• The Korea Journal of Herbology
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• v.28 no.6
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• pp.155-160
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• 2013

Objectives : Gastric cancer is a leading cause of cancer-related deaths, worldwide. Houttuynia cordata Thunberg (H. cordata) has been used as a medicinal plants and it has an anti-cancer activity in human colorectal cancer and leukemic cancer. However, the potential anti-cancer activity and mechanisms of H. cordata for human gastric cancer cells have not been tested so far. Thus, this study examined the biological effects of H. cordata on the human gastric cancer cell line SNU-1 and AGS. Methods : Inhibition of cell proliferation and cell cycle by H. cordata was carried out by MTT assay and Muse cell cycle analysis and the expressions of protein associated with apoptosis and cell cycle regulation were investigated with Western blot analysis. Results : In MTT assay, the proliferation of SNU-1 and AGS cells was significantly inhibited by H. cordata in a time and dose dependent manner, Inhibition of cell proliferation by H. cordata was in part associated with apoptotic cell death, as shown by changes in the expression ratio of Bax to Bcl-2 by H. cordata. Also, H. cordata regulated the expression of cell cycle regulatory proteins such as pRb, cyclin D1, cyclin E, CDK4, CDK2, p21 and p15. Conclusion : The antiproliferative effect of H. cordata on SNU-1 and AGS gastric cancer cells revealed in this study suggests that H. cordata has intriguing potential as a chemopreventive or chemotherapeutic agent.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.77-77
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• 2020

Purple loosestrife-Lythrum anceps (Koehne) Makino is a herbaceous perennial plant belonging to the Lythraceae family. It has been used for centuries in Korea and other Asian traditional medicine. It has been showed pharmacological effects, including anti-oxidant and anti-microbial effects. However, the mechanisms underlying its anti-cancer mechanisms are not yet understood. In this study, we investigated the mechanism of apoptosis signaling pathways by ethanol extract of Lythrum anceps (Koehne) Makino (ELM) in human leukemia U937 cells. Treatment with ELM significantly inhibited cell growth in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies (ApoBDs), DNA fragmentation and increased populations of sub-G1 ratio. Induction of apoptosis by ELM was connected with up-regulation of death receptor (DR) 4 and DR5, pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 protein, and inhibitor of apoptosis protein (IAP) family proteins (XIAP, cIAP-1, survivin), depending on dosage. This induction was associated with Bid truncation, mitochondrial dysfunction, proteolytic activation of caspases (-3, -8 and -9) and cleavage of poly(ADP-ribose) polymerase protein. Therefore, our data indicate that ELM suppresses U937 cell growth by activating the intrinsic and extrinsic apoptosis pathways, and thus may have applications as a potential source for an anti-leukemic chemotherapeutic agent.

• Korean Journal of Radiology
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• v.24 no.7
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• pp.606-625
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• 2023

Transarterial chemoembolization (TACE) was introduced in 1977 with the administration of chemotherapeutic agent to gelatin sponge particles through the hepatic artery in patients with hepatocellular carcinoma (HCC) and was established as conventional TACE using Lipiodol in the 1980s. In the 2000s, drug-eluting beads were developed and applied clinically. Currently, TACE is a commonly used non-surgical treatment modality for patients with HCC who are unsuitable for curative treatment. Considering the vital role of TACE in the management of HCC, it is crucial to organize current knowledge and expert opinions regarding patient preparation, procedural techniques, and post-treatment care in TACE, which can enhance therapeutic efficacy and safety. A group of 12 experts in the fields of interventional radiology and hepatology, convened by the Research Committee of the Korean Liver Cancer Association (KLCA), has developed expert consensus-based practical recommendations in TACE. These recommendations have been endorsed by the Korean Society of Interventional Radiology and provide useful information and direction in performing TACE procedure as well as pre- and post- procedural patient care.

• Journal of Gastric Cancer
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• v.4 no.4
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• pp.257-262
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• 2004

Purpose: We reported our preliminary result in 2001. At that time, the follow-up period was too short to evaluate the survival benefit of adjuvant chemotherapy in gastric cancer without serosal invasion. Therefore, we followed those patients for 66 months to determine the long-term effects of adjuvant chemotherapy. Materials and Methods: We analyzed the recurrence pattern, the survival rate, and the disease-specific survival of 135 patients by reviewing their medical records and calling the patients or their relatives. All enrolled patients were included in the intention-to-treat analysis of efficacy. Results: The follow-up rate was $89.6\%$ (121/135), and the median follow-up duration was 66 months. Among the 135 patients, 4 relapsed in group 1 (5-FU+cisplatin), 7 in group 2 (mitomycin C+oral 5-FU), and 6 in group 3 (oral 5-FU only). The overall survival rate was $89\%$ in group 1, $84\%$ in group 2, and $82\%$ in group 3. There were no differences in the overall survival rates and the disease-specific survival rates among the three groups. Conclusion: Oral chemotherapeutic agents have an acceptable effect for adjuvant chemotherapy compared with intravenous agent. However, a large-scale, prospective, randomized study, including a control group, is needed for an exact evaluation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.925-928
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• 2014

Background: Gestational trophoblastic neoplasia (GTN) is a spectrum of disease with abnormal trophoblastic proliferation. Treatment is based on FIGO stage and WHO risk factor scores. Patients whose score is 12 or more are considered as at extremely high risk with a high likelihood of resistance to first line treatment. Optimal therapy is therefore controversial. Objective: This study was conducted in order to summarize the regimen used for extremely high risk or resistant GTN patients in our institution the in past 10 years. Materials and Methods: All the charts of GTN patients classified as extremely high risk, recurrent or resistant during 1 January 2002 to 31 December 2011 were reviewed. Criteria for diagnosis of GTN were also assessed to confirm the diagnosis. FIGO stage and WHO risk prognostic score were also re-calculated to ensure the accuracy of the information. Patient characteristics were reviewed in the aspects of age, weight, height, BMI, presenting symptoms, metastatic area, lesions, FIGO stage, WHO risk factor score, serum hCG level, treatment regimen, adjuvant treatments, side effects and response to treatment, including disease free survival. Results: Eight patients meeting the criteria of extremely high risk or resistant GTN were included in this review. Mean age was 33.6 years (SD=13.5, range 17-53). Of the total, 3 were stage III (37.5%) and 5 were stage IV (62.5%). Mean duration from previous pregnancies to GTN was 17.6 months (SD 9.9). Mean serum hCG level was 864,589 mIU/ml (SD 98,151). Presenting symptoms of the patients were various such as hemoptysis, abdominal pain, headache, heavy vaginal bleeding and stroke. The most commonly used first line chemotherapeutic regimen in our institution was the VAC regimen which was given to 4 of 8 patients in this study. The most common second line chemotherapy was EMACO. Adjuvant radiation was given to most of the patients who had brain metastasis. Most of the patients have to delay chemotherapy for 1-2 weeks due to grade 2-3 leukopenia and require G-CSF to rescue from neutropenia. Five form 8 patients were still survived. Mean of disease free survival was 20.4 months. Two patients died of the disease, while another one patient died from sepsis of pressure sore wound. None of surviving patients developed recurrence of disease after complete treatment. Conclusions: In extremely high risk GTN patients, main treatment is multi-agent chemotherapy. In our institution, we usually use VAC as a first line treatment of high risk GTN, but since resistance is quite common, this may not suitable for extremely high risk GTN patients. The most commonly used second line multi-agent chemotherapy in our institution is EMA-CO. Adjuvant brain radiation was administered to most of the patients with brain metastasis in our institution. The survival rate is comparable to previous reviews. Our treatment demonstrated differences from other institutions but the survival is comparable. The limitation of this review is the number of cases is small due to rarity of the disease. Further trials or multicenter analyses may be considered.

• Korean Journal of Medicinal Crop Science
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• v.25 no.5
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• pp.322-327
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• 2017

Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.45-52
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• 2001

Background: Many types of cancer become resistant to current chemotherapeutic and radiotherapeutic intervention. To overcome this situation application of gene therapy by the introduction of suicide genes followed by their prodrugs may be promising. A viral enzyme, Herpes simplex thymidine kinase (HSV-tk), which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining prodrug-activating gene therapy and irradiation might result in enhanced antitumor effects. Methods: The HSV-tk gene was cloned into the retroviral vector, pLXSN and established the clones producing retroviruses carrying the HSV-tk gene. The carcinoma cell line, HCT116 and Huh-7 were transduced with high-titer recombinant retroviruses. These cell lines were treated with ganciclovir before or after irradiation for the defining combinational effect of suicide gene therapy and radiotherapy. Results: The titers of cloned PA3 17 amphotropic retroviruses ranged from 4 to 6 X $10^6CFU/ml4$. After selectional periods, the expression of HSV-tk was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The growth of cells expressing HSV-tk was inhibited as increase of GCV dose after 48 hr and the growth inhibitory effect of GCV was much higher after 72 hr. When the cells transduced with HSV-tk gene were exposed to radiation, the growth inhibitory effect of GCV was significantly increased, as compared with non-transduced parental cells. Conclusions: The results suggest that the addition of HSV-tk gene therapy to standard radiation therapy may improve the effectiveness of treatment for solid tumors.

• The Korean Journal of Pharmacology
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• v.9 no.1
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• pp.39-46
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• 1973

It has been reported previously that 2,2-methylene bis(3,4,6-trichlorophenoxy acetic acid) (MTPA) is effective treating for clonorchiasis and less toxic to the hosts. In this studies the absorption, distribution and excretion of MTPA were observed. For this purpose $^{14}C-MTPA$ was synthesised from bis(2-hydroxy-3,5,6-trichlorophenoxyl) methan $^{14}C$ and administerd to the normal rabbit in a single dose of 10mg/kg IV or 20 mg/kg P.O. or to the Clonorchis infected rabbit in dose of 20 mg/kg/day for 6 days. Radioactivity in blood, tissue, bile, urine, feces and tissue of the fluke was measured after the drug was given. The concentration of MTPA in these samples were calcurated from the radioactivity. The result obtained as followes. 1. The increase in concentration of MTPA in blood and urine after oral administration of MTPA was so slow that the absorption of MTPA from the gastrointestinal tract appears very slow. 2. It is presumed that the excretion of MTPA also is slow because the reduction of MTPA concentration in blood after IV injection was very slow. 3. Large amount of MTPA was excreted from the bile. 4. During repeat dose of 20mg/kg/day for 6 days the concentration of MTPA in blood and tissue gradually increased. 5. The highest concentration of MTPA in the kidney and liver, heart, lung, spleen and muscle in decreasing order and the lowest concentration in the brain was noted. 6. During daily dose of 20 mg/kg of MTPA for 6 days of administration the concentration of MTPA gradually increased in urine and feces and the concentration of MTPA in feces was higher than of in urine. It appeares that MTPA take place enterophepatic circulation. 7. It is assumed that accumulation in large amount of MTPA in the liver and tissue of clonorchis, excretion of large amount from the bile is a favorable property of MTPA as a chemotherapeutic agent for clonorchiasis.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.103-114
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• 1995

Platinum coordination complexes are currently one of the most compounds used in the treatment of solid tumors. However, its use is limited by severe side effects such as renal toxicity. Our platinum-based drug discovery program is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (Ⅱ) complex analogue containing 1,2-diaminocyclohexane (dach) as carrier ligand and 1,2-bis(diphenylphosphino) ethane (DPPE) as a leaving group. Furthermore, nitrate was added to improve the solubility. A new series of [Pt(trans-ddach)(DPPE).$2NO_3(PC)$ was synthesized and characterized by their elemental analysis and by various spectroscopic techniques [infrared (IR), $^{13}carbon$ nuclear magnetic resonance (NMR)]. PC demonstrated acceptable antitumor activity aganist P388, L-1210 lymphocytic leukemia cells and SK=OV3 human ovarian adenocarcinoma cells, and significant. activity as compared with that. cisplatin. The toxicity of PC was found quite less than thar of cisplatin using MTT, $[^3H]$ thymidine uptake and glucose consumption tests in rabbit proximal tubule cells, human kidney cortical cells and human renal cortical tissues. Based on these results, this novel platinum compound represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low toxicity.

• Journal of Life Science
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• v.27 no.8
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• pp.951-957
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• 2017

To understand the cytotoxic activity of Machilus thunbergii, which has been used as a traditional oriental medicine, the mechanism underlying the cytotoxic effect of its extract on human acute Jurkat T cells was investigated. The methanol extract of roots (3 kg) of M. thunbergii was evaporated, dissolved in, and then extracted by water. The water-extracted active substance was designated MTWE. When Jurkat T cells were treated with MTWE at concentrations of 0, 25, 50, and $100{\mu}g/ml$, the apoptotic phenomenon of cells accompanying several subsequent biochemical reactions, such as mitochondrial cytochrome c release, activation of caspase-3, and ICAD degradation, was detected in the Jurkat T cells. Moverover. the expression of Bcl-xL, which is a suppressor for mitochondrial cytochrome c release pathway, was reduced in the Jurkat T cells. As DUSP6, a growth suppressor of cancer cells, ranged from 0, 25, 50, $100{\mu}g/ml$ of MTWE, the expression level was elevated in the Jurkat T cells. The apoptotic morphological change of the nuclei was observed by DAPI staining. Although the potential involvement of the other factors and DUSP6 is currently being investigated in more detail, these findings support the notion that MTWE is able to achieve the apoptosis of Jurkat T cells, and it seems that MTWE is useful as a method of evaluating a chemotherapeutic agent or tonic materials for human acute leukemia.