Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.
Anti-bone resorption properties of the Korean herbal medicine, CEDR, which is comprised 5 herbs of [Drynariae Rhizoma, Loranthi Ramus, Cibotii Rhizoma, Amydae carapax, Psoraleae semen], were investigated. Mouse calvarial osteoblast cells were isolated and cultured. Mouse osteoblasts, which were stimulated by PTH, $1,25(OH)_2D_3$, $TNF-\alpha$ and IL-1 as bone resorption agents, showed increased collagenolysis by producing the active gelatinase. IL-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. IL-1 stimulated bone resorption and produced marked resorption when present simultaneously. The results of in vitro cytotoxicities showed that CEDR extracts have no any cytotoxicities in concentrations of $1-60{\mu}g/ml$ and furthermore there is no any cytotoxicity even in concentration of $120{\mu}g/ml$ on mouse calvarial bone cells. CEDR extracts had protective activity against PTH (5 units/ml, or $IL-1{\alpha}$ (1 ng/ml) or $TNF-\alpha$ or $1,25(OH)_2D_3$ (20 ng/ml), $IL-1{\alpha}$ and $IL-1{\beta}-induced$ collagenolysis in the mouse calvarial cells. Pretreatment of the CEDR extracts for 1 h, which by itself had little effect on cell survival, did not enhance the collagenolysis, nor significantly reduced the collagenolysis by pretreatment. Furthermore, the medicinal extracts were shown to have the protective effects against collagenolysis induced by $IL-1{\alpha}$ and $IL-1{\beta}$. Pretreatment of the extracts for 1 h significantly reduced the collagenolysis. Interestingly, the CEDR extracts were shown to have the inhibiting effects against gelatinase enzyme and processing activity induced by the bone resorption agents of PTH, $1,25(OH)_2D_3$, $TNF-\alpha$, $IL-1{\beta}$ and $IL-1{\alpha}$ with strong protective effect in pretreatment with the extracts. CEDR extracts were shown to have the inhibiting effects against $IL-1{\alpha}-$ and $IL-1{\beta}-stimulated$ bone resorption and the effect of the pretreatment with a various concentrations of the medicinal extracts were significant. These results indicated that the CEDR extracts are highly stable and applicable to clinical uses in osteoporosis.
Two crystal structures of bromine sorption complexes of vacuum dehydrated Cd(ll)-exchanged zeolite A have been determined by single-crystal xray diffraction techniques in the cubic space group Pm3m at 21(1) ℃. Both crystals were ion exchanged in flowing streams of exchange solution In which mole ratio of Cd(NO3)2 and Cd(OOCCH3)B was 1:1 with a total concentration of 0.05 M. First crystal was dehydrated at 450℃ and 2 ×10-6 Torr for two days. Second crystal was dehydrated at 650℃ and 2 ×10-6 Torr for two days. Both crystals were then treated with 160 Torr for two days. Second crystal was dehydrated at 650℃ and 2 × 10-6 Torr for two days. Both crystals were then treated with 160 Torr of zeolitically dried bromine vapor at 24℃. Full-matrix least-squares refinements of toe first crystal(a: 12.250(1) A )· and the second crystal(a: 12.204(2) A ) have contecoed to final error indices, Rl:0.075 and Ra:0.079 with 212 reflections, and Rl : 0.089 and Ra = 0.078 with 128 reflections, respectively, for which I >3σ(I). Crystallographic analyses of both crystals show that six Cd2+ ions are located on two different threefold axes of unit cell associated with 6-ring oxygens. Each 4.5 Cd2+ ion is recessed ca.0. 441 A Into the large cavity to complex either with Brsor with Br3from the (111) plane of 0(3), whereas each 1.5 Cd2+ ions recessed ca. 0.678 A into we sodalite unit. Approximately 1.5 Br5-and 1.5 Br3-ions are sorbed per unit cell. Each Brsion interacts and stabilized by complexing with two Cd2+ ions and framework oxide ions, while each Br3ion interacts with one Cd2+ ion and framework oxide ions. Because of residual water molecules the following reactions may be occurred inside of zeolite cavity:
Background: $^{99m}Tc$ MIBI(Methoxyisobutylisonitrile complex), a member of the isonitrile class of coordination compounds, is a lipophilic cation presently under investigation for clinical use as myocardial perfusion imaging agent and is widely used to detect myocardial infarction. Preliminary reports indicate that $T_1$-201 accumulate in human neoplasm and several authors reported $^{99m}Tc$ MIBI may also localized in primary malignant tumor and metastatic deposits from lung cancer. We evaluated the uptake of $^{99m}Tc$ MIBI in lung cancer and localization of mediastinal and other site metastasis, and compared the benign lesion of the lung. Method: Thirty four patients of lung cancer and ten patients of benign lung lesion were studied with chest CT and $^{99m}Tc$ MIBI Lung SPECT. $^{99m}Tc$ MIBI uptake ratio was assessed by TR/NL(Lung lesion/ Normal area), HT/NL (Heart/Normal area) and HT/TR(Heart/Lung lesion). Results: 1) All lung cancer patients showed increased uptakes of $^{99m}Tc$ MIBI in malignant lung lesion and Tc-99m MIBI uptake was also increased in mediastinal and lymph node metastasis except two cases. 2) There was significant different ratio of TR/NL between malignant and benign lesion, $3.79{\pm}1.82$ and $1.67{\pm}0.63$ on planar images, respectively(p<0.001). 3) There was no significant difference of $^{99m}Tc$ MIBI uptake ratio between squamous cell carcinoma, small cell carcinoma and adeno carcinoma($3.64{\pm}1.66$, $3.57{\pm}0.72$, $4.31{\pm}2.28$ respectively). Conclusion: $^{99m}Tc$ MIBI lung SPECT was useful in the localization of tumor and mediastinal or other site metastatic lesion in lung cancer and also in the differential diagnosis between benign and malignant lesion.
Cell surface antigenic relationships between pathogenic mycobacteria have been investigated by the enzyme-linked immunosorbent assay using phenolkilled cells and their rabbits antisera. Homologous and heterologous reactions of Mycobacterium avium-intracellulare antisera before and after homologous and heterologous absorption revealed a close antigenic relationship between strains of the same species and between species if they were members of M. avium(MA)-intracellulare(MI)-scrofulaceum(MG) complex. MAI sera showed a considerable reaction with M. kansasii(MK) and tuberculosis(MTB), but not with the other species. MA(K40004) antiserum reacted with other mycobacteria except few strains of MI and 50~89% of homologous reaction was reduced by heterologous absorption with cells of MI or MS. Intraspecific reaction of MI antisera was natural1y stronger than interspecific reaction and different in extent due to a magnitude of antigenic sharing. Antigenic relationships between N-260D, N-260R, N-260T, and K41014 was somewhat closer than that with N-242D, N-257T, N-28ID, and N-275T. M. nonchromogenicum(MNC) antisera showed a strong interspecific reaction with exception of M. chelonei(MC) and triviale(MTV) to which they reacted weakly or none. Antigenic sharing with M. terrae(MTR) and MG(K30003) was next to intraspecific sharing. NC-3 shared antigens considerably with MA, MC, and M. fortuitum(MF) while NC-11 did not. MTR antisera showed a strong cross-reaction with MI but their homologous reaction was not reduced by MI absorption indicating a paucity of shared antigen of MTR surface. Intraspecific antigenic sharing of course was large with on exception between T-8 and T-13. A considerable amount of antigenic sharing was also found with MNC, MC and MF. Unlike T-8 serum, T-13 antiserum strongly cross-reacted with MA, MG, MK, and MTB. In general, antigenic relationships of mycobacteria, that have been elucidated in this study, well conformed to taxons delineated by the various biological and biochemical means.
Park, Kyeong Seon;Kim, Yu Jin;Yoon, Jin Young;Kyung, Sun Young;An, Chang Hyeok;Lee, Sang Pyo;Park, Jeong Woong;Jeong, Sung Hwan
Tuberculosis and Respiratory Diseases
/
v.65
no.6
/
pp.504-511
/
2008
Background: Particulate matter may be toxic to human tissue. Ambient air particulate matter ${\leq}10{\mu}m$ in aerodynamic size ($PM_{10}$), which changes under different environmental conditions, is a complex mixture of organic and inorganic compounds. The Asian dust event caused by meteorological phenomena can also spread unique particulate matter in affected areas. We evaluated production of ROS, $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$ by exposing normal epithelial cells to Asian dust particulate matter. Methods: Bronchial epithelial cells were exposed to 0, 50, ${\leq}100{\mu}g/ml$ of a suspension of $PM_{10}$ for 24 h. ROS were detected by measurement of DCF release from DCF-DA by FACScan. $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$ were detected by western blotting. Results: $PM_{10}$ exposure increased the expression of $TGF-{\beta}$, fibronectin, and $NF{\kappa}B$. ROS production and $TGF-{\beta}$ levels were significantly higher with 50 or ${\leq}100{\mu}g/ml$$PM_{10}$. Fibronectin and $NF{\kappa}B$ production were significantly higher after ${\leq}100{\mu}g/ml$ of $PM_{10}$. Conclusion: $PM_{10}$ from Asian dust particles might have fibrotic potential in bronchial epithelial cells via ROS induction after $PM_{10}$ exposure.
Park, Kyung Lok;Hong, Sung Wook;Kim, Young Joon;Kim, Soo Jae;Chung, Kun Sub
Microbiology and Biotechnology Letters
/
v.41
no.3
/
pp.327-334
/
2013
For the development of hardy kiwi wine, we arranged for the post-maturity of hardy kiwi fruit, treated them with calcium carbonate and a pectinase enzyme complex, investigated the resulting physicochemical properties and conducted a sensory evaluation. The period determined for creating post-maturity in the hardy kiwi fruit was determined as 5 days storage at room temperature following maturity. During this time the yield of fruit juice was increased from 22.1% to 53.5% using 0.1% (v/v) cytolase PCL5 for 2 h at room temperature. 0.1% (w/v) calcium carbonate was also added during the process of aging, for the reduction of the sour taste. The fermentation trial of the hardy kiwi wine was prepared using water (25% or 50%), sugar ($24^{\circ}brix$), 0.1% (w/v) $CaCO_3$, 0.1% (v/v) cytolase PCL5, $K_2S_2O_5$ (200 ppm), and yeast ($1.5{\times}10^7$ cell/ml). Fermentation then occurred for 2 weeks at $20^{\circ}C$. The pH value, total acidity, alcohol, and reducing sugar content of the resulting hardy kiwi wines of 25% (v/w) and 50% (v/w) water, were in a range of pH 3.4-3.7, 1.12-1.21%, 14.3-14.4%, and 15-16 g/l, respectively. Citric acid and fructose constituted the major organic acids and the free sugar of the 25% and 50% hardy kiwi wine, respectively. Volatile flavor components, including 10 kinds of esters, 8 kinds of alcohols, 5 kinds of acids, 3 kinds of others and aldehydes, were determined by GC analysis. The results of sensory evaluation demonstrated that 50% hardy kiwi wine is more palatable than 25% hardy kiwi wine.
Ha, Jun Young;Kim, Mi Kyeong;Lee, Jun Young;Choi, Eun Bi;Hong, Chang Oh;Lee, Byong Won;Bae, Chang Hwan;Kim, Keun Ki
Journal of Life Science
/
v.25
no.1
/
pp.53-61
/
2015
In this study, we tried to separate the photosensitizer that induces apoptosis of leukemia cells (U937) from perilla leaves. Perilla leaves (Perilla frutescens Britt var. japonica Hara) are a popular vegetable in Korea, being rich in vitamins (A and E), GABA, and minerals. Dried perilla leaves were extracted with methanol to separate the photosensitizer by various chromatographic techniques. The structure of the isolated compound (PL9443) was identified by 1D-NMR, 2D-NMR, and FAB-mass spectroscopy. Absorbance of the UV-Vis spectrum was highest at 410 nm and was confirmed by the 330, 410, and 668 nm. PL9443 compound was determined to be pheophorbide, an ethyl ester having a molecular weight of 620. It was identified as a derivative compound of pheophorbide structure when magnesium comes away from a porphyrin ring. Observation of morphological changes in U937 cells following cell death induced by treated PL9443 compound revealed representative phenomena of apoptosis only in light irradiation conditions (apoptotic body, vesicle formation). Results from examining the cytotoxicity of PL9443 substance against U937 cells showed that inhibition rates of the cell growth were 99.9% with the concentration of 0.32 nM PL9443. Also, the caspase-3/7 activity was 99% against U937 cells with the concentration of 0.08 nM of PL9443 substance. The result of the electrophoresis was that a DNA ladder was formed by the PL9443. The PL9443 compound is a promising lead compound as a photosensitizer for photodynamic therapy of cancer.
In this study to evaluate the involvement of EGFR, HER-2/neu and ALCAM (CD166) oncogene products in canine mammary neoplastic lesions, sections of archived paraffin-embedded samples of 49 mammary tumors were analyzed immunohistochemically using antibodies against human EGFR and HER-2/neu and ALCAM. These 49 tumors were divided into 2 groups: 22 benign (19 adenoma, 3 benign mixed tumors) and 27 malignant tumors (2 simple adenocarcinomas, 5 complex adenocarcinomas, 3 solid carcinoma, 5 sclerosing carcinoma, 8 malignant mixed tumors and 4 malignant myoepithelioma). As a result of immunostaining, 31.8% (7/22) of the benign tumors and 29.6% (8/27) of the malignant tumors expressed the HER-2/neu oncogene product, EGFR expression was detected in 27.3% (6/22) of benign tumors and in 22.2% (6/27) of the malignant tumors. ALCAM expression was detected in 40.9% (9/22) of benign tumors and in 7.4% (2/27) of the malignant tumors. These results suggest that some of the biological and morphological characteristics of the tumor are associated with canine mammary gland tumors, as also reported for human breast cancer, the possibility of using anti-HER-2/neu antibodies in the treatment of canine mammary tumors.
Jung, Hoo Kil;Kim, Sun Jin;Seok, Min Jeong;Cha, Hyun Ah;Yoon, Seul Ki;Lee, Nah Hyun;Kang, Kyung Jin
Journal of Dairy Science and Biotechnology
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v.33
no.2
/
pp.111-118
/
2015
Probiotic, prebiotic, and synbiotic substances as well as microorganisms were added to infant formula in an attempt to influence the intestinal microflora with an aim to stimulate the growth of lactic acid bacteria, especially bifidobacteria and lactobacilli. Over the last 10 years, new synbiotic infant formulas containing probiotics and prebiotics have been proposed in order to simulate the effect of breast-feeding on the intestinal microflora. Owing to their synergistic effect, the new synbiotics are expected to be more helpful than using probiotics and prebiotics individually. Maintenance of the viability of the probiotics during food processing and the passage through the gastrointestinal tract should be the most important consideration, since a sufficient number of bacteria ($10^8cfu/g$) should reach the intended location to have a positive effect on the host. Storage conditions and the processing technology used for the manufacture of products such as infant formula adversely affect the viability of the probiotics. When an appropriate and cost-effective microencapsulation methodology using the generally recognized as safe (GRAS) status and substances with high biological value are developed, the quality of infant formulas would improve. The effect of probiotics may be called a double-effect, where one is an immunomodulatory effect, induced by live probiotics that advantageously alter the gastrointestinal microflora, and the other comprises anti-inflammatory responses elicited by dead cells. At present, a new terminology is required to define the dead microorganisms or crude microbial fractions that positively affect health. The term "paraprobiotics" (or ghost probiotics) has been proposed to define dead microbial cells (not damaged or broken) or crude cell extracts (i.e., cell extracts with complex chemical composition) that are beneficial to humans and animals when a sufficient amount is orally or topically administered. The fecal microflora of bottle-fed infants is altered when the milk-based infant formula is supplemented with probiotics or prebiotics. Thus, by increasing the proportion of beneficial bacteria such as bifidobacteria and lactobacilli, prebiotics modify the fecal microbial composition and accordingly regulate the activity of the immune system. Therefore, considerable attention has been focused on the improvement of infant formula quality such that its beneficial effects are comparable to those of human milk, using prebiotics such as inulin and oligosaccharides and potential specific probiotics such as bifidobacteria, which selectively stimulate the proliferation of beneficial bacteria in the microflora and the indigenous intestinal metabolic activity of the microflora.
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