• The Korean Journal of Nuclear Medicine
• /
• v.19 no.1
• /
• pp.119-126
• /
• 1985

To evaluate the performance characteristics of CA 19-9 radioimmunoassay and the clinical significance of serum CA 19-9 assay in patients with malignancy, serum CA 19-9 levels were measured by radioimmunoassay using monoclonal antibody in 135 normal controls, 81 patients with various untreated malignancy, 9 patients of postoperative colon cancer without recurrence and 20 patients with benign gastrointestinal diseases, who visited Seoul National University Hospital from June, 1984 to March, 1985. The results were as follows; 1) The CA 19-9 radioimmunoassay was simple to perform and can be completed in one work day. And the between-assay reproducibility and the assay recovery were both excellent. 2) The mean serum CA 19-9 level in 135 normal controls was $8.4{\pm}4.2U/mL$. Normal upper limit of serum CA 19-9 was defined as 21.0 U/mL. 4 out of 135(3.0%) normal controls showed elevated CA 19-9 levels above the normal upper limit. 3) One out of 20(5.0%) patients with benign gastrointestinal diseases showed elevated serum CA 19-9 level above the normal upper limit. 4) In 81 patients with various' untreated malignancy, 41 patients(50.6%) showed elevated serum CA 19-9 levels. 66.7% of 18 patients with colorectal cancer, 100% of 2 patients with pancreatic cancer, 100% of 3 patients with common bile duct cancer, 47.1% of 17 patients with stomach cancer, 28.6% of 28 patients with hepatoma and 60.0% of 5 other gastrointestinal tract cancers showed elevated serum CA 19-9 levels. 5) The sensitivities of serum CA 19-9 related to resectability in colorectal and stomach cancer were 33.3% in resectable colorectal cancer, 83.3% in unresectable colorectal cancer, 41.7% in resectable stomach cancer, 60.0% in unresectable stomach cancer respectively. 6) The sensitivity of serum CA 19-9 in 9 patients of postoperative colorectal cancer without recurrence were 33.3% and significantly decreased compared with that of untreated colorectal cancer, 66.7% (p<0.05). 7) In patients with colorectal cancer, simultaneous measurement of serum CA 19-9 and serum CEA levels increased sensitivities. From above results, we concluded that serum CA 19-9 radioimmunoassay is simple to perform and reproducible, and is a useful indicator reflecting tumor extent and responses to the treatment in patients with malignancy.

• Nutrition Research and Practice
• /
• v.4 no.5
• /
• pp.351-355
• /
• 2010

Our previous proteomic study demonstrated that oxidative stress and antioxidant delphinidin regulated the cellular level of $p27^{kip1}$ (referred to as p27) as well as some heat shock proteins in human colon cancer HT 29 cells. Current study was conducted to validate and confirm the regulation of these proteins using both in vitro and in vivo systems. The level of p27 was decreased by hydrogen peroxide in a dose-dependent manner in human colon carcinoma HCT 116 (p53-positive) cells while it was increased upon exposure to hydrogen peroxide in HT 29 (p53-negative) cells. However, high concentration of hydrogen peroxide (100 ${\mu}M)$ downregulated p27 in both cell lines, but delphindin, one of antioxidative anthocyanins, enhanced the level of p27 suppressed by 100 ${\mu}M$ hydrogen peroxide. ICR mice were injected with varying concentrations of hydrogen peroxide, delphinidin and both. Western blot analysis for the mouse large intestinal tissue showed that the expression of p27 was upregulated by 25 mg/kg BW hydrogen peroxide. To investigate the association of p27 regulation with hypoxia-inducible factor 1-beta (HIF-$1{\beta}$), the level of p27 was analyzed in wild-type mouse hepatoma hepa1c1c7 and Aryl Hydrocarbon Nuclear Translocator (arnt, HIF-$1{\beta}$)-defective mutant BPRc1 cells in the absence and presence of hydrogen peroxide and delphinidin. While the level of p27 was responsive to hydrogen peroxide and delphinidin, it remained unchanged in BPRc1, suggesting that the regulation of p27 requires functional HIF-$1{\beta}$. We also found that hydrogen peroxide and delphinidin affected PI3K/Akt/mTOR signaling pathway which is one of upstream regulators of HIFs. In conclusion, hydrogen peroxide and antioxidant delphinidin seem to regulate intracellular level of p27 through regulating HIF-1 level which is, in turn, governed by its upstream regulators comprising of PI3K/Akt/mTOR signaling pathway. The results should also encourage further study for the potential of p27 as a biomarker for intracellular oxidative or antioxidant status.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.31 no.4
• /
• pp.691-695
• /
• 2002

This study was performed to examine the cytotoxic effects of the distilled pine-needle extracts against several cancer cell lines. First, cell lines including mice leukemic cancer cell line (L1210), sarcoma 180 and human monocyte-like cancer cells (U937) were tested using XTT methods in uitro. Pine-needle extracts were prepared by pressing the pine needles and distilling it at below 98$^{\circ}C$ and then added to the growth medium in a final dilution of 10, 20, and 40 times. Growth of three kinds of cancer cells was significantly inhibited by more than 50% with the addition of the extracts. Fifty six to seventy six % of inhibition was shown with the 40 times dilution of the extracts. Greater inhibition was achieved with the 20 times dilution (81~90%) and the 10 times dilution (77~89%) of the extracts. Next, other human cancer cell lines including 3 kinds of breast cancer cell lines (T47D, MDA-MB-231 and MW7A) and one hepatoma cell line (SNU-354) were tested with the 20 times dilution of the extract. T47D and MDA-MB-231 cell lines showed lower inhibition (12%) with the addition of the extract. However, MH7A and SNU-354 cell lines showed 64% and 72% inhibition with the extract, respectively. These results suggest that the distilled pine-needle extracts have strong cytotoxic effect on certain cancer cell lines and the intensity of the effect may vary depending on the process of the pine needle.

• Current Research on Agriculture and Life Sciences
• /
• v.31 no.1
• /
• pp.51-55
• /
• 2013

Licorice, Glycyrrhizae radix, is one of the oldest and most frequently used botanicals in the oriental medicine. Our previous study showed that dehydrolyasperin C (DGC) isolated from licorice had antioxidant activity and induced phase 2 detoxifying enzymes in mouse hepatoma cells. Therefore, this study was conducted to investigate the effect of exposure time to DGC on quinone reductase (QR), one of the anticarcinogenic biomarkers, and antioxidant potential of plasma using animal model. ICR mice were divided into 7 groups, in which mice in each group were injected with DGC (5 mg/kg b.w.) for 0, 2, 4, 6, 8, 12, 24 hours respectively. Following the treatment the organs including liver, kidney, lung, stomach, large intestine, small and large intestines were collected and subjected to QR activity assay, western blotting, and FRAP assay. Exposure to DGC caused a significant induction of QR activity in stomach and large intestine of mice. Ferric reducing activity of plasma, a typical biomarker for antioxidative potentialshowed that DGC improved antioxidant potential in mice. However, no significant effect of DGC was observed in the other organs.

• The Korean Journal of Nuclear Medicine
• /
• v.21 no.1
• /
• pp.9-16
• /
• 1987

It is well-known that hepatic scintigraphv have been found to be less sensitive and specific in the detection of the diffuse hepatocellular diseases than that of the space-occupying lesions. To obtain the higher diagnostic specificity and sensitivity, we, using the computer quantitation, have attempted to analyze hepatic and extrahepatic $^{99m}Tc-tin$ colloid uptake patterns in various diffuse hepatocellular diseases retrospectively. The studied groups consisted of 116 cases of normal, 67 cases of acute hepatitis, 112 cases of chronic hepatitis, 61 cases of liver cirrhosis, 47 cases of fatty liver, 12 cases of hepatoma and 9 cases of metastasis, making total 424 cases. Scintigraphic imagings were obtained in the anterior, right lateral and posterior projections using high-resolution collimation, and simultaneously these gamma data were acquisited into the computer system. Both large region of interest (ROI) using light pen and ROI computer program were placed over right lobe, left lobe of liver, spleen and cardiac blood pool. Total counts in ROI were divided by the number of pixels in the ROI, and mean count rate per pixels calculated. Mean right-lobe counts were divded by mean-left lobe counts to determine right-to-left hepatic lobe ratio and mean spleen counts were divided by mean liver counts to determine spleen to liver ratio. The results were as follows. 1) Of 424 cases, 292 were male and 132 were female. The majority of age distribution was in $30\sim49$ (54.5%). 2) Inter-observer between two independant operators and inter-method between drawing by light-pen and ROI computer program variations were not significant. 3) The uptake count values (per pixel) determined at each area in normal group were $106.53{\pm}18.35$ in right lobe, $79.00{\pm}13.82$ in left lobe, $17.52{\pm}8.31$ in spleen and $8.09{\pm}3.43$ in cardiac blood pool. 4) In liver cirrhosis, right lobe uptake was decreased but spleen and cardiac blood pool uptakes were increased (p<0.01). 5) Right-to-left hepatic lobe uptake ratio was $1.37{\pm}0.24$ in normal group and significantly low in chronic hepatitis, liver cirrhosis and fatty liver, and more or less low in acute hepatitis. 6) Spleen-to-right hepatic lobe uptake ratio was $0.17{\pm}0.09$ in normal group and high in chronic hepatitis and liver cirrhosis. 7) The computer-quantitation of hepatic and extrahepatic uptake patterns thought to be sensitive and useful method in the interpretation of liver scintigram.

• Journal of Life Science
• /
• v.19 no.12
• /
• pp.1731-1736
• /
• 2009

Recent studies determined that a chronic western-style diet increased the endogenous small heterodimer partner (SHP) protein levels in mice. In experiments with cell cultures, chenodeoxy cholic acid (CDCA) treatment increased endogenous SHP protein levels and reduced the degradation rate of exogenously expressed flag-SHP levels in the human hepatoma cell line, HepG2 cells. In addition, bile acid-induced intestinal fibroblast growth factor-19 (FGF-19) increased the half-life of the exogenously expressed SHP when HepG2 cells were transfected with ad-flag-SHP. However, both the expression level and the degradation rate of the endogenous SHP in response to cholic acid and FGF-19 have not been well understood, either in mice or in cultured HepG2 cells. This study examined the effects of cholic acid treatment on the endogenous SHP protein levels in mice and the effects of FGF-19 on the degradation rate of the endogenous SHP protein in HepG2 cells. Mice fed 0.5% cholic acid in normal chow showed an increase in endogenous SHP protein levels during both 12 hr and 24 hr treatment periods as compared to control mice fed only normal chow. In cultured HepG2 cells, treatment with CDCA did not noticeably change the rate of degradation in the endogenous SHP protein from cells not treated with CDCA. Although consistent with the previous studies on the exogenous ad-flag-SHP protein, treatment with FGF-19 significantly decreased the degradation rate of the endogenous SHP protein when HepG2 cells were treated with cyclohexamide. These results suggest that both bile acids and FGF-19 increase the endogenous SHP protein levels in mouse liver and HepG2 cells.

• Journal of Life Science
• /
• v.14 no.1
• /
• pp.154-162
• /
• 2004

Thrombospondin-1 (TSP-1), a negative regulator in tumor growth and angiogenesis, is cell-type specifically regulated and at transcriptional level by external stimuli. Previously, we found that phorbol 12-myristate 13-acetate (PMA) suppressed TSP-1 expression in porcine aortic endothelial (PAE) cell, but enhanced in hepatoma cell line, Hep 3B cell. A region between -767 and -723 on the tsp-1 promoter was defined as a responsive site to the suppression in PAE cell. eased on the previous results, the molecular mechanism of TSP-1 expression was determined by characterizing interactions between cis-elements and trans-factors using three overlapped oligonucleotide probes, oligo a-1 (from -767 to -738), a-2 (-759 to -730) and a-3 (-752 to -723). The results from electromobility shift assay showed that PMA-induced suppression of TSP-1 transcription in PAE cell might be caused via a negative regulator binding to the region from -752 to -730 and additionally generated by lacking two positive regulators binding to the sites from -767 to -760 and from -752 to -730. Especially, PMA enhanced the binding ability of the negative regulator to the site from -752 to -730 in PAE cell, but anti-c-Jun did not affected its binding ability.

• Korean Journal of Acupuncture
• /
• v.18 no.1
• /
• pp.11-20
• /
• 2001

Cancer chemoprevention refer to the use of natural or synthetic substances to prevent the initiational and promtional events that occur during the process of carcinogenesis. The effect of Prunella Herba Vulgaris L. Aqua-acupuncture Solution (PVAS) and Prunella Herba Vulgaris L. Water-extracted Solution (PVWS) on the induction of phase II detoxification enzyme (quinone reductase, Glutathione S-transferase) and inhibition of phase I enzyme (cytochrome P4501A1) and benzo[a]pyrene-DNA adduct formation was examined. PVAS is potent inducers of quinone reductase activity. Glutathione levels were increased with PVAS, in cultured murine hepatoma Hepa1c1c7 cells. In addition glutathione S-transferase levels were increased with PVAS. However, there was 45.2% inhibition in the activity of cytochrome P4501A1 enzyme with the treatment of PVAS, $5{\times}$. At concentration of $1{\times}$ and $3{\times}$ of PVAS, the binding of $[^3H]B[a]P$ metabolites to DNA of NCTC-clone 1469 cell was inhibited by 25.3%, 45.0%, respectively. These results suggest that PVAS has chemopreventive potential by inducing quinone reductase and glutathione S-transferase activities, increasing GSH levels, inhibiting the activity of cytochrome P4501A1 and benzo[a]pyrene-DNA adduct formation.

• Journal of Life Science
• /
• v.18 no.3
• /
• pp.381-386
• /
• 2008

Deep sea water was tested for cancer chemopreventive activity by measuring the activities of ${\beta}-$ naphthoflavone $({\beta}-NF)-induced$ cytochrome P 450 1A2 (CYP 1A2), quinone reductase (QR) and glutathione-S-transferase (GST), glutathione (GSH) levels, and ornithine decarboxylase (ODC) activity. The in vitro incubation of rat liver microsome with deep sea water (a hardness range of $100{\sim}1,000$) showed a hardness-dependent inhibition of CYP 1A2 activity. QR and GST activities were induced about $1.1{\sim}1.2$ fold with the treatment of deep sea water in murine hepatoma Hepa 1clc7 cells. In addition GSH levels were increased $1.3{\sim}1.4$ fold in a hardness range of $100{\sim}1,000$. The deep sea water showed 20.3 and 35.0% inhibition of 12-O- tetradecanoylphorbol-13-a-cetate (TPA)-induced ODC activity at hardness 800 and 1,000, respectively. Therefore, deep sea water is worth further investigation with respect to cancer chemoprevention or therapy.

• Archives of Pharmacal Research
• /
• v.29 no.10
• /
• pp.859-865
• /
• 2006

With an approach to study the anti-tumor effects and mechanism of selenium compound, we investigated the anti-tumor activity and mechanism of $Na_5SeV_5O_{18}{\cdot}3H_2O$ (NaSeVO) in K562 cells. The results showed that $0.625{\sim}20\;mg/L$ NaSeVO could significantly inhibit the proliferation of K562 cells in vitro in a time- and concentration-dependent manner as determined by microculture tetrazolium (MTT) assay, the IC50 values were 14.41 (4.45-46.60) and 3.45 (2.29-5.22) mg/L after 48 hand 72 h treatment with NaSeVO respectively. In vivo experiments demonstrated that i.p. administration of 5, 10 mg/kg NaSeVO exhibited an significant inhibitory effect on the growth of transplantation tumor sarcoma 180 (S180) and hepatoma 22 (H22) in mice, with inhibition rate 26.8% and 58.4% on S180 and 31.3% and 47.4% on H22, respectively. Cell cycle studies indicated that the proportion of G0/G1 phase was increased at 2.5 mg/L while decreased at 10 mg/L after treatment for 24, 48 h. Whereas S phase was decreased at 2.5-5 mg/L and markedly increased at 10 mg/L after treatment for 48 h. After treatment for 24 h, 10 mg/L NaSeVO also markedly increased S and G2/M phases. Take together, the result clearly showed that NaSeVO markedly increased S and G2/M phases at 10 mg/L. The study of immunocytochemistry showed that the expression bcl-2 is significantly inhibited by 10 mg/L NaSeVO, and bax increased. Morphology observation also revealed typical apoptotic features. NaSeVO also significantly caused the accumulation of $Ca^{2+}$ and $Mg^{2+}$, reactive oxygen species (ROS) and the reduction of pH value and mitochondrial membrane potential in K562 cells as compared with control by confocal laser scanning microscope. These results suggest that NaSeVO has anti-tumor effects and its mechanism is attributed partially to apoptosis induced by the elevation of intracellular $Ca^{2+}$, $Mg^{2+}$ and ROS concentration, and a reduction of pH value and mitochondria membrane potential (MMP).