• Journal of Chest Surgery
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• v.29 no.4
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• pp.414-419
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• 1996

To determine the efficacy of OK-432 as pleural sclerosant, we examined the outcomes in 81 patients (age : 27 to 82 years) with malignant pleural effusion and the outcomes in 64 patients ecieving OK-432 3-10KE(1 Klinische Einheit unit) through a chest tube for malignant pleural effusions. Of 81 patients with malignant pleural effusion, 40 patients had lung cancer. Lung cancer is the most frequent cause of malignant pleural effusion in men and women, in which 57 oyo of it was adenocarcinoma. Eighty seven percent of patient had respiratory symptom. Of the 64 patients with intracavitary injection of OK-432 for malignant pleural effusion, 59 patients had a complete short-term response (no fluid reaccumulation during 1 month after intracavitary injection of OK-432). Five patiens of the non-responders had partial control of effusion, with improvement in respiratory symptoms and these patients underwent thoracentesis. Of the 51 patients who survived longer than 1 month, 48 patients did not have re- accumulation of the fluid during follow up. Fever after intracavitary injection of OK-432 was a majors side effect although but that was easily controlled with non-steroidal anti inflammatory drug therapy, Thus the efficacy of intracavitary OK-4)2 injection for malignant pleural effusion was very helpful.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1979-1985
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• 2016

Background: Complementary and alternative medicine has been highly appreciated as a supportive regimen for classical treatment strategies. Here we offer a nutrition-based adjuvant therapy for liver fibrosis, a major risk factor for cirrhosis and hepatocellular carcinoma. Aim of the study: To evaluate the possible hepatoprotective effects of Jerusalem artichoke tubers (JAT) in combination with interferon and ribavirin. Materials and Methods: Twelve groups of rats were administered JAT, interferon and ribavirin either separately or in combination from day one of $CCL_4$ administration until the end of the study. Animals were killed after 8 weeks of $CCL_4$-induced hepatotoxicity. Results: Hepatocytes from rats treated with triple combination of interferon, ribavirin, and JAT showed more less normal architecture compared to $CCL_4$-treated rats. We also detected significantly higher hepatic protein expression levels of p53, BAX and transforming growth factor-${\beta}$ (TGF-${\beta}$) in the $CCL_4$-intoxicated group compared to normal controls, as evidenced by immunohistochemical staining and western blotting analyses. Addition of JAT as a supportive regimen improved response to ribavirin and interferon and effectively participated in retaining normal histopathological and biochemical criteria and significantly lowered protein expression of p53, BAX, and TGF-${\beta}$. Conclusions: We suggest that addition of JAT as a supportive r egimen to interferon and ribavirin effectively potentiates their anti-fibrotic effects.

• Molecules and Cells
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• v.26 no.1
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• pp.93-99
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• 2008

Transcriptional silencing is regulated by promoter methylation and histone modifications such as methylation and acetylation. We constructed a Schizosaccaromyces pombe reporter strain, KCT120a, to identify modifiers of transcriptional silencing, by inserting the $ura4^+$ gene into a heterochromatic telomere region. Two compounds inhibited the activity of histone deacetylases, induced acetylation of histone H3 and caused apoptotic cell death in HeLa cells. Expression of gelsolin and $p21^{waf1/cip1}$ also increased, as it does in response to HDAC inhibitors such as TSA. Therefore, these compounds appear to be potent inhibitors of HDACs, and hence potential anti-cancer drugs. Our observations suggest that a yeast cell-based assay system for transcriptional silencing may be useful for identifying histone deacetylase inhibitors and other agents affecting chromatin remodeling.

• Journal of Nutrition and Health
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• v.51 no.6
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• pp.498-506
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• 2018

Purpose: Lycopene, a carotenoid with anti-oxidant properties, occurs naturally in tomatoes and pink grapefruit. Although the beneficial effects of lycopene on various disorders have been established, little attention has been paid to the possible anti-diabetic effects of lycopene focusing on ${\beta}$-cells. Therefore, this study investigated the potential of lycopene to protect ${\beta}$-cells against apoptosis induced by a cytokine mixture. Methods: For toxicity experiments, the cells were treated with 0.1 ~ 10 nM of lycopene, and the cell viability in INS-1 cells (a rat ${\beta}$-cell line) was measured using a MTT assay. To induce cytokine toxicity, the cells were treated with a cytokine mixture (20 ng/mL of $TNF{\alpha}$ + 20 ng/mL of IL-$1{\beta}$) for 24 h, and the effects of lycopene (0.1 nM) on the cytokine toxicity were measured using the MTT assay. The expression levels of the apoptotic proteins were analyzed by Western blotting, and the level of intracellular reactive oxidative stress (ROS) was monitored using a DCFDA fluorescent probe. The intracellular ATP levels were determined using a luminescence kit, and mRNA expression of the genes coding for anti-oxidative stress response and mitochondrial function were analyzed by quantitative reverse-transcriptase PCR. Results: Exposure of INS-1 cells to 0.1 nM of lycopene increased the cell viability significantly, and protected the cells from cytokine-induced death. Lycopene upregulated the mRNA and protein expression of B-cell lymphoma-2 (Bcl-2) and reduced the expression of the Bcl-2 associated X (Bax) protein. Lycopene inhibited apoptotic signaling via a reduction of the ROS, and this effect correlated with the upregulation of anti-oxidative stress response genes, such as GCLC, NQO1, and HO-1. Lycopene increased the mRNA expression of mitochondrial function-related genes and increased the cellular ATP level. Conclusion: These results suggest that lycopene reduces the level of oxidative stress and improves the mitochondrial function, contributing to the prevention of cytokine-induced ${\beta}$-cell apoptosis. Therefore, lycopene could potentially serve as a preventive and therapeutic agent for the treatment of type 2 diabetes.

• Molecules and Cells
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• v.37 no.2
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• pp.178-186
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• 2014

Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.

• IMMUNE NETWORK
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• v.1 no.2
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• pp.109-115
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• 2001

Background: The role of the interferon consensus sequence binding protein (ICSBP), a member of interferon regulatory factor family, in protecting against a vesicular stomatitis virus (VSV) infection has not been firmly elucidated. Thus, it was investigated utilizing the human promyelocytic leukemia HL-60 cells which do not express ICSBP. Methods: HL-60 cells were stably transfected with plasmid containing cDNA for either ICSBP or DNA binding domain (DBD) and tested for their VSV-susceptibilities. The susceptibility of each transfectant group to a VSV infection was determined by a plaque assay at 1 h, 24 h, and 48 h post-infection in the presence (500 IU/ml) or absence of interferon ${\alpha}$ ($IFN{\alpha}$). Results: In the absence of $IFN{\alpha}$, the three groups showed similar sensitivities to a VSV infection. However, when pre-treated with IFN, the viral titers in both the ICSBP and control clones steadily decreased over 48 h of incubation, indicating the existence of $IFN{\alpha}$-mediated protection against VSV infection. The $IFN{\alpha}$-treated ICSBP clones appeared to be more resistant to infection compared with the control clones, although the difference was not great. On the contrary, the viral titers in the $IFN{\alpha}$-treated DBD clones increased at 24 h then decreased by 48 h. Conclusion: The expression of truncated ICSBP (DBD) does not appear to underlie the impaired protection against a VSV infection in the DBD clones, since even the control clones lacking ICSBP were protected from a VSV infection. This suggests that ICSBP does not play a critical role in the $IFN{\alpha}$- mediated anti-VSV response of HL-60 cells, although it appears to confer some resistance to a VSV infection.

• Toxicological Research
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• v.26 no.3
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• pp.217-222
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• 2010

Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary fibrosis as a side effect. However, few investigations have focused on the dose-response effects of bleomycin on pulmonary fibrosis. Therefore, in the present study, we investigated the effects of different doses of bleomycin in male mice. ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The animals were sacrificed at 7 and 24 days postinstillation. The severity of pulmonary fibrosis was evaluated according to inflammatory cell count and lactate dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF), and lung tissues were histologically evaluated after hematoxylin and eosin (H&E), and Masson's trichrome staining. BT groups exhibited changed cellular profiles in BAL fluid compared to the VC group, which had an increased number of total cells, neutrophils, and lymphocytes and a modest increase in the number of macrophages at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose-dependent increase in LDH levels and inflammatory cell counts. However, at 24 days after treatment, collagen deposition, interstitial thickening, and granulomatous lesions were observed in the alveolar spaces in addition to a decrease in inflammatory cells. These results indicate that pulmonary fibrosis induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg. These data will be utilized in experimental animal models and as basic data to evaluate therapeutic candidates through non-invasive monitoring using the pulmonary fibrosis mouse model established in this study.

• Toxicological Research
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• v.23 no.3
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• pp.231-238
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• 2007

Evaluation of potentials of chemicals to alter expression of genes that are involved in carcinogenesis may serve useful tools in toxicological research. In this investigation, we developed reporter cell lines that expressed luciferase in response to transactivation of hypoxia inducible factor-1, P53 tumor suppressor and Nur77 of which roles have been well established in cancer development and progression. Whereas these reporter cell lines displayed low constitutive backgrounds, the reporter activities were significantly enhanced in response to $desferriosamine/CoCl_2$, adriamycin or 6-mercaptopurine, which are hypoxia mimicking chemicals, P53 activator or Nur77 inducer, respectively. The activation of the reporter was time- and dose-dependent. Known tumor initiators and promoters, such as phorbol 12-myristate 13-acetate and phorbol 12, 13-dicaprinate induced the reporter activity at as low as 10nM in these stable cell lines. Further, known anti-tumor promoters, such as ascorbic acid and ${\beta}-carotene$ repressed the reporter activities. These results indicate that our stable reporter cell lines could serve as a useful system for rapid assessment of carcinogenicity of toxic chemicals.

• BMB Reports
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• v.52 no.8
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• pp.520-525
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• 2019

Dihydroartemisinin (DHA) has been reported to possess anti-cancer activity against many cancers. However, the pharmacologic effect of DHA on HBV-positive hepatocellular carcinoma (HCC) remains unknown. Thus, the objective of the present study was to determine whether DHA could inhibit the proliferation of HepG2.2.15 cells and uncover the underlying mechanisms involved in the effect of DHA on HepG2.2.15 cells. We found that DHA effectively inhibited HepG2.2.15 HCC cell proliferation both in vivo and in vitro. DHA also reduced the migration and tumorigenicity capacity of HepG2.2.15 cells. Regarding the underlying mechanisms, results showed that DHA induced cellular senescence by up-regulating expression levels of proteins such as p-ATM, p-ATR, ${\gamma}-H_2AX$, P53, and P21 involved in DNA damage response. DHA also induced autophagy (green LC3 puncta gathered together and LC3II/LC3I ratio increased through AKT-mTOR pathway suppression). Results also revealed that DHA-induced autophagy was not linked to senescence or cell death. TPP1 (telomere shelterin) overexpression could not rescue DHA-induced anticancer activity (cell proliferation). Moreover, DHA down-regulated TPP1 expression. Gene knockdown of TPP1 caused similar phenotypes and mechanisms as DHA induced phenotypes and mechanisms in HepG2.2.15 cells. These results demonstrate that DHA might inhibit HepG2.2.15 cells proliferation through inducing cellular senescence and autophagy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.5
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• pp.664-670
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• 2016

Cheonggukjang (CKJ) is a Korean traditional food made of fermented soybeans. In comparison to normal intake of soybeans, Cheonggukjang has high digestibility with bioactive, antioxidant substances, and thrombolytic enzymes. Recent studies have reported anti-oxidant, anti-cancer, anti-inflammatory, anti-obesity activities as well as inhibitory activities against osteoporosis for CKJ. In this study, we identified the effects of CKJ on osteoblast differentiation by increasing the polyglutamic acid (PGA) content of CKJ. Alkaline phosphatase (ALP) activity and mineralization significantly increased in response to treatment with both natural CKJ (CKJ A) and PGA-increased CKJ (CKJ B). However, CKJ B exhibited higher ALP activity and mineralization than CKJ A. Real-time reverse transcription PCR demonstrated that mRNA expression of osteoblastic-associated genes such as type I collagen, alkaline phosphatase, osteocalcin, and osteopontin in C2C12 cells was significantly up-regulated by CKJ A or B treatment. These results indicate that treatment with CKJ has an anabolic effect on bone by increasing osteoblastic differentiation and ALP activity. Increasing PGA content in CKJ had a greater effect than CKJ A on up-regulation of osteoblastic gene expression in osteoblast cells.