• Title/Summary/Keyword: 5-$HT_{1A}$

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Combination Therapy of Lactobacillus plantarum Supernatant and 5-Fluouracil Increases Chemosensitivity in Colorectal Cancer Cells

  • An, JaeJin;Ha, Eun-Mi
    • Journal of Microbiology and Biotechnology
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    • v.26 no.8
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    • pp.1490-1503
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    • 2016
  • Colorectal cancer (CRC) is the third most common cancer in the world. Although 5-fluorouracil (5-FU) is the representative chemotherapy drug for colorectal cancer, it has therapeutic limits due to its chemoresistant characteristics. Colorectal cancer cells can develop into cancer stem cells (CSCs) with self-renewal potential, thereby causing malignant tumors. The human gastrointestinal tract contains a complex gut microbiota that is essential for the host's homeostasis. Recently, many studies have reported correlations between gut flora and the onset, progression, and treatment of CRC. The present study confirms that the most representative symbiotic bacteria in humans, Lactobacillus plantarum (LP) supernatant (SN), selectively inhibit the characteristics of 5-FU-resistant colorectal cancer cells (HT-29 and HCT-116). LP SN inhibited the expression of the specific markers CD44, 133, 166, and ALDH1 of CSCs. The combination therapy of LP SN and 5-FU inhibited the survival of CRCs and led to cell death by inducing caspase-3 activity. The combination therapy of LP SN and 5-FU induced an anticancer mechanism by inactivating the Wnt/β-catenin signaling of chemoresistant CRC cells, and reducing the formation and size of colonospheres. In conclusion, our results show that LP SN can enhance the therapeutic effect of 5-FU for colon cancer, and reduce colorectal cancer stem-like cells by reversing the development of resistance to anticancer drugs. This implies that probiotic substances may be useful therapeutic alternatives as biotherapeutics for chemoresistant CRC.

Cytotoxicity of Lignans from Lindera erytherocarpa Makino

  • Lee, Sang-Myung;Baek, Seung-Hwa;Lee, Choong-Hwan;Lee, Hyang-Burm;Kho, Yung-Hee
    • Natural Product Sciences
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    • v.8 no.3
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    • pp.100-102
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    • 2002
  • Three lignans were isolated from a methanol extract of Lindera erytherocarpa Makino (Lauraceae) are evaluated in vitro cytotoxicity using three cancer cell line assay. The compounds were identified as methyllinderone (1), linderone (2), and kanakugiol (3) by spectroscopic methods. Amongst the compounds, methyllinderone (1) showed significant cytotoxicity against mouse melanoma (B16-FlO), human acetabulum fibrosarcoma (HT1080), and choronic myelogenous leukemia (K562) cancer cell lines with $ED_{50}$ values of 2.2, 2.5, 8.3 ${\mu}g/ml$, respectively.

A Study on the Cytotoxic Activity of Garlic(Allium Sativum) Extract Against Cancer Cells (마늘중 지용성 성분의 암세포증식 억제효과 연구)

  • 손흥수
    • Journal of Nutrition and Health
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    • v.23 no.2
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    • pp.135-147
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    • 1990
  • This study was devised to observe the cytotoxic activities of garlic extracts against various cancer cells, that is, murine leukemic lymphocyte(L1210 and P388) and human rectal(HRT-18) and colon cancer cells(HCT-48 and HT-29) in vitro, and murine ascitic tumor cell(S-180) in vivo. Each cell-line except S-180 was cultured in medium containing serial concentration of the garlic extract in vitro. Inhibitory effect n the growth rate of the cancer cells was stronger in extracts of petroleum ether than that of ethanol. A lipid soluble compound in the extracts of garlic was cytocidal to murine leukemic cells, human rectal and colon cancer cells in vitro. The growth rates of the cancer cells in medium containing garlic extracts were inhibited gradually to a significant degree in proportion to the increase of the extract concentration. The cytotoxic activity of garlic active fraction from TLC was about 2.3 times more potent than that of crude garlic extract, one unit of cytotoxic activity against L1210 cells being equivalent to 4.2$\mu\textrm{g}$ and 1.8$\mu\textrm{g}$ from the crude garlic and active fraction, respectively. The Rf value of the active fraction on silica-gel TLC was 0.18 in condition that petroleum ether/ethyl ether/acetic acid mixture(90:10:1, v/v/v) was used as a developing solvent. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times in the groups treated with garlic extract(through i.p. and oral administration) compared with their control group(no garlic extract treatment). Observations were carried out on S-180. Ethanol extracts of garlic injured markedly tumor cells within 3 hours after injection.

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The Effect of Neuroactive Compounds on Settlement of Pacific Oyster, Crassostrea gigas Pediveliger Larvae (굴, Crassostrea gigas 부착기 유생의 부착에 미치는 신경전달물질종의 영향)

  • Hur, Youngbaek;Jo, Qtae;Byun, Soongyu;Mun, Tesek
    • The Korean Journal of Malacology
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    • v.30 no.4
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    • pp.343-351
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    • 2014
  • We determined the effects of neuroactive compounds known as synthetic larval settlement inducers on the settlement of the Pacific oyster C. gigas pediveliger on the larval collector. Six types of the inducers, serotonin (5-HT), ${\gamma}$-amino butyric acid (GABA), L-3,4-dihydroxyphenylalanine (L-DOPA), norepinephrine, epinephrine and methyl bromide (MB) were tested. All the chemicals induced larval settlement, MB being the most effective with settlement rate of $42.7{\pm}2.7%$, followed by GABA ($35.4{\pm}2.0%$), 5-HT ($29.1{\pm}2.2%$), L-DOPA ($19.2{\pm}2.1%$), epinephrine ($15.2{\pm}0.9%$), and norepinephrine ($11.0{\pm}1.2%$). The chemicals ${\gamma}$-amino butyric acid and methyl bromide were also better in terms of settled density on the collector with their respective density of $1.97{\pm}1.42$ and $2.37{\pm}1.86ind/cm^2$, reminiscent of being most effective candidates for a larval settlement inducer in the oyster hatchery.

A Study on the Cyclic Hardening Property and the Low Cycle Fatigue Behavior of Marine Materials (박용재료(舶用材料)의 반복경화(反復硬化) 및 저(低)싸이클 피로특성(疲勞特性)에 관한 연구)

  • S.M. Cho;K. Horikawa
    • Journal of the Society of Naval Architects of Korea
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    • v.28 no.1
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    • pp.108-116
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    • 1991
  • In the non-linear behavior of many materials, there is difference between the monotonic behavior by static load and the cyclic behavior by cyclic load. In particular, the short fatigue cracks to propagate in elasto-plastic stress concentrations(notches), are governed significantly by the cyclic behavior of materials. Accordingly, it is needed to investigate and compare the monotonic and cyclic behavior of materials. In the pressent study, the stress-strain relations of materials by monotonic and cyclic load tests were examined for 2 kinds of steels(SS41, HT80) and 5 kinds of Al-alloys(A5083-O, A6N01-T5, A7N01-T4, A7016-T6, A7178-T6). And the constants for mechanical properties of the materials were determined by experimental results, Moreover, when a notch was subjected to cyclic load, the effect of cyclic hardening property of materials on the variation of stress-strain amplitude in the notch tip was discussed by the application of Neuber's rule and experiments for a center notched plate.

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The Effect of Neuroactive Compounds on Settlement of Pacific Oyster, Crassostrea gigas Pediveliger Larvae (굴 Crassostrea gigas 부착기 유생의 부착에 미치는 신경전달물질종의 영향)

  • Hur, Young Baek;Cho, Kyu Tae;Byun, Soon Gyu;Jeon, Chang Young;Cho, Kee Chae
    • The Korean Journal of Malacology
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    • v.29 no.2
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    • pp.139-146
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    • 2013
  • We determined the effects of neuroactive compounds known as synthetic larval settlement inducers on the settlement of the Pacific oyster C. gigas pediveliger on the larval collector. Six types of the inducers, serotonin (5-HT), ${\gamma}$-amino butyric acid (GABA), L-3,4-dihydroxyphenylalanine (L-DOPA), norepinephrine, epinephrine and methyl bromide (MB) were tested. All the chemicals induced larval settlement, MB being the most effective with settlement rate of $42.7{\pm}2.7%$, followed by GABA ($35.4{\pm}2.0%$), 5-HT ($29.1{\pm}2.2%$), L-DOPA ($19.2{\pm}2.1%$), epinephrine ($15.2{\pm}0.9%$), and norepinephrine ($11.0{\pm}1.2%$). The chemicals ${\gamma}$-amino butyric acid and methyl bromide were also better in terms of settled density on the collector with their respective density of $1.97{\pm}1.42$ and $2.37{\pm}1.86\;ind/cm^2$, reminiscent of being most effective candidates for a larval settlement inducer in the oyster hatchery.

Experimental Studies of the Blood Gas Transport during Normothermic Hemodilution Perfusion (상온하 혈액희석 체외순환에 있어서 혈액 GAS 동태에 관한 실험적 연구)

  • 박희철
    • Journal of Chest Surgery
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    • v.13 no.2
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    • pp.85-91
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    • 1980
  • Extracorporeal circulation by hemodilution technique has been currently used with its clinical safety and good peripheral tissue perfusion in open heart surgery. There is no doubt that $O_{2}$ carrying capacity of the blood is disturbed by decreased hemoglobin level resulting from hemodilution of the circulating blood. From the view point of the blood gas exchange, these experimental studies were undertaken to determined the sate limit of hemodilution in the condition of cardiopulmonary bypass with a constant perfusion flow rate. Twelve adult mongrel dogs weighing 10 to 13 Kg. were anesthetized with pentobarbital and then respiration was controlled with Harvard volume respirator using room air. The cardiopulmonary by pass was performed by use of Sarns heart lung machine (console 5000, 5 head and 2 roller pumps) and Travenol pediatric bubble oxygenator. The perfusion rate during bypass was maintained at a constant rate of 80 ml/min/Kg of body weight. The ratio of oxygen gas flow to blood flow was kept in 3 to 1 constantly. International hemodilution was attained by serial blood withdrawals and immediate infusion of equal volumes of diluants composed of Ringer's lactate, 5% dextrose in water and 25% mannitol solution, proportionally 60%, 30%, and 10%. Arterial and venous blood samples were obtained between 15 and 20 minutes following each hemodilution. Hematocrits and hemoglobin values, $PO_{2}$, $PCO_{2}$ and pH were measured. Oxygen and carbon dioxide contents oxygen consumption and carbon dioxide elimination were calculated groups according to different hematocrit values and the correlations were evaluated. Result were as follows. 1. the arterial $O_{2}$ tension and $O_{2}$ saturation were maintained at the physiological level irrespective of the hematocrit value. 2. The venous $O_{2}$ tension and $O_{2}$ saturation showed a tendency to decline with the decrease in hematocrit value and positive correlation between them (r = +0.49, r = +0.76), The mean values of venous $O_{2}$ tension and $O_{2}$ saturation, however, were not decreased when the hematocrit levels were lower than 20%. 3. The arterial $O_{2}$ content declined lineally in proportion to the fall of hematocrit level with a positive correlation between them (r = +0.95). 4. The venous $O_{2}$ contents were decreased gradually as the hematocrit value decreased with positive correlation between them ( r =+0.89). The trend of diminution of venous $O_{2}$ content, however, was became low according to progressive decrease of hematocrit level. 5. Systemic oxygen consumption was in higher range than $O_{2}$ requirement of basal metabolism when the hematocrit value was above 20%, but abruptly decreased when the hematocrit value became to below 20%. 6. The arterial $CO_{2}$ tension and $CO_{2}$ content showed trend of increasing with progressive decrease of hematocrit value but exhibited a rather broad range and there was no relationship between those value and the hematocrit value. 7. The venous $CO_{2}$ tension and $CO_{2}$ content have also no correlation with change of Ht. value but related directly to those value of arterial blood with positive correlation between them (r = +0.78, r = +0.95_. 8. A-V difference of $CO_{2}$ content and $CO_{2}$ elimination wasnot significantly influenced by Ht. value. From the results, we obtained that feasible limit in inteneional hemodilution is above the hematocrit value of 20% under the given experimental condition.

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A Study on the Antitumor Activity of Panax ginseng (고려인삼의 항암효과에 관한 연구)

  • Hwang, Woo-lk
    • Journal of Ginseng Research
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    • v.17 no.1
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    • pp.52-60
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    • 1993
  • Panax ginseng has been extensively used in the traditional oriental medicine as a restorative, tonic and Prophylactic agent. Recently, several reports regarding to anticancer effects of Panax ginseng has accumulated. These studies emphasized the fact that the anticancer activities might be due to a glycoside group called ginsenoside or pan.u saponin which has a water soluble characteristic. However, the authors and collaborates demonstrated that a highly lipid soluble component in extract of Panax ginseng roots contains a considerable cytotoxic activities against marine leukemic cells (L1210, P388) and human censer cells (HRT-18, HT-29, HCT48). This study was devised to observe the cytotoxic activities of Petroleum-ether extract of Panax giuseng roots (crude GBD and its Partially Purified fraction from silicic acid column chromatography (7 : 3 GX) against sarcoma-180 (5-180) and Walker carcinosar- coma 256 (Walker 256) in vivo, and murine leukemic Lymphocytes (L1210) and human rectal cancer cells (HRT-18) and human colon cancer cells (HT-29 and HCT48) in vitro. Each cell-line was cultured in medium containing serial concentration of the crude GX or 7 : 3 GX in vitro. A highly lipid soluble compound in the extract of Panax ginseng root was cytocidal to murine leukemic cells and human colon and rectal cancer cells in vitro. In the meantime, ginseng saponin derivatives did not have cytotoxic effects at its corresponding concentration. The growth rates of the cancer cells in medium containing ginseng extracts were inhibited gradually to a significant degree roughly in proportion to the increase of the extract concentration. The cytotoxic activity of 7 : 3 GX was about 3 times more potent than that of crude GX, one unit of cytotoxic activity against L1210 cells being equivalent to 2.54 Ug and 058 Ug for the crude GX and 7 : 3 GX, respectively. The Ri value of the active compound on silica- gel thin layer chromatography with petroleum-ether/ethyl ether/acetic acid mixture (90 : 10 : 1, v/v/v) as a developing so lvent was 053. While, the Panaxydol and Panaxynol as active compounds were purified from Petroleum-ether extract of Panax ginseng root by Drs. Ahn and Kim, and author found out that the one unit of cytotoxic activity of the Panaxydol and Panaxynol against L1210 cells being equivalent to 056 Ug and 0.3918 respectively. The survival times of mice inoculated with S-180 cells were extended about 1.5 to 2 times by the 7 : 3 GX treatment compared with their control group. The significantly decreased hemoglobin values of rats after inoculation with Walker 256 were recovered to normal range by oral administration of the crude Gt The synthetic levels of protein, DNA and RNA in human colon and rectal cancer cells were significantly diminished by treatment with the crude GX, which can explain a part of the origin of its anticancer activity.

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Anticarcinogenic Effects of Sargassum fulvellum Fractions on Several Human Cancer Cell Lines in vitro (모자반 분획물의 in vitro에서의 항발암효과)

  • 배송자
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.33 no.3
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    • pp.480-486
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    • 2004
  • Despite many therapeutic advances in the understanding of the processes in carcinogenesis, overall mortality statistics are unlikely to change until there is reorientation of the concepts for the use of natural products as new anticarcinogenic agents. In this study, we investigated the anticarcinogenic activity, antioxidant and DPPH scavenging activity of Sargassum fulvellum (SF). SF was extracted with methanol, which was further fractionated into five different types: hexane (SFMH), ethylether (SFMEE), ethyl acetate (SFMEA), butanol (SFMB) and aqueous (SFMA) partition layers. We determined the cytotoxic effect of these layers on human cancer cells by MTT assay. Among various partition layers of SF, at starting concentration of 100 $\mu\textrm{g}$/mL, SFMEE showed very high cytotoxicity which were 92, 90 and 84% and kept high throughout 5 concentration levels sparsed by 100 $\mu\textrm{g}$/mL against all three human cancer cell lines: HepG2, HT-29 and HeLa. SFMEA showed a low cytotoxicity at the beginning concentration level, but as the concentration became denser, growth inhibition effect of cancer cell lines started to increase and at 500 $\mu\textrm{g}$/mL, it hit the highest, which were 91, 96 and 98% against the same three cell lines as above. We observed QR induced effect in all fraction layers of SF. SFMEE showed similar tendensy of QR induced effect as did against cytotoxicity. The QR induced effect of SFMEE on HepG2 cells at 25 $\mu\textrm{g}$/mL concentration indicated 3 times higher than the control value of 1.0 and SFMH tended to be concentration-dependent on HepG2 cells. At 100 $\mu\textrm{g}$/mL, the QR induced effects resulted a ratio, which was 2.5 times higher than the control value. In search for antioxidation effects of SF extract and partition layer, the reducing activity on the 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging potential was sequentially screened. The SFM has similar antioxidant activity as to BHT and vitamin C groups.

Glutamate-Induced Serotonin Depletion in Fetal Rat Brainstem Cultures (흰쥐태 뇌간의 배양에서 Glutamate에 의한 Serotonin의 고갈)

  • Park, Sang-Wook;Wie, Myung-Bok;Song, Dong-Keun;Kim, Yong-Sik;Kim, Yung-Hi
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.189-193
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    • 1993
  • Exposure of dissociated cultures from fetal rat brainstem to glutamate for upto 6 h decreased cellular contents of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in a concentration- and time-dependent manner. In addition, glutamate induced lactate dehydrogenase leakage. Tetrodotoxin did not block the effects induced by glutamate. MK-801 $(1{\mu}M)$, an N-methyl-D-aspartate (NMDA) channel blocker, but not 6-cyano-2,3-dihydroxy-7-nitro-quinoxazoline $(CNQX;\;3{\mu}M)$, a non-NMDA receptor antagonist, blocked glutamate-induced effects, indicating that these glutamate-induced responses are mediated through NMDA receptors.

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