• 한국환경성돌연변이발암원학회지
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• 제19권2호
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• pp.108-111
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• 1999

Correlation between the tumorigenic dose (TD) and the maximum tolerated dose (MTD) was examined to search for the most relevant TD values related to the MTD. Using benzo(a)pyrene (B(a)P) 2-yr bioassay data, correlation coefficients between values of $TD_{1-}$50/ and the MTD were estimated from linearized or non-linearlized dose-response curves. The highest correlation coefficients (0.9966-1.0000) were obtained from T $D_{1-}$10/ in linearized dose-response curves while the highest (0.9966-1.0000) were estimated from $TD _{5-}$10/ in non-linearized dose-response eurves. These data suggest that TDs-lo were more closely related to the MTD than the ,$TD_{5-}$10/ in B(a)P 2-yr bioassay and that in lieu of the $TD_{50}$ they could be efficiently applicable to risk assessment and management.ent.

• Molecules and Cells
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• 제27권4호
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• pp.491-492
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• 2009

We present the result of our research on the tumorigenic ability of single cell clones isolated from an aggressive murine breast cancer cell line in a matched allografting mouse model. Tumor formation is basically dependent on the cell numbers injected per location. We argue that in vivo tumor formation from single cell clones, isolated in vitro from cancer cell lines, may not provide conclusive evidence to disprove the cancer stem cell (CSC) theory without additional data.

• BMB Reports
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• 제39권6호
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• pp.649-655
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• 2006

The NSAID activated gene (NAG-1), a member of the TGF-$\beta$ superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-$\beta$ superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-$3{\beta}$ pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.

• Natural Product Sciences
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• 제10권3호
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• pp.129-133
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• 2004

Quercetin is a dietary anticancer chemical that is capable of inducing apoptosis in tumor cells. However, little is known about its biological effect in nonmalignant hepatic cells. Using embryonic normal hepatic cell line (BNL CL.2) and its SV40-transformed tumorigenic cell line (BNL SV A.8), we evaluated the effects of quercetin on cell proliferation and apoptosis. As the results, our present study demonstrated that quercetin had a selective growth inhibition in normal versus tumorigenic hepatic cells such that BNL SV A.8 cells were very sensitive to the quercetin-mediated cytotoxicity. In particular, as evidenced by the increased number of positively stained cells in the TUNEL assay, the induction of characteristic nuclear DNA ladders, and the migration of many cells to sub-G1 phase in the BNL SV A.8 cells, quercetin treatment more sensitively induced apoptosis in BNL SV A8 cells than in BNL CL.2 cells. Collectively, our findings suggest that quercetin can be approached as a potential agent that is capable of inducing selective growth inhibition and apoptosis of hepatic cancer cells.

• Toxicological Research
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• 제12권2호
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• pp.271-275
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• 1996

Carcinogenic potential of HPV-16 DNA and NNK in a human keratinocyte cell line was assessed to study effects of viral-chemical interaction. Human cells were transfected with HPV-16 DNA and 6 clonal cell lines were subsequently obtained. Clonal line-3 and 6 at passage 7 showed characteristics of tumor cells such as increases of saturation density, soft-agar colony formation, cell aggregation and foci appearance. Among cells treated with 1$\mu M$, 10$\mu M$, 100$\mu M$ or 1 mM of NNK for 4 weeks, 100$\mu M$ treatment showed most tumorigenic characteristics at passage 7. These results indicate that either HPV-16 or NNK alone is tumorigenic in this in human in vitro model. When cells transfected with HPV-16 were subsequently exposed by 100 uM NNK for 4 weeks, all the clonal cells except clone-1 showed higher levels of tumor cell characteristics than HPV-16 DNA or NNK exposure alone. Clonal line-6, the most tumorigenic cells, showed higher transcriptional level of fibronectin and lower level of TGF-$\beta_1$, as compared to control cells, suggesting that alteration of growth factor or extracellular matrix may play a role in carcinogenesis process induced by HPV-16 and NNK. Taken together, the present study indicates that viral-chemical interactions between HPV-16 DNA and NNK enhance carcinogenic potentials of human cells and implies that smoking among people infected with human papillomavirus may pose an additional risk of causing cancer.

• Natural Product Sciences
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• 제10권2호
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• pp.74-79
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• 2004

Dietary flavonoids are currently receiving considerable attention in developing novel cancer-preventive approaches because of their potential capacities to actively induce apoptosis of cancer cells. In our previous report, a flavonoid fraction, which consisted mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein and named RCMF (RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS) that is traditionally used as food additive and herbal medicine. In this study, we evaluated the effects of the RCMF on cell proliferation and apoptosis using SV40-transformed tumorigenic hepatocytes, BNL SV A.8. Tritium uptake assay showing the proliferative capacity of the cells was strongly suppressed in the presence of RCMF. This anti-proliferative effect was further confirmed through trypan blue exclusion. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increase in DNA fragmentation, low fluorescence intensity in nuclei after propidium iodide staining, and the appearance of DNA laddering. Collectively, this study demonstrated that RCMF can be approached as a potential agent that is capable of significantly inhibiting cell growth of hepatic cancer cells.

• BMB Reports
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• 제55권7호
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• pp.348-353
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• 2022

Gastrointestinal cancer is associated with a high mortality rate. Here, we report that the splice variant of NRP/B contributes to tumorigenic activity in highly malignant gastric cancer through dissociation from the tumor repressor, HDAC5. NRP/B mRNA expression is significantly higher in the human gastric cancer tissues than in the normal tissues. Further, high levels of both the NRP/B splice variant and Lgr5, but not the full-length protein, are found in highly tumorigenic gastric tumor cells, but not in non-tumorigenic cells. The loss of NRP/B markedly inhibits cell migration and invasion, which reduces tumor formation in vivo. Importantly, the inhibition of alternative splicing increases the levels of NRP/B-1 mRNA and protein in AGS cells. The ectopic expression of full-length NRP/B exhibits tumor-suppressive activity, whereas NRP/B-2 induces the noninvasive human gastric cancer cells tumorigenesis. The splice variant NRP/B-2 which loses the capacity to interact with tumor repressors promoted oncogenic activity, suggesting that the BTB/POZ domain in the N-terminus has a crucial role in the suppression of gastric cancer. Therefore, the regulation of alternative splicing of the NRP/B gene is a potential novel target for the treatment of gastrointestinal cancer.

• 한국식품과학회지
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• 제29권2호
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• pp.362-368
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• 1997

한국산 겨우살이를 이용한 암예방 기능성 식품의 개발을 위한 기초연구로써, 한국산 겨우살이가 Balb 3T3 cell line으로부터 얻어진 비종양성 A3l 세포와 종양성 MSV 세포에 미치는 세포독성 효과를 조사하였다. 겨우살이 생즙은 $ID_{50}$ 치가 $3.94\;{\mu}g/mL$로 강한 세포독성을 나타낸 반면, 열처리즙은 $30\;{\mu}g/mL$까지 세포독성을 나타내지 않았다. 한편, 낮은 농도의 열처리즙은 비종양성 A3l 세포의 증식을 촉진시키면서 종양성 MSV 세포의 증식을 억제시키는 효과를 나타내었다. 또한 galactose, lactose, glucose, mannose, fructose, sucrose 및 starch 등과 같은 탄수화물이 겨우살이의 세포독성에 미치는 영향을 조사한 결과, 생즙과 탄수화물의 처리는 큰 변화를 주지 못하였으나, 열처리즙과 lactose, galactose, glucose 및 fructose등과 같은 당을 함께 처리하였을 때 A3l 세포의 증식촉진, MSV 세포의 증식억제효과는 더욱 증가됨을 알 수 있었다. 이러한 결과에서 알 수 있듯이, 한국산 겨우살이가 당의 첨가나 첨가 없이 가열처리공정에 의해서 암 예방 기능성 식품의 재료로써 이용될 수 있음을 암시해준다. 그리고 발효에 의한 한국산 겨우살이의 세포독성 변화를 조사하기 위하여, 겨우살이 생즙과 열처리즙을 각각 Lactobacillus plantarum을 접종하여 발효시켰다. 생즙발효가 1, 3, 5, 7일간 진행되는 동안 종양성 MSV 세포의 세포독성에는 변화가 없었으나 비종양성 A3l 세포에서는 점차적인 증식촉진효과를 나타내었다. 그러나 열처리즙 발효의 경우에는 발효초기에 열처리즙 고유의 A3l 세포 증식촉진효과가 발효가 진행됨에 따라 그 효과가 점차 감소됨을 나타내었다.

• 대한의생명과학회지
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• 제11권2호
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• pp.185-192
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• 2005

Dietary chlarella has known as one of the best candidates for development of multifunctional probiotic foods owing to an excellent nutritional value such as high amount of proteins and various, valuable fatty acids. So many efforts were devoted to studying the chlorella as therapeutic agents or foods fighting against many diseases in the aged people such as cardiovascular diseases and cancers. In this study, we investigated sizes and weights of tumors derived from mice injected subcutaneously with tumorigenic cells to see if antitumor activity would be found in mice dieted with the chlarella complex. After BALB/c mice were dieted with $5\%$ organic cultured chlorella complex diet throughout for 19weeks, the fibrosarcoma was induced by subcutaneous injection of tumorigenic cells at the 3 weeks before sacrifice. The average weight of tumors in the diet group were significantly reduced to $60\%\;(P=0.012)$ of the one in control group, indicating that diet with the chlarella complex may have anticancer activity in mice. When the mice were dieted with $5\%$ organic cultured chlorella complex for 4 weeks before injecting the tumorigenic cells in order to see tumor-preventive effect of the diet, the potential preventive activity of the diet against cancer was implicated by the observation that the tumors were greatly reduced in the diet group to $37\%$ (P=0.l44) of the control group. Especially, when the $5\%$ diet were applied to mice after injecting with the tumorigenic cells, the tumors derived from the $5\%$ diet group were also decreased to $95\%$ (P=0.002) of those in the control group, suggesting that the diet with the organic cultured chlorella complex may also have therapeutic effect against tumor formation. As results, it was shown that the chlorella complex tested in this study had preventive and therapeutic effects on fighting against tumorigenesis. Therefore, the identification and further mechanistic study of the components which may be associated with antitumor activity from diet of the chlorella complex in the future will contribute to the development of anticancer probiotic foods, alternative therapeutic treatment against cancer, and a new anticancer drug.

• 한국동물학회지
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• 제31권1호
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• pp.49-55
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• 1988

SV80와 같은 SV40로 형질전환된 사람세포는 종양을 일으킬 수 있는 능력을 가지고 있으나 면역기구인 흉선이 없는 누드마우스에서는 거부반응을 일으켜 종양을 일으키지 않는다. 그러나, 예외적으로 WI18/VA-2세포는 누드마우스에서 종양을 일으키며 이에서 얻는 두클론중 NW18C11은 종양을 일으키나 NW18C12는 종양을 일으키지 않는다. 본 실험에서는 이들 두 클론의 차이점들을 조사하였다. 실험결과, NW18C11은 NW18C12보다 더 많은수의 SV40 sequence를 포함하고 있음을 southern blot방법을 통해 확인하였으며 또한 immunofluoresce와 immunoprecipitation방법을 사용하여 두 클론 모두 정상크기의 SV40유전자산물인 large T와 small t 단백질을 생성함을 확인하였다. 한편 두 클론내에 포함되어 있는 바이러스유전자가 비형질전환새포로 하여금 생체내에서 악성종양 형성능력을 획득하도록 형질전환시킬수 있는지 확인하기 위해 두 클론의 DNA를 추출하여 마우스 NIH3T3세포에 주입시켜 형질전환된 세포를 선별하였다. 이 세포들은 모두 large T단백질을 생성하였으며 누드마우스에서 종양을 일으켰다. 이들 결과로써 NW18C12세포의 형질전환능은 완전하며, 이 세포가 누드마우스에서 거부반응에 기인하는 것으로 생각된다.