated fatty acid that circulates in high levels in obese women. In our previous study, we found that PA inhibited the proliferation of trophoblasts developing into the placenta, induced apoptosis, and regulated the number of cleaved halves derived from transfer RNAs (tRNAs). However, it is not known how the expression of tRNA-derived stress-induced RNAs (tiRNAs) changes in response to PA treatment at concentrations that induce inflammation in human trophoblasts. We selected concentrations that did not affect cell viability after dose-dependent treatment of HTR8/SVneo cells, a human trophoblast cell line. PA (200 μM) did not affect the expression of apoptotic proteins in HTR8/SVneo cells. PA significantly increased the expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. In addition, 200 μM PA significantly increased the expression of tiRNAs compared to 800 μM PA treatment. These results suggest that PA impairs placental development during early pregnancy by inducing an inflammatory response in human trophoblasts. In addition, this study provides a basis for further research on the association between PA-induced inflammation and tiRNA generation.

A Phospholipase $A_2$ Inhibitor Isolated from Umilicaria esculenta (Umbilicaria esculenta가 생산하는 Depside계 화합물의 구조 및 Phospholipase $A_2$ 저해활성)

  • Kim, Jin-Woo;Song, Kyung-Sik;Chang, Hyeun Wook;Yu, Seung-Hun;Yoo, Ick-Dong
    • Microbiology and Biotechnology Letters
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    • v.23 no.5
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    • pp.526-530
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    • 1995
  • Phospholipase A$_{2}$ (PLA$_{2}$) is lipolytic enzyme that has known to be involved in inflammation. In the course of our screening for antiinflammatory compounds from natural products, a compound having PLA$_{2}$ inhibitory activities was isolated from the methanol extract of Umbilicaria esculenta. The compound was identified as lecanoric acid based on various NMR studies including DEPT, HETERO-COSY and HMBC experiments. Lecanoric acid inhibited human rheumatoid synovial PLA$_{2}$ activity with IC$_{50}$ of 0.17 mM and also exhibited antitumor activity (ED$_{50}$=2.7 $\mu $g/ml) against skin tumor cell line (LOX-IMVI).

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Radiosensitizing and Antitumor Effect of the Seed of Benincasae hispida (동과자(冬瓜子)의 항암활성과 방사선에 대한 감작효과)

  • Choi, Hye-Ran;Lee, Keyong-Ho;Kim, Chang-Han
    • Korean Journal of Food Science and Technology
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    • v.35 no.3
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    • pp.479-482
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    • 2003
  • Radiosensitizing and antitumor effects of hot water extract derived from the seed of Benincasae hispida were investigated. The extract showed maximum survival rate of 21% at 0.1 g/kg against L1210 cells implanted in BDF1 mice. Radiosensitivity of human tumor cell line was evaluated through sulforhodamine assay. Inhibition rate of SK-OV-3 cells after 5 Gy radiation by Benincasae hispida seed extract at 2 mg/mL was 86%.

Antitumor Activity of LB42907, a Potent and Selective Farnesyltransferase Inhibitor: Synergistic Effect in Combination with Other Anticancer Drugs

  • Park, Ji-Hyun;Koo, Sun-Young;Kim, Dong-Myung;Kim, Kwi-Hwa;Jeong, Shin-Wu;Chung, Hyun-Ho;Cho, Heung-Soo;Park, Joong-Hoon;Yim, Hyeon-Joo;Lee, Jin-Ho;Koh, Jong-Sung;Kim, Se-Mi
    • Bulletin of the Korean Chemical Society
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    • v.29 no.7
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    • pp.1303-1310
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    • 2008
  • Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

Tumorigenesis after Injection of Lung Cancer Cell Line (SW-900 G IV) into the Pleural Cavity of Nude Mice (누드마우스의 흉강에 폐암세포주의 주입에 의한 종양형성과 HER2/neu와 TGF-${\beta}_1$의 발현)

  • Park, Eok-Sung;Kim, Song-Myung;Kim, Jong-In
    • Journal of Chest Surgery
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    • v.43 no.6
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    • pp.588-595
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    • 2010
  • Background: Base on types of tumor, the types of expressed tumor is diverse and the difference in its expression rate is even more various. Due to such reasons an animal model is absolutely needed for a clinical research of lung cancer. The author attempted oncogenesis by cultivating a cell line of non-small cell carcinoma and then injecting it inside thoracic cavities of nude mice. The author conducted quantitative analyses of HER2/neu tumor gene - an epidermal growth factor receptor (EGFR) related to lung cancer, and TGF-${\beta}_1$, which acts as a resistance to cell growth inhibition and malignant degeneration. In order to investigate achievability of the oncogenesis, histological changes and the expression of cancer gene in case of orthotopic lung cancer is necessary. Material and Method: Among 20 immunity-free male BALB/c, five nude mice were selected as the control group and rest as the experimental group. Their weights ranged from 20 to 25 gm (Orient, Japan). After injection of lung cancer line (SW900 G IV) into the pleural cavity of nude mice, They were raised at aseptic room for 8 weeks. HER2/neu was quantitatively analyzed by separating serum from gathered blood via chemiluminiscent immunoassay (CLIA), and immunosandwitch method was applied to quantitatively analyze TGF-${\beta}_1$. SPSS statistical program (SPSS Version 10.0, USA) was implemented for statistical analysis. Student T test was done, and cases in which p-value is less than 0.05 were considered significant. Result: Even after lung cancer was formed in the normal control group or after intentionally injected lung cancer cell line, no amplification of HER2/neu gene showed reaction. However, the exact quantity of TGF-${\beta}_1$ was $28,490{\pm}8,549pg/mL$, and the quantity in the group injected with lung cancer cell was $42,362{\pm}14,449pg/mL$, meaning 1.48 times highly Significant (p<0.483). It proved that HER2/neu gene TGF-${\beta}_1$ had no meaningful interconnection. Conclusion: TGF-${\beta}_1$ gene expressed approximately 1.48 times amplification in comparison to the control group. The amplification of TGF-${\beta}_1$ meant somatic recuperation inhibition mechanism due to carcinogenesis in nude mice was definitely working. It may be implemented as a quantitative analysis that allows early detection of lung cancer in human body.