• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.166-166
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• 2003

Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. The transcription of CYP3A4 is regulated by the Pregnenolone X receptor (PXR),of which human form is Steroid and Xenobiotics receptor (SXR).(omitted)

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.192-198
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• 1995

The affinity of mequitazine, a non-sedating antihistamine, for muscarinic receptors was evaluated in the guinea-pig ventricle and ileum by in vitro binding techniques and functional studies. In binding studies, [$^3$H]quinuclidinyl benzilate (QNB) identified a single class of muscarinic receptors with similar apparent $K_{D}$ value of about 100 pM in two tissues. Mequitazine inhibited [$^3$H]QNB binding to muscarinic receptors competitively. Analysis of the mequitazine inhibition curve of [$^3$H]QNB binding to ventricular microsome and ileal homogenate indicated the presence of a single homogeneous binding site with Ki value of 25 nM and 18 nM, respectively. In functional studies, mequitazine caused parallel rightward shifts of concentration-response curves for carbachol and histamine in the isolated guinea-pig ileum. The slope values obtained from Schild plot analysis for the antagonistic action of mequitazine on muscarinic and histamine $H_1$-receptors were not significantly different from unity. The p $A_2$values of mequitazine for muscarinic and histamine $H_1$-receptors were about 7.6 ( $K_{M}$= 25.1 nM) and 8.88 ( $K_{H}$= 1.32 nM), respectively. These results indicate that the muscarinic receptor blocking action of mequitazine is 15 times less potent than the $H_1$receptor blocking action, but high concentration of this drug may cause the peripheral muscarinic receptor blocking effect.t.t.t.

• BMB Reports
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• v.39 no.4
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• pp.448-451
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• 2006

Chemopreventive and cytotoxic effect of genistein against human breast cancer cell lines was investigated. Genistein inhibited cell proliferation in estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) human breast carcinoma cell lines. Cytochrome P450 (CYP) 1A1-mediated ethoxyresorufin O-deethylase (EROD) activity was inhibited by genistein in a concentrationdependent manner. Genistein significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxy-genase-2 activity and protein expression at the concentrations of 10 (p < 0.05), 25 (p < 0.05) and 50 mM (p < 0.01). In addition, ornithine decarboxylase (ODC) activity was reduced to 53.8 % of the control after 6 h treatment with 50 mM genistein in MCF-7 breast cancer cells. These results suggest that genistein could be of therapeutic value in preventing human breast cancer.

• Journal of Yeungnam Medical Science
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• v.11 no.2
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• pp.314-322
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• 1994

This study aimed to investigate the existence of GABA receptor and the mechanisms of action of GABA and diazepam on the trachealis muscle isolated from dog. Horizontal muscle strips of $2mm{\times}15mm$ were prepared from canine trachea, and isometric myography in isolated muscle chamber bubbled with 95/5%-$O_2/CO_2$at $36^{\circ}C$, at the pH of 7.4 was performed. Muscle strips contracted responding to the electrical field stimulation (ESP) by 2~20 Hz, 20 msec, monophasic square wave of 60 VDC GABA and diazepam suppressed the EFS-induced contractions to the similar extent, significantly. (p<0.05) Bicuculline, a $GABA_A$ receptor antagonist blocked both GABA- and diazepam- inhibitions; but DAVA, a $GABA_B$ receptor antagonist did not affect either of them. These results suggest that in the canine trachealis muscle, there may be only $GABA_A$ receptor, and GABA and diazepam inhibit the contractility via $GABA_A$A receptor.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8633-8636
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• 2016

Background: To investigate the expression of insulin-like growth factor-I receptor (IGF-IR) and sushi domain containing protein 3 (SUSD3) in breast cancer tissue, and analyze their relationship with clinical parameters and the correlation between the two proteins. Materials and Methods: The expression of IGF-IR and SUSD3 in 100 cases of breast cancer tissues and adjacent normal breast tissues after surgery was detected by immunohistochemical technique MaxVisionTM, and the relationship with clinical pathological features was further analyzed. Results: The positive rate of IGF-IR protein was 86.0% in breast cancer, higher than 3.0% in adjacent normal breast tissue (P<0.05). The positive expression rate of SUSD3 protein was 78.0% in breast cancer, higher than 2.0% in adjacent normal breast tissue (P<0.05). The expression of IGF-IR and SUSD3 was related to estrogen receptor and pathological types (P<0.05),but not with age, stage, the expression of HER-2 and Ki-67 (P>0. 05). The expression of IGF-IR and SUSD3 in breast cancer tissue was positively related (r=0.553, P<0.01). Conclusions: The expression of IGF-IR and SUSD3 may be correlated to the occurrence and development of breast cancer. The combined detection of IGF-IR, SUSD3 and ER may play an important role in judging prognosis and guiding adjuvant therapy after surgery of breast cancer.

• The Korean Journal of Pharmacology
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• v.19 no.2
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• pp.57-67
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• 1983

The influence of electrolyte concentrations on the action of morphine and naloxone was studied in the myenteric plexus-longitudinal muscle preparation of guinea-pig ileum to examine whether opiate receptor binding obseved in vitro with homogenates represents binding to the pharmacological receptor. The preparations were suspended in a modified Krebs-Henseleit bicarbonate buffer solution and electrically stimulated at 0.2 Hz. Morphine inhibited electrically evoked contractions; the concentration of morphine required for a 50-percent inhibition was 190 nM. This inhibitory action of morphine was potentiated in a medium containing lower concentrations of : $Na^+\;or\;K^+$, or by the addition of $Mn^{2+}$ to the medium, and weakened by increasing the concentration of $Ca^{2+}$ or decreasing the concentration of $Mg^{2+}$. Naloxone antagonized these actions of morphine: however, $pA_2values$ for naloxone (indices of affinity for antagonists, approximately 8.8) were unaffected by these electrolyte concentrations. Thus, changes in the inhibitory action of morphine caused by alterations in electrolyte concentrations are probably not the result of changes in the affinity of the receptor for opiates, but due to alterations in the events which precede or follow the receptor binding. Effects of electrolytes on the affinity of the functional opiate receptor for naloxone in guinea-pig ileum are apparently different from those reported with the specific binding sites for opiates in brain homogenate.

• Animal cells and systems
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• v.5 no.2
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• pp.145-151
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• 2001

p62 is a phosphotyrosine-independent ligand of the SH2 domain of $p56^{Ick}$, a T-cell specific Src family tyrosine kinase. Recently p62 has been shown to interact with a number of proteins, such as $PKC\varsigma$ and ubiquitin, and implicated in important cellular functions such as cell proliferation. Since the two p62 interacting proteins, $p56^{Ick}$ and $PKC\varsigma$, have been reported to play roles in cell death, 1 have addressed the potential role of p62 during apoptosis in Jurkat cells in this study. Herein 1 show that p62 was specifically cleaved into two peptides by a caspase-3-like activity during Fas-receptor mediated apoptosis in Jurkat cells. This cleavage generated two fragments with molecular weights of about 35 kDa that differed in subcellular localizations. The N-terminal cleaved fragment was present in the detergent-insoluble fraction whereas the C-terminal fragment was found in the detergent-soluble fraction. In addition, the C-terminal fragment appeared to be subjected to further degradation as apoptosis prolonged. Moreover, overexpression of p62 in Jurkat cells attenuated the Fas receptor mediated apoptosis, suggesting that p62 is involved in apoptotic signal transduction pathway in lymphocytes.

• BMB Reports
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• v.47 no.7
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• pp.361-368
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• 2014

Lipid components in biological membranes are essential for maintaining cellular function. Phosphoinositides, the phosphorylated derivatives of phosphatidylinositol (PI), regulate many critical cell processes involving membrane signaling, trafficking, and reorganization. Multiple metabolic pathways including phosphoinositide kinases and phosphatases and phospholipases tightly control spatio-temporal concentration of membrane phosphoinositides. Metabolizing enzymes responsible for PI 4,5-bisphosphate (PI(4,5)P2) production or degradation play a regulatory role in Toll-like receptor (TLR) signaling and trafficking. These enzymes include PI 4-phosphate 5-kinase, phosphatase and tensin homolog, PI 3-kinase, and phospholipase C. PI(4,5)P2 mediates the interaction with target cytosolic proteins to induce their membrane translocation, regulate vesicular trafficking, and serve as a precursor for other signaling lipids. TLR activation is important for the innate immune response and is implicated in diverse pathophysiological disorders. TLR signaling is controlled by specific interactions with distinct signaling and sorting adaptors. Importantly, TLR signaling machinery is differentially formed depending on a specific membrane compartment during signaling cascades. Although detailed mechanisms remain to be fully clarified, phosphoinositide metabolism is promising for a better understanding of such spatio-temporal regulation of TLR signaling and trafficking.

• Investigative Magnetic Resonance Imaging
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• v.19 no.3
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• pp.137-145
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• 2015

Purpose: To investigate correlations of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor type 2 (HER2) statuses with magnetic resonance imaging (MRI) features and clinicohistological characteristics in patients with invasive lobular carcinoma (ILC). Materials and Methods: Data from 64 histologically confirmed ILCs were analyzed retrospectively. Preoperative breast MRI was reviewed for morphology and dynamic contrast-enhanced kinetics of the tumor. Pathologic reports were reviewed for ER, PR, and HER2 positivity, tumor size, lymph node metastasis, and the number of metastatic lymph nodes. Furthermore, there was an investigation of the MRI features and clinicohistologic characteristics, according to the ER, PR, and HER2 statuses. Results: A significant difference in MRI features and clinicohistological tumor characteristics were observed only in relation to PR status. Of the 64 ILCs, 10 (15.6%) were PR negative. PR negative cancers, compared with PR positive cancers, were more likely to present as non-mass enhancement (P = 0.027); have a significantly larger mean tumor size ($5.00{\pm}1.05cm$ vs. $2.57{\pm}0.21cm$, P = 0.021); and have significantly more metastatic lymph nodes (P = 0.010). Conclusion: PR negative ILC presented more frequently as non-mass enhancement on MRI, with larger tumors and increased numbers of metastatic lymph nodes. Therefore, the PR status plays an important role in determining MRI features and clinicohistological characteristics of ILC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.2
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• pp.55-65
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• 2009

Purpose: We determined the therapeutic effects of blockade of epidermal growth factor(EGF) and vascular endothelial growth factor(VEGF) receptor tyrosine kinases on the growth of oral squamous cell carcinoma(OSCC) xenografted in athymic nude mice. Experimental Design: We investigated the in vivo antitumor effects of a tyrosine kinase inhibitor for EGFR and VEGFR-2, AEE788 in a mouth floor(orthotopic) tumor model. Nude mice with orthotopic tumors were randomized to receive AEE788, paclitaxel, a combination of AEE788 and paclitaxel, or control. Antitumor mechanisms of AEE788 were determined by immunohistochemical/immunofluorescent and apoptosis assays. Results: Tumors of mice treated with AEE788 demonstrated down-regulation of phosphorylated EGFR, phosphorylated VEGFR and their downstream mediators(pMAPK and pAkt), decreased proliferative index, decreased microvessel density(MVD). As a result, growth of the primary tumor and nodal metastatic potentials were inhibited by AEE788. Conclusion: These data show that EGFR and VEGFR can be molecular targets for the treatment of OSCC.