• Journal of Veterinary Clinics
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• v.17 no.2
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• pp.311-315
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• 2000

Recombinant interleukin-2 (IL-2) has been demonstated as an antineoplastic agent in mice and human, and the route of administration is important to IL-2-induced therapeutic responses. Therefore, the current experiment was undertaken to clarify the effect of IL-2 administration route on antitumor response against subcutaneous Meth-A tumor in mice. At the beginning of each experiment, normal BALB/c mice were injected subcutaneously with $5{\times}10^6$ Meth-A tumor cells. Beginning on day 7, experimental groups were treated with a 5-day course of IL-2 (intraperitoneal or subcutaneous injection of 30, 000 IU every 12 hours for 5 days). The result of this experiment revealed that Meth-A tumor grew progressively in control mice. Intraperitoneal IL-2 treatment decreased significantly tumor growth and prolonged survival, compared with control mice. Subcutaneous IL-2 treatment decreased significantly tumor growth until day 11 and tumor cells, grew progressively thereafter, but mice in this group survived longer than control mice.

• Journal of Veterinary Clinics
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• v.17 no.2
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• pp.305-314
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• 2000

Recombinant inteileukin-2 (IL-2) is a potent inductive stimulus for nitric oxide synthesis (NO.) and has been demonstrated as an antineoplastic agent in mice and human. But it is not let clear whether NO. can contribute to IL-2-induced therapeutic responses. Therefore, the current experiment was undertaken to clarify the effect of IL-2 on antitumor response against subcutaneous Meth-A tumor in mice. At the beginning of each experiment, normal BALB/c mice were injected subcuta-neously with $5{\times}10^6 Meth-A$ tumor cells. Some mice were implanted with osmotic minipumps con- taining 225 $\mu$l of 3.38 M $N^{\gamma}$ -monomethyl-L-arginine (MLA. an NOS inhibitor). Beginning on day 7, experimental groups were treated with a f-day course of IL-2 (50,000 lU,75,000 nJ,100,0007, 50,000 IU+MLA, 75,000 IU+MLA, 100,000 IU+MLA intraperitoneal injection every 12 hours for 5 days). The result of this experiment revealed that Meth-A tumor grew progressively in control mice. Intraperitoneal IL-2 treatment decreased tumor growth and prolonged survival. compared with con-trol mice. But no significant differences among 50.000 lU.75.000 lU and 100,000 lU of 7-2 treat-ment were observed. MLA administration prevented partially the decrease tumor growth and prolong survival of IL-2 treated mice compared with mice receiving IL-2 alone.

• Journal of Life Science
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• v.5 no.2
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• pp.81-89
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• 1995

The antitumor activities of the cell bound polysaccharide(CBP), water soluble polysaccharide(WSP) and sulfated polysaccharide(SP) of Zoogloea sp. were observe. The results obtained were as follows : 1) The CBP, WSP, and SP showed cytotoxic effect on the Meth A cells in vitro, however, the effect of CBP and WSP was more ten-fold greater than that pf SP. 2) When CBP, WSP, and SP was inoculated into the peritoneal cavity of the Meth A cells transplanted mice, the average survival days tended to prolonged slightly as compared with the control. 3) When Meth A cells were transplanted subcutaneously into the back side of mice, and then CBP, WSP, and Sp was inoculated into the peritoneal cavity of mice, the tumor growth inhibition ratio was 46.9% for WSP, 40.4% for CBP, and 16.2% for SP. 4) The phagocytic activity of peritoneal macrophages elicited with CBP, WSP, and SP was significantly increased than that of control. 5) The production of nitric oxide in the peritoneal macrophages stimulated with CBP, WSP, SP, and LPS aloneo was not increased than that of control. The production of nitric oxide in the peritoneal macrophages stimulated with IFN-r and CBP, IFN-r and WSP and IFN-r and SP was significantly increased than that of control, but in the case of stimulated with IFN-r and WSP was increased 50% for CBP and SP. These results suggest that the CBP, WSP and SP of Zoogloea sp. showed direct cytotoxic effect and tumor growth inhibition on Meth A cells in vitro and in vivo, and induced nitric oxide production of activated macrophages.

• Journal of Haehwa Medicine
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• v.9 no.1
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• pp.193-200
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• 2000

Basidiomycete, Agaricus blazei murill has grown Brazil naturally. It was first cultivated 1997 in Korea. Proteoglycan or polysaccharide which have the effect of immunopotency and anticancer were extracted from it. From the mycelium of cultivated mushroom, were extracted lectin, linoleic acid, FIII-2-b, and simmilar to glucomannan from fruit body of Basidiomycete Agaricus blazei. Fruit body was more studied than mycelium. The experiments were most in vivo study. The effect were shown on S-180, MethA tumor, Ehrlich ascites carcinoma, Shionogi carcinoma 42, Meth A fibrosarcoma by transferation of tumor cell line, specially effectiveness on the S-180. About immunopotenciation, were shown as activation of NK cell, pancreatic T-cell, helper T cell, enhancement of population of cytotoxity T cell. It was effect on the MethA tumor cells in vitro cell cytotoxity and has induction of apoptosis. Forthermore cytotoxity of many other tumor cell line, aneiognensis, cell cyle studies will be needed.

• Journal of Life Science
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• v.5 no.2
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• pp.25-25
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• 1995

The antitumor activities of the cell bound polysaccharide(CBP), water soluble polysaccharide(WSP) and sulfated polysaccharide(SP) of Zoogloea sp. were observe. The results obtained were as follows : 1) The CBP, WSP, and SP showed cytotoxic effect on the Meth A cells in vitro, however, the effect of CBP and WSP was more ten-fold greater than that pf SP. 2) When CBP, WSP, and SP was inoculated into the peritoneal cavity of the Meth A cells transplanted mice, the average survival days tended to prolonged slightly as compared with the control. 3) When Meth A cells were transplanted subcutaneously into the back side of mice, and then CBP, WSP, and Sp was inoculated into the peritoneal cavity of mice, the tumor growth inhibition ratio was 46.9% for WSP, 40.4% for CBP, and 16.2% for SP. 4) The phagocytic activity of peritoneal macrophages elicited with CBP, WSP, and SP was significantly increased than that of control. 5) The production of nitric oxide in the peritoneal macrophages stimulated with CBP, WSP, SP, and LPS aloneo was not increased than that of control. The production of nitric oxide in the peritoneal macrophages stimulated with IFN-r and CBP, IFN-r and WSP and IFN-r and SP was significantly increased than that of control, but in the case of stimulated with IFN-r and WSP was increased 50% for CBP and SP. These results suggest that the CBP, WSP and SP of Zoogloea sp. showed direct cytotoxic effect and tumor growth inhibition on Meth A cells in vitro and in vivo, and induced nitric oxide production of activated macrophages.

• The Journal of Korean Society of Virology
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• v.30 no.2
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• pp.141-150
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• 2000

The effectiveness of noninfectious recombinant adenovirus encoding murine granulocyte-macrophage colony stimulating factor (mGM-CSF) for the treatment of Meth A fibrosarcoma was investigated in syngeneic BALB/C model. Meth A and HeLa cells transduced with the recombinant adenovirus (Ad.mGM-CSF) produced substantial amounts of mGM-CSF, while WEH1164 cells transduced with the virus did not produce mGM-CSF. Mice inoculated subcutaneously with $1{\times}10^6$ Meth A cells, followed by injection of Ad.dE1 as a control, developed large tumors that reached a mean tumor size of 22 mm by day 30. However, tumor development and tumorigenicity were significantly inhibited in mice with a single intratumoral injection of Ad.mGM-CSF at $1{\times}10^8\;pfu$. Histological examination of the tumors injected with Ad.mGM-CSF revealed dense infiltrates of neutrophils, histiocytes, lymphocytes, and eosinophils associated with apoptotic cell death. The results suggest that the recombinant adenovirus encoding GM-CSF have a potential use for cancer gene therapy.

• Journal of Microbiology and Biotechnology
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• v.16 no.12
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• pp.1919-1927
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• 2006

Tumor cells genetically engineered to secrete cytokines are effective in tumor therapy, but various unexpected side effects are observed, which may result from the bulk activation of various bystander cells. In this study, we tested tumor vaccines expressing various membrane-bound forms of IL-2 (mbIL-2) on MethA fibrosarcoma cells to focus antitumor immune responses to CTL. Chimeric forms of IL-2 with whole CD4, deletion forms of CD4, and TNF were expressed on the tumor cell surface, respectively. Tumor clones expressing mbIL-2 or secretory form of IL-2 were able to support the cell growth of CTLL-2, an IL-2-dependent T cell line, and the proliferation of spleen cells from 2C TCR transgenic mice that are responsive to the $p2Ca/L^d$ MHC class I complex. Expression of mbIL-2 on tumor cells reduced the tumorigenicity of tumor cells, and the mice that once rejected the live IL-2/TNF tumor clone acquired systemic immunity against wild-type MethA cells. The IL-2/TNF clone was inferior to other clones in tumor formation, and superior in the stimulation of the CD8+ T cell population in vitro. These results suggest that the IL-2/TNF clone is the best tumor vaccine, and may stimulate CD8+ T cells by direct priming. Expression of IL-2/TNF on tumor cells may serve as an effective gene therapy method to ameliorate the side effects encountered in the recombinant cytokine therapy and the conventional cytokine gene therapy using the secretory form of IL-2.

• IMMUNE NETWORK
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• v.13 no.2
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• pp.63-69
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• 2013

IL-12 is a secretory heterodimeric cytokine composed of p35 and p40 subunits. IL-12 p35 and p40 subunits are sometimes produced as monomers or homodimers. IL-12 is also produced as a membrane-bound form in some cases. In this study, we hypothesized that the membrane-bound form of IL-12 subunits may function as a costimulatory signal for selective activation of TAA-specific CTL through direct priming without involving antigen presenting cells and helper T cells. MethA fibrosarcoma cells were transfected with expression vectors of membrane-bound form of IL-12p35 (mbIL-12p35) or IL-12p40 subunit (mbIL-12p40) and were selected under G418-containing medium. The tumor cell clones were analyzed for the expression of mbIL-12p35 or p40 subunit and for their stimulatory effects on macrophages. The responsible T-cell subpopulation for antitumor activity of mbIL-12p35 expressing tumor clone was also analyzed in T cell subset-depleted mice. Expression of transfected membranebound form of IL-12 subunits was stable during more than 3 months of in vitro culture, and the chimeric molecules were not released into culture supernatants. Neither the mbIL-12p35-expressing tumor clones nor mbIL-12p40-expressing tumor clones activated macrophages to secrete TNF-${\alpha}$. Growth of mbIL-12p35-expressing tumor clones was more accelerated in the $CD8^+$ T cell-depleted mice than in $CD4^+$ T cell-depleted or normal mice. These results suggest that $CD8^+$ T cells could be responsible for the rejection of mbIL-12p35-expressing tumor clone, which may bypass activation of antigen presenting cells and $CD4^+$ helper T cells.

• Molecules and Cells
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• v.21 no.2
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• pp.213-217
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• 2006

Although AIMP1 (previously known as p43) is one of three auxiliary proteins bound to a macromolecular aminoacyl tRNA complex, it is also secreted as a cytokine controlling both angiogenesis and immune responses. Here we show that systemically administered purified recombinant human AIMP1 had anti-tumor activity in mouse xenograft models. In Meth A-bearing Balb/c mice, tumor volume increased about 28 fold in the vehicle treatment group, while an increase of about 16.7 fold was observed in the AIMP1-treated group. We also evaluated the anti-tumor activity of AIMP1 in combination with a sub-clinical dose of the cytotoxic anti-tumor drug, paclitaxel. The growth of NUGC-3 human stomach cancer cells was suppressed by 84% and 94% by the combinations of 5 mg/kg paclitaxel + 25 mg/kg AIMP1 (p = 0.03), and 5 mg/kg paclitaxel + 50 mg/kg AIMP1 (p = 0.02), respectively, while 5 mg/kg paclitaxel alone suppressed growth by only 54% (p = 0.02). A similar cooperative effect of AIMP1 and paclitaxel was observed in a lung cancer xenograft model. These results suggest that AIMP1 may be useful as a novel anti-tumor agent.

• Journal of Gastric Cancer
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• v.21 no.4
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• pp.379-391
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• 2021

Purpose: Promoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD). Materials and Methods: CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM]). Results: In the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001). Conclusions: CDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor.