• Molecules and Cells
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• v.42 no.12
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• pp.869-883
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• 2019

Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4⁺ T, CD8⁺ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

• 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.

• Korean Journal of Veterinary Research
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• v.45 no.1
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• pp.85-91
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• 2005

Much of the interest on the chemopreventive properties of herbs and plants has been raised, whereas little is regarding to anti-tumor effect of farming and aquatic products. In the present study, the anti-tumor effect of hot-water extract of a seaweed, BLC (Sargassum fulvellum) and BLC/HEN egg was investigated using MCF-7 cells in vitro and in vivo systems. We found that the BLC extract and BLC/HEN egg inhibited cell proliferation in a dose-dependent manner, which might be mediated through up-regulation of p53. Furthermore, this test compound can directly induce apoptosis in MCF-7 cells, which might be mediated through up-regulation of a pro-apoptotic Bax protein and down-regulation of a anti-apoptotic Bcl-2 protein, not by immune system. Nude mice bearing established breast tumors (with exogenous estradiol) were treated with BLC extract and BLC/HEN egg. Treatment BLC extract and BLC/HEN egg caused a 42% and 71% inhibition of tumor growth, respectively. Both agents caused a significant inhibition of volume and weight growth of estrogen independent human breast tumors established from MCF-7 cells. Our results suggested that BLC extract and BLC/HEN egg have the efficacious effect of human breast cancer not only in vitro but also in vivo.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.7-15
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• 1991

Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the $O_2$ affinity of hemoglobin by increasing 2,3-DPG levels, thereby increasing the $O_2$ release from RBC. Nicotinamide (NA) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the Fsall murine fibrosarcoma by oxygenating the hypoxic cells. We obsewed a significantly enhanced radiation-induced growth delay of the FSaII tumors by PENTO+NA. Thus the enhancement ratio was between 2.5 and 2.8 in growth delay assay. The $TCD_{50}$ of control tumors was about 57 Gy, but that of PENTO+NA treated tumors was about 32Gy. Thus $TCD_{50}$ was modified by a factor of 1.8. We also observed that PENTO+NA exerted no effect on the radiation-induced skin damage after the legs without bearing tumors were exposed to X-irradiation. In order to clarify radiosensitizing effects of PENTO+ NA, changes in tumor blood flow and intratumor pOf were measured using laser Doppler flowmetry and $O_2$ microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+ NA. Furthermore, we also found that PENTO+ NA significantly increased intratumor $pO_2$ from 8 to 19 mmHg. We concluded that PENTO+MA was far more effective than NA alone or PENTO alone. The increase in the response of tumors in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted.

• Journal of Acupuncture Research
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• v.40 no.1
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• pp.35-43
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• 2023

Background: This study aimed to examine the effect of Scutellaria baicalensis extract (SBE) on ameliorating pain response and inflammation in an animal model. Methods: The effects of SBE on joint inflammation-induced rats and pain writhing response were measured. In rats with monosodium iodoacetate (MIA)-induced knee osteoarthritis (OA), the weight-bearing distribution of the hind legs was measured, the actual joint condition was visually confirmed, and serum cytokines were extracted from whole blood and measured. In addition, the acetic acid-induced pain was measured by the number of abdominal wall contractions and writhing responses. Results: 1. The weight-bearing distribution of the hind limbs of the SBE group was remarkably improved compared with that of the control group 7 days after MIA treatment, and the SBE 300 group was improved similarly to that of the indomethacin group. 2. Cartilage erosion was significantly recovered in the SBE and indomethacin groups, and the degree of healing of cartilage erosion by SBE was similar to that by indomethacin. 3. The serum levels of cytokines interleukin-1β, tumor necrosis factor-α, and interleukin-6 were significantly decreased in the SBE group compared with that in the control group, and the SBE 300 group had reduced levels of cytokines similar to the indomethacin group. 4. As regards acetic acid-induced writhing response, the number of writhes was significantly reduced in the SBE and ibuprofen groups, and the SBE 600 group had fewer writhes than the ibuprofen group. Conclusion: SBE significantly improves knee OA and pain and is expected to show similar therapeutic effects to indomethacin and ibuprofen.

• Journal of Ginseng Research
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• v.43 no.1
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• pp.68-76
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• 2019

Background: In colorectal cancer (CRC), 40-60% of patients develop metastasis. The epithelial-mesenchymal transition (EMT) is a pivotal and intricate process that increases the metastatic potential of CRC. The aim of this study was to investigate the effect of Korean Red Ginseng extract (RGE) on colorectal metastasis through inhibition of EMT and the metastatic abilities of CRC cells. Methods: To investigate the effect of RGE on the metastatic phenotypes of CRC cells, CT26 and HT29 cells were evaluated by using an adhesion assay, a wound-healing assay, an invasion assay, zymography, and real-time reverse transcription-polymerase chain reaction. Western-blot analysis was conducted to elucidate the molecular mechanisms of RGE, which showed an inhibitory effect on the transforming growth factor-${\beta}1$ ($TGF-{\beta}1$)-induced EMT in HT29 cells. Additionally, the antimetastatic effect of RGE was evaluated in a mouse model of lung metastasis injected with CT26 cells. Results: RGE decreased the adhesion and migration ability of the CT26 cells and TGF-${\beta}1$-treated HT29 cells. The invasion ability was also reduced by RGE treatment through the inhibition of matrix metalloproteinase-9 expression and activity. Moreover, RGE suppressed the TGF-${\beta}1$-induced EMT via TGF-${\beta}1$/Smad-signaling-mediated Snail/E-cadherin expression in HT29 cells and lung tissue in CT26 tumor-bearing mice. Conclusion: Our results demonstrated that RGE inhibited colorectal lung metastasis through a reduction in metastatic phenotypes, such as migration, invasion, and the EMT of CRC cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.4
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• pp.726-731
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• 2000

This study was performed to evaluate the antitumor activities of water and ethanol (EtOH) extract of Salvia miltiorrhiza in vitro and in vivo. The proliferation of the human hepatoma (HepG2), rectum cancer (HRT-18) and colon cancer (HT-29) cells was inhibited by administration of extracts in a dose-dependent manner. Particularly, EtOH extract inhibited proliferation of the cells more effectively than water extract did. The morphology of cells induced by EtOH extract was characterized by reduction of cell size and deformatin. Oral administration of the EtOH extract (3 mg/head) to tumor-bearing mice inhibited the tumor (sarcoma-180) growth by 35% and prolonged their survival rate by 61%. The EtOH extract was shown to be nontoxic at 37.5% mg/head/day on the acute toxicity test. These studies suggest that the EtOH extract of Salvia miltiorrhiza may have antitumor activity in vitro and in vivo.

• Toxicological Research
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• v.27 no.2
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• pp.77-83
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• 2011

The objective of this study was to evaluate and compare the antitumor activity of different solvent fractions (ethanol, dichloromethane, ethyl acetate, butanol and water) of the Auricularia auricula-judae 70% ethanol extract on the P388D1 macrophage and sarcoma 180 cells. A dose-dependent antitumor activity of each solvent fraction (from 0.01 mg/ml to 0.3 mg/ml) was shown against both cell types. These cytotoxic effects of all the tested fractions were confirmed on the MTT and SRB assays, without statistical differences each other. $IC_{50}$ value of dichloromethane fraction was 94.2 ${\mu}g/ml$ against sarcoma 180 cells lower than any other solvent fractions. The potent antitumor effect of the dichloromethane (DCM) fraction was also found against solid tumor in BALB/c mice. The splenomegaly and higher splenic index were found in tumor-bearing mice, with the DCM fraction returning to the negative control values. Thus, the results indicated the dichloromethane fraction may have potential ingredients as antitumor candidates.

• Korean Journal of Head & Neck Oncology
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• v.25 no.1
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• pp.3-7
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• 2009

Background and Objectives : Panax ginseng C.A. Meyer is a medical plant that has been widely utilized as a tonic and nutritional agent since ancient times in Korea. Ginseng has anti-metastatic property of cancer and immunomodulating activity. The novel acidic polysaccharide compound(MB40) was isolated from the leaves of Panax ginseng C.A. Meyer. To determine immunomodulating activities of MB40, we evaluate anti-cancer and anti-metastatic effects of MB40 in tumor bearing immune competent mice. Material and Methods : C3H mice were divided into three equal groups(Cisplatin treatment group, MB40 treat-ment group, Cisplatin and MB40 treatment group) and were transplanted SCC(Squamous Cell Carcinoma) cells(2${\times}$106) to the lateral side of abdomen. From day 4 after transplantation, MB40 was administrated at dose of 10mg/kg, respectively, every other day by intratumoral injection. Cisplatin was systemically administrated at doses of 1mg/kg, respectively, every week by intraperitoneal injection. Results : 5 days after administration, tumors can be palpated in every mice group. After 13 days of administration, the mice group to which MB40 were administrated exhibited reduction in tumor size respectively, compared to cisplatin group. Overall status of mice such as body weight and activity were superior in MB40 group than cisplatin group. Conclusion : The result of this study indicates MB40 may have significant therapeutic effect and decreases complications induced by systemic chemotheraphy. MB40 may be developed as a novel and potent immunotropics to improve the cell immune system and anti-cancer drug for the treatment of cancer patients in head and neck squamous cell carcinoma.

• Radiation Oncology Journal
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• v.29 no.2
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• pp.83-90
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• 2011

Purpose: Flavopiridol enhanced radiation-induced apoptosis of cancer cells in our previous in vitro study. The purpose of this study was to assess if flavopiridol could enhance the radioresponse of mouse mammary tumors in vivo. Materials and Methods: Balb/c mice bearing EMT-6 murine mammary carcinoma were treated with flavopiridol only, radiation only, or both for 7 days. Flavopiridol was administered 2.5 mg/kg twice a day intraperitoneally (IP). Radiation was delivered at a 4 Gy/fraction at 24-h intervals for a total dose of 28 Gy. Tumor volume was measured and compared among the different treatment groups to evaluate the in vivo radiosensitizing effect of flavopiridol. Tumors were removed from the mice 20 days after treatment, and TUNEL and Immunohistochemical stainings were performed. Results: Significant tumor growth delay was observed in the radiation only and combined treatment groups, when compared with the control group. However, there was no significant difference between the tumor growth curves of the control and flavopiridol only group or between the radiation only and combination treatment group. Apoptotic cells of different treatment groups were detected by terminal deoxynucleotidyl transferase-medicated nick end labeling (TUNEL) staining. The expressions of Ku70 in tumor tissues from the different groups were analyzed by immunohistochemistry. Similarly, no significant difference was found between the apoptotic rate or Ku70 expression among the different treatment groups. Conclusion: Flavopiridol did not show evidence of enhancing the radioresponse of mouse mammary tumors in this study.