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Domperidone, a Dopamine Receptor D2 Antagonist, Induces Apoptosis by Inhibiting the ERK/STAT3-Mediated Pathway in Human Colon Cancer HCT116 Cells

  • So Jin Sim;Jeong-Hoon Jang;Joon-Seok Choi;Kyung-Soo Chun
    • Biomolecules & Therapeutics
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    • v.32 no.5
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    • pp.568-576
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    • 2024
  • Colorectal cancer (CRC) continues to demonstrate high incidence and mortality rates, emphasizing that implementing strategic measures for prevention and treatment is crucial. Recently, the dopamine receptor D2 (DRD2), a G protein-coupled receptor, has been reported to play multiple roles in growth of tumor cells. This study investigated the anticancer potential of domperidone, a dopamine receptor D2 antagonist, in HCT116 human CRC cells. Domperidone demonstrated concentration- and time-dependent reductions in cell viability, thereby inducing apoptosis. The molecular mechanism revealed that domperidone modulated the mitochondrial pathway, decreasing mitochondrial Bcl-2 levels, elevating cytosolic cytochrome C expression, and triggering caspase-3, -7, and -9 cleavage. Domperidone decreased in formation of β-arrestin2/MEK complex, which contributing to inhibition of ERK activation. Additionally, treatment with domperidone diminished JAK2 and STAT3 activation. Treatment of U0126, the MEK inhibitor, resulted in reduced phosphorylation of MEK, ERK, and STAT3 without alteration of JAK2 activation, indicating that domperidone targeted both MEK-ERK-STAT3 and JAK2-STAT3 signaling pathways. Immunoblot analysis revealed that domperidone also downregulated DRD2 expression. Domperidone-induced reactive oxygen species (ROS) generation and N-acetylcysteine treatment mitigated ROS levels and restored cell viability. An in vivo xenograft study verified the significant antitumor effects of domperidone. These results emphasize the multifaceted anticancer effects of domperidone, highlighting its potential as a promising therapeutic agent for human CRC.

Clinical Usefulness of Contrast Echocardiography: The Dose Effect for Left Ventricle Visualization in Dogs (심초음파의 조영제의 임상적 유용성: 개에서 좌심영상화에 대한 조영제 용량의 영향)

  • Shin, Chang-ho;Hwang, Tae-sung;Yoon, Young-min;Jung, Dong-in;Yeon, Seong-chan;Lee, Hee-chun
    • Journal of Veterinary Clinics
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    • v.32 no.6
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    • pp.486-490
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    • 2015
  • Two-demensional echocardiography is routinely used for evaluation of cardiac function. Visualization of the endocardial border is essential for the assessment of global and regional left ventricular with cardiac disease. SonoVue$^{TM}$ is a microbubble contrast agent that consists of sulfur hexafluoride-filled microbubbles in a phospholipid shell. There were many studies about contrast echocardiographic examination using SonoVue$^{TM}$ contrast agent, and various doses of SonoVue$^{TM}$ were used. To our knowledge, in published veterinary medicine, there was not reported for diagnostic efficient dose of SonoVue$^{TM}$ to evaluate contrast enhanced left ventricular endocardial border delineation (LVEBD). The purpose of this study is to compare the visualization time of LVEBD and find efficient dose of SonoVue$^{TM}$ for using various doses in dogs. Ten healthy Beagles were recruited to the study. Three different doses (0.03 ml/kg, 0.05 ml/kg and 0.1 ml/kg) of SonoVue$^{TM}$ were injected. Endocardial segments were assigned based on previously established methodology, where by the four-chamber views of the LV were divided into 6 segments. In this study, Contrast enhancement of the LVEBD after each injection was evaluated visually at the time point of overall contrast enhancement (Segmental scoring 5+) in the LV by three investigators in a blind manner. Statistical analysis was performed with SPSS version 14.0. All data were analyzed using one-way ANOVA, the multiple comparison Scheffe test. When data for the three offsite readers were combined, mean durations of useful contrast were $3.54({\pm}2.14)$, $6.15({\pm}2.61)$, and $24.39({\pm}11.10)$ seconds for the 0.03 ml/kg, 0.05 ml/kg, and 0.1 ml/kg SonoVue$^{TM}$ doses, respectively. After injection of contrast agent, there were no significant change in side effects such as urticaria, angioedema, hypersensitivity reactions, and digestive system disorders. This study suggests that efficient dose of SonoVue$^{TM}$ contrast agent for improvement of the left ventricle visualization is 0.1 ml/kg. The duration of useful enhancement of LVEBD and the reproducibility were also the highest at the 0.1 ml/kg dosage.

A study on the curing characteristics of multi-concentrating UV-LED Curable Coating (다중 집광성 UV-LED 경화형 코팅의 경화특성에 관한 연구)

  • Jung, Chan-Gwon;Kim, Beom-Su;Park, Dae-Hee
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.10
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    • pp.339-345
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    • 2018
  • We investigated the curing properties of cured coatings for a multi-focal UV-LED. The coatings are for LEDs that operate at multiple UV wavelengths, unlike conventional single-wavelength UV-LEDs. Using UV-LED light sources with wavelengths of 365, 395, 420, and 450 nm, we analyzed the optical characteristics such as the direction of light flux and light source. We also analyzed the curing characteristics at each UV-LED wavelength to optimize the LED for composite wavelengths. The curing performance state was predicted through computer simulation for when the multiple wavelengths of UV light sources are superimposed, and then actual LEDs were designed and fabricated. To improve the internal high-speed curing, a multi-spot module was fabricated, in which each LED is condensed, and multiple wavelengths are synthesized and condensed at the same position. The adhesive strength, surface hardness, and internal hardness of the curing agent were tested by varying the wavelength combination conditions. The surface hardening and internal hardening were compared and analyzed using a hardness tester and FT-IR analyzer. As a result, the characteristics of the surface and internal hardness were improved by a multi-spot method in which four wavelengths were overlapped in a UV-LED rather than a single wavelength.

A Study on the Revision of Transport Documents under ISBP 745 (ISBP 745에서의 운송서류 개정 사항 연구)

  • Park, Sae-Woon
    • International Commerce and Information Review
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    • v.15 no.2
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    • pp.261-283
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    • 2013
  • ISBP745 has new provisions about sea waybill, road, rail or inland waterway transport documents which ISBP681 did not have provisions about. The main revisions of ISBP745 which were not existent or different from ICC Opinion are as follows: First, where B/L is required when multimodal transport is used as a modes of transport, the revisions stipulates that it is subject to UCP600 article19. this differs from previous ICC Opinion. Second, when a credit requires a transport document to indicate the name, address and contact details of a delivery agent, for the place of final destination or port of discharge, the address need not be one that is located at the place of destination or port of discharge or within the same country as that of the place of destination or port of discharge. Third, in case there exist a number of shippers and a consignee, multiple transport documents are issued. This rule has a clear stipulation on this case. Transport industry regards the indication of "LCL/FCL" or "CFS/CY" common in this case as that requiring multiple transport documents. However, ISBP745 does not regard it the case as that requiring multiple transport documents. This may cause some confusion in examination of documents. Forth, when partial shipment is allowed, and more than one set of original transport documents are presented as part of a single presentation made under one covering schedule and incorporate different dates of shipment, the earliest of these dates is to be used of the calculation of an presentation period.

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Targeted Therapies and Radiation for the Treatment of Head and Neck Cancer (두경부 암의 표적 지향적 방사선 치료)

  • Kim, Gwi-Eon
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.77-90
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    • 2004
  • Purpose: The purpose of this review Is to provide an update on novel radiation treatments for head and neck cancer Recent Findings: Despite the remarkable advances In chemotherapy and radiotherapy techniques, the management of advanced head and neck cancer remains challenging. Epidermal growth factor receptor (EGFR) Is an appealing target for novel therapies In head and neck cancer because not only EGFR activation stimulates many important signaling pathways associated with cancer development and progression, and importantly, resistance to radiation. Furthermore, EGFR overexpression Is known to be portended for a worse outcome in patients with advanced head and neck cancer. Two categories of compounds designed to abrogate EGFR signaling, such as monoclonal antibodies (Cetuxlmab) and tyrosine kinase inhibitors (ZD1839 and 051-774) have been assessed and have been most extensively studied In preclinical models and clinical trials. Additional TKIs In clinical trials include a reversible agent, Cl-1033, which blocks activation of all erbB receptors. Encouraging preclinical data for head and neck cancers resulted In rapid translation Into the clinic. Results from Initial clinical trials show rather surprisingly that only minority of patients benefited from EGFR inhibition as monotherapy or In combination with chemotherapy. In this review, we begin with a brief summary of erbB- mediated signal transduction. Subsequently, we present data on prognostic-predictive value of erbB receptor expression in HNC followed by preclinlcal and clinical data on the role of EGFR antagonists alone or in combination with radiation In the treatment of HNC. Finally, we discuss the emerging thoughts on resistance to EGFR biockade and efforts In the development of multiple-targeted therapy for combination with chemotherapy or radiation. Current challenges for investigators are to determine (1 ) who will benefit from targeted agents and which agents are most appropriate to combine with radiation and/or chemotherapy, (2) how to sequence these agents with radiation and/or cytotoxlc compounds, (3) reliable markers for patient selection and verification of effective blockade of signaling in vivo, and (4) mechanisms behind intrinsic or acquired resistance to targeted agents to facilitate rational development of multi-targeted therapy, Other molecuiar-targeted approaches In head and neck cancer were briefly described, Including angloenesis Inhibitors, farnesyl transferase inhibitors, cell cycle regulators, and gene therapy Summary: Novel targeted theraples are highly appealing in advanced head and neck cancer, and the most premising strategy to use them Is a matter of intense Investigation.

The moderating effects of converging smart work and supervisor's support in the study of turnover on job satisfaction in call centers (콜 센터에서 이직요인이 직무만족에 미치는 영향에 있어 스마트워크와 상사지원 융복합 서비스의 조절효과에 관한 연구)

  • Kim, Kye-Chul;Cheong, Ki-Ju
    • Journal of Digital Convergence
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    • v.13 no.4
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    • pp.101-114
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    • 2015
  • The purpose of this study is first to understand agent's turnover from both academic and perspectives. Then we suggest convergence of smart work paradigm and supervisor's support as the relieving factors of turnover, The research model of this study is based upon reviews of turnover literature, the smart work and supervisor's support as moderating variables from which research hypotheses were derived. The data came from the survey from financial sector agents such as banking, insurance, and others. The analyses has been done by SPSS 20.0, We used multiple regressions to test the effects of the tested variables on the dependent variable, job satisfaction. The results of this study find significant relations of smart work and supervisor's supports in relations to personal and job-related turnover. The implication is smart work and supervisor's supports play significant role in increasing job satisfactions. Major finding is too much supervisor's supports ignoring agent's situations may bring reverse effects on relieving turnover.

THE EFFECT OF MOISTENING OF ETCHED DENTIN AND ENAMEL SURFACE ON THE MICROLEAKAGE OF COMPOSITE RESINS (복합레진 수복시 상아질 표면 처리가 미세 변연 누출에 미치는 영향에 관한 연구)

  • Jeon, Cheol-Min;Kwon, Hyuk-Choon;Lee, Chung-Sik;Lee, Myung-Jon;Um, Chung-Moon
    • Restorative Dentistry and Endodontics
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    • v.21 no.1
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    • pp.321-338
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    • 1996
  • The purpose of this study was to evaluate the effect of moistening and air-drying of acid conditioned dentin and enamel on the marginal microleakage. In this study, Class V cavity were prepared on both buccal and lingual surface of sixty extracted human premolars with cementum margin. These specimens were randomly devided into three groups and three dentin adhesives(Scotchbond Multi-Purpose, All bond 2, Prisma Universal Bond 3) were applied to each group. The specimens in each group were subdevided into four groups (Wet/primed, Dry/primed, Wet/not primed, Dry/not primed) and the etched dentin and enamel surface were treated these four surface treatments prior to the placement of a bonding agent or adhesive. Wet/primed group was simply blot-dried with a damp facial tissue before primer placement ; Dry/primed group was air dried for 30 seconds before the placement of a primer ; Wet/not primed group and Dry/not primed group were not primed after blot dried and air dried for 30 seconds each group. The bonding agent and composite resin were applied for each group. All specimens were exposed to 500 cycle of thermal stress. Specimens were placed in a silver nitrate solution and then sectioned buccolingually through the center of the restoration. The dye penetrations of the specimens were observed with a stereo microscope. The statistical test were applied to the results using a one way analysis variance (ANOVA) and Duncan's multiple range test. The aspects of silver ion penetration into the resin/dentin interface were examined under scanning electron microscopy. The results were as follows. 1. In all groups, the enamel margin showed significantly lower leakage value than the cementum margin (p<0.05). 2. Regardless of various surface treatment and dentin adhesives, there was no significant difference at the enamel margins (p>0.05). 3. At the dentin margins, the leakage values of Dry/not primed group showed significantly higher than that of the other groups (p<0.05). The leakage values of Wet/primed group showed significantly lower than that of the other groups, but, there was no significant difference between Wet group and Dry group. 4. There was no significantly difference between the dentin adhesives regarding the surface treatments in all groups(p>0.05). 5. On the backscatterd scanning electron microscopy observation, the penetration of the silver ion occured at the bonding resin/dentin interface. In the Wet/primed group, resindentin hybrid zone and resin penetration into the dentin was observed. The resin tags were compactively formed to a thickness of $3\sim4{\mu}m$ at the upper part of dentinal tubules. In the Dry/primed group, the thickness of the hybrid zone and the diameter, depth of the resin tags diminished. In the Non-primed groups, the hybrid zone was not identified and few resin tag was observed. There was the gap formation in the resin/dentin interface.

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Susceptibility to FAS induced apoptosis in mycoplasma contaminated HCE cells (Mycoplasma가 오염된 배양 각막상피 세포의 FAS 유도 세포고사의 민감성)

  • Kim, Jai-Min
    • Journal of Korean Ophthalmic Optics Society
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    • v.12 no.2
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    • pp.79-86
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    • 2007
  • The aim of the present study was to determine mechanisms of corneal epithelial cell apoptosis in vitro following exposure to anti-FAS and anti-FAS ligand antibody and during infection with mycoplasma sp.. A cultured human corneal epithelial(HCE) cell line was treated with anti-FAS antibody or anti-FAS ligand antibody for 2 and 4 days. The original cell line was found to be contaminated by mycoplasma removal agent(MRA) was used to eliminate the bacterium from the cell line. MRA($0.5{\mu}{\ell}$ tissue culture medium) was added to the cell line and incubated for 1 week. The cell line underwent multiple passages in media not contaminating MRA and cells were grown to 50-80% confluency on coverslips and stained using the Hoechst stain provided in the kit to ensure mycoplasma removal. Apoptosis experiments were performed before and after mycoplasma removal. The apoptotic index of anti-FAS and anti-FAS ligand antibody on mycoplasma contaminated cell line was studied using Hoechst 33342 staining and Annexin V-FITC and Propidium Iodide Staining. In conclusion, anti-FAS antibody induces apoptosis in HCE cells in a time and concentration-dependent mechanism. Cell lines contaminated with mycoplasma have an incresed susceptibility to FAS induced apoptosis.

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Studies on the Antimicrobial Susceptibility of Enterococci isolated at Doctorless areas and Seoul National University Hospital (일부 무의촌지역과 병원에서 분리한 Enterococci의 항균제 감수성에 관한 연구)

  • Kim, Ik-Sang;Shin, Hee-Sup;Rhee, Kwang-Ho;Chang, Woo-Hyun;Lim, Jung-Kyoo
    • The Journal of the Korean Society for Microbiology
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    • v.13 no.1
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    • pp.63-73
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    • 1978
  • 28 strains of Enterococci isolated at doctorless areas in Korea from Oct. 1976 through Mar. 1977 and 30 strains of Enterococci isolated at Seoul National University Hospital from Sep. 1976 through Dec. 1976 were examined for susceptibilities to 14 antimicrobial agents by agar dilution method. The susceptibilities of two groups to each antimicrobial agent were compared and incidence of resistant strains in each antimicrobial agent, incidence of multiply resistant strains and correlations in the antimicrobial susceptibility of 58 strains of Enterococci among 14 antimicrobial agents were analyzed. 1. With Tetracycline, Oxytetracline, Doxycycline, Minocycline and Erythromycin, the mean MIC's of Enterococci isolated at Seoul National University Hospital were 1.9-2.5 times higher than those of Enterococci isolated at doctorless areas, though there were no statistical significance. 2. Frequency of resistant strains in Enterococci isolated at Seoul National University Hospital was the highest with Cephalexin(100%), Gentamicin(100%), and Streptomycin(100%), followed by Kanamycin(93.3%), Carbenicillin(90%), Tetracycline(26.7%), Oxytetracycline(26.7%), Doxycycline(26.7%), Minocycline(20%), Erythromycin(10%), Troleandomycin(10%), Penicillin(6.7%), Cotrimoxazole(6.7%) and Ampicillin(0%). 3. Frequency of resistant strains in Enterococci isolated at doctorless areas was the highest with Kanamycin(100%) and Streptomycin(100%), followed by Cephalexin(96.4%), Gentamicin(96.4%), Carbenicillin(92.9%), Tetracycline(10.7%), Oxytetracycline(10.7%), Doxycycline(10.7%), Minocycline(10.7%), Cotrimoxazole(10.7%), Penicillin(3.6%), Ampicillin(0%), Erythromycin(0%), and Troeandomycin(0%). 4. In study with Penicillin, Ampicillin, Tetracycline, Cotrimoxazole, Erythromycin and Troleandomycin, there were no multiply resistant strains in Enterococci isolated at doctorless areas, while 4 strains of Enterococci isolated at Seoul National University Hospital showed multiple resistance. 5. There were high correlation in susceptibility of 58 strains of Enterococci among Tetracycline, Oxytetracycline, Doxycycline and Minocycline(correlation coefficients 0.86-0.97). Correlation coefficients of susceptibility among penicillin analogues(Penicillin, Ampicillin, Carbenicillin and Cephalexin) ranged between 0.75-0.89. Correlation coefficients of susceptibility among aminoglycosides(Kanamycin, Gentamicin and Streptomycin) ranged between 0.09-0.51.

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A Simple Method for the Preparation of Crude Gintonin from Ginseng Root, Stem, and Leaf

  • Pyo, Mi-Kyung;Choi, Sun-Hye;Shin, Tae-Joon;Hwang, Sung-Hee;Lee, Byung-Hwan;Kang, Ji-Yeon;Kim, Hyeon-Joong;Lee, Soo-Han;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.35 no.2
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    • pp.209-218
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    • 2011
  • Ginseng has been used as a general tonic agent to invigorate the human body as an adaptogenic agent. In a previous report, we have shown that ginseng contains a novel glycolipoprotein called gintonin. The main function of gintonin is to transiently enhance intracellular free $Ca^{2+}$ $[Ca^{2+}]_i$ levels in animal cells. The previous method for gintonin isolation included multiple steps using organic solvents. In the present report, we developed a simple method for the preparation of crude gintonin from ginseng root as well as stem and leaf, which produced a higher yield of gintonin than the previous one. The yield of gintonin was 0.20%, 0.29%, and 0.81% from ginseng root, stem, and leaf, respectively. The apparent molecular weight of gintonin isolated from stem and leaf through sodium dodecyl sulfate polyacrylamide gel electrophoresis was almost same as that from root but the compositions of amino acids, carbohydrates or lipids differed slightly between them. We also examined the effects of crude gintonin from ginseng root, stem, and leaf on endogenous $Ca^{2+}$-activated $Cl^-$ channel (CaCC) activity of Xenopus oocytes through mobilization of $[Ca^{2+}]_i$. We found that the order of potency for the activation of CaCC was ginseng root > stem > leaf. The $ED_{50}$ was $1.4{\pm}1.4$, $4.5{\pm}5.9$, and $3.9{\pm}1.1$ mg/mL for root, stem and leaf, respectively. In the present study, we demonstrated for the first time that in addition to ginseng root, ginseng stem and leaf also contain gintonin. Gintonin can be prepared from a simple method with higher yield of gintonin from ginseng root, stem, and leaf. Finally, these results demonstrate the possibility that ginseng stem and leaf could also be utilized for ginstonin preparation after a simple procedure, rather than being discarded.