• Radiation Oncology Journal
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• v.16 no.3
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• pp.225-231
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• 1998

Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

• Journal of Haehwa Medicine
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• v.12 no.2
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• pp.157-175
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• 2004

The purpose of this study was to investigate the effects of Hangamdan(抗癌丹). The clinical study was carried out 320 cases of patients with cancer treated by Hangamdan(抗癌丹) from May 1st 1998 to September 1st 1999. The results were summarized as follows; 1. The effects of improvement in the symptoms with traditional oriental cancer therapy(47.6%) were higher than combined treatment of western and oriental therapy(37.4%). 2. In the analysis of hematology, maintenance and increasing of WBC(86.2%), Hgb(87.2%), P1atelet(97.6%) RBC(81.1%) were observed. In the analyses of tumor marker, maintenance and decreasing of CEA(76%), CA19-9(88.8%), AFP(69.2%) were observed. 3. In the analysis of safety, maintenance and decreasing of AST(93.1%), ALT(95%), BUN(92.2%), Creatinine(93.6%) were observed. 4. In the analysis of QOL attached by cancer, combined treatment of western and oriental therapy(maintenance and improvement; 91.8%) was higher than traditional oriental cancer therapy(maintenance and improvement; 79.3%) 5. In the analysis of survival in patients with terminal cancer, above 6 months(46.3%), 12 months(19.2%). 6. In the analysis of antitumor effects, combined treatment of western and oriental therapy(maintenance 71.6% improvement 12.8%) was higher than traditional oriental therapy (maintenance 66.7% improvement 9.5%). 7. In the analysis of curative evaluation, combined treatment of western and oriental therapy(maintenance 40.4% improvement 41.8%) was higher than traditional oriental therapy (maintenance 23.8% improvement 46.1%). 8. In the analysis of IL-12 and IFN-$\gamma$ attached by cancer, increasing of IL-12(32.3%), IFN-$\gamma$(41.5%) were observed. From the above results, it is suggested that Hangamdan has significant effects of antitumor and immune activity, also could be usefully applied for cancer patients by combination with western therapy or alone.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.4
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• pp.261-270
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• 2018

The aim of this study was to evaluate the antitumor activities of Typhae pollen (TP) by confirming in vitro cytotoxicity and in vivo anti-tumor and immune-modulatory effect with anti-cachexia effect. The MTT assay is used in HepG2 cell to detect potential cytotoxic activities of aqueous extract of Typhae pollen (TPe). After HepG2 tumor cell implantation, eight mice per groups were assigned to six groups. Three different dosages of TPe (500, 250 and 125 mg/kg) were orally administered in the amount of $10m{\ell}/kg$ and sorafenib also administered 20mg/kg, every day for 35 days from 28 days after the tumor cell implantation. We observed the changes on body weights, tumor volume and weights, lymphatic organ, serum interferon $(IFN)-{\gamma}$ levels, splenocytes and peritoneal NK cell activity, splenic tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-10 contents. Periovarian fat weights, serum IL-6 levels, thicknesses of deposited periovarian adipose tissue and mean diameters were also detected to monitor the tumor-related anticachexic effects. In tumor masses, the immunoreactivities of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (cleaved PARP) - apoptotic marks, cyclooxygenase-2 (COX-2), inducible nitric oxide synthases (iNOS) and tumor necrosis factor $(TNF)-{\alpha}$ were additionally observed by immunohistochemistry. The results were compared with sorafenib. Decreases of COX-2 were demonstrated in sorafenib and TPe treated mice and also increases of iNOS in tumor masses were observed in TPe, not in sorafenib. TPe increased periovarian fat pad weights compared with tumor-bearing controls and sorafenib treated mice. TPe showed increases of splenic $TNF-{\alpha}$, IL-10 and $IL-1{\beta}$, serum $IFN-{\gamma}$ and NK cell activities corresponding to increases of spleen weights, lymph node weights and non-atrophic changes of lymph nodes. Our results show oral treatment of TPe 500, 250 and 125 mg/kg has potent in vitro and in vivo antitumor activities through modest cytotoxic effects, immunomodulatory effects and apoptotic activities in HepG2 tumor cells. In addition, TPe can prevent cancer related cachexia.

• YAKHAK HOEJI
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• v.50 no.1
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• pp.8-14
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• 2006

A 1 : 1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine is currently being evaluated as a possible antitumor agent in preclinical studies. Guanosine is known to potentiate the anticancer activity of some compounds. However, the distributions of trypaflavine (TRF) or proflavine (PRF) have not been investigated in mammals. We, therefore, investigated the distribution of TRF and PRF after i.m. administration of the combination mixture (ACF and guanosine) at a dose of 30 mg/kg ACF in rats. to analyze TRF and PRF levels in biological samples, we used an HPLC-based method. The calibration curves for TRF and PRF in the samples were linear over the concenration range of $0.05{\sim}200\;{\mu}g/ml$. The intra- and inter-day assay accuracies of this method were within ${\pm}15\%$ of norminal values and the precision did not exceed $15\%$ of relative standard diviation. The lower limits of quantitation were 50 ng/ml for both TRF and PRF. The distribution of TRF or PRF was determined by 48 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF. TRF and PRF were distributed as the following order; kidney>lung>liver>small intestine>muscle. Of the various tissues, TRF and PRF were mainly distributed to the kidney and lung. The concentrations of TRF or PRF in the tissues 24 h after i.m. administration decreased to undetectable levels. The concentrations of TRF or PRF in the blood cells were comparable to those for the plasma. However, the concentrations of TRF or PRF in the both plasma and blood cells 12 h after i.m. administration were not detected. The number of the platelets in the 1 ml of the blood was calculated to be $0.183{\times}10^8/ml$ of blood. The PRF concentration in platelets was higher than that of TRF at initial times after i.m. administration of the combination mixture. However, both the TRF and PRF concentrations in the plateles 24 h after i.m. administration of the combination mixture were below the quantifiable limit. In conclusion, the concentrations of TRF or PRF in the various tissues, plasma, blood cells, and plateles decreased to undetectable levels 24 h after i.m. administration of the combination mixture at a dose of 30 mg/kg ACF.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.71-87
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• 1998

Even though appropriate immune response is necessary for the survival of the individual, excessive or insufficient immune Response might cause autoimmune or allergic disease. So the immune response must be controlled to the degree that is beneficial for the well being of the individual. This study was undertaken to know the effects of Gunleetang Gagambang on the immune system of the mouse. Gunleetang Gagambang has been used for cure of tumor as a traditional medicine without any experimental evidence to support the rational basis for its clinical use. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Gunleetang Gagambang extract against tumor, and to carry out some mechanisms responsible for its effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S180 cells). Treatment of the Gunleetang Gagambang on water-extract(dailly 1mg/mouse, i. p.) was continued for 7 days prior to tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Gunleetang Gagambang decreased not only the frequency of tumor production but also the number and the weight of tumors per tumor bearing mice(TBM). Gunleetang Gagambang on also significantly suppressed the development of 3LL cell and S180 cell-implanted tumors in occurrence-frequency and their size. and some developed tumors were regressed by the continuous treatment of Gunleetang Gagambang extract into TBM. In vitro, treatment of Gunleetang Gagambang extract had no effect on the growth of some kinds of cell line such as FsaII, A431 strain but significantly inhibited the proliferation of 3LL, S180 cells and augmented the DNA synthesis of mitogen-activated lymphocytes. Gunleetang Gagambang also stimulated the migrative ability of leukocyte, the MIF and IL-2 production of T lymphocytes, but not IL 6 production of B cells. Gunleetang Gagambang administration to mice enhanced NK cells activities. These results demonstrated that Gunleetang Gagambang extract exhibited a significant prophylactic benefits against tumors and its antitumor activity was manifested depending on the type of tumor cells. And these results also suggested that effect of Gunleetang Gagambang might be chiefly due to nonspecitie enhancement of NK cell activities and cell-mediated immune responses.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.6 no.1
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• pp.165-180
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• 2000

Clinical studies were carried out 83 cases of patients with colorectal cancer treated by Hangamdan(抗癌丹) from January 1th 1998 to September 30th 2000. The results were summarized as follows; 1. Distribution of those attached by colorectal cancer, by sex, showed that Male is more then Female, by age, showed that the number of fifties is majority. 2. Distribution of diagnostic stage, in descending order; stage III(53%, top), stage IV(45.8%). 3. The effects of maintenance and improvement in the symptoms with traditional oriental therapy(83.3%) and combined treatment of western and oriental therapy(92.1%) were observed. The effects of the symptoms were as follows: diarrhea(37.3%), abdominal pain (25.3%), general body weakness(22.9%), nausea(20.5%) and etc. in orders. 4. Analysis of hematology attached by colorectal cancer, maintenance and increasing of WBC(89.9%), RBC(74.7%), Hgb(81.1%), Platelet(92.4%) were observed. After taken Hangamdan, the safety of the liver and kidney were as follows; maintenance and decreasing of AST(85.9%), ALT(94.8%), GTP(87.5%), Creatinine(90.9%) were observed. 5. of IL-12 and $IFN-\gammer$ attached by colorectal cancer, increasing of IL-12(53.3%), IFN-{\gammer}(80%)$) were observed. 6. Analysis of QOL attached by colorectal cancer, maintenance and improvement of combined treatment of western and oriental therapy(89.6%), traditional oriental therapy(83.3%) were observed. 7. Analysis of survival in patients with IV stage of colorectal cancer, above 7 months(18.4%), 12 months(65.8%). 8. Analysis of antitumor effects, maintenance of traditional oriental therapy(83.3%) and maintenance and improvement of combined treatment of western and oriental therapy(80.5%) were observed. Analysis of tumor marker attached by colorectal cancer, maintenance and decreasing of CEA(78.8%) were observed. 9. Analysis of curative valuation, maintenance and improvement of traditional oriental therapy(83.3%), combined treatment of western and oriental therapy(72.7%) were observed. From the above results, it is suggested that Hangamdan has significant effects of antitumor and immune activity, also could be usefully applied for colorectal cancer patients by combination with western therapy or alone.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4037-4043
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• 2012

Despite progress in elucidating mechanisms associated with colorectal cancer and improvement of treatment methods, it remains a frequent cause of death worldwide. New and more effective therapies are therefore urgently needed. Recent studies have shown that immunogenicity of whole ovarian tumor cells and subsequent T cell response were potentiated by oxidation modification with hypochlorous acid (HOCl) in vitro and ex vivo. These results prompted us to investigate the protective antitumor response with an HOCl treated CT26 colorectal cancer cell vaccine in an in vivo mouse model. Administration of HOCl modified vaccine triggered robust antitumor immunity to autologous tumor cells in mice and prolonged survival period significantly. In addition, increased necrosis and apoptosis were found in tumor tissue from the oxidation group. Interestingly, ELISPOT assays showed that specific T cell responses were not elicited in response to the immunizing cellular antigen, in contrast to raising sera antibody titer and antibody binding activity shown by ELISA assay and flow cytometry. Further evaluation of the mechanisms underlying HOCl modified vaccine mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results combined with previous studies suggest that HOCl oxidation modified whole cell vaccine has wide applicability as a cancer vaccine because it can target both T cell- and B cell-specific responses. It may thus represent a promising approach for the immunotherapy of colorectal cancer.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.65-73
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• 2000

Objectives : The effects of cotreatment of adriamycin and ethanol extract of herb (Palgin-tang hab Hwajuck-hwan a traditional medicine for cancer treatment in oriental medicine) on the induction of apoptotic cell death were investigated in human liver origin cell lines, Chang. Methods : Chang(ATCC) liver cells were cultured in RPMI-1640(Gibco SRL Co, Gaithersburg, MD) badge including 10% fetal bovine serum. Chang liver cells were treated with various concentrations(from 10 to $0.16{\mu}l$) of adriamycin and herb extract(from 500 to $31.25{\mu}l$) After 48h later, the cells were tested for viability by Crystal violet staining assay. Adriamycin and Herb extract induced ladder pattern of DNA fragmentation in Chang cells. Genomic DNA was isolated and separated on 1.5% agarose gels. The DNA was stained with ethidium bromide and visualized under UV light. Results : The death of Chang cells was synergistically induced by the cotreatment of adriamycin and ethanol extract of herb. In addition, the cotreatment-induced cell death of Chang cells was mediated by apoptotic death signal processes. The phosphotransferase activity of JNK1 remained in a basal level in Chang cells which was treated individually with the adriamycin and ethanol extract of herb. However, it was markedly increased in Chang cells which was cotreated with adriamycin and ethanol extract of herb. In addition, the expression of Fas and FasL was markedly induced by the cotreatment of adriamycin and herb extract. For a while, the expression of Sax was a eminently increased by the ethanol extract of herb. However, Scl2 expression was not affected by the individual or cotreatment of adriamycin and herb extract. Conclusions : our results suggest that the cotreatment of adriamycin aM ethanol extract of herb induces synergistic apoptotis of human liver origin Chang cells via the upregulation of JNK, Fas, FasL and Bax.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.33-42
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• 2015

Objectives : The aim of this study was to evaluate the antitumor effects of Cheongpyesagan-tang(CST) and YKK012 on colon cancer. Methods : MTT assay was used to evaluate the cytotoxicity of Single herbs and combinations of CST and YKK012 on murine colon cancer cells, Colon 38. To explain effects of apoptosis in colon cancer, we performed the western blot. Effects of CST and YKK012 on antitumor activity of CPT-11 using the murine colon38 allograft tumor in BDF1 mice. Results : Single herbs and combinations of CST and YKK012 was tested in vitro, Rhei Radix (RH) and Scutellariae Radix (SC) and YKK012 showed dose-response cytotoxicity on Colon 38. This might be due to the apoptosis, as we see Bax and Caspase-3, which are apoptotic factors, was expressed in RH and SC treated cells. YKK012 also showed increased expression of Caspase-3. In mouse colorectal cancer xenograft model of colon38 cells, herbal combinations showed tendencies of tumor regression, but was not significant. Furthermore, because toxicity was observed in CST group, we reduced the dose of CST for the next experiment. The anti-tumor effects of herbal combinations were insufficient to be used as single anti-tumor agent. With simultaneous usage of CPT-11, contrary to that CST showed no synergistic effects, YKK012 which was composed by the combination of four $ER{\beta}$ selective herbs, significantly reduced the size of tumor and Bax expression was increased. Conclusions : We suggest YKK012 can be a effective cancer adjuvant therapy with CPT-11 on colon cancer.

• Journal of Haehwa Medicine
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• v.10 no.1
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• pp.121-131
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• 2001

Clinical studies were carried out 62 cases of patients with lung cancer treated by Hangamdan(抗癌丹) from January 1th 1998 to September 30th 2000. The results were summarized as follows; 1. Distribution of those attached by lung cancer, by sex, showed that Male is more then Female, by age, showed that the number of sixties is majority. 2. Distribution of diagnostic stage, in descending order; stage IV(43.6%,top), stage III(35.5%), stage II(17.7%), stage I(3.2%). 3. The effects of maintenance and improvement in the symptoms with traditional oriental therapy(83.3%) and combined treatment of western and oriental therapy(84.0%) were observed. The effects of the symptoms were as follows; cough(50.0%), anorexia(48.4%), chest discomfort(31.0%), sputum(24.2%), general body weakness(11.3%), hemoptysis(9.7%) and etc. in orders. 4. Analysis of hematology attached by lung cancer, maintenance and increasing of WBC(98.4%), RBC(74.2%), Hgb(71.0%), Platelet(96.7%) were observed. After taken Hangamdan, the safety of the liver and kidney were as follows; maintenance and decreasing of AST(91.5%), ALT(93.2%), ${\gamma}-GTP$(95.0%), BUN(82.7%), Creatinine(93.3%) were observed. 5. Analysis of IL-12 and $IFN-{\gamma}$ attached by lung cancer, increasing of IL-12(31.3%), $IFN-{\gamma}$(72.7%) were observed. 6. Analysis of QOL attached by lung cancer, maintenance and improvement of combined treatment of western and oriental therapy(94.0%), traditional oriental therapy(91.7%) were observed. 7. Analysis of survival in patients with IV stage of lung cancer, above 7 months(22.2%), 12 months(70.4%). 8. Analysis of antitumor effects, maintenance of traditional oriental therapy(50.0%) and maintenance and improvement of combined treatment of western and oriental therapy(80.0%) were observed. 9. Analysis of curative valuation, maintenance and improvement of traditional oriental therapy(50.0%), combined treatment of western and oriental therapy(60.0%) were observed. From the above results, it is suggested that Hangamdan has significant effects of antitumor and immune activity, also could be usefully applied for lung cancer patients by combination with western therapy or alone.