• The Journal of Internal Korean Medicine
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• v.24 no.2
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• pp.315-328
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• 2003

This study was performed to investigate the effect of Bunsimgieum on antitumor effect after sarcoma-180 cells transplantation into peritoneal cavity or left groin and immune responses on the depressed immunity induced by methotrexate in mice. The Bunsimgieum extract of 10mg/kg was orally administered 14 days for antitumor effects and 21 days for immune responses. 50% inhibitory concentration($IC_{50}$) of SUN-1, SUN-C4, and SUN-396 cancer cell, mean sunvival days and body weight of tumor bearing mice, and growth of tumor mass for antitumor effect; delayed type hypersentivity, hemagglutinin titer, hemolysis titer, rosette forming cells, natured killer cell activity, lymphocyte transformation, productivity of interleukin-2, and phagocytic activity for their immune responses were measured in ICR mice. Significance in antitumor effect is noted in the enlongation of mean life days and inhibition of tumor growth(p<0.01, respectively). Significance of immune responses is also noted in hemolysis titer, lymphocyte transfumotion, IL-2 productivity, phagocytic activity, and natural killer cell activity at E/T ratio 100:1(p<0.01, respectively). Significant in rosette cell formation was seen at dosage of 20mg/kg(p<0.01). However, Difference of body weight as antitumor effect, delayed type hypersensitivity, and hemagglutinin titer were not shown significantly. According to the above results, it could be suggested that Bunsimgieum has prominent antitumor and immunity enhancing effect.

• The Korean Journal of Pharmacology
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• v.17 no.1 s.28
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• pp.41-46
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• 1981

Eighty of Sarcoma 180 bearing mice, averaging 30 gm of body weight, were divided into eight groups of animals receiving Saline as the control, Corynebacterium parvum, Tubercin-3 and Cyclophosphamide alone and Cyclophosphamide combined with C. parvum, with Tubercin-3 and with both C. parvum and Tubercin-3 and Tubercin-3 combined with C. parvum respectively. Treatment was initiated 4.8 hours after tumor implantation and repeated three times once a day. Doses were suspended or dissolved in 0.2 ml of Saline: 1.4 mg of C. parvum: 0.5 micrograms of Tubercin-3; and 2.7 mg of Cyclophosphamide either in alone or in combination. All the agents given were administered subcutaneously but Cyclophosphamide was given intraperitoneally. The observation on the general conditions of animal took place twice a day following the treatment until the time of death after tumor implantation was determined. Average survival days in each group were as follows: In Control, Saline (11.2 days), C. parvum (14.8 days), Tubercin-3 (16.7 days), Cyclophosphamide(18.7 days). In combination therapy, Cyclophosphamide with C. parvum(22.8 days) with Tubercin-3 (26.9 days). Cyclophosphamide with both C. parvum an Tubercin-3, however, was somewhat longer than in Cyclophosphamide alone but shorter than in combined with either one of C. parvum or Tubercin-3. Finally, in combination with immunotherapeutic agents, Tubercin-3 and C. parvum each other it (8.2 days) was shorter even than Control. Life span of host is, in generally, inversely related to the number of malignant cells and conclusively, the therapeutic potentiation was reflected to be extended survival in combined treatment of a chemotherapeutic Cyclophosphamide with either one of immunotherapeutics, Tubercin-3 or C. parvum. Tubercin-3 and C. parvum in combination, however, appeared to be antagonistic each other.

• Journal of the Korean Society of Food Science and Nutrition
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• v.23 no.6
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• pp.922-926
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• 1994

This study was carried out to detemrine the efficacy of combined treatment of cyclophosphamide with tubericin-3 and or picibanil. One hundred sixty sarcoma-180 bearing mice were divided eight groups. Each group received saline, tubercin-3, picibanil , and cyclophosphamide along and/or received cyclophosphamide with tubercin-3 , with picibanil or with both tubercin-3 and picinanil, respectively.Average surviving time of each group of animals was as follows ; control was 10.9days, tubercin-3 was 15.1 days. picibanil was 12.6 days, and cylophosphamide was 17.9 days, In combined therapyy that cylophosphamide injected with tubercin-3 , the surviving time was 26.8 days an din the case of other therapy that cyclophosphamide injected with tubercin-3, the surviving time was 26.8 days an din the case of other therapy that cyclophosphamide injected with picibanil, the surviving time was 21.9 day and cyclophosphamide treated with both turbercin03 and picibanil, the surviving time was found to be 18.2 days, conclusively , the therapeutic potentiation seemed to be extended when combined tretment of the chemotherapeutics cyclophosphamide with either one of immunotherapeutics tubericin-3 or picibanil was tried, Combinatin of tubercin-3 and picibanil showed to be atagonistic each other. Yield of ascites fluid were determined 7 days after injectino of sarcoma-180 ascites tumor cells. Adminitration of cyclophosphamide, tubercin-3 , and picibanil alone and their various combinations reduced the yield of ascites fluid except for picibanil group.

• Journal of Korean Neurosurgical Society
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• v.46 no.6
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• pp.552-557
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• 2009

Objective : Interferon-$\beta$, (IFN-$\beta$) has been used in the treatment of cancers. Inhibition of the enzyme cyclooxygenase (COX) with celecoxib had a significantly suppressive effect on tumor growth, angiogenesis, and metastasis in a variety of tumors. The aim of this study was to elucidate the antiglioma effect of combined treatment with IFN-$\beta$ and celecoxib in U87 glioma model. Methods : The in vitro effects of IFN-$\beta$ (50-1,000 IU/mL) and celecoxib ($50-250\;{\mu}M$) alone or combination of both on the proliferation and apoptosis of U87 cells were tested using MTT assay, FACS analysis and DNA condensation. To determine the in vivo effect, nude mice bearing intracerebral U87 xenograft inoculation were treated with IFN-$\beta$ intraperitoneally ($2{\times}10^5\;IU/day$ for 15 days), celecoxib orally (5, 10 mg/kg) or their combination. Results : IFN-$\beta$ or celecoxib showed an inhibitory effect on the proliferation of U87 cells. When U87 cells were treated with IFN-$\beta$ and celecoxib combination, it seemed that IFN-$\beta$ interrupted the antiproliferative and apoptotic activity of celecoxib. No additive effect was observed on the survival of the tumor bearing mice by the combination of IFN-$\beta$ and celecoxib. Conclusion : These results suggest that IFN-$\beta$ seems to inhibit the antiglioma effect of celecoxib, therefore combination of IFN-$\beta$ and celecoxib may be undesirable in the treatment of glioma.

• Advances in Traditional Medicine
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• v.5 no.2
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• pp.100-109
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• 2005

In South America, natural products with unknown drug effects are used as folk remedies and for preventive medicine. Among South American natural products, we directed our attention to Propolis, which have been known as medicinal plants, and examined the mechanisms by which these substances affect antioxidant activity, anti-tumor activity and immunoresponse. When the antioxidant activities of Propolis were examined by the DPPH and Rhoudan iron methods, since Propolis contains high levels of flavonoids, it is thought that flavonoids may be responsible for the antioxidant activity in this study. In the examination of immunoenhancement activity, we measured lymphocyte versus polymorphonuclear leukocyte ratios (L/P activity). The number of lymphocytes was significantly increased in groups treated with Proplolis. Specifically, slightly high levels of $IFN-{\gamma}$ were measured in mice bearing the S-180 carcinoma, after administration of Propolis. This strongly suggests that cellular immunity is especially activated by treatment with Propolis, because production of $IFN-{\alpha}$ is limited to the T cells and NK cells stimulated by mitogen and sensitized antigen. $TNF-{\alpha}$ shows a different extent and mechanism of action depending on the target cells. When $TNF-{\alpha}$ was measured in mice bearing the S-180 carcinoma, mice treated with Propolis showed slightly higher $TNF-{\alpha}$ levels as compared to the control group. This suggests that activated macrophages produce $TNF-{\alpha}$ in mice treated with Prapolis, since activated macrophages and lymphocytes are the source of most $TNF-{\alpha}$. When anti-tumor action was examined using two kinds of sarcoma (Ehrlich solid carcinoma and Sarcoma-180 carcinoma), tumor-suppressive ratios after treatment with Propolis was 29.1%. When Sarcoma-180 solid carcinoma was used, tumor-suppressive ratios were 62%. Thus, Propolis showed strong anti-tumor activity against two kinds of solid carcinoma. Taken altogether, this strongly suggests that Propolis enhances original functions of macrophages and NK cells, and as a result, secondarily enhances the immune reaction and suppresses tumor growth.

• IMMUNE NETWORK
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• v.3 no.3
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• pp.188-200
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• 2003

Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-${\gamma}$ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3293-3298
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• 2012

The present study was conducted to evaluate in vivo anticancer activity of two novel mononuclear ruthenium(II) compounds, namely Ru(1,10-phenanthroline)$_2$(2-nitro phenyl thiosemicarbazone)$Cl_2$(Compound $R_1$) and Ru (1,10-phenanthroline)$_2$(2-hydroxy phenyl thiosemicarbazone)$Cl_2$(Compound $R_2$) against Ehrlich ascites carcinoma (EAC) mice and in vitro cytotoxic activity against IEC-6 (small intestine) cell lines and Artemia salina nauplii using MTT [(3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide)] and BLT [brine shrimp lethality] assays respectively. The tested ruthenium compounds at the doses 2 and 4 mg/kg body weight showed promising biological activity especially in decreasing the tumor volume, viable ascites cell counts and body weights. These compounds prolonged the life span (% ILS), mean survival time (MST) of mice bearing-EAC tumor. The results for in vitro cytotoxicity against IEC-6 cells showed the ruthenium compound $R_2$ to have significant cytotoxic activity with a $IC_{50}$ value of $20.0{\mu}g/mL$ than $R_1$ ($IC_{50}=78.8{\mu}g/mL$) in the MTT assay and the $LC_{50}$ values of $R_1$ and $R_2$ compounds were found to be 38.3 and $43.8{\mu}g/mL$ respectively in the BLT assay. The biochemical and histopathological results revealed that there was no significant hepatotoxicity and nephrotoxicity associated with the ruthenium administration to mice.

• The Korean Journal of Nuclear Medicine
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• v.33 no.3
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• pp.289-297
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• 1999

Purpose: Misonidazole is a radiosensitizer that binds in hypoxic cells. The purpose of this study was to find out the feasibility of I-131-Iodomisonidazole (IMISO) for imaging of tumor hypoxia. Materials and Methods: Tosyl precursor was dissolved in acetonitrile and I-131-NaI was added to synthesize IMISO. Balb/c mice inoculated with CT-26 adenocarcinoma were injected with IMISO. Mice were sacrificed at 1, 2, 4, 24 hr and % of injected dose per gram of tissue (%ID/g) was determined. For scintigraphy and MRI, mouse bearing CT-26 adenocarcinoma was administered with IMISO and imaging was performed 4 hr after. Then, mouse body was fixed and microtomized slice was placed on radiographic film for autoradiography Results: %ID/g of tumor was 1.64 (1h), 0.98 (2h), 0.85 (4h) and 0.20 (24h), respectively. At 24h, %ID/g of tumor was higher than that of all other tissues except thyroid. Tumor to muscle ratio increased with time and tumor to blood ratio also increased with time and reached 1.53 at 24 hr. On autoradiogram, tumor was well visualized as an increased activity in central hypoxic area of the tumor which corresponds to the area of high signal intensity on T2-weighted MR image. On scintigraphy, tumor uptake was visualized. Conclusion: This results suggest that IMISO may have a potential for tumor hypoxia imaging in mouse model. However, further study is needed to improve it's localization in tumor tissue and to achieve acceptable images of tumor hypoxia.

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.35-38
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• 2001

Various analogues of 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) such as 2- or 6-(1-hydro-xyiminoalkyl)-DMNQs were prepared and evaluated for the antitumor action. (1-Hydroxyiminoalkyl)-DMNQ derivatives expressed greater antitumor action than (1 -hydroxyalkyl)- or acyl-DMNQ derivatives. Moreover, 6-(1-hydroxyiminoalkyl)-DMNQ derivatives expressed higher anti-tumor action than 2-sudstituted ones, suggestive of a steric effect. Some of 6-(1-propyloxyalkyl)-DMNQ derivatives with an alkyl group of butyl to octyl moiety showed T/C values of > 400 %.

• Preventive Nutrition and Food Science
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• v.4 no.2
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• pp.117-121
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• 1999

The anititumor and immunologic activities of the glycoproteins extracted from sea cucumber (Stichopus japonicus) on mice bearing sarcoma 180 cells were investigated . Maximum tumor suppression (64%) occurred at the dose of 100mg glycoprotein/kg. The highest prolongation ratio was achieved at the level of 100mg/kg an dincreased by 395 more than that of control. Glycoproteins from sea cucumber exhibited direct cytotoxic effect on the tumor cells. Dose dependent increase of leucocyte, peritoneal exudate cell and weights of immunoorgans revealed the improvement of immunity. When the glycoportein-administered group was compared with the control, a significant difference was not noted in the clinico-chemical values such as S-GOT, S-GPT , alkaline phoshatse activity, total protein, cholesterol, triglyceride, urea nitrogen and glucose levels in blood. These results suggests that the antitumor activity of sea cucumber glycoprotein is associated with activation of cells in the immune system.