• Tuberculosis and Respiratory Diseases
• /
• v.64 no.1
• /
• pp.15-21
• /
• 2008

Background: The melanoma antigen-encoding (MAGE) genes are known to be expressed in various cancer cells, including non-small cell lung cancer (NSCLC), and are silent in all normal tissues except for the testis. In patients with peripheral NSCLC, bronchial washing fluid can be used to detect the MAGE genes, suggesting a diagnosis of lung cancer. In order to evaluate the diagnostic utility of the MAGE test in patients with peripheral NSCLC, bronchial washing fluid was investigated in patients with peripheral pulmonary nodules, which were invisible as detected by bronchoscopy. Methods: Bronchial washing fluid from 37 patients was used for cytological examinations and MAGE gene detection, using RT-nested-PCR of common A1-A6 mRNA. Results were compared to a final diagnosis of patients as confirmed by pathology. Results: Among the 37 subjects, NSCLC was diagnosed in 21 patients, and benign pulmonary diseases were diagnosed in 16 patients. MAGE mRNA was detected in 10 of 21 (47.6%) NSCLC patients, while conventional cytology examinations were positive for MAGE expression in 2 of 21 (9.5%) cases. MAGE expression was observed in 4 of 16 (25%) benign pulmonary disease patients. Conclusion: The MAGE test of bronchial washing fluid can be used as a sensitive predictor of peripheral NSCLC patients.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.37 no.7
• /
• pp.834-840
• /
• 2008

In order to improve the use of pumpkin seed, the present study was performed to isolate compositions of the bitter components which were not seen in pumpkin seed itself but newly biosynthesized during germination of the seed. The compositions isolated were then further purified by TLC and preparative HPLC in which a fraction with Rf 0.73 and RT 10.3 was obtained. Cucurbitacin E with molecular weight of 557 from the fraction was finally identified by subsequent structural analysis of LC-MS/MS. The production of cucurbitacin E peaked with 224.7 mg/kg at 4 days of germination at $20^{\circ}C$ with the water supply at ntervals of 48 hrs in the darkness, while that of cucurbitacin E reached 146.7 mg/kg in the brightness. In vitro-cell based assays demonstrated that the isolated and purified cucurbitacin E inhibited proliferation of A549 lung cancer cells and suppressed expression of the IL-$1{\beta}$- or PMA-induced cyclooxygenase-2, an inflammatory protein in A549 cells, suggesting its anti-proliferative and anti-inflammatory activities.

• Korean Journal of Environmental Agriculture
• /
• v.19 no.2
• /
• pp.147-153
• /
• 2000

Cigarette smoking deals a harmful effect directly to smokers and even to non-smokers through environmental tobacco smoke. The major damaging component in cigarette smoke is nicotine which converts to various carcinogens. Among the carcinogenic metabolites, nitrosamine-4-(methylnitrosamino)-1- (3-pyridyl)-1- butanone (NNK) is responsible for many types of lung cancers. Recent studies report that activation of NNK is markedly inhibited in the presence of cotinine, a safer metabolite from nicotine. It is well known that tea extract have potentials to prevent cancers. This study aims to correlate green tea's potential for cancer prevention with an accelerated formation of cotinine. In the presence of tea extract, a nicotine to cotinine conversion was studied in established cell lines and xenopus oocytes. Among three lines of cell used, PLC/PRF5 and 293 cells showed a fast turnover from nicotine to cotinine while HepG2 cell line showed a marginal difference between groups treated and non-treated with tea extract. A microinjection procedure using Xenopus oocyte was utilized to probe for the effect of tea extract in accelerating nicotine conversion to cotinine. According to this procedure, tea extract's unusual potential for converting nicotine to cotinine is also substantiated. Overall, this present study indicated that tea extract have an unusual effect on conversion of nicotine to cotinine in cells.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.2
• /
• pp.929-935
• /
• 2014

Two types of nanosized titanium dioxide, anatase ($anTiO_2$) and rutile ($rnTiO_2$), are widely used in industry, commercial products and biosystems. $TiO_2$ has been evaluated as a Group 2B carcinogen. Previous reports indicated that $anTiO_2$ is less toxic than $rnTiO_2$, however, under ultraviolet irradiation $anTiO_2$ is more toxic than $rnTiO_2$ in vitro because of differences in their crystal structures. In the present study, we compared the in vivo and in vitro toxic effects induced by $anTiO_2$ and $rnTiO_2$. Female SD rats were treated with $500{\mu}g/ml$ of $anTiO_2$ or $rnTiO_2$ suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment with $anTiO_2$ or $rnTiO_2$ increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in the $anTiO_2$ treated group compared to the $rnTiO_2$ treated group. Expression of $MIP1{\alpha}$ mRNA and protein in lung tissues treated with $anTiO_2$ and $rnTiO_2$ was also significantly up-regulated, with $MIP1{\alpha}$ mRNA and protein expression significantly lower in the $anTiO_2$ group than in the $rnTiO_2$ group. In cell culture of primary alveolar macrophages (PAM) treated with $anTiO_2$ and $rnTiO_2$, expression of $MIP1{\alpha}$ mRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarly to the in vivo results, $MIP1{\alpha}$ mRNA and protein expression was significantly lower in the $anTiO_2$ treated cultures compared to the $rnTiO_2$ treated cultures. Furthermore, conditioned cell culture media from PAM cultures treated with $anTiO_2$ had less effect on A549 cell proliferation compared to conditioned media from cultures treated with $rnTiO_2$. However, no significant difference was found in the toxicological effects on cell viability of ultra violet irradiated $anTiO_2$ and $rnTiO_2$. In conclusion, our results indicate that $anTiO_2$ is less potent in induction of alveolar macrophage infiltration, 8-OHdG and $MIP1{\alpha}$ expression in the lung, and growth stimulation of A549 cells in vitro than $rnTiO_2$.

• Tuberculosis and Respiratory Diseases
• /
• v.56 no.5
• /
• pp.465-484
• /
• 2004

Background : Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) inhibits the proliferation of non-small cell lung cancer (NSCLC) cells by inducing apoptosis. Methods : In this study, we investigated whether hypermethylation of IGFBP-3 promoter play an important role in the loss of IGFBP-3 expression in NSCLC. We also studied the mechanisms that mediate the silencing of IGFBP-3 expression in the cell lines which have hypermethylated IGFBP-3 promoter. Results : The IGFBP-3 promoter has hypermethylation in 7 of 15 (46.7%) NSCLC cell lines and 16 (69.7%) of 23, 7 (77.8%) of 9, 4 (80%) of 5, 4 (66.7 %) of 6, and 6 (100%) of 6 tumor specimens from patients with stage I, II, IIIA, IIIB, and IV NSCLC, respectively. The methylation status correlated with the level of protein and mRNA in NSCLC cell lines. Expression of IGFBP-3 was restored by the demethylating agent 5'-aza-2'-deoxycytidine (5'-aza-dC) in a subset of NSCLC cell lines. The Sp-1/ Sp-3 binding element in the IGFBP-3 promoter, important for promoter activity, was methylated in the NSCLC cell lines which have reduced IGFBP-3 expression and the methylation of this element suppressed the binding of the Sp-1 transcription factor. A ChIP assay showed that the methylation status of the IGFBP-3 promoter influenced the binding of Sp-1, methyl-CpG binding protein-2 (MeCP2), and histone deacetylase (HDAC) to Sp-1/Sp-3 binding element, which were reversed by by 5'-aza-dC. In vitro methylation of the IGFBP-3 promoter containing the Sp-1/Sp-3 binding element significantly reduced promoter activity, which was further suppressed by the overexpression of MeCP2. This reduction in activity was rescued by 5'-aza-dC. Conclusion : These findings indicate that hypermethylation of the IGFBP-3 promoter is one mechanism by which IGFBP-3 expression is silenced and MeCP2, with recruitment of HDAC, may play a role in silencing of IGFBP-3 expression. The frequency of this abnormality is also associated with advanced stages among the patients with NSCLC, suggesting that IGFBP-3 plays an important role in lung carcinogenesis/progression and that the promoter methylation status of IGFBP-3 may be a marker for early molecular detection and/or for monitoring chemoprevention efforts.

• Korean Journal of Medicinal Crop Science
• /
• v.10 no.1
• /
• pp.51-57
• /
• 2002

The biological activities of immune modulating activities of the extracts from Echinacea purpurea, Chrysanthmum indicum L. and Circium japonicum var. ussuriense KITAMURA were compared. About 70% of the growth of human hepatocarcinoma and 80% of human gastric cancer cell was inhibited in adding 0.5mg/ml of the ethanol extracts of Echinacea purpurea, Chrysanthmum indicum L. and Circium japonicum var. ussuriense KITAMURA, respectively. The growth of human breast cancer cells was also inhibited in adding 0.5mg/ml of the extracts as well as 60% of the human cancer cells. It was proved that the growth of human normal lung cell, scored as 15% for the extracts. Overall selectivity of the extracts on several human cancer cell line was over 3, which is higher than those from the conventional herbs. The growth of both human immune B and T cells was enhanced up to 1.4 to 2.0 times by adding the extracts, compared to the controls. The secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$ from T cell was also increased up to 94 pg/ml in adding the Echinacea purpurea ethanol extract (0.5mg/ml). Circium japonicum var. ethanol extract also increased up to about 96 pg/ml of interleukin-6(IL-6) from B cell.

• Korean Journal of Medicinal Crop Science
• /
• v.11 no.1
• /
• pp.5-12
• /
• 2003

The biological activities of extracts from Rubus coreanus Miq. were compared. About 70% of the growth of human hepatocarcinoma and 79% of human gastric cancer cell was inhibited in adding 1.0 mg/ml of the extracts of Rubus coreanus Miq. respectively. The growth of human breast cancer cells was also inhibited in adding 1.0 mg/ml of the extracts as well as 78% of the human cancer cells. It was proved that the growth of human normal lung cell, scored as 15% for the extracts. Overall selectivity of the extracts on several human cancer cell line was over 5, which is higher than those from the Rubus coreanus Miq. The growth of both human immune B and T cells was enhanced up to 1.4 to 1.8 times by adding the extracts, compared to the controls. The secretion of tumor necrosis $factor-alpha(TNF-{\alpha})$ from T cell was also increased up to 78.8 pg/ml in adding the ethanol extract (0.5 mg/ml). Ethanol extract also increased up to about 70 pg/ml of interleukin-6(IL-6) from B cell. For screening regulate function of blood pressure, angiotensin converting enzyme(ACE) activity was inhibited up to 25% by adding the ethanol extract (1.0 mg/ml). In testing the hypoglycemic activity, 20% of ${\alpha}-glucosidase$ activity was inhibited for the extracts (0.5 mg/ml). GST activity was increased in the range of 1.2 to 1.6 times by adding extracts.

• Korean Journal of Medicinal Crop Science
• /
• v.11 no.1
• /
• pp.13-18
• /
• 2003

The biological activities of extracts from Rosa rugosae Radix were compared. About 78% of the growth of human hepato- carcinoma and 68% of human gastric cancer cell was inhibited in adding 0.5 mg/ml of the extracts of Rosa rugosae Radix respectively. The growth of human breast cancer cells was also inhibited in adding 0.5 mg/ml of the extracts as well as 66% of the human cancer cells. It was proved that the growth of human normal lung cell, scored as 20% for the extracts. Overall selectivity of the extracts on several human cancer cell line was over 4, which is higher than those from the Rosa rugosae Radix. The growth of both human immune B and T cells was enhanced up to 1.2 to 1.5 times by adding the extracts, compared to the controls. The secretion of tumor necrosis factor-alpha$(TNF-{\alpha})$ from T cell was also increased up to 61.9 pg/ml in adding the ethanol extract (0.5 mg/ml). Ethanol extract also increased up to about 61.3 pg/ml of interleukin-6(IL-6) from B cell.

• Radiation Oncology Journal
• /
• v.19 no.2
• /
• pp.181-189
• /
• 2001

Purpose : Changes in the balance between MMP and TIMP can have a profound effect on the composition in the extracellular matrix (ECM) and affect various cellular functions including adhesion, migration, differentiation of cells, and fibrosis and invasion and metastasis of cancer cells. Radiation therapy is a popular treatment modality for benign and malignant tumor, but the study for radiation effect on MMP and TIMP is scarce. In the current study, we have examined the expression of TIMP in fibrosis-prone (C57BL/6) mice after radiation. Methods and Materials : Adult female mice of $10\~12$ weeks were used. The whole body were irradiated using a Varian CL-4/100 with 2 and 10 Gy. Immunohistochemical staining was peformed according to Avidin Biotin complex method and evaluated by observing high power field. For TIMP-1, TIMP-2 antibodies, reactivity was assessed in the parenchymal cell and in the stromal cell. The scale of staining was assessed by combining the quantitative and qualiative intensity of staining. Results : TIMP-1 immunoreactivity did not change in lung. But, in liver, TIMP-1 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell. in kidney, TIMP-1 immunoreactivity was localized in cytoplasm of some tubular cell. Temporal variations were not seen. Dose-response relationship was not seen except kidney. TIMP-2 immunoreactivity in lung was a score (++) at 0 Gy and elevated to a score (+++) at 2 Gy. TIMP-2 immunoreactivity was a score (++) in liver at 0 Gy. TIMP-2 immunoreactivity was localized in cytoplasm of hepatocyte and Kupffer cell as same as patterns of TIMP-1 immunoreactivity. The TIMP-2 immunoreactivity in liver was elevated to (+++) at 2 Gy. Immunoreactivity to TIMP-2 in kidney was a score (+++) at 0 Gy and was not changed at 10 Gy. The score of TIMP-2 immunoreactivity was reduced to (++) at 2 Gy. TIMP-2 immunoreactivity was confined to tubules in kidney. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIMP-2 immunoreactivity was not seen. Conclusions : Differences between intensity of expression of TIMP-1 and TIMP-2 in each organ was present. Expression of TIMP was localized to specific cell in each organ. Irradiation increased TIMP-1 immunoreactivity in the liver and the kidney. Irradiation increased TIMP-2 immunoreactivity in the lung. But, in the liver and the kidney, TIMP-2 expression to radiation was irregular. Temporal variation of TIMP-2 immunoreactivity was irregular. Dose-response relationship of TIHP-2 immunoreactivity was not seen. In the future, we expect that the study of immunohistochemical staining of longer period of postirradiation and quantitative analysis using western blotting and northern blotting could define the role of TIMP in the radiation induced tissue fibrosis.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.17
• /
• pp.7195-7200
• /
• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.