• The Korean Journal of Nuclear Medicine
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• v.29 no.3
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• pp.332-342
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• 1995

This study was designed to evaluate the effects of various factors on the therapeutic effect of the I-131 labeled anti-carcinoembryonic antigen monoclonal antibody(anti-CEA antibody). Tetrazolium-based colorimetric assay (MTT) was used to compare in vitro cytotoxicity of 3 Korean colon cancer cell lines (SNU-C2A, SNU-C4, SNU-C5) for selection of proper 2 cell lines in this study. The changes of the size of tumor which was xenografted to nude mice (balb/c nu/nu) were compared in 4 groups (group treated I-131 labeled anti-CEA antibody, group treated with non-radiolabeled anti-CEA antibody, group treated with I-131 labeled anti-human chorionic gonadotropin monoclonal antibody (anti-hCG antibody) as nonspecific antibody, and group injected with normal saline as a control). Immunohistochemical staining and in vivo autoradiography were performed after excision of the xenografted tumor. The results were as below mentioned. The in vitro cytotoxic effect of I-131 labeled anti-CEA antibody is most prominent in SNU-C5 cell line between 3 cancer cell lines. The changes of xenografted tumor size in both SNU-C4 and SNU-5S cell tumors at the thirteenth day after injection of the antibodies were smallest in the group treated with I-131 labeled anti-CEA antibody (SNU-C4/SNU-C5; 324/342%) comparing with other groups, group treated with anti-CEA antibody (622/660%), group treated with I-131 anti-hCG antibody (538/546%), and control group(1030/724%)(P<0.02 in SNU-C4 and P<0.1 in SNU-C5 at the 13th day after injection of antibodies). On the thirteenth day after injection of the antibodies nude mice were sacreficed to count the radiouptake of tumor and to check the changes of tumor size. Correlations between radiouptake and change of tumor size were calculated in each groups and significant negative correlation was only obtained in the group treated with I-131 anti-CEA antibody (p<0.05). There were no correlations between antigenic expression of carcinoembryonic antigen and distribution of anti-CEA antibody in both SNU-C4 and SNU-C5 cell tumors on immunoperoxidase staining. On in vivo autoradiography the distributions of anti-CEA antibody were heterogeneous and the intensities of binding were various in SNU-C4 and SNU-C5 cell tumors. It is concluded that I-131 labeled tumor-specific monoclonal antibody, anti-CEA antibody is effective in suppressing the xenografted tumor growth and the effect is influenced by sensitivity of tumor cell itself to the radiolabeled antibody and other local factors instead of specificity of antibody.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.118-125
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• 2003

Background: Disialoganglioside GD2 is a tumor-associated antigen that is overexpressed on tumor cells of neuroectodermal origin, such as melanoma and neuroblastoma. Anti-idiotypic antibodies that mimic GD2 may induce more effective immune responses than GD2 antigen itself, because they are protein antigens and are known to be able to break immune tolerance. In this study, to explore the potential of anti-idiotypic antibodies as tumor vaccines, the ability of anti-idiotypic antibodies (Ab2) to induce anti-anti-idiotypic antibodies (Ab3) that bind to the original antigen GD2 was investigated. Methods: Six monoclonal anti-idiotypic antibodies (1A8, 1G5, 2B6, 3A4, 3D6, 3H9) to monoclonal antibody M2058, which is a monoclonal antibody to GD2, were produced in mice. Three (1A8, 3A4, 3H9) of them were selected based on their ability to inhibit the binding of Ab1 to D142.34 (murine melanoma cell expressing GD2). These 3 different Ab2 were injected into rabbits, and rabbit Ab3 induced by each of them were characterized. Results: Ab3-containing sera from two rabbits immunized with 1A8, 3A4, or 3H9 bound significantly (P<0.05) to D142.34 but not to B78.96 (GD2-negative cell), and bound significantly (P<0.05) to isolated GD2 but not to GD1a. Ab3-containing sera from two rabbits immunized with 3A4 or 3H9 inhibited significantly (P<0.05) the binding of Ab1 M2058 to D142.34, and inhibited significantly (P<0.05) the binding of Ab1 M2058 to the Ab2. Conclusion: These results suggest that anti-idiotypic antibodies 3A4 and 3H9 have a potential to be used as vaccines against tumors expressing GD2 by inducing GD2-specific antibodies (Ab3).

• Korean Journal of Plant Resources
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• v.24 no.5
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• pp.557-563
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• 2011

Platycodon grandiflorum (Korean name, Doraji) has been widely used in traditional herbal medicine as an expectorant for pulmonary disease and a remedy for respiratory disorders in Asia. Here, we investigated the effects of BtOH extract saponin fraction of P. gradiflourm (PGS) on phagocytosis and anti-tumor activity with related cytokine productions in RAW264.7 macrophage cells. The results showed that PGS increased phagocytosis, anti-tumor activity, TNF-${\alpha}$ and nitric oxide (NO) production without direct tumor cell cytotoxicity. To further investigate whether NO is involved in anti-tumor and phagocytic activities of PGS, cells were co-treated with specific iNOS inhibitors, L-NIL (N6-(1-iminoethyl)-L-lysine, dihydrochloride), to block NO production. PGS decreased anti-tumor activity in L-NIL-treated cells, whereas phagocytic activity was not inhibited under the same conditions, indicating that the anti-tumor activity by PGS appears to be conducted by NO. These findings suggest that P. grandiflorum could be used a potential nutrition therapeutic agent for cancer patients.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.36-44
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• 2005

Background: The anti-tumor therapeutic effect of autologous tumor cell lysate pulseddendritic cells (DCs) was studied for non-immunogenic and immune suppressive lung cancer model. To test the possibility as an adjuvant therapy, minimal residual disease model was considered in mouse in vivo experiments. Methods: Syngeneic 3LL lung cancer cells were inoculated intravenously into the C57BL/6 mouse. Autologous tumor cell (3LL) or allogeneic leukemia cell (WEHI-3) lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, tumor formation in the lung and the tumor-specific systemic immunity were observed. Tumor-specific lymphocyte proliferation and the IFN-${\gamma}$ secretion were analyzed for the immune monitoring. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with tumor cell lysate for 18 hrs. Results: Compared to the saline treated group, tumor formation was suppressed in 3LL tumor cell lysate pulsed-DC treated group, while 3LL-specific immune stimulation was minimum. WEHI-3-specific immune stimulation occurred in WEHI-3 lysate-pulsed DC treated group, which had no correlation with tumor regression. Conclusion: The data suggest the possible anti-tumor effect of cultured DCs as an adjuvant therapy for minimal residual disease state of lung cancer. The significance of immune modulation in DC therapy including the possible involvement of NK cell as well as antigen-specific cytotoxic T cell activity induction was discussed.

• Molecules and Cells
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• v.43 no.5
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• pp.479-490
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• 2020

Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4⁺ T cells, CD8⁺ T cells, NK cells, and M1 macrophages considerably increased in the lungs of the mice injected with IL-9 expressing cells. Among them, the M1 macrophage subset was the most significantly enhanced. Furthermore, peritoneal macrophages, which were stimulated with either sIL-9 or mbIL-9 expressing transfectant, exerted higher anti-tumor cytotoxicity compared with that of the mock control. The IL-9-stimulated peritoneal macrophages were highly polarized to M1 phenotype. Stimulation of RAW264.7 macrophages with sIL-9 or mbIL-9 expressing cells also significantly increased the cytotoxicity of those macrophages against wild-type B16F10 cells. These results clearly demonstrate that IL-9 can induce an anti-metastasis effect by enhancing the polarization and proliferation of M1 macrophages.

• The Journal of Internal Korean Medicine
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• v.25 no.1
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• pp.92-105
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• 2004

In order to evaluate the anti-tumor and synergic effect of BoJungIkKeeHapDaeChilKi-Tang on doxorubicin, the inhibitory concentration(IC), IC50 and IC90 of single use of doxorubicin and BoJungIkKeeHapDaeChilKi-Tang with their concomitant treatment against MKN-45(Human stomach carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst MKN-45 cell lines. BoJungIkKeeHapDaeChilKi-Tang has only mimic direct anti-tumor effect against to MKN-45 cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that BoJungIkKeeHapDaeChilKi-Tang extracts were reduced by the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and BoJungIkKeeHapDaeChilKi-Tang extracts.

• Herbal Formula Science
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• v.12 no.2
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• pp.119-137
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• 2004

In order to evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against Colon-26(Murine Rectum Carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to Colon-26 cell lines. Soonkiwhajungtang has only mimic direct anti-tumor effect against to Colon-26 cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Soonkiwhajungtang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubidn and Soonkiwhajungtang extracts.

• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.183-194
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• 2004

In order to evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin, the inhibitory concentration(IC), IC50 and IC90 of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against Colon-26(Murine Rectum Carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models against 3LL cell lines. Soonkiwhajungtang may only mimic direct anti-tumor effects against 3LL cell lines, but signs of worsening induced by implantation of tumor cell lines generally decreased, while the total WBC and lymphocyte numbers increased. Therefore, experimentation suggests that Soonkiwhajungtang extracts reduced the critical toxicity of doxorubicin, and that Soonkiwhajungtang extracts have favorable synergic effects when combined with doxorubicin.

• Herbal Formula Science
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• v.12 no.1
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• pp.131-148
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• 2004

In order to evaluate the anti-tumor and synergic effect of Bojungikkeehapdaechilkitang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Bojungikkeehapdaechilkitang with their concomitant treatment against 3LL(Lewis lung carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to 3LL cell lines. Bojungikkeehapdaechilkitang has only mimic direct anti-tumor effect against to 3LL cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Bojungikkeehapdaechilkitang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and Bojungikkeehapdaechilkitang extracts.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3569-3573
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• 2013

Aim: Pendulous monkshood root is traditionally used for the treatment of several inflammatory pathologies such as rheumatisms, wounds, pain and tumors in China. In this study, the anti-inflammatory and anticancer activities and the mechanism of crude ethanol extract of pendulous monkshood root (EPMR) were evaluated and investigated in vitro. Materials and Methods: The cytotoxic effects of EPMR on different tumor cell lines were determined by the MTT method. Cell apoptosis and cell nucleus morphology were assessed by Hoechst 33258 staining. Moreover, nitric oxide (NO) levels and intracellular oxidative stress in peritoneal macrophages were determined to further elucidate mechanisms of action. Results: The data showed that EPMR could produce significant dose-dependent toxicity on three kinds of tumor cells. Furthermore, EPMR displayed obvious anti-inflammatory effects on LPS-induced mouse peritoneal macrophages at the dosage of 4 - 200 ${\mu}g/mL$. The results demonstrated the therapeutic potential of Pendulous Monkshood Root on cancer and inflammatory diseases. Conclusion: Our results indicate that EPMR has anti-inflammatory and anticancer properties, suggesting that pendulous monkshood root may be a useful anti-tumor and anti-inflammatory reagent in the clinic.